Schwartz - Principles and Practice of Emergency Medicine 4th

Principles and Practice of Emergency Medicine 4th edition (January 15, 1999) by George R. Schwartz (Editor), Paul B. Roth (Editor), James S. Cohen (Editor) By Lippincott, Williams & Wilkins

By OkDoKeY

Principles and Practice of Emergency Medicine CONTENTS Preface Acknowledgments Associate Editor Acknowledgments Contributors Dedication Editors

PART I: RESUSCITATION CHAPTER 1 MECHANISMS OF DYING AND TECHNIQUES OF RESUSCITATION 1–1 Pathophysiology of Dying and Reanimation George R. Schwartz 1–2 Post Intubation: Airway and Ventilator Management George J. Rubeiz, Georges S. Yacoub, Basim A. Dubaybo CHAPTER 2 CARDIOVASCULAR SYSTEM FAILURE AND SHOCK 2–1 Shock Max Harry Weil, Eric C. Rackow 2–2 Shock: Clinical Treatment George R. Schwartz CHAPTER 3 SUDDEN DEATH AND RESUSCITATION 3–1 Sudden Death Barbara K. Hanke, George R. Schwartz 3–2 Cardiopulmonary-Cerebral Resuscitation Peter Safar, Norman S. Abramson 3–3 Advanced Cerebral Resuscitation: The Cutting Edge of ACLS Aiming at Maximal Functional Recovery Peter Safar CHAPTER 4 BRAIN DEATH AND ORGAN RETRIEVAL James L. Bernat, George R. Schwartz CHAPTER 5 ETHICAL ISSUES IN RESUSCITATION George R. Schwartz, Kenneth V. Iserson

PART II: TECHNIQUES AND TIPS CHAPTER 6 PAIN MANAGEMENT James R. Ungar, Daniel Brandes, Bruce M. Reinoehl, George R. Schwartz, Al Ritter CHAPTER 7 WOUND MANAGEMENT Barbara K. Hanke CHAPTER 8 ENT TECHNIQUES 8–1 Cricothyrotomy and Tracheotomy William W. Montgomery, David M. Bowling, George R. Schwartz 8–2 Transtracheal Ventilation Peter Safar, George R. Schwartz 8–3 Myringotomy and Tympanocentesis William W. Montgomery, David M. Bowling 8–4 Epistaxis (Nosebleed) and Post-tonsillectomy Hemorrhage Donald R. Paugh, Michael J. Sullivan 8–5 Dislocation of the Jaw Cherie A. Hargis 8–6 Dysphonia Andrew Blitzer 8–7 Sudden Hearing Loss Wallace Rubin CHAPTER 9 FOREIGN BODY REMOVAL 9–1 External Auditory Canal Stuart R. Fritz, Gabor D. Kelen 9–2 Nose Howard A. Werman 9–3 Skin Robert A. Rusnak 9–4 Ocular Foreign Bodies Stephen F. Larson 9–5 Swallowed Objects Marsha D. Rappley, Sid M. Shah 9–6 Food and Foreign Body Asphyxiation Michael P. Poirier, George R. Schwartz 9–7 Coin Ingestion George R. Schwartz CHAPTER 10 ROUTES FOR DRUGS AND FLUIDS

James S. Cohen CHAPTER 11 IMAGING 11–1 Overview of Imaging Modalities Robin Gaupp, Gloria Birkholz 11–2 Imaging Techniques for Specific Conditions James R. Ungar, George R. Schwartz 11–3 What Test for Blunt Abdominal Trauma—CT, DPL, or Ultrasound? Craig A. Meek, Stephen A. Colucciello, John A. Marx CHAPTER 12 GENITOURINARY TECHNIQUES 12–1 Bladder Catheterization Nanakram Agarwal, Ellen E. Anderson 12–2 Suprapubic Bladder Drainage Nanakram Agarwal, Ellen E. Anderson CHAPTER 13 GASTROINTESTINAL TECHNIQUES: NASOGASTRIC TUBE INSERTION Nanakram Agarwal, Ellen E. Anderson CHAPTER 14 PRACTICE PARAMETERS, CLINICAL POLICIES, PRACTICE GUIDELINES John Dale Dunn

PART III: TRAUMA CHAPTER 15 TRAUMATOLOGY AND TRAUMA SYSTEMS 15–1 Kinematics Norman E. McSwain, Jr. 15–2 Injury Control Arthur L. Kellermann, Knox Todd 15–3 Forensic Emergency Medicine John E. Smialek, George R. Schwartz CHAPTER 16 PREHOSPITAL MANAGEMENT OF TRAUMA Paul E. Pepe CHAPTER 17 EMERGENCY MANAGEMENT OF TRAUMA 17–1 Initial Trauma Evaluation Peter Stewart, Frank Ehrlich 17–2 Tips for Evaluation of Trauma: Injury Patterns George R. Schwartz CHAPTER 18 TRAUMA TO THE HEAD 18–1 General Considerations Thomas A. Gennarelli 18–2 Head Injuries: Specific Emergency Department Management Issues George R. Schwartz, Thom A. Mayer, H. Warren Goldman 18–3 Spinal Injuries John R. Mangiardi, George R. Schwartz 18–4 Trauma to the Face Thom A. Mayer, Errikos Constant CHAPTER 19 TRAUMA TO THE NECK: GENERAL CONSIDERATIONS Prakashchandra M. Rao, Rao R. Ivatury, George R. Schwartz CHAPTER 20 THORACIC TRAUMA 20–1 General Considerations and Technique of Tube Thoracostomy George R. Schwartz, Paul Pepe 20–2 Emergency Department Patient Management of Chest Trauma Panagiotis N. Symbas CHAPTER 21 ABDOMINAL TRAUMA C. Gene Cayten CHAPTER 22 INJURIES OF THE GENITOURINARY TRACT E. James Seidmon, A. Richard Kendall CHAPTER 23 TRAUMA TO THE PERIPHERAL VASCULAR SYSTEM David V. Feliciano CHAPTER 24 TRAUMA TO THE HAND AND NAIL 24–1 Trauma to the Hand Mark T. Jobe, E. Jeff Justis, Jr. 24–2 Nail Evaluation and Procedures Richard K. Scher, Karin H. Satra CHAPTER 25 SPECIAL CONSIDERATIONS 25–1 Trauma in Pregnancy Cloyd B. Gatrell, George R. Schwartz 25–2 Trauma in the Elderly Gerald B. Demarest, George R. Schwartz, Clark Chipman 25–3 Pediatric Trauma George R. Schwartz 25–4 Burns Alan R. Dimick, Russell G. Wagner 25–5 Fat Embolism Syndrome Jose A. Acosta

PART IV: NONTRAUMA EMERGENCIES

A. Cardiovascular CHAPTER 26 CARDIOVASCULAR EMERGENCIES 26–1 Evaluation of Chest Pain George R. Schwartz, James R. Ungar, Marvin A. Wayne, Rosanne Carrero 26–2 Diagnosis and Treatment of Arrhythmias Ruth Ann Greenfield, Raymond N. Vitullo, Martin E. Bacon, J. Marcus Wharton, Joseph C. Howton Appendix/ECG Illustrative Tracings 26–3 Electrolyte Abnormalities Affecting the Heart Jamie Dananberg CHAPTER 27 CARDIOVASCULAR PROCEDURES 27–1 Synchronized and Unsynchronized Cardioversion of Arrhythmias Grant La Farge 27–2 Pericardiocentesis Grant La Farge 27–3 Emergency Pacemaker Use and Evaluation James C. Blankenship, T. Duncan Sellers 27–4 Use of Flow-Directed, Balloon-Tipped Catheters Grant La Farge, Steven G. Rothrock, George I. Litman 27–5 Emergency Physician’s Use of Echocardiography Joseph Rosenblum, James V. Talano CHAPTER 28 CARDIAC EMERGENCIES 28–1 Acute Myocardial Infarction and Unstable Angina James S. Cohen, George R. Schwartz 28–2 Thrombolytic Therapy for Acute Myocardial Infarction James S. Cohen 28–3 Cardiogenic Shock Mark Mandell 28–4 Congestive Heart Failure and Pulmonary Edema Charles L. Emerman, Robert J. Zimmerman 28–5 Myocarditis, Cardiomyopathies, and Pericardial Disease Joseph Rosenblum, James V. Talano 28–6 Infective Endocarditis Philip L. Henneman 28–7 Valvular Heart Disease Morton J. Kern, Lawrence M. Lewis 28–8 Prosthetic Heart Valves: Identification, Function, and Failure Anthony C. Pearson, Satyanarayana Tatineni, Brent Ruoff, Michel Vandormael CHAPTER 29 VASCULAR EMERGENCIES 29–1 Hypertensive Emergencies Abdul M. Memon, Kathleen S. Schrank 29–2 Aortic Aneurysms and Peripheral Arterial Diseases James S. Cohen, Steven G. Rothrock, Nicholas Balsano, C. Gene Cayten, Steven Sornsin 29–3 Carotid Artery Disease Charles L. Emerman, John E. Duldner 29–4 Venous Diseases Earl J. Reisdorff, David E. Pawsat

B. Adult Respiratory CHAPTER 30 ACUTE RESPIRATORY INSUFFICIENCY: OVERVIEW Sandra Schneider CHAPTER 31 DYSPNEA 31–1 Evaluation of Dyspnea Robert H. Dailey 31–2 Acute Upper Airway Obstruction Gerard R. Cox, Suzanne M. Shepherd 31–3 Mediastinal Emergencies Sheldon Jacobson CHAPTER 32 EVALUATION OF PULMONARY FUNCTION IN THE EMERGENCY DEPARTMENT Georges S. Yacoub, Basim A. Dubaybo CHAPTER 33 SPECIFIC RESPIRATORY CONDITIONS 33–1 Pulmonary Embolism Terence D. Valenzuela 33–2 Acute Asthma in Adults Steven E. Gentry, Sandra M. Schneider, Joseph C. Howton 33–3 Hemoptysis Francis L. Counselman 33–4 Pneumothorax Jonathan Vargas 33–5 Aspiration J. Stephen Huff 33–6 Atelectasis J. Stephen Huff CHAPTER 34 RESPIRATORY PHARMACOTHERAPY IN ASTHMA AND OBSTRUCTIVE LUNG DISEASE

Morton S. Skorodin, Nathan C. Skorodin

C. Gastrointestinal CHAPTER 35 ABDOMINAL PAIN: EVALUATION George R. Schwartz, Steven G. Rothrock, Daniel J. Shea, Paul I. Bulat CHAPTER 36 GASTROINTESTINAL BLEEDING 36–1 Overview and General Approach to the Patient Eddy D. Palmer 36–2 Upper Gastrointestinal Bleeding Frederic E. Eckhauser, Steven E. Raper, James A. Knol 36–3 Lower Gastrointestinal Bleeding Gail V. Anderson, Paul F. Cunningham CHAPTER 37 ESOPHAGEAL EMERGENCIES AND DYSPHAGIA Sid M. Shah, Vincent Pflug, Gregory P. Hess CHAPTER 38 ACUTE GASTROENTERITIS Louis J. Wilson, Christopher Truss CHAPTER 39 APPENDICITIS John R. Clarke, John M. Schoffstall, Steven G. Rothrock, George R. Schwartz CHAPTER 40 PERFORATED VISCUS James K. Bouzoukis CHAPTER 41 INTRA-ABDOMINAL INFECTIONS Henry W. Murray CHAPTER 42 GASTRITIS AND PEPTIC ULCER DISEASE Michael W. Mulholland, Frederic E. Eckhauser CHAPTER 43 CROHN DISEASE AND ULCERATIVE COLITIS Mark A. Peppercorn CHAPTER 44 DIVERTICULITIS AND DIVERTICULOSIS C. Gene Cayten, George R. Schwartz CHAPTER 45 ACUTE GALLBLADDER AND BILIARY TRACT DISEASE Richard E. Burney CHAPTER 46 LIVER DISEASE AND HEPATITIS 46–1 Liver Disease Daniel G. Murphy 46–2 Viral Hepatitis Daniel G. Murphy, George R. Schwartz CHAPTER 47 PANCREATIC DISEASE Bernard M. Schuman CHAPTER 48 ANORECTAL DISORDERS George R. Schwartz, Steven G. Rothrock, Monica Ann Rosenthal

D. Renal and Genitourinary CHAPTER 49 RENAL FAILURE Demetrius Ellis, Ellis D. Avner, John C. Maino, II, George R. Schwartz CHAPTER 50 URINARY TRACT INFECTIONS, CYSTITIS, PYELONEPHRITIS Mike Kozminski, George R. Schwartz CHAPTER 51 HEMATURIA Patricia L. Lamb CHAPTER 52 MALE GENITAL PROBLEMS Scott B. Freeman CHAPTER 53 ACUTE URINARY RETENTION AND BLADDER DRAINAGE Lester Karafin, A. Richard Kendall CHAPTER 54 NEUROGENIC BLADDER: CAUSES AND EVALUATION Scott B. Freeman CHAPTER 55 RENAL CALCULI (KIDNEY STONES) John J. Pahira

E. Obstetrics and Gynecology CHAPTER 56 OBSTETRIC EMERGENCIES 56–1 Emergency Delivery Stephen D. Higgins 56–2 Ectopic Pregnancy Russell J. Carlisle, Barbara Hanke 56–3 Hypertensive Disorders of Pregnancy and Preeclampsia Russell J. Carlisle 56–4 Medical Disorders of Pregnancy Van H. Miller 56–5 Medication Use in Pregnancy Robert R. Whipkey 56–6 Medication and Breast Milk Ronald K. Smith 56–7 Postpartum Infections Mark D. Westfall CHAPTER 57 GYNECOLOGIC EMERGENCIES 57–1 Pelvic Pain in Women: Evaluation Stephen J. Wheeler 57–2 Vaginal Infections

Christopher K. Wuerker, Joseph C. Howton 57–3 Vaginal Bleeding Arthur Shapiro CHAPTER 58 THE SEXUALLY ASSAULTED PATIENT Stephen D. Higgins, George R. Schwartz

F. Infectious Disease CHAPTER 59 IMMUNOLOGY 59–1 Anaphylaxis David N. Zull 59–2 Vaccines and Immunoprophylaxis: Measles, Mumps, Rubella, Diphtheria, Pertussis, Varicella, Rabies, Tetanus, and Other Communicable Diseases David N. Zull 59–3 Needlestick Protocols, HIV Contamination, and Vaccination for Hepatitis B Donald A. Romig CHAPTER 60 INFECTIOUS DISEASE 60–1 Patients at Higher Risk for Infection George R. Schwartz 60–2 Fever and Sepsis Sid M. Shah, James J. Gordon, M. Jevitz Patterson, Steven G. Rothrock, George R. Schwartz 60–3 Antibiotic Choices Mary Anne Mangelsen, Kenneth A. Murphy, Jr. CHAPTER 61 SPECIFIC INFECTIONS 61–1 Acute Pharyngitis Jean T. Martin 61–2 Sinusitis Arnold M. Cohn, John R. Jacobs 61–3 Ear Infections Donald R. Paugh, Steven A. Telian 61–4 Infections Causing Obstruction of the Upper Airway Suzanne M. Shepherd, Gerard R. Cox 61–5 Community-acquired Pneumonia Ghiath Bayasi, Georges S. Yacoub, Basim A. Dubaybo 61–6 Meningitis and Meningoencephalitis Mary Anne Mangelsen 61–7 Herpes Simplex Meningoencephalitis George R. Schwartz 61–8 Other Infections: Osteomyelitis, Tetanus, Miliary Tuberculosis, Coccidioides, Histoplasmosis, Blastomyces George R. Schwartz 61–9 Diarrhea W. McDowell Anderson, Robert R. Brinson, George R. Schwartz CHAPTER 62 ABSCESSES 62–1 Abscesses of the Head and Neck John R. Jacobs, Arthur W. Weaver 62–2 Cutaneous Abscesses, Necrotizing Fasciitis, and Gas Gangrene John I. Ellis, George R. Schwartz, Patrick Connell CHAPTER 63 SEXUALLY TRANSMITTED DISEASES 63–1 Sexually Transmitted Diseases Sumner E. Thompson, George R.Schwartz, Ralph K. Della Ratta 63–2 HIV-Related Illness in the Emergency Department Gregory J. Moran

G. Endocrine and Metabolic Balance CHAPTER 64 DIABETES AND COMPLICATIONS 64–1 Diabetic Ketoacidosis David K. English, Joseph C. Howton 64–2 Hypoglycemia R. Carter Clements 64–3 Nonketotic Hypertonicity in Diabetes Mellitus Kristi Koenig, Eric Stirling, Joseph C. Howton 64–4 Lactic Acidosis Douglas M. Salyards, Joseph C. Howton CHAPTER 65 ADRENAL INSUFFICIENCY AND ADRENAL CRISIS David Baldwin, Jr. CHAPTER 66 INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE David L. Vesely CHAPTER 67 THYROID DISORDERS 67–1 Hypothyroidism and Myxedema Coma Joseph C. Howton 67–2 Hyperthyroidism and Thyroid Storm Joseph C. Howton CHAPTER 68 PHEOCHROMOCYTOMA Mukarem A. Siddiqui, Sushma Reddy, James R. Sowers CHAPTER 69 THE PORPHYRIAS Barbara H. Greene

H. Hematologic CHAPTER 70 ANEMIA Ronald L. Rhule, Les Puretz CHAPTER 71 ACQUIRED HEMORRHAGIC DISORDERS Rajalaxmi McKenna CHAPTER 72 EMERGENCY MANAGEMENT OF COMMON CONGENITAL BLEEDING SYNDROMES: HEMOPHILIA AND ALLIED DISORDERS Wadie F. Bahou CHAPTER 73 BLOOD CELL DISORDERS 73–1 Thrombocytopenic Disorders Steve Hulsey, Joseph C. Howton 73–2 Leukocyte Dysfunction and Neutropenia Martin R. Klemperer, Joseph C. Howton 73–3 Polycythemias Eric Stirling CHAPTER 74 SICKLE CELL DISEASE William Reed, Elliott Vichinsky CHAPTER 75 SPLENOMEGALY Lawrence Dall, Lori Eakin CHAPTER 76 TRANSFUSION THERAPY IN EMERGENCY MEDICINE Steven J. Davidson, Ilya M.Chern CHAPTER 77 ONCOLOGIC EMERGENCIES George R. Schwartz, Timothy G. Janz, James Ungar

I. Neurologic CHAPTER 78 NEUROLOGICAL PROCEDURES Venkat Narayan, William F. Bouzarth CHAPTER 79 EMERGENCY EVALUATION OF NEUROLOGIC DISORDERS J. Stephen Huff, Thomas P. Bleck, Aron S. Buchman CHAPTER 80 HEADACHE AND FACIAL PAIN 80–1 General Approach George R. Schwartz 80–2 Migraine Joel R. Saper 80–3 Facial Pain, Trigeminal Neuralgia, and Tics George R. Schwartz CHAPTER 81 SYNCOPE 81–1 Evaluation and General Considerations Stephen L. Adams, Gary J. Martin 81–2 Selected ED Presentations of Syncope Milton N. Luria, George R. Schwartz CHAPTER 82 CONFUSION Arthur P. Safran, Thomas D. Sabin CHAPTER 83 THE COMATOSE PATIENT Michael C. Smith, George Katsamakis CHAPTER 84 SEIZURES Kevin M. Kelly, James P. Valeriano CHAPTER 85 DIZZINESS OR VERTIGO Kevin M. Kelly, Steven A. Telian, Thomas M. Stein CHAPTER 86 STROKE AND TRANSIENT ISCHEMIC ATTACKS Stephen J. Marks, Alan J. Tuchman CHAPTER 87 NONTRAUMATIC SPINAL CORD SYNDROMES Philippe D. Vaillancourt, George R. Schwartz CHAPTER 88 NEUROMUSCULAR EMERGENCIES James W. Albers, Mark B. Bromberg CHAPTER 89 INCREASED INTRACRANIAL PRESSURE Thomas P. Bleck CHAPTER 90 HYDROCEPHALUS SHUNTS IN THE EMERGENCY DEPARTMENT Robert C. Dauser CHAPTER 91 NEUROLEPTIC MALIGNANT SYNDROME Barbara S. Koppel

J. Ophthalmology CHAPTER 92 OCULAR EVALUATION AND PROCEDURES: GENERAL CONSIDERATIONS George L. Spaeth, John Purcell, Jr., John B. Jeffers, John A. Milton CHAPTER 93 OCULAR TRAUMA John J. Purcell, George L. Spaeth, John A. Milton CHAPTER 94 ACUTE VISUAL LOSS Douglas D. Brunette, Steven R. Bennett CHAPTER 95 THE ACUTE PAINFUL EYE Michael E. Whiting CHAPTER 96 COMMON EYE INFECTIONS Theodore Rabinovitch, Scott S. Weissman, Robert A. Nozik CHAPTER 97 NEURO-OPHTHALMOLOGIC EMERGENCIES Douglas D. Brunette, Steven R. Bennett CHAPTER 98 THE EYE AND SYSTEMIC DISEASE

Scott S. Weissman, Theodore Rabinovitch, Robert A. Nozik CHAPTER 99 OPHTHALMOLOGIC PHARMACOTHERAPY IN EMERGENCIES Scott S. Weissman, Theodore Rabinovitch, Robert A. Nozik

K. Dermatology CHAPTER 100 DERMATOLOGIC EXAMINATION Philip D. Shenefelt, Neil A. Fenske CHAPTER 101 PRURITUS George R. Schwartz, Howard M. Simons CHAPTER 102 CUTANEOUS SIGNS OF SYSTEMIC DISEASE Eric Stirling CHAPTER 103 LIFE-THREATENING DERMATOSES Jeffrey P. Callen, Carol L. Kulp-Shorten CHAPTER 104 DERMATITIS Joseph F. Fowler, Jr. CHAPTER 105 PURPURA George R. Schwartz, Howard M. Simons CHAPTER 106 SKIN INFECTIONS George R. Schwartz, Howard M. Simons CHAPTER 107 VESICULOBULLOUS ERUPTIONS George R. Schwartz, Howard M. Simons CHAPTER 108 DRUG ERUPTIONS Jeffrey P. Callen, Carol L. Kulp-Shorten CHAPTER 109 URITICARIA Marc D. Brown

L. Orthopedics CHAPTER 110 ORTHOPEDIC PROCEDURES James R. Ungar CHAPTER 111 MUSCULOSKELETAL INJURIES 111–1 Trauma to the Extremities and Soft Tissues James R. Ungar, William R. MacAusland, Leo Capobianco, Barbara K. Hanke 111–2 Salter Classification of Growth Plate Injuries James R. Ungar CHAPTER 112 ACUTE LOW-BACK PAIN Charles M. Grudem, George R. Schwartz CHAPTER 113 EMERGENCIES IN SPORTS James G. Garrick, James R. Ungar, Marie D. Schafle, George R. Schwartz CHAPTER 114 EMERGENCY RHEUMATOLOGY 114–1 Systemic Rheumatic Diseases Rita K. Cydulka, Steven B. Sorin 114–2 The Swollen Joint 114–2.1 Monoarticular Arthritis Rita K. Cydulka, Steven B. Sorin 114–2.2 Polyarticular Arthritis Rita K. Cydulka, Steven B. Sorin

M. Dental and Periodontal CHAPTER 115 INTRAORAL LOCAL ANESTHESIA Craig S. Miller, Donald Falace CHAPTER 116 TOOTHACHE AND PAIN OF DENTAL ORIGIN 116–1 Odontogenic Pain: Toothache and Pain of Dental Origin Bruce R. Rothwell 116–2 Tooth Avulsions and Fractures Jeffrey B. Dembo CHAPTER 117 GINGIVA 117–1 Gingival Hemorrhage James T. Amsterdam 117–2 Gingival and Periodontal Abscesses James T. Amsterdam

N. Psychiatric and Behavioral Emergencies CHAPTER 118 TRIAGE Stephanie von Ammon Cavanaugh, William S. Gilmer CHAPTER 119 TIPS FOR INITIAL EVALUATION OF THE NEUROPSYCHIATRIC PATIENT Craig A. Taylor, Barbara C. Good CHAPTER 120 EMERGENCY DEPARTMENT PSYCHIATRIC EMERGENCIES Stephanie von Ammon Cavanaugh, William S. Gilmer CHAPTER 121 PSYCHIATRIC MEDICAL LEGAL CONSIDERATIONS: CODES, RESTRAINTS, COMMITMENTS, TRANSFERS, AND COBRA REGULATIONS Stephanie von Ammon Cavanaugh, William S. Gilmer CHAPTER 122 ORGANIC BRAIN SYNDROMES AND DISORDERS Stephanie von Ammon Cavanaugh CHAPTER 123 ANXIETY OR PANIC DISORDERS Wayne J. Katon CHAPTER 124 SOMATOFORM DISORDERS

Beverly Fauman CHAPTER 125 DOMESTIC ABUSE, ELDER ABUSE, AND THE ABUSED, ASSAULTED ADULT Susan V. McLeer, Margo J. Krasnoff

PART V: SPECIAL POPULATIONS O. Pediatrics CHAPTER 126 EVALUATON 126–1 Approach to the Pediatric Emergency Patient Thom A. Mayer, Robert C. Luten, Michael F. Altieri 126–2 Altered Mental Status in Children Daniel J. Isaacman CHAPTER 127 RESUSCITATION 127–1 Neonatal Resuscitation and Selected Neonatal Emergencies Kent F. Argubright, Kristi Watterberg 127–2 Pediatric Cardiopulmonary Resuscitation Paula C. Fink CHAPTER 128 AIRWAYS 128–1 Management of the Pediatric Airway Thom A. Mayer 128–2 Pediatric Asthma Robert G. Bolte CHAPTER 129 INFECTIONS 129–1 Infection and Bacteremia: Management of the Febrile Child Under Two Years Daniel J. Isaacman, Paul N. Seward 129–2 Acute Respiratory Emergencies in Children: Croup, Epiglottitis, Bronchiolitis, Pneumonia Michael F. Altieri, Thom A. Mayer 129–3 Pediatric Viral Infections: Measles, Mumps, Rubella “Fifth” Disease, Roseola, Chicken Pox, Herpes Virus, Cytomegalovirus, Infectious Mononucleosis, Rotavirus, Adenovirus, Polio, Conjunctivitis, Gingivostomatitis, Rabies Michael R. Sayre, George R. Schwartz CHAPTER 130 SYSTEMS 130–1 Pediatric Cardiac Emergencies Karen S. Rheuban 130–2 Dehydration, Gastrointestinal Emergencies, Pediatric Appendicitis, Urinary Tract Infections, Hematologic Emergencies, and Neurologic Emergencies (including Meningitis) George R. Schwartz, Thom A. Mayer, Garrett E. Bergman, Ellen B. Bishop 130–3 Sudden Infant Death Syndrome and Apparent Life-Threatening Events Michele R. Wadsworth, George R. Schwartz 130–4 Evaluation and Management of Child Abuse George R. Schwartz, Steve Lesser, Garrett E. Bergman

P. Geriatrics CHAPTER 131 GERIATRIC EMERGENCY MEDICINE: OVERVIEW George R. Schwartz, Gideon Bosker CHAPTER 132 ACUTE MENTAL STATUS CHANGE IN THE ELDERLY Curt E. Dill, Dennis P. Price, George R. Schwartz CHAPTER 133 SEPSIS IN THE ELDERLY George R. Schwartz

PART VI: ENVIRONMENTAL AND TOXICOLOGY EMERGENCIES Q. Environmental CHAPTER 134 HIGH ALTITUDE ILLNESS: ACUTE MOUNTAIN SICKNESS, PULMONARY EDEMA, CEREBRAL EDEMA, RETINAL HEMORRHAGE, BRONCHITIS James R. Tryon CHAPTER 135 ENVIRONMENTAL PRESSURE 135–1 Diving and Altitude Emergencies George R. Schwartz, Jeffrey Sipsy, Barbara K. Hanke 135–2 Hyperbaric Medicine Barbara K. Hanke CHAPTER 136 NEAR-DROWNING Barbara K. Hanke, George R. Schwartz, James E. Gerace CHAPTER 137 BITES 137–1 Mammalian Bites Edward Newton 137–2 Diagnosis and Treatment of Snakebite James R. Roberts 137–3 Toxic Bites and Stings Loren Johnson 137–4 Tick-Borne Diseases Mary Anne Mangelsen CHAPTER 138 LIGHTNING AND ELECTRICAL INJURIES 138–1 Lightning Injuries Edgar B. Billowitz 138–2 Electrical Injuries Edgar B. Billowitz 138–3 Laser and Microwave Injuries

George R. Schwartz, Leon Goldman 138–4 Radiation Injury George L. Voelz CHAPTER 139 SMOKE INHALATION Dennis P. Price, Harvey Silverman, George R. Schwartz CHAPTER 140 TRAVEL MEDICINE 140–1 Introduction to Travel Medicine David Gregory 140–2 Wilderness Medicine Kenneth V. Iserson 140–3 Wilderness Infectious Diseases Sharon Kolber 140–4 Sun-Induced Disorders David A. Kramer, Philip Shayne 140–5 Hypothermia Loren Johnson 140–6 Frostbite and Other Cold Injuries Loren Johnson 140–7 Heat Stress Diseases Audrey Urbano-Brown, Robert P. Proulx, George R. Schwartz

R. Toxicology CHAPTER 141 POISON CONTROL CENTERS Randall J. Berlin, Martin J. Smilkstein CHAPTER 142 PREHOSPITAL AND INTERHOSPITAL CARE OF THE POISONED OR OVERDOSED PATIENT Theodore I. Benzer, Neal Flomenbaum CHAPTER 143 THE POISONED PATIENT: OVERVIEW George R. Schwartz CHAPTER 144 CRITICAL CARE MEDICAL TOXICOLOGY Howard C. Mofenson, Thomas R. Caraccio, Joseph Greensher, G. Brady APPENDIX 144A_INDEX OF SUBSTANCES Howard C. Mofenson, Thomas R. Caraccio, Joseph Greensher, G. Brady CHAPTER 145 DRUG ABUSE AND TOXICITY James R. Ungar, George R. Schwartz, David G. Levine CHAPTER 146 ALCOHOL 146–1 Alcohol Toxicodynamics and Forensic Considerations Harold Osborn, James Celentano, John Munyak 146–2 Alcohol Substitutes: Treatment of Poisonings by Methanol, Ethylene Glycol, and Isopropyl Alcohol Harold Osborn 146–3 Alcohol Withdrawal: Differential Diagnosis and Emergency Treatment David B. McMicken 146–4 Alcohol-Related Diseases: Emergency Department Management John I. Ellis, Michael Whiting, Martha Roper CHAPTER 147 OCCUPATIONAL EXPOSURES AND ART HAZARDS Steven H. Lesser, Steven J. Weiss CHAPTER 148 FOOD POISONING George R. Schwartz

PART VII: MISCELLANEOUS S. Emergency Medical Services (EMS) Systems CHAPTER 149 EMS SYSTEMS DEVELOPMENT IN THE UNITED STATES Alexander Kuehl CHAPTER 150 EMS SYSTEMS FACTORS AND SURVIVAL OF CARDIAC ARREST Mickey S. Eisenberg CHAPTER 151 THE EFFECT OF EMS SYSTEMS FACTORS ON TRAUMA SURVIVAL George R. Schwartz CHAPTER 152 GROUND AND AIR EMERGENCY TRANSPORT Gregory W. Hendey CHAPTER 153 DISASTER PLANNING AND OPERATION IN THE EMERGENCY DEPARTMENT Theresa M. Schwab, Eric K. Noji CHAPTER 154 INTERNATIONAL PERSPECTIVE OF EMS SYSTEMS DEVELOPMENT 154–1 Germany Markus D.W. Lipp, Andreas R. Thierbach 154–2 Emergency Care “Skoraya” in Russia Michail V. Grinev 154–3 Australia Harry F. Oxer 154–4 Terrorism: EMS Issues and Management John E. Prescott, Thom A. Mayer

T. Emergency Department Management CHAPTER 155 INTRODUCTION TO MANAGEMENT: DEFINITIONS, UTILIZATION, AND WORKFORCE ISSUES James S. Cohen CHAPTER 156 THE WORK ENVIRONMENT IN EMERGENCY MEDICINE: STRESS, SHIFT WORK, AND AVOIDING BURNOUT George R. Schwartz CHAPTER 157 THE ROLE OF THE EMERGENCY DEPARTMENT DIRECTOR

Stephen J. Dresnick CHAPTER 158 TIPS FOR CONTINUOUS QUALITY IMPROVEMENT Thom A. Mayer CHAPTER 159 FAST-TRACK CARE AND OCCUPATIONAL MEDICINE David Brooke CHAPTER 160 TIPS FOR CONTRACTING WITH MANAGED CARE ORGANIZATIONS Thom A. Mayer CHAPTER 161 FINANCIAL ASPECTS OF EMERGENCY MEDICINE James S. Cohen CHAPTER 162 EDUCATION IN EMERGENCY DEPARTMENTS: FOCUS ON DECISION MAKING Sheldon Jacobson, George R. Schwartz CHAPTER 163 COMPUTERS AND EMERGENCY MEDICINE Mark Mandell, Ashraf Nashed, John Horning

U. Medicolegal Aspects of Emergency Care CHAPTER 164 MEDICOLEGAL ISSUES IN EMERGENCY MEDICINE John D. Dunn APPENDIX A: NORMAL REFERENCE VALUES Dennis R. Ehrhardt APPENDIX B: USEFUL TABLES

CONTRIBUTORS Norman S. Abramson, M.D. Professor of Emergency Medicine Ohio State University Columbus, Ohio Jose A. Acosta, M.D., F.A.C.S. Attending Surgeon Department of General Surgery and Critical Care National Naval Medical Center Bethesda, Maryland Stephen L. Adams, M.D., F.A.C.P., F.A.C.E.P. Associate Professor of Medicine Northwestern University Medical School Associate Chief, Division of Emergency Medicine Department of Medicine Clinical Practice Director, Emergency Medicine Northwestern Medical Faculty Foundation Associate Medical Director, Emergency Medical Services Northwestern Memorial Hospital Chicago, Illinois Nanakram Agarwal, M.D. New York Medical College Our Lady of Mercy Medical Center Bronx, New York James W. Albers, M.D., Ph.D. Professor of Neurology Director, Neuromuscular Program Department of Neurology University of Michigan Medical Center Ann Arbor, Michigan Michael F. Altieri, M.D., F.A.A.P., F.A.C.E.P. Associate Clinical Professor Department of Emergency Medicine and Pediatrics George Washington University Georgetown University Washington, D.C. Associate Clinical Professor Department of Pediatrics University of Virginia Charlottesville, Virginia James T. Amsterdam, D.M.D., M.D. Professor of Emergency Medicine Department of Emergency Medicine Northeastern Ohio Universities College of Medicine Rootstown, Ohio Ellen E. Anderson, M.D. Currently Missionary Physician in Africa Gail V. Anderson, Jr., M.D., M.B.A., F.A.C.E.P. Associate Professor Department of Surgery (Emergency Medicine) Emory University School of Medicine Senior Vice President Department of Medical Affairs Grady Health System Atlanta, Georgia W. McDowell Anderson, M.D. Associate Professor of Medicine Division of Pulmonary and Critical Care Medicine University of Southern Florida College of Medicine Tampa, Florida Kent F. Argubright, M.D. Albuquerque, New Mexico Ellis D. Avner, M.D. Professor of Pediatrics Director, Division of Nephrology Children’s Hospital and Medical Center University of Washington Medical School Seattle, Washington Martin E. Bacon, M.D. National Naval Medical Center Department of Cardiology Bethesda, Maryland Wadie F. Bahou, M.D. Associate Professor of Medicine Division of Hematology Department of Internal Medicine State University of New York

University Hospital and Medical Center Stony Brook, New York David Baldwin, Jr., M.D. Assistant Professor of Medicine Department of Internal Medicine Rush Medical College Chicago, Illinois Nicholas Balsano, M.D. Bronx, New York Ghiath Bayasi, M. D. Genesee Lung Associates Burton, Michigan Steven R. Bennett, M.D. Clinical Assistant Professor Department of Ophthalmology University of Minnesota Minnesota, Minnesota Theodore I. Benzer, M.D., Ph.D. Lecturer in Medicine Harvard Medical School Emergency Department Massachusetts General Hospital Boston, Massachusetts Garrett E. Bergman, M.D. Clinical Professor of Pediatrics Department of Pediatrics Allegheny University of the Health Sciences Philadelphia, Pennsylvania Randall J. Berlin, M.D., D.A.C.E.P. Clinical Instructor Department of Emergency Medicine Oregon Health Sciences University Portland, Oregon James L. Bernat, M.D. Professor of Neurology Dartmouth Medical School Hanover, New Hampshire Neurology Service Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire Edgar B. Billowitz, M.D., F.A.C.E.P. Staff Physician Department of Emergency Medicine St. Vincent Hospital Santa Fe, New Mexico Gloria Birkholz, R.N., J.D. Professor of Nursing College of Nursing University of New Mexico Albuquerque, New Mexico Ellen B. Bishop, M.D., F.A.A.P. Department of Pediatrics Lehigh Valley Hospital Allentown, Pennsylvania James C. Blankenship, M.D., F.A.C.C., F.S.C.A.I. Director, Cardiac Catheterization Laboratories Department of Cardiology, Geisinger Medical Center Pennsylvania State Geisinger Health System Danville, Pennsylvania Thomas P. Bleck, M.D. Assistant Professor Health and Science Center Department of Neurology University of Virginia Medical Center Charlottesville, Virginia Andrew Blitzer, M.D., D.D.S. Professor of Clinical Otolaryngology Columbia University Director, New York Center for Voice and Swallowing Disorders New York, New York Robert G. Bolte, M.D., F.A.A.P., F.A.C.E.P. Professor of Pediatrics University of Utah School of Medicine Director, Emergency Services Primary Children’s Medical Center

Salt Lake City, Utah Gideon Bosker, M.D., F.A.C.E.P. Assistant Clinical Professor Department of Emergency Medicine Yale University School of Medicine New Haven, Connecticut James K. Bouzoukis, M.D., F.A.C.S., F.A.A.E.M. Program Director Department of Emergency Medicine Medical Center of Delaware Newark, Delaware David M. Bowling, M.D., F.A.C.S. Clinical Instructor in Otology & Laryngology Harvard Medical School Department of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear Infirmary Boston, Massachusetts G. Brady, M.D. Daniel Brandes, M.D., F.A.C.E.P. Emergency Physician Department of Emergency Medicine Maui Memorial Hospital Kahului, Maui, Hawaii Robert R. Brinson, M.D. Montgomery, Alabama Mark B. Bromberg, M.D., Ph.D. Associate Professor Department of Neurology University of Utah Medical Center Salt Lake City, Utah David Brooke, M.D., F.A.C.E.P. Medical Director Department of Emergency Services Lakeland Regional Medical Center Lakeland, Florida Marc D. Brown, M.D. Associate Professor of Dermatology Department of Dermatology University of Rochester Strong Memorial Hospital Rochester, New York Douglas D. Brunette, M.D. Department of Emergency Medicine Hennepin County Medical Center Minneapolis, Minnesota Aron S. Buchman, M.D. Associate Professor Department of Neurology Rush-Presbyterian St. Luke’s Medical Center Chicago, Illinois Paul I. Bulat, M.D., F.A.C.E.P. Instructor in Medicine Division of Emergency Medicine The University of Massachusetts Medical School Director of Emergency Services St. Luke’s Hospital of New Bedford, Inc. New Bedford, Massachusetts Richard E. Burney, M.D., F.A.C.S. Professor of Surgery University of Michigan Ann Arbor, Michigan Jeffrey P. Callen, M.D. Professor and Chief Department of Medicine Division of Dermatology University of Louisville School of Medicine Louisville, Kentucky Leo J. Capobianco, D.O. Morristown Memorial Hospital Emergency Medicine/Travel Medicine Emergency Medical Associates Livingston, New Jersey Thomas R. Caraccio, Pharm.D. Clinical Manager Long Island Regional Poison Control Center

Winthrop University Hospital Mineola, New York Assistant Professor of Emergency Medicine University Hospital State University of New York at Stony Brook Stony Brook, New York Russell J. Carlisle, M.D., F.A.C.E.P. Medical Director Emergency Department Providence Seattle Medical Center Clinical Instructor Department of Internal Medicine University of Washington Seattle, Washington Rosanne Carrero, M.D. St. Joseph Hospital Bellingham, Washington Ketchikan General Hospital Ketchikan, Alaska C. Gene Cayten, M.D., M.P.H., F.A.C.S. Professor of Surgery and Preventive and Community Medicine Director, Institute for Trauma and Emergency Care Director, Department of Surgery, Our Lady of Mercy Medical Center New York Medical College Valhalla, New York James J. Celentano, M.D., Ph.D. Attending Physician Department of Emergency Medicine Lincoln Medical and Mental Health Center Bronx, New York Ilya M. Chern, M.D., F.A.C.E.P. Chief Department of Emergency Medicine Plantation General Hospital Plantation, Florida Clark Chipman, M.D. Emergency Physician Emanuel Hospital and Health Center Clinical Associate Professor of Emergency Medicine Department of Emergency Medicine Oregon Health Sciences University Portland, Oregon John R. Clarke, M.D., F.A.C.S. Professor of Surgery Allegheny University of the Health Sciences Philadelphia, Pennsylvania R. Carter Clements, M.D., F.A.C.E.P. Clinical Instructor in Medicine Department of Internal Medicine Division of Emergency Medicine University of California, San Francisco San Francisco, California Assistant Chief/CQI Coordinator Department of Emergency Medicine ACMC Highland Hospital Oakland, California James S. Cohen, M.D., D.A.B.E.M., D.A.B.I.M., F.A.A.E.M. Attending Physician Saratoga Emergency Physicians Saratoga Springs, New York Arnold M. Cohn, M.D. Professor Department of Otolaryngology-Head and Neck Surgery Wayne State University Medical School Detroit, Michigan Stephen A. Colucciello, M.D., F.A.C.E.P. Director, Clinical Services Trauma Coordinator Department of Emergency Medicine Carolinas Medical Center Charlotte, North Carolina Patrick Connell, M.D. Department of Emergency Medicine Highland General Hospital Oakland, California Errikos Constant, M.D., D.D.S., F.A.C.S. College of Human Medicine Michigan State University East Lansing, Michigan Sparrow Hospital

St. Lawrence Hospital Ingram Medical Center Lansing, Michigan Francis L. Counselman, M.D., F.A.C.E.P. Associate Professor and Chairman Department of Emergency Medicine Eastern Virginia Medical School Norfolk, Virginia Gerard R. Cox, M.D., M.H.A., F.A.C.E.P. Commander Medical Corps, U.S. Navy Clinical Assistant Professor Department of Military and Emergency Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland Clinical Assistant Professor Department of Emergency Medicine University of South Alabama School of Medicine Mobile, Alabama Paul A. Cunningham, M.B., B.S., F.A.C.E.M. Emergency Physician Emergency Department Concord Hospital Sydney, Australia Rita K. Cydulka, M.D., F.A.C.E.P. Residency Director Department of Emergency Medicine Metro Health Medical Center Assistant Professor Department of Surgery Case Western Reserve University Cleveland, Ohio Robert H. Dailey, M.D., F.A.C.E.P. Clinical Professor Department of Medicine University of California, San Francisco San Francisco, California Lawrence Dall, M.D. Professor of Medicine Chief, Section of Infectious Diseases University of Missouri-Kansas City School of Medicine Kansas City, Missouri Jamie Dananberg, M.D. Clinical Research Physician Diabetes Care and Endocrinology Lilly Research Laboratories Indianapolis, Indiana Robert C. Dauser, M.D. Assistant Professor University of Michigan Ann Arbor, Michigan Steven J. Davidson, M.D., M.B.A. Chairman Department of Emergency Medicine Maimonides Medical Center Professor of Clinical Emergency Medicine Department of Emergency Medicine State University of New York Health Sciences Center Brooklyn, New York Ralph K. Della Ratta, M.D. Mineola, New York Gerald B. Demarest, M.D. Director, Burn and Trauma Service University of New Mexico Medical Center Albuquerque, New Mexico Jeffrey B. Dembo, D.D.S., M.S. Professor of Oral and Maxillofacial Surgery Department of Oral Health Practice University of Kentucky College of Dentistry Lexington, Kentucky Curt E. Dill, M.D. Alan R. Dimick, M.D. Professor of Surgery Director, Burn Center Department of Surgery University of Alabama Birmingham, Alabama

Stephen J. Dresnick, M.D., F.A.C.E.P. Clinical Professor Department of Emergency Medicine University of North Carolina Chapel Hill, North Carolina President Sterling Health Care Group Miami, Florida Basim A. Dubaybo, M.D. Associate Professor of Medicine Department of Internal Medicine Wayne State University School of Medicine Detroit, Michigan John E. Duldner, M.D. Clinical Research Fellow Department of Emergency Medicine MetroHealth Medical Center Cleveland, Ohio John Dale Dunn, M.D., J.D., F.A.C.E.P., F.A.C.L.M., F.A.A.F.P. Director Emergency Services and Physician Advisor Brownwood Regional Medical Center Brownwood, Texas Lori Eakin, M.D. Instructor, Clinical Pediatrics University of Missouri-Kansas City School of Medicine Kansas City, Missouri Frederic E. Eckhauser, M.D. Professor of Surgery Department of Surgery Chief, Division of Gastrointestinal Surgery University of Michigan Medical Center Ann Arbor, Michigan Dennis R. Ehrhardt, M.D. St. Vincent Hospital Santa Fe, New Mexico Frank Ehrlich, M.D., F.A.C.S. Chairman, Department of Surgery St. Joseph’s Hospital and Medical Center Paterson, New Jersey Mickey S. Eisenberg, M.D., Ph.D. Professor of Medicine Director of Emergency Medicine Service University of Washington Medical Center Seattle, Washington Demetrius Ellis, M.D. Professor of Pediatrics and Nephrology Director of Pediatric Nephrology University of Pittsburgh School of Medicine Children’s Hospital of Pittsburgh Pittsburgh, Pennsylvania John I. Ellis, M.D. Assistant Clinical Professor Department of Medicine Division of Emergency Medicine University of California San Francisco San Francisco, California Doctor’s Medical Center San Pablo, California Charles L. Emerman, M.D. Chairman Department of Emergency Medicine MetroHealth Medical Center Cleveland, Ohio David K. English, M.D. Medical Student Director Department of Emergency Medicine Alameda County Medical Center Oakland, California Assistant Clinical Professor of Medicine Department of Medicine University of California San Francisco San Francisco, California Donald Falace, M.D. Professor and Chief of Oral Diagnosis and Oral Medicine Department of Oral Health Science University of Kentucky College of Dentistry

Lexington, Kentucky Beverly J. Fauman, M.D., F.A.P.A, F.A.C.Psych. Associate Professor of Psychiatry University of Maryland School of Medicine Senior Psychiatrist Walter P. Carter Center University of Maryland Medical Systems Baltimore, Maryland David V. Feliciano, M.D., F.A.C.S. Professor of Surgery Emory University School of Medicine Chief of Trauma and Tumor Services Grady Memorial Hospital Atlanta, Georgia Neil A. Fenske, M.D., F.A.C.P. Professor and Director Department of Cutaneous Surgery University of South Florida College of Medicine Tampa, Florida Paula C. Fink, M.D., F.A.A.P. Clinical Assistant Professor of Pediatrics Department of Pediatrics University of Minnesota, Childrens Health Care Minneapolis, Minnesota Neal Flomenbaum, M.D. Professor of Clinical Medicine Cornell University Medical College Chief, Emergency Medicine The New York Hospital New York, New York Joseph F. Fowler, Jr., M.D. Associate Clinical Professor of Dermatology Director, Occupational Dermatology and Patch Test Clinic University of Louisville School of Medicine Louisville, Kentucky Scott B. Freeman, M.D., F.A.C.E.P. Residency Director and Assistant Professor Section of Emergency Medicine Wayne State University Detroit Receiving Hospital and University Health Center Emergency Department Detroit, Michigan Stuart R. Fritz, M.D., F.A.C.E.P. Emergency Physicians Professional Association Minneapolis, Minnesota James G. Garrick, M.D. Director, Center for Sports Medicine St. Francis Memorial Hospital San Francisco, California Cloyd B. Gatrell, M.D., F.A.C.E.P. Colonel, Medical Corps Commander Munson Army Community Hospital Fort Leavenworth, Kansas Robin J. Gaupp, M.D., D.A.B.R. Attending Radiologist Santa Fe Radiology St. Vincent Hospital Santa Fe, New Mexico Thomas A. Gennarelli, M.D., F.A.C.S. Professor and Chair Department of Neurosurgery Allegheny University of the Health Sciences Philadelphia, Pennsylvania Steven E. Gentry, M.D. Assistant Professor of Medicine Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia James E. Gerace, M.D. Medical Director USA MCO Chief of Staff Phoenix Memorial Hospital Phoenix, Arizona William S. Gilmer, M.D. Assistant Professor

Department of Psychiatry & Behavioral Sciences Northwestern University Medical School Medical Director, Clinical Program Asher Center for Study & Treatment of Depressive Disorders Chicago, Illinois H. Warren Goldman, Ph.D., M.D. Clinical Professor and Vice Chairman Department of Neurosurgery Jefferson Medical College Director, Center for Minimally Invasive Brain Surgery Wills Neurosensory Institute Thomas Jefferson University Hospital Philadelphia, Pennsylvania Barbara C. Good, Ph.D. Senior Medical Writer Neurosciences Research Center Allegheny University of the Health Sciences Pittsburgh, Pennsylvania James G. Gordon, M.D., F.A.C.P. Assistant Clinical Professor of Medicine Department of Medicine Wayne State University Detroit, Michigan Barbara H. Greene, M.D. Associate Professor of Medicine Division of General Medicine Emory University Atlanta, Georgia Ruth Ann Greenfield, M.D. Assistant Professor of Medicine Division of Cardiology Duke University Medical Center Durham, North Carolina Joseph Greensher, M.D. Medical Director and Associate Chairman Department of Pediatrics Associate Director Long Island Regional Poison Control Center Winthrop University Hospital Mineola, New York Professor of Pediatrics University of New York at Stony Brook Stony Brook, New York David Gregory, M.D. Captain, United States Public Health Service Senior Consultant in Infectious Disease Indian Health Service Santa Fe Indian Hospital Santa Fe, New Mexico Michail V. Grinev, M.D., Ph.D. Professor Director of Institute of Emergency Care Djanelidze Research Institute of Emergency Care St. Petersburg, Russia Charles M. Grudem, M.D., D.A.B.E.M., F.N.A.S.S., F.A.A.D.E.P. Medical Director Managed Disability UNICARE Atlanta, Georgia Barbara K. Hanke, M.D., F.A.C.E.P. Staff Emergency Physician St. Vincent Hospital Santa Fe, New Mexico Clinical Assistant Professor of Family and Community Medicine University of New Mexico School of Medicine Albuquerque, New Mexico Cherie A. Hargis, M.D. Attending Physician Department of Emergency Medicine Alameda County Medical Center, Highland Campus Oakland, California Gregory W. Hendey, M.D. Assistant Clinical Professor of Medicine University of California San Francisco University Medical Center Fresno, California Philip L. Henneman, M.D. Vice Chair Department of Emergency Medicine Harbor-University of California Los Angeles Medical Center

Torrance, California Associate Professor of Medicine University of California Los Angeles School of Medicine Los Angeles, California Gregory P. Hess, M.D. Georgetown Medical Center Washington, D.C. Stephen D. Higgins, M.D. Medical Director Department of Emergency Services St. Francis Medical Center Lynwood, California John Horning, M.D. Staff Physician Department of Emergency Medicine Elliot Hospital Manchester, New Hampshire Joseph C. Howton, M.D. Assistant Clinical Professor of Medicine Department of Medicine University of California School of Medicine San Francisco, California Attending Physician Department of Emergency Medicine Good Samaritan Hospital Puyallup, Washington J. Stephen Huff, M.D. Associate Professor of Emergency Medicine and Neurology Department of Emergency Medicine University of Virginia Health Sciences Center Charlottesville, Virginia Steve Hulsey, M.D. Assistant Professor Department of Surgery University of Vermont Burlington, Vermont Daniel J. Isaacman, M.D., F.A.A.P. Division Director Pediatric Emergency Medicine Children’s Hospital of the King’s Daughters Associate Professor of Pediatrics Eastern Virginia Medicine School Norfolk, Virginia Kenneth V. Iserson, M.D., M.B.A., F.A.C.E.P. Professor of Surgery Director, Arizona Bioethics Program University of Arizona College of Medicine Tucson, Arizona Rao R. Ivatury, M.D., F.A.C.S. Associate Professor of Surgery New York Medical College Chief of Trauma Co-Director of SICU Lincoln Hospital Bronx, New York John R. Jacobs, M.D. Professor Otolaryngology-Head and Neck Surgery Wayne State University Medical School Director, Head and Neck Cancer Program Karmanos Cancer Institute Detroit, Michigan Sheldon Jacobson, M.D. Professor and Chairman Department of Emergency Medicine Mount Sinai School of Medicine New York, New York Timothy G. Janz, M.D. Associate Professor Department of Emergency Medicine and Pulmonary/Critical Care Division Department of Medicine Wright State University School of Medicine Dayton, Ohio John B. Jeffers, D.V.M., M.D. Director Emergency Department Wills Eye Hospital

Philadelphia, Pennsylvania Mark T. Jobe, M.D. Assistant Professor Department of Orthopaedic Surgery University of Tennessee-Campbell Clinic Memphis, Tennessee Loren A. Johnson, M.D., F.A.C.E.P. Medical Director Emergency Department Sutter Davis Hospital Davis, California E. Jeff Justis, Jr., M.D. Clinical Associate Professor Department of Orthopedics University of Tennessee-Campbell Foundation Memphis, Tennessee Lester J. Karafin, M.D. Professor Emeritus Department of Urology Temple University Professor Emeritus Department of Urology Medical College of Pennsylvania Philadelphia, Pennsylvania Wayne Katon, M.D. Professor and Chief Division of Consultation-Liaison Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine Seattle, Washington George Katsamakis, M.D. Department of Neurological Sciences Rush-Presbyterian-St. Luke’s Medical Center Chicago, Illinois Gabor D. Kelen, M.D. Professor and Chair Johns Hopkins University Emergency Physician-in-Chief Johns Hopkins Hospital Department of Emergency Medicine Baltimore, Maryland Arthur L. Kellermann, M.D., M.P.H., F.A.C.E.P. Professor of Emergency Medicine Director, Center for Injury Control Rollins School of Public Health of Emory University Atlanta, Georgia Kevin M. Kelly, M.D., Ph.D. Associate Professor Department of Neurology Allegheny University of the Health Sciences Pittsburgh, Pennsylvania A. Richard Kendall, M.D. Professor of Urology Temple University Hospital Department of Urology Philadelphia, Pennsylvania Morton J. Kern, M.D. Cardiac Catheterization Laboratory St. Louis, Missouri Martin R. Klemperer, M.D. Professor of Pediatrics University of South Florida Medical Director, Bone Marrow Transplantation Services Department of Pediatrics All Children’s Hospital St. Petersburg, Florida James A. Knol, M.D. Associate Professor of Surgery University of Michigan Medical School Ann Arbor, Michigan Kristi Koenig, M.D. Associate Professor of Medicine University of California San Francisco Department of Emergency Medicine Alameda County Medical Center/Highland General Hospital Oakland, California

Sharon S. Kolber, M.D. Staff Physician Emergency Department Lovelace Medical Center Clinical Assistant Professor University of New Mexico School of Medicine Department of Emergency Medicine Albuquerque, New Mexico Barbara S. Koppel, M.D. Professor of Clinical Neurology Department of Neurology New York Medical College New York, New York Mike Kozminski, M.D., F.A.C.S. Private Practice Urologist Phoenix Urology of St. Joseph, Inc. St. Joseph, Missouri David A. Kramer, M.D., F.A.C.E.P. Associate Professor Department of Emergency Medicine Emory University School of Medicine Atlanta, Georgia Margo J. Krasnoff, M.D. Associate Professor of Clinical Medicine Department of Internal Medicine State University of New York at Buffalo Millard Fillmore Health System Buffalo, New York Alexander Kuehl, M.D., M.P.H., F.A.C.E.P., F.A.C.S. Associate Professor of Surgery and Public Health Cornell University Medical College New York, New York Emergency Physician-in-Chief Champlain Valley Physicians Hospital Plattsburgh, New York Carol L. Kulp-Shorten, M.D. Assistant Professor of Medicine (Dermatology) Department of Medicine Division of Dermatology University of Louisville Louisville, Kentucky C. Grant LaFarge, M.D., F.A.C.C., F.A.C.P., F.A.P.S. Pediatric Cardiologist Department of Pediatrics, Cardiology Santa Fe Pediatric Cardiology, PC Santa Fe, New Mexico Clinical Professor of Internal Medicine and Pediatrics University of New Mexico Albuquerque, New Mexico Patricia L. Lamb, M.D. Attending Staff Physician W.A. Foote Memorial Hospital Jackson, Michigan Clinical Instructor, University of Michigan Emergency Services Ann Arbor, Michigan Stephen F. Larson, M.D. Department of Emergency Medicine Alta Bates Medical Center Berkeley, California Steven H. Lesser, M.D., F.A.C.E.P. Associate Professor Medicine Section of Emergency Medicine Charity Hospital of New Orleans Louisiana State University New Orleans, Louisiana David G. Levine, M.D., F.A.P.A. Associate Clinical Professor Department of Psychiatry University of California Medical Center San Francisco, California Lawrence M. Lewis, M.D., F.A.C.E.P. St. Louis University Hospital St. Louis, Missouri Markus D.W. Lipp, M.D., D.D.S., Ph.D. Senior Lecturer, Anesthesiologist Chief Emergency Physician

Clinic of Anesthesiology University of Mainz Mainz, Germany George I. Litman, M.D., F.A.C.C. Professor of Medicine Chief of Cardiology Akron General Medical Center Northeastern Ohio Universities College of Medicine Akron, Ohio Milton N. Luria, M.D., F.A.C.P. Professor Emeritus of Medicine Department of Medicine University of Rochester School of Medicine and Dentistry Rochester, New York Robert C. Luten, M.D. Professor, Pediatric Emergency Services University of Florida Health Science Center Jacksonville, Florida William MacAusland, M.D. Faulkner Hospital Jamaica Plain, Massachusetts John C. Maino II, M.D., F.A.C.E.P. Associate Medical Director Department of Emergency Medicine W.A. Foote Memorial Hospital University of Michigan School of Medicine Jackson, Michigan Mark Mandell, M.D., F.A.C.E.P. Chairman and Program Director Department of Emergency Medicine Morristown Memorial Hospital Morristown, New Jersey Mary Anne Mangelsen, Ph.D., M.D. Clinical Assistant Professor of Emergency Medicine Department of Emergency Medicine University of Michigan Ann Arbor, Michigan John R. Mangiardi, M.D. Chief of Neurosurgery Lenox Hill Hospital Chairman Foundation for Neurosurgical Research New York, New York Stephen J. Marks, M.D. Associate Professor of Clinical Medicine Department of Neurology New York Medical College Valhalla, New York Director Department of Neurology Saint Agnes Hospital White Plains, New York Gary J. Martin, M.D., F.A.C.C. Professor of Medicine Chief, Division of General Internal Medicine Department of Medicine Northwestern University Medical School Northwestern Medical Faculty Foundation Chicago, Illinois Jean T. Martin, M.D., F.A.C.E.P. Medical Director Emergency Department Centennial Healthcare Plaza Englewood, Colorado John A. Marx, M.D. Chairman Department of Emergency Medicine Carolinas Medical Center Charlotte, North Carolina Thomas A. Mayer, M.D. Professor of Emergency Medicine and Pediatrics Georgetown University School of Medicine George Washington University School of Medicine Washington, D.C. Chairman Department of Emergency Medicine, Fairfax Hospital

Falls Church, Virginia Rajalaxmi McKenna, M.D. Associate Professor Department of Medicine and Pharmacology Former Director Venous Thrombosis, Radiohematology and Platelet Function Laboratories Hinsdale, Illinois Susan V. McLeer, M.D. Professor and Chairman Department of Psychiatry State University of New York at Buffalo Buffalo, New York David McMicken, M.D., F.A.C.E.P. Clinical Assistant Professor of Family and Preventive Medicine Emory University School of Medicine President, Acute Care Express Columbus, Georgia Norman E. McSwain, Jr., M.D. Professor of Surgery Department of Surgery Tulane Medical School New Orleans, Louisiana Craig A. Meek, M.D., F.A.C.E.P. Attending Physician Department of Emergency Medicine Brackenridge Hospital Austin, Texas Abdul M. Memon, M.D., F.A.C.P., F.A.C.E.P. Associate Professor Division of Emergency Medicine Department of Medicine University of Miami School of Medicine Miami, Florida Craig S. Miller, D.M.D. Associate Professor of Oral Medicine Oral Health Science University of Kentucky College of Dentistry Lexington, Kentucky Van H. Miller, M.D. Chairman Department of Emergency Medicine St. Francis Medical Center Lynwood, California John A. Milton, M.D. Wills Eye Hospital Philadelphia, Pennsylvania Howard C. Mofenson M.D., D.A.B.M.T., F.A.A.P., F.H.A.C.T. Medical Director Long Island Regional Poison Control Center Winthrop University Hospital Professor of Pediatrics and Emergency Medicine University Hospital Medical School State University of New York at Stony Brook Mineola, New York William W. Montgomery, M.D. , F.A.C.S. John M. Merriam Professor of Otolaryngology Harvard Medical School Department of Otolaryngology Massachusetts Eye and Ear Infirmary Boston, Massachusetts Gregory J. Moran, M.D., F.A.C.E.P. Assistant Professor of Medicine University of California Los Angeles School of Medicine Department of Emergency Medicine Division of Infectious Diseases Olive View-University of California Los Angeles Medical Center Sylmar, California Michael W. Mulholland, M.D., Ph.D. Professor Department of Surgery University of Michigan Ann Arbor, Michigan John Munyak, M.D. Assistant Residency Director Department of Emergency Medicine Director of Sports Medicine Lincoln Medical and Mental Health Center

Bronx, New York Daniel G. Murphy, M.D., F.A.C.E.P. Medical Director Department of Emergency Medicine Maimonides Medical Center Brooklyn, New York Kenneth A. Murphy, Jr., Pharm.D., B.C.P.S. Clinical Manager Department of Pharmacy W.A. Foote Memorial Hospital Jackson, Michigan Adjunct Assistant Professor of Clinical Pharmacy Ferris State University Big Rapids, Michigan Henry W. Murray, M.D. Professor and Associate Chairman Department of Medicine Cornell University Medical Center New York, New York Venkat Narayan, M.D., F.A.C.S., F.I.C.S. Staff Neurosurgeon St. Vincent Hospital Santa Fe, New Mexico Ashraf Nashed, M.D. Assistant Program Director Residency in Emergency Medicine Department of Emergency Medicine Morristown Memorial Hospital Morristown, New Jersey Edward Newton, M.D. Vice Chairman Department of Emergency Medicine LAC and University of Southern California Medical Center Los Angeles, California Eric Noji, M.D. World Health Organization Geneva, Switzerland Robert A. Nozik, M.D. Clinical Professor of Ophthalmology Department of Ophthalmology University of California San Francisco Research Ophthalmologist Proctor Foundation San Francisco, California Harold Osborn, M.D. Professor and Chairman Department of Emergency Medicine New York Medical College Valhalla, New York Harry F. Oxer, M.A., M.B., B.Chir., F.R.C.A. Medical Director Western Australian Ambulance Service St. John Ambulance, WA Perth, Western Australia John H. Pahira, M.D. Professor of Urology Director, Center for Kidney Stone Disease Department of Surgery Georgetown University Medical Center Washington, D.C. Eddy D. Palmer, M.D., M.A.C.P. Private Practice Schooley’s Mt., New Jersey M. Jevitz Patterson, M.D. Professor, Microbiology and Pediatrics Michigan State University East Lansing, Michigan Donald R. Paugh, M.D. Department of Otolaryngology-Head and Neck Surgery Wenatchee Valley Clinic Wenatchee, Washington David E. Pawsat, D.O. Clinical Instructor Michigan State University College of Human Medicine Michigan Capital Medical Center Lansing, Michigan

Anthony C. Pearson, M.D. Louisville, Kentucky Paul E. Pepe, M.D., M.P.H., F.A.C.E.P., F.C.C.M. Professor and Chairman Department of Emergency Medicine Allegheny University of the Health Sciences Director, Emergency Services Allegheny General Hospital Pittsburgh, Pennsylvania Mark A. Peppercorn, M.D. Professor of Medicine Harvard Medical School Director, Center for Inflammatory Bowel Disease Division of Gastroenterology Beth Israel Deaconess Medical Center Boston, Massachusetts Vincent Pflug, M.D. Michael P. Poirier, M.D. Assistant Professor of Pediatrics Children’s Hospital of The King’s Daughters Eastern Virginia Medical School Norfolk, Virginia John E. Prescott, M.D., F.A.C.E.P. Professor and Chair Department of Emergency Medicine West Virginia University School of Medicine Morgantown, West Virginia Dennis P. Price, M.D. Attending Physician Emergency Department Bellevue Hospital Center Emergency Medical Services New York, New York Robert P. Proulx, M.D., F.A.C.E.P. Department of Emergency Medicine St. Joseph Medical Center Burbank, California John J. Purcell, Jr., M.D. Associate Clinical Professor of Ophthalmology St. Louis University School of Medicine St. Louis, Missouri Les M. Puretz, D.O. Assistant Professor College of Human Medicine Michigan State University Lansing, Michigan Theodore Rabinovitch, M.D., F.R.C.S.C. Lecturer University of Toronto Department of Ophthalmology Toronto, Ontario, Canada Eric C. Rackow, M.D. Professor and Vice Chairman Department of Medicine New York Medical College Chairman, Department of Medicine St. Vincent’s Hospital and Medical Center New York, New York Prakashchandra M. Rao, M.D., F.R.C.S.(C), F.A.C.S. Associate Professor of Clinical Surgery New York Medical College Chief of Head and Neck Surgery Chief of Surgical Endoscopy Lincoln Medical and Mental Health Center Bronx, New York Steven A. Raper, M.D., F.A.C.S. Associate Professor of Surgery Department of Surgery University of Pennsylvania School of Medicine Philadelphia, Pennsylvania Marsha D. Rappley, M.D. Associate Professor Department of Pediatrics and Human Development College of Human Medicine Michigan State University

East Lansing, Michigan Sushma Reddy, M.D. Assistant Professor of Medicine Division of Endocrinology and Hypertension Harper and Grace Hospitals Wayne State University School of Medicine Detroit, Michigan William Reed, M.D. Fellow in Hematology and Transfusion Medicine Department of Hematology/Oncology Children’s Hospital of Oakland Oakland, California Bruce M. Reinoehl, M.D. Associate Professor of Medicine Michigan State University Assistant Chairman, Emergency Department Sparrow Hospital Lansing, Michigan Earl J. Reisdorff, M.D., F.A.C.E.P. Program Director Michigan State University, Emergency Medicine Residency Michigan Capital Medical Center, Sparrow Hospital Lansing, Michigan Karen Rheuban, M.D. Professor of Pediatrics Department of Pediatrics University of Virginia Charlottesville, Virginia Ronald L. Rhule, D.O., F.A.C.O.E.P. Medical Director and Chairman Department of Emergency Medicine Sparrow Hospital Lansing, Michigan Albert W. Ritter, M.D. Emergency Medicine Staff Physician Department of Emergency Medicine Mountainside Hospital Montclair, New Jersey James R. Roberts, M.D., F.A.A.E.M., F.A.C.M.T. Professor and Vice Chair Department of Emergency Medicine Director, Division of Toxicology Allegheny University of the Health Sciences Mercy Health Systems Director, Institute for the Treatment of Bites and Stings Mercy Hospital of Philadelphia Philadelphia, Pennsylvania Donald A. Romig, M.D. Associate Clinical Professor Department of Internal Medicine University of New Mexico Medical School Albuquerque, New Mexico Martha Roper, M.D. Highland General Hospital Oakland, California Joseph Rosenblum, D.O., F.A.C.C., F.A.C.P. Assistant Clinical Professor Department of Cardiology University of Chicago Chicago, Illinois Monica Ann Rosenthal, M.D., F.A.C.E.P. Assistant Chief, Emergency Medicine Highland General Hospital Assistant Clinical Professor of Medicine University of California at San Francisco Oakland, California Richard Eric Rothman, M.D., Ph.D. Instructor Department of Emergency Medicine The Johns Hopkins University School of Medicine Baltimore, Maryland Steven G. Rothrock, M.D., F.A.A.E.M., F.A.A.P., F.A.C.E.P. Department of Emergency Medicine Orlando Regional Medical Center Orlando, Florida Clinical Adjunct Assistant Professor Division of Emergency Medicine

University of Florida Gainesville, Florida Department of Emergency Medicine Loma Linda University School of Medicine Loma Linda, California Bruce R. Rothwell, D.M.D., M.S.D. Director, Hospital Dentistry University of Washington Department of Restorative Dentistry Seattle, Washington George J. Rubeiz, M.D. Assistant Professor of Medicine Wayne State University Detroit, Michigan Wallace Rubin, M.D. Clinical Professor Department of Otolaryngology & Bio-Communications Louisiana State University School of Medicine New Orleans, Louisiana Brent E. Ruoff, M.D., F.A.C.E.P. Associate Chief Emergency Medicine Division Washington University School of Medicine St. Louis, Missouri Robert A. Rusnak, M.D. Associate Physician Department of Emergency Medicine Hennepin County Medical Center Minneapolis, Minnesota Thomas D. Sabin, M.D. Clinical Professor Department of Neurology Tufts University School of Medicine Boston, Massachusetts Peter Safar, M.D., Dr.h.c., F.C.C.M., F.C.C.P. Distinguished Professor of Resuscitation Medicine Safar Center for Resuscitation Research Pittsburgh, Pennsylvania Arthur P. Safran, M.D. Department of Neurology Columbia-MetroWest Medical Center Framingham, Massachusetts Douglas M. Salyards, M.D. Emergency Department W.A. Foote Memorial Hospital Jackson, Michigan Joel R. Saper, M.D. Director, Michigan Head-Pain & Neurological Institute Ann Arbor, Michigan Karin H. Satra, M.D. Associate in Clinical Dermatology Department of Dermatology Columbia Presbyterian Medical Center New York, New York Michael R. Sayre, M.D. Assistant Professor Department of Emergency Medicine University of Cincinnati Cincinnati, Ohio Marie D. Schafle, M.D. Director, Sports and Performing Arts Clinic Student Health Service San Francisco State University San Francisco, California Richard K. Scher, M.D. Professor of Clinical Dermatology Department of Dermatology College of Physicians and Surgeons Columbia University New York, New York Sandra M. Schneider, M.D., F.A.C.E.P. Professor and Chair Department of Emergency Medicine University of Rochester/Strong Memorial Hospital

Rochester, New York John M. Schoffstall, M.D. Assistant Professor Department of Emergency Medicine Allegheny University of the Health Sciences Philadelphia, Pennsylvania Kathleen S. Schrank, M.D., F.A.C.E.P., F.A.C.P. Professor of Medicine Division of Emergency Medicine University of Miami School of Medicine Miami, Florida Bernard M. Schuman, M.D., F.A.C.P., M.A.G.G. Professor of Medicine Department of Medicine Director, Special Procedures and Endoscopy Unit Section of Gastroenterology and Hepatology Medical College of Georgia Augusta, Georgia Theresa M. Schwab, M.D. Associate Professor of Medicine Department of Emergency Medicine University of California San Francisco University Medical Center Fresno, California George R. Schwartz, M.D. Director Emergency Medicine of the Southwest Santa Fe, New Mexico Adjunct Associate Professor of Emergency Medicine Allegheny University of the Health Sciences Philadelphia, Pennsylvania T. Duncan Sellers, Jr., M.D., F.A.C.C. Electrophysiologist Department of Cardiology Memorial Hospital Colorado Springs, Colorado Paul N. Seward, M.D., F.A.C.E.P., F.A.A.P. Clinical Assistant Professor of Emergency Medicine Medical College of Georgia Emergency Department University Hospital Augusta, Georgia Sid M. Shah, M.D., F.A.C.E.P. Assistant Clinical Professor College of Human Medicine Michigan State University Michigan Capital Medical Center Lansing, Michigan Arthur G. Shapiro, M.D., F.A.C.O.G., F.A.C.E. Department of Obstetrics and Gynecology University of Florida School of Medicine Miami, Florida Philip Shayne, M.D., F.A.C.E.P. Assistant Professor Division of Emergency Medicine Emory University School of Medicine Atlanta, Georgia Daniel J. Shea, M.D., F.A.C.E.P. Assistant Professor of Emergency Medicine University of Massachusetts Medical School Associate Director, Emergency Services St. Luke’s Hospital New Bedford, Massachusetts Philip D. Shenefelt, M.D., M.S. Associate Professor Division of Dermatology and Cutaneous Surgery Department of Internal Medicine University of South Florida Tampa, Florida Suzanne Moore Shepherd, M.D., F.A.C.E.P. Associate Professor and Program Director Department of Emergency Medicine University of Pennsylvania Medical Center Philadelphia, Pennsylvania Mukarem A. Siddiqui, M.D. Harvey Silverman, M.D. Adjunct Assistant Professor of Clinical Medicine

Dartmouth Medical School Emergency Physician Catholic Medical Center Manchester, New Hampshire Jeffrey Sipsey, M.D. Los Angeles County Department of Health Sciences Emergency Medical Services Medical Alert Center Los Angeles, California Morton S. Skorodin, M.D. Staff Physician Ambulatory Care Service Muskogee VA Medical Center Muskogee, Oklahoma Professor of Medicine Department of Medicine University of Oklahoma Tulsa Medical College Tulsa, Oklahoma Nathan C. Skorodin, Pharm.D. Clinical Pharmacist Heartland Home Infusions Hinsdale, Illinois John E. Smialek, M.D. Professor and Head Division of Forensic Pathology Department of Pathology University of Maryland School of Medicine Baltimore, Maryland Martin Smilkstein, M.D., A.C.M.T. Associate Professor of Emergency Medicine Department of Emergency Medicine Oregon Health Sciences University Portland, Oregon Michael C. Smith, M.D. Director, Rush Epilepsy Center Department of Neurological Sciences Rush-Presbyterian-St. Luke’s Medical Center Associate Professor Department of Neurological Sciences Rush Medical College Chicago, Illinois Ronald K. Smith, D.O., F.A.C.E.P. Quality Improvement Coordinator Department of Emergency Medicine Westmoreland Regional Hospital Greensburg, Pennsylvania Steven B. Sorin, M.D. Assistant Professor of Medicine Case Western Reserve University Chief of Rheumatology Mt. Sinai Medical Center Cleveland, Ohio Steven M. Sornsin, M.D., F.A.C.E.P. Highland General Hospital Oakland, California James R. Sowers, M.D. Professor of Medicine and Physiology Director, Division of Endocrinology, Metabolism and Hypertension Department of Internal Medicine Wayne State University School of Medicine Detroit, Michigan George L. Spaeth, M.D., F.A.C.S. Professor of Ophthalmology Jefferson Medical College Director, William Anna Goldberg Glaucoma Service Wills Eye Hospital Philadelphia, Pennsylvania Thomas M. Stein, M.D., F.A.C.E.P. Director, Emergency Medical Support Services Medical Director Life Flight Department of Emergency Medicine Allegheny University of the Health Sciences Allegheny Campus Pittsburgh, Pennsylvania Peter J. Stewart, M.D. Director, Trauma/Surgical Critical Care Department of Surgery St. Joseph’s Hospital and Medical Center

Patterson, New Jersey Eric Stirling, M.D., F.A.C.E.P. Staff Physician Emergency Department Fairbanks Memorial Hospital Fairbanks, Arkansas Michael J. Sullivan, M.D. W.A. Foote Memorial Hospital Ann Arbor, Michigan Panagiotis N. Symbas, M.D. Professor of Cardiothoracic Surgery Department of Cardiothoracic Surgery Emory University School of Medicine Director Department of Cardiothoracic Surgery Grady Memorial Hospital Atlanta, Georgia James V. Talano, M.D., M.M., F.A.C.C. Chief, Division of Cardiovascular Medicine Department of Medicine Tulane University Medical School New Orleans, Louisiana Satyanarayana Tatineni, M.D., F.A.C.C., F.A.C.P. Department of Cardiology The Heart Group Evansville, Indiana Craig A. Taylor, M.D. Community Neuropsychiatric Services, Inc. Leetsdale, Pennsylvania Steven A. Telian, M.D. University of Michigan W.A. Foote Memorial Hospital Ann Arbor, Michigan Andreas R. Thierbach, Dr.M.E.D. Consultant Anesthesiologist Chief Emergency Physician Clinic of Anesthesiology University of Mainz Mainz, Germany Knox Todd, M.D., M.P.H. Associate Professor Department of Emergency Medicine Emory University School of Medicine Atlanta, Georgia Christopher Truss, M.D. Professor of Medicine Department of Medicine University of Alabama at Birmingham Birmingham, Alabama James R. Tryon, M.D., F.A.C.E.P. New Mexico Family Practice Associates, Inc. Albuquerque, New Mexico Alan J. Tuchman, M.D. Professor of Neurology New York Medical College Valhalla, New York James R. Ungar, M.D., F.A.C.E.P. Co-Director Center for Emergency Medicine Assistant Medical Director Air Med Team Redding Medical Center Redding, California Audrey Urbano-Brown, M.D., F.A.C.E.P. Assistant Professor Department of Emergency Medicine University of New Mexico School of Medicine Albuquerque, New Mexico Philippe D. Vaillancourt, M.D. Assistant Professor of Neurology State University of New York Stony Brook, New York Terence D. Valenzuela, M.D. Professor of Surgery University of Arizona

College of Medicine Tucson, Arizona James P. Valeriano, M.D. Associate Professor Department of Neurology Allegheny University of the Health Sciences Pittsburgh, Pennsylvania Michel Vandormael, M.D. Hôpital de la Citadelle Liege, Belgium Jonathan Vargas, M.D., F.A.C.E.P. Clinical Associate Professor of Emergency Medicine Wright State University Dayton, Ohio David L. Vesely, M.D., Ph.D., F.A.C.P., F.A.C.E. Professor of Medicine, Physiology and Biophysics Department of Internal Medicine Chief of Endocrinology and Metabolism University of South Florida for Health Sciences Tampa Veterans Administration Hospital Tampa, Florida Elliott P. Vichinsky, M.D. Director Department of Hematology/Oncology Children’s Hospital of Oakland Oakland, California Raymond N. Vitullo, M.D. Duke University Medical Center Durham, North Carolina George L. Voelz, M.D. Occupational Health Specialist Occupational Medical Group Los Alamos National Laboratory Los Alamos, New Mexico Stephanie von Ammon Cavanaugh, M.D. Professor and Chief, Section of Psychiatry and Medicine Department of Psychiatry Rush Presbyterian St. Luke’s Medical Center Chicago, Illinois Michele R. Wadsworth, M.D. Assistant Professor of Pediatrics Eastern Virginia Medical School Norfolk, Virginia Russel G. Wagner, M.D. Assistant Professor Department of Emergency Medicine University of Alabama at Birmingham Birmingham, Alabama Kristi Watterberg, M.D. Associate Professor Department of Pediatrics, Division of Newborn Medicine Pennsylvania State University College of Medicine Hershey, Pennsylvania Marvin A. Wayne, M.D., F.A.C.E.P. Clinical Associate Professor University of Washington Clinical Assistant Professor Yale University Medical Director of Emergency Medical Services Bellingham, Washington Senior Attending Emergency Department St. Joseph Hospital Bellingham, Washington Arthur W. Weaver, M.D. University Health Center Detroit, Michigan Max Harry Weil, M.D., Ph.D. Distinguished University Professor and President Institute of Critical Care Medicine Northwestern University Medical School and University of Southern California School of Medicine Palm Springs, California Steven J. Weiss, M.D. Associate Professor Department of Emergency Medicine Vanderbilt University

Nashville, Tennessee Scott S. Weissman, M.D. Associate Director Department of Ophthalmology New York Eye and Ear Infirmary New York, New York Howard A. Werman, M.D. Associate Professor of Clinical Emergency Medicine The Ohio State University College of Medicine and Public Health Columbus, Ohio Mark Westfall, M.D. Department of Emergency Medicine Mercy Hospital Dubuque, Iowa J. Marcus Wharton, M.D. Duke University Medical Center Durham, North Carolina Stephen J. Wheeler, M.D. Department of Emergency Medicine Royal Jubilee Hospital Victoria, Canada Robert R. Whipkey, M.D., F.A.C.E.P. Director, Department of Emergency Medicine Westmoreland Regional Hospital Greensburg, Pennsylvania Michael E. Whiting, M.D. Staff Physician Emergency Department St. Vincent Hospital Santa Fe, New Mexico Louis J. Wilson, M.D. Fellow in Gastroenterology Department of Medicine University of Alabama Birmingham Birmingham, Alabama Christopher K. Wuerker, M.D., F.A.C.E.P. Assistant Clinical Professor of Emergency Medicine George Washington University Medical Center Medical Director MedSTAR Transport Washington Hospital Center Washington, D.C. Georges S. Yacoub, M.D. Chief Fellow, Pulmonary and Critical Care Medicine Department of Internal Medicine Wayne State University Detroit, Michigan Robert J. Zimmerman, M.D. Department of Emergency Medicine MetroHealth Medical Center Cleveland, Ohio David N. Zull, M.D., F.A.C.E.P. Associate Professor of Medicine Northwestern University Associate Firm Chief (Medicine) Northwestern Memorial Hospital Chicago, Illinois

Dedication This work is dedicated to the men and women who have worked ardently to make this edition happen; to the editors, secretaries, typesetters, production people, and in particular Joyce Murphy and Helen Powers. To shorten, refine, and distill the textbook has been a difficult assignment, and one needed by the practitioners of emergency medicine. This work also is dedicated to the men and women who practice emergency medicine—those who labor joyfully to help their patients and advance their chosen field. Theodore Roosevelt said: It is not the critic who counts—not the man or woman who points out how the strong man stumbled or where the doer of deeds could have done better. The credit belongs to the men and women who are actually in the arena, whose faces are marred by dust and sweat and blood; who strive valiantly...

Editor-in-Chief George R. Schwartz, M.D. Director, Emergency Medicine of the Southwest Santa Fe, New Mexico Partner, Brain Resuscitation Research, LLC Sewickley, Pennsylvania Adjunct Associate Professor of Emergency Medicine Allegheny University of the Health Sciences Philadelphia, Pennsylvania

Associate Editors Barbara K. Hanke, M.D. Staff Emergency Physician St. Vincent Hospital Santa Fe, New Mexico Clinical Assistant Professor of Family and Community Medicine University of New Mexico School of Medicine Albuquerque, New Mexico Thomas A. Mayer, M.D. Professor of Emergency Medicine and Pediatrics Georgetown University School of Medicine George Washington University School of Medicine Washington, D.C. Chairman Department of Emergency Medicine, Fairfax Hospital Falls Church, Virginia James S. Cohen, M.D. Attending Physician Saratoga Emergency Physicians Saratoga Springs, New York John Dale Dunn, M.D., J.D. Director Emergency Services and Physician Advisor Brownwood Regional Medical Center Brownwood, Texas Joseph C. Howton, M.D. Assistant Clinical Professor of Medicine Department of Medicine University of California School of Medicine San Francisco, California Attending Physician Department of Emergency Medicine Good Samaritan Hospital Puyallup, Washington Daniel J. Isaacman, M.D. Division Director Pediatric Emergency Medicine Children’s Hospital of the King’s Daughters Associate Professor of Pediatrics Eastern Virginia Medicine School Norfolk, Virginia Paul B. Roth, M.D. Dean, University of New Mexico, School of Medicine Associate Vice President for Clinical Affairs, Health Sciences Center Professor of Emergency Medicine Director, Center for Disaster Medicine Department of Emergency Medicine University of New Mexico Medical Center Albuquerque, New Mexico Steven G. Rothrock, M.D. Department of Emergency Medicine Orlando Regional Medical Center Orlando, Florida Clinical Adjunct Assistant Professor Division of Emergency Medicine University of Florida Gainesville, Florida Department of Emergency Medicine Loma Linda University School of Medicine Loma Linda, California James R. Ungar, M.D. Co-Director Center for Emergency Medicine Assistant Medical Director Air Med Team Redding Medical Center Redding, California

PREFACE The Fourth Edition of Principles and Practice of Emergency Medicine breaks new ground with a refined and streamlined edition. Clinical usefulness has been the touchstone. We have maintained the encyclopedic and authoritative nature of the previous editions, but have aimed for a single, user-friendly volume, which brings the essential knowledge, time orientation, and procedures required for emergency medicine. To help achieve our goals we have expanded our use of tables, guidelines, charts, radiographs and photographs. We have listened to our readers who require “cutting-edge” accessible information in a single volume rather than ponderous presentations in a multivolume format. The use of capsules, heads, and subheads allows easier indexing and rapid availability of needed information. Clinical pitfalls have been highlighted as have medical-legal pearls. Whenever possible, we have offered access to ways to network, including databases, national contact telephone numbers, and Internet addresses. The field of emergency medicine has changed to include many experienced and board-certified practitioners who do not need the extensive pathophysiology found in prior editions. This edition of Principles and Practice of Emergency Medicine has a new section on “tips and techniques” that organizes information on common emergency conditions, such as foreign bodies in the skin, eyes, ears, esophagus, airway, and nose and a new chapter dealing with the most common ingestion—that of coins, in an accessible format. Aspirated foreign bodies are an important focus (e.g., balloons in children), and a chapter is devoted to this life-threatening event. Common techniques such as reduction of jaw dislocation and epistaxis are presented in easy-to-use formats. At the beginning of each chapter the usual emergency procedures (e.g., emergency delivery leads the obstetrics/gynecology section, emergency burr-holes leads the neurology/neurosurgery section) are presented to allow the reader rapid access to that information. The emergency medicine services (EMS) section has changed to a focussed format that shows what can be done in the field to aid survival in acute illness and injury based on scientific data—with all of the “bells and whistles” we are now looking at what actually works. Nine additional associate editors who are active practitioners as well as scholars have contributed to this edition. All of the editors understand the reality of being faced with myriad emergencies in a busy emergency department (ED) where the emergency physician is alone and is the “trauma center” instead of being in an academic environment where multiple specialists are seconds away. As a result, the tendency to be “academic” and not practical has been avoided. Time and critical decision making have been an important focus. What is the time of appendiceal perforation, how much time is there for a successful outcome from a leaking abdominal aortic aneurysm, how much time for successful thrombolytic therapy in myocardial infarction and stroke? How long is the time period to treat meningitis to avoid complications? The flowering of the art of the emergency physician has always been that of understanding the added dimension of time and the need for rapid diagnosis and action. Changes in health care have been rapid. To this end we have completely revised and updated the sections related to management and added new sections on practice parameters, guidelines, and standards as well as the various regulations with which we must live. On this twentieth anniversary year of our first edition, we hark back to the original reviews that hailed the publication of the first textbook defining clinical standards in emergency medicine. Now, in the fourth edition, Principles and Practice of Emergency Medicine is still the book for the clinical practitioner who wants rapid, authoritative standard-of-care answers. We have created a lean and ready work. With its comprehensive and encyclopedic coverage, the fourth edition of Principles and Practice of Emergency Medicine will be the book used in the emergency department — open on the desk, coffee stained, cover frayed, but ready for action—ready for the man or woman “in the arena.” George R. Schwartz, M.D. Editor-in-Chief Principles and Practice of Emergency Medicine, Fourth Edition

ACKNOWLEDGMENTS To shorten, consolidate, and focus an expansive textbook such as the Principles and Practice of Emergency Medicine was a formidable task as we were going into the fourth edition. There are many books published, and we were acutely aware that most don’t survive into multiple editions, but Principles and Practice of Emergency Medicine had weathered some storms since the first edition in 1978. As the original comprehensive text in emergency medicine, our task was to adjust to the changing need for rapid and focused access to pertinent material in the most convenient form, rather than continue with a two-, three -, or even four-volume unwieldy format. Kathleen Schwartz, my indomitable wife, kept the work on course and Corie Conwell used her formidable computer skills to allow a worldwide search in new areas. Family is all important, and our many children helped in the ways they could. As we had changed publisher (to Williams and Wilkins) there were many adjustments to be made. Katey Millet, editor, took the project on with energy and stamina, and when she needed a leave, Joyce Murphy, managing editor, filled the breach and worked to keep the book on a reasonable schedule and edited, coordinated, and stepped in wherever there was a need. Keith Murphy ably assisted Joyce (no relation) as she and Katey encouraged, cajoled, and ordered essential cutting and shortening. For this I am very grateful, and they did it all with charm, grace, and continued good humor. As to the many accomplished contributors who took the time to update or develop their chapters, these thanks are a humble tribute. The associate editors listed on the cover helped to bring forgotten areas to light and entered in at important stages. Drs. James Ungar, Joseph Howton, and James S. Cohen took time out of their busy schedules and came to Santa Fe to help steer the fourth edition. Certainly the previous editors and associates brought us to where we are today. It is a competitive world of books and Principles and Practice of Emergency Medicine throughout its three editions was able to garner superior reviews and, most important, reader feedback that confirmed the usefulness of the text. Drs. Peter Safar, Dave Wagner, Jim Roberts, and many others have helped to support these endeavors, and I take my hat off to them. I would like to offer particular thanks to Saul Cohen, friend and attorney, who helped with legal issues and scheduling, working with Susan Gay and Ted Hutton, senior executives who took over when George Stamathis left to pursue other interests. George’s early work set the stage, and I wish to acknowledge his fervent approach. To the many production people, to Helen Powers and staff, and to others who worked in the arenas, in the trenches, diligently, but unsung, I offer thanks.

ASSOCIATE EDITOR ACKNOWLEDGMENTS Barbara Kate Hanke, M.D.: To my wonderful family: Rod, Austin and Will, who continue to put up with the odd hours. To all the hard-working front-line emergency physicians who find the personal motivation to work compassionately and expertly, taking care of the tides of humanity at their most vulnerable. Thomas A. Mayer, M.D.: To my wife, Maureen, and our sons, Josh, Kevin and Gregory, whose love and support sustain me in all things. James S. Cohen, M.D.: To Major W. Bradshaw, M.D. and Richard B. Pesikoff, M.D. “Minds are like parachutes: they work best when opened.” Thanks for being good skydivers. To Joseph Braver, M.D.: You don’t play golf or tie toe tags but your sense of ethics and clinical acumen exceeds that of any emergency physician I have ever known. To Joel R. Gernsheimer, M.D.: Your dedication to emergency medicine is an inspiration to us all. Thank you for being my residency director. John Dale Dunn, M.D., J.D.: To Dale E. Dunn, M.D., gone now, but still my inspiration, and thanks to my love, Patty, for advice and support. Daniel J. Isaacman, M.D.: For Fran, Alissa, and Michael. You make life wonderful. I am forever grateful for your love and support. Steven G. Rothrock, M.D.: To Angela, for her love, support, patience, and encouragement. To the students, residents, colleagues, and mentors who are the source of my professional inspiration and growth. James R. Ungar, M.D.: I would like to acknowledge all students of emergency medicine whose quest for knowledge stimulate and inspire us to produce a work of enduring quality. Also to the medical students, interns, and residents at St. Barnabas and Morristown Memorial Hospitals whose challenges, enthusiasm, and motivation provided impetus to see this work culminate in reality. Within these pages may you find what you seek. And specials thanks to my wife Jill whose loving support, constant encouragement, and incomparable friendship made this work possible.

Chapter 1.1 Pathophysiology of Dying and Reanimation Principles and Practice of Emergency Medicine

CHAPTER 1 MECHANISMS OF DYING AND TECHNIQUES OF RESUSCITATION

1 Pathophysiology of Dying and Reanimation George R. Schwartz Introduction Cardiac Arrest The Terminal State Experimental Studies Resuscitation and the Postresuscitation Syndrome Fundamental Mechanisms of Rapid Dying and Resuscitation Alternatives to Tracheal Intubation Other Airway Control Procedures Use of Open-Chest CPR

INTRODUCTION The clinical practice of cardiopulmonary resuscitation (CPR) has been expanded to cardiopulmonary cerebral resuscitation (CPCR) ( 1). Its scientific basis, “resuscitology” (2) or “reanimatology” (3), has also expanded to encompass a variety of acute dying processes, including the derangements of the entire organism. Resuscitation potentials have also expanded beyond emergency resuscitation into prolonged life support, which is sometimes necessary with multiorgan system failure from postresuscitation disease. The derangements after cardiac arrest, in order of acute importance, involve the microcirculation, brain, cardiovascular-pulmonary system, kidneys, and the gastrointestinal, hematologic, immune, and endocrine systems. This order of importance seems different after prolonged shock-trauma states, a condition in which the brain is less likely to suffer ischemic damage but kidneys and lungs frequently fail and endocrine derangements are important. Sepsis has also gained recognition as a final common pathway in dying processes. The scientific importance of resuscitology lies in its ability to establish the pathophysiologic mechanisms of the postresuscitation syndrome ( 4,5). This helps define the ultimate potentials and limitations of resuscitation for the treatment of cardiac arrest. When CPR attempts inside or outside the hospital have succeeded in restoring some cerebral oxygenation within about 4 minutes of arrest, and adequate spontaneous circulation was accomplished within minutes thereafter, one-half to two-thirds of patients so treated have recovered, with central nervous system (CNS) function grossly equivalent to the prearrest state ( 6,7,8 and 9). Most of the remaining patients died before leaving the hospital from complications secondary to coma or from underlying disease. Among the long-term survivors of all CPR attempts, including the delayed attempts, about 5 to 20% seem to have a permanent major neurologic deficit ( 6,7 and 8,10), depending on the type and quality of post-CPR life support. The use of selective hypothermia will likely alter the neurologic status. Young, healthy people who suffer accidental deep hypothermia and circulatory arrest have shown little neurologic deficit even after prolonged time ( 10A).

CARDIAC ARREST Death in the terminal stages of incurable disease does not result from sudden cardiac arrest. We define sudden cardiac arrest as “the clinical picture of abrupt cessation of circulation in a person who was not expected to die at that time” ( 1). Cardiac arrest is clinically diagnosed when the following four conditions coexist: 1. Unconsciousness (Fig. 1–1.1, Fig. 1–1.2, Fig. 1–1.3 and Fig. 1–1.4).

Figure 1–1.1. Phases and steps of cardiopulmonary-cerebral resuscitation. (See protocols for ACLS details ) (Reprinted with permission from Safar P. Cardiopulmonary cerebral resuscitation. Stavanger, Norway: Asmund S. Laerdal, 1981.)

Figure 1–1.2. Life-supporting first aid for an unconscious person (wallet card). If the patient is unconscious, control the airway (A). If the patient is not breathing, give mouth-to-mouth ventilation (B). If the patient is not breathing or is injured, use supported spine-aligned position (B). If the patient is unconscious and breathing, use the stable side position (A). (Reprinted with permission from Caroline N. Life supporting resuscitation and first aid: a manual for instructors of the lay public. Geneva, Switzerland, prepared for the League of Red Cross Societies and the World Federation of Societies of Anesthesiologists, 1984.)

Figure 1–1.3. Positioning of the unconscious patient. Supported supine-aligned position—for resuscitation or for an injured person. Hold the head, neck, and chest aligned with slight traction. With both hands at the sides of the face, provide a jaw thrust, open the patient's mouth, and moderate backward tilt of the head. Prevent flexion and rotation of the head. (Reprinted with permission from Safar P. Cardiopulmonary cerebral resuscitation. Stavanger, Norway: Asmund S. Laerdal, 1981.)

Figure 1–1.4. Stable side position—for the spontaneously breathing unconscious patient. A. Flex the leg closest to you. B. Put hand closest to you under the patient's buttocks. C. Gently roll the patient onto his side. D. Tilt the patient's head backward and keep his face low. Put his upper hand under his lower cheek to maintain head tilt and to prevent him from rolling onto his face. The lower arm behind his back prevents him from rolling backward. (Reprinted with permission from Safar P. Cardiopulmonary cerebral resuscitation. Stavanger, Norway: Asmund S. Laerdal, 1981.)

2. Apnea or gasping respirations ( Fig. 1–1.5; in cases of choking).

Figure 1–1.5. Life-supporting first aid for choking (wallet card). If patient is choking, use back blows and clearing of mouth and throat. (Reprinted with permission from Caroline N. Life supporting resuscitation and first aid: a manual for instructors of the lay public. Geneva, Switzerland, prepared for the League of Red Cross Societies and the World Federation of Societies of Anesthesiologists, 1984.)

3. Pulselessness in large arteries (carotid, femoral) ( Fig. 1–1.6).

Figure 1–1.6. Life-supporting first aid for bleeding and shock (wallet card). If the patient is bleeding, elevate and compress (A). If the patient is in shock (and conscious), place him horizontally (face up) (B). (Reproduced with permission from Caroline N. Life supporting resuscitation and first aid: a manual for instructors of the lay public. Geneva, Switzerland, prepared for the League of Red Cross Societies and the World Federation of Societies of Anesthesiologists, 1984.)

4. Deathlike appearance. Examples of primary cardiac arrest include ventricular fibrillation (VF) (common) or asystole (less common) in patients with ischemic heart disease and in VF from electric shock (Fig. 1–1.7, conditions 1 and 2). Such sudden primary cessation of circulation in well-oxygenated persons results in unconsciousness within about 10 seconds and an isoelectric electroencephalogram (EEG) in about 30 seconds; agonal gasping may continue for 30 to 60 seconds; and apnea and maximal pupillary dilation begin at about 60 seconds. Oxygen stores are used up in 10 seconds ( 11,12 and 13).

Figure 1–1.7. Stages and reversibility of dying. Flow chart illustrating the development of circulatory arrest from eight basic variations of terminal states; clinical death with reversible brain failure, with its presently undefinable duration; and the various possible outcomes.

Examples of rapid secondary cardiac arrest include alveolar anoxia (e.g., inhalation of oxygen-free gas, fulminating pulmonary edema), asphyxia (airway obstruction, apnea), and exsanguination ( Fig. 1–1.7, conditions 3 through 5; Table 1–1.1).

Table 1–1.1. Specific Mechanisms of Rapid Dying and Reanimation

Examples of slow secondary cardiac arrest include moderate hypoxemia, as in subacute pulmonary edema or consolidation, various shock states, and intracranial pathology (Fig. 1–1.7, conditions 6 through 8), any of which may stop the circulation within minutes, hours, or days. Although the basic steps of CPR (airway, breathing, circulation) are applicable in most cases of sudden death ( 1), definitive therapeutic measures (CPR steps D, E, and F) and prolonged life support differ with the different mechanisms of terminal states ( 14) (Fig. 1–1.2, Table 1–1.2). The addition of G, H, and I includes the additional focus on monitoring, cerebral resuscitation, and intensive care. The need for rapid airway control requires positioning and manual clearing of the airway (Fig. 1–1.8, Fig. 1–1.9, Fig. 1–1.10 and Fig. 1–1.11). The issue of health care professionals reduced willingness to perform mouth-to-mouth resuscitation (less than 50%) has not been adequately addressed ( 14A).

Table 1–1.2. Phases, Steps, and Measures of Cardiopulmonary-Cerebral Resuscitation a

Figure 1–1.8. Backward tilt of head. A. Hypopharyngeal obstruction by the tongue in coma with head in midposition or flexed. B,C. Backward tilt of the head stretches anterior neck structures and thereby lifts the base of the tongue off the posterior pharyngeal wall. B. Neck lift, which is easier to teach; and C. chin support, which better controls opening of the mouth. (Reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation. Stavanger, Norway: Asmund S. Laerdal, 1981.)

Figure 1–1.9. Techniques for backward tilt of head. Backward tilt of the head, by neck-lift, plus positive pressure inflation by mouth-to-mouth (left) and mouth-to-nose (right) exhaled air inflations. (Reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation. Stavanger, Norway: Asmund S. Laerdal, 1981.)

Figure 1–1.10. Triple airway maneuver. Tilt the head backward, displace the mandible forward, and open the mouth. A. Operator at the patient's vertex (for spontaneously breathing patients.) B. Operator at side of the patient for direct mouth-to-mouth ventilation. Seal the nose with your cheek for mouth-to-mouth breathing. Seal the mouth with your other cheek for mouth-to-nose breathing. C. Modified triple airway maneuver by the thumb-jaw lift method (for relaxed patient only). (Reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation. Stavanger, Norway: Asmund S. Laerdal, 1981.)

Figure 1–1.11. Three methods force the mouth open for clearing, finger sweeping, suctioning, and inserting of airways or laryngoscope. A. “Crossed-finger” maneuver, for the moderately relaxed jaw. B. “Finger behind teeth” maneuver, for the tight jaw. C. “Tongue-jaw lift” maneuver, for the relaxed jaw. (Reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation. Stavanger, Norway: Asmund S. Laerdal, 1981.)

THE TERMINAL STATE The “terminal state” begins with decompensation of the organism's defenses against failure of vital organ systems. The concept of arterial oxygen (O 2) transport (arterial O 2 content times blood flow) is crucial for understanding dying processes for the entire organism (cardiac output) and for specific organs (regional blood flow), e.g., cerebral blood flow (CBF). The pathophysiologic pattern and duration of the terminal state vary to some extent with the initiating cause of dying ( Fig. 1–1.7). In exsanguination cardiac arrest, for instance, the terminal state includes the following ( 3): 1. Sequential losses, first of rational mentation, then of consciousness, airway, breathing, and circulation. 2. Terminal apnea when profound hypotension or pulselessness supervenes. 3. Agonal state, i.e., the period during which, after onset of clinical pulselessness (apparent cessation of circulation) and the brief period of terminal apnea, gasping respiration and sometimes also low arterial pressure pulsations return transiently. 4. Clinical death, namely coma, apnea, no gasping, no pulse (no blood flow), but CNS failure still reversible. The mobilization of compensatory mechanisms (e.g., protection of the cerebral cortex by maximal vasodilation) depends on the rapidity of arrest. Although in acute respiratory insufficiency or shock states, tissue deprivation of oxygen and substrate usually progresses slowly enough for compensatory mechanisms to assist, whereas rapid exsanguination and other sudden causes of cardiac arrest do not permit these mechanisms to be effective in delaying clinical death. Basic to most derangements of vital organ systems function during dying, and to the final destruction of cells, is the fact that glucose energy metabolism in all tissues, particularly in the brain, is switched from the highly energy-efficient aerobic glycolysis to the highly inefficient anaerobic glycolysis. After exhaustion of glucose stores, there is a total lack of energy, leading to a rapid breakdown of phospholipids and lipoproteins and a failure of enzyme systems ( 11,12,13,14,15,16,17,18 and 19), which, in the absence of reperfusion, results in fairly homogeneous dissolution of cell membranes, organelles, and cell nuclei ( 20,21,22,23,24,25 and 26). If reperfusion and reoxygenation occur, cell recovery and cell death processes, which often proceed side-by-side, are complex and inhomogeneously distributed.

EXPERIMENTAL STUDIES Exsanguination In dogs under opiate or barbiturate sedation, exsanguination through a femoral artery cannula induces hyperventilation, arterial hypotension, tachycardia, and agitation within the first 1 to 2 minutes because of the protective reflexes of the carotid and aortic pressoreceptors and chemoreceptors and to discharges from many regions of the brain. From 5 to 8 minutes, the heart rate begins to decrease, the electrocardiogram (ECG) shows signs of myocardial ischemia, and the animal begins to grow somnolent. From 8 to 15 minutes, the animal continues to breathe regularly, but at a slower rate; the heart rate decreases further (because of increased vagal tone); and the mean systemic arterial pressure falls to 20 to 30 mm Hg when about half of the blood volume has been lost. Such rapid hemorrhage results in an acute decrease in hematocrit, caused by a decrease in intravascular pressure and subsequent transfer of extravascular fluid into the vascular compartment. At this point, sludging and segmentation become apparent in the retinal arteries, and the brain begins to fail; the animal is comatose, the cerebral arteriovenous oxygen difference is greatly increased, and brain metabolism begins to switch from the aerobic form to the more primitive anaerobic form (glycolysis) ( 11,12 and 13,27,28,29 and 30). Just before the onset of pulselessness, electrocortical silence and apnea occur; although the arterial PO 2 is still normal, the arterial P CO2 is low (from hyperventilation and low blood flow). The mixed venous PCO2 is elevated (because of low blood flow) and the blood base deficit is only slight because terminal circulation is inadequate to wash out fixed acids accumulating in the ischemic, anoxic tissues. Circulation and bleeding stop when total blood loss is about one-half to two-thirds of estimated blood volume, with a mean pressure in the aorta of about 15 mm Hg without pulse waves. Electrocardiographic complexes continue. Onset of pulselessness is accompanied by abolition of corneal and lid reflexes, pupillary dilation, and cessation of retinal capillary flow. The rate at which hypotension, coma, and pulselessness develop depends on the speed of exsanguination, the anesthesia used, and several other factors. Usually, circulation stops in asystole. In about 5% of the dogs, spontaneous VF developed after about 4 to 5 minutes of pulselessness. A higher incidence of VF occurred later, during resuscitative efforts, when the heart was massaged. The agonal state, which follows, is of varying duration (2 or more minutes) and is characterized by resumption of gasping respirations, which are a sign that the bulbar centers are still active. The agonal gasps are insufficient to ventilate the lungs, because inspiratory, expiratory, and auxiliary muscles contract simultaneously. In about 50% of the animals, the mean pressure rises transiently to about 20 to 50 mm Hg with good pulsations, which may occasionally be accompanied by a brief recovery of the EEG and consciousness. When these last flickers of life, which are inadequate for “self-resuscitation,” cease, clinical death begins. The ECG

complexes continue for some time during clinical death at a diminishing rate (anoxic depression), first with sinus rhythms, and finally (at the end of 5 minutes of clinical death) with bizarre biphasic or monophasic ventricular complexes. During dying, cerebral cortical function fails first, and the phylogenetically older brainstem and medulla (respiratory and vasomotor centers) continue to function, although in a disorganized fashion. When mean arterial pressure decreases to about 30 mm Hg or less, the EEG develops high-amplitude sinusoidal delta waves and, with progressive ischemia and anoxia, a decrease in frequency and amplitude; finally, there is electrical silence. Electric discharges from the reticular formation are the last to cease. Ventricular Fibrillation In dogs under inhalational general anesthesia, electrically induced VF results in immediate pulselessness, gasping for 10 to 30 seconds, and then apnea (31,32,33,34,35 and 36). Aortic PO2 remains normal for up to 20 minutes of clinical death unless VF was preceded by hypoxemia. Blood during stasis seems to develop substances that hamper resuscitation. Cardiac arrest from exsanguination ( 3,4,34,37,38,39,40 and 41) might be tolerated better by the brain (is reversed more easily) than cardiac arrest of the same duration caused by VF. With standard CPR alone, asphyxial cardiac arrest is easier to reverse than VF cardiac arrest, but asphyxial arrest results in more brain damage than the same duration of VF cardiac arrest ( 34,42,43). This is probably because of more severe brain acidosis developing during asphyxiation. Protection and preservation of cerebral function is termed advanced cerebral resuscitation (see also Chapter 3). The major worldwide problem remains—survival with the least disability ( 43,44).

RESUSCITATION AND THE POSTRESUSCITATION SYNDROME The pattern of recovery after cardiac arrest, starting with restoration of circulation, varies with different species, mechanisms of dying, experimental models, and the resuscitation and postresuscitation life-support techniques used ( 12,34,45,46). 1. In normothermic, lightly anesthetized dogs after exsanguination cardiac arrest, complete neurologic recovery was consistently possible if clinical death lasted up to about 5 minutes and was occasionally possible after cardiac arrest of 5 to 15 minutes ( 4,38,39 and 40). 2. The maximal duration of VF cardiac arrest, followed occasionally by grossly complete neurologic recovery, after special intensive care and brain resuscitation measures, was 10 to 12 minutes (8,32,47). 3. After asphyxial cardiac arrest of 7 minutes or more, despite special intensive care and brain resucitation measures, severe brain damage was always seen ( 43). Generally, asphyxial cardiac arrest is more injurious, probably because it produces a period of hypoxic tissue acidosis before arrest ( 11,12 and 13). Exsanguination cardiac arrest, however, seems less injurious because up to 15 minutes of arrest have been tolerated by the entire organism ( 4,15). Resuscitation From Exsanguination Cardiac Arrest: Lessons from the Laboratory For resuscitation from exsanguination cardiac arrest, Negovsky ( 3) used rapid arterial reinfusion of the arterially shed, oxygenated, heparinized blood (which, under clinical circumstances, is not immediately available) with epinephrine added ( 3,48). Intermittent positive pressure ventilation (IPPV) with air was also provided ( 3,4). Cardiac compression is not necessary in this situation because the arterial reinfusion perfuses the coronary arteries, restarting cardiac electrical activity within seconds. Within 1 to 2 minutes, after 10 to 20% of the shed blood has been reinfused, spontaneous circulation with near normal arterial perfusion pressure is reestablished ( 3,4). When volume is repleted through the venous route, circulation can be restored only with external or internal cardiac compression. Spontaneous circulation returns, but not as rapidly as with arterial reperfusion; however, venous infusion is effective also with the use of readily available plasma substitutes (Ringer's solution, dextran) and bank blood, whereas these nonoxygenated, acidic solutions often fail to restore spontaneous circulation when given through the arterial route ( 38,39 and 40). Venous infusion plus CPR permits oxygenation of blood and blood substitutes on the way through the lungs. Different blood substitutes, however, vary in their effectiveness. The infusion of Ringer's solution alone, for example, in a volume 2½ times that of the volume of blood shed, can restore circulation but cannot sustain arterial pressure. With more salt solution, tissue edema occurs. In contrast, colloid solutions infused in volumes equal to those of the blood shed enable survival in 100% of animals. With either the arterial or venous technique, heart pumping action can be easily restored, even after circulatory arrest of up to about 10 minutes. The ECG recovers in mirror image sequence of its disappearance—first with ventricular, then nodal, and finally sinus rhythms. After 4 minutes of reperfusion, spontaneous breathing resumes, signaling respiratory center recovery. Spontaneous breathing returns first with agonal gasping, which is replaced by a pattern of periodic respirations (Cheyne-Stokes) with a higher than normal frequency, and then by normal respiratory patterns with interposed gasps, which progressively diminish until a fully normal breathing pattern is established ( 3,4). In clinical practice, however, controlled ventilation with IPPV (with or without positive end-expiratory pressure [PEEP] to counteract pulmonary shunting) should be used during postanoxic coma, at least until weaning to coordinated adequate spontaneous breathing is possible (ideally, as long as coma persists), to prevent pulmonary edema and consolidation, which often occur when spontaneous breathing is permitted earlier. The vasomotor center recovers at the same time as breathing begins ( 3,4). Continuation of the more primitive gasping type of respirations for longer than 20 minutes after reperfusion is a poor prognostic sign in terms of cerebral recovery. After return of the first gasps, corneal reflexes, EEG, and muscular tone recover in rapid sequence. At about 5 minutes of reperfusion, the pupils start to constrict. Recovery of the Brain The cerebral cortex is more vulnerable than the brainstem to the effects of hypoperfusion, and, therefore, recovers more slowly. Although anesthesia and hypothermia induced before and maintained during circulatory arrest protect the cortex to some extent, in normothermic unanesthetized animals the sequence of EEG recovery is not the mirror image of the disappearance of electric impulses during dying, probably because of many small, scattered areas of underperfusion persisting in the brain during the postresuscitative period ( 49). (See also Chapter 3.) Postresuscitation Syndrome The known symptomatology of the postresuscitation syndrome is as follows: there is prolonged protracted reduction in cardiac output in dogs and humans, in spite of normotension. Evidence suggests a combination of cardiac pump failure and microcirculatory obstructions throughout the body, resulting in increased systemic vascular resistance. Pulmonary insufficiency after arrest seems to be related to lack of advanced respiratory intensive care. Conversely, isolated brain ischemia can trigger dysrhythmias (50,51,52 and 53), renal problems (3,51), and pulmonary edema and consolidation (4,51,54). Acute renal and hepatic failure, are common after shock (27,55,56), and after cardiac arrest. After long periods of cardiac arrest and reperfusion, demonstrated renal and hepatic derangements have been severe when no prolonged intensive care life support was used ( 4), but only slight with intensive care ( 5,34). Prolonged cardiac arrest seems to first induce hypercoagulability of the blood, as seen in traumatic shock, which is followed later by hypocoagulability ( 4,16). We have observed large vessel clotting at the end of normothermic cardiac arrest of 20 minutes or longer and hypothermic cardiac arrest of 40 minutes or longer in dogs and rats ( 57). After reperfusion, these prolonged arrest states are followed by hemorrhagic diatheses. Postischemic hypoperfusion, which seems to occur also in other organs such as the liver and kidney, sets up the vicious cycle of postresuscitation disease: hypoperfusion—ischemic anoxia—edema—hypoperfusion and resultant deterioration. Clotting disturbances in the recuperative phase are poorly characterized. Hypercoagulability with spotty areas of intravascular coagulation in dogs seems to accompany circulation cessation and is a byproduct of the sympathoadrenal system activation. During resuscitation, there seems to be an early period of hypocoagulability, then normal clotting starting at about 1 hour, followed by alternating episodes of hypocoagulability and hypercoagulability throughout the recovery phase (4). During dying and the early phases of resuscitation, the nature of the metabolic changes depends greatly on the pattern of dying. For instance, in exsanguination or VF, hyperventilation causes a low arterial P CO2, and normal or elevated PO 2, whereas poor peripheral perfusion leads to lactic acidosis in the venous blood; asphyxia, in contrast, results in hypercarbia, hypoxemia, and lactacidemia, owing to the combined effects of hypoventilation and hypoperfusion before arrest.

Although metabolic abnormalities during dying vary with the mechanism of dying, during resuscitation these derangements seem to follow a similar pattern, irrespective of the initiating insult. There is a washout of CO 2 and inorganic acids from tissues, producing transient hypercarbia, which is quickly changed by spontaneous or artificial hyperventilation to hypocarbia. There is, as well, a prolonged rise in arterial lactate values (to 5 to 10 times normal), resulting in a low arterial pH (about 7.0) and a concomitant reduction in cardiac output for several hours, even 2 to 3 days ( 4,32,58,59). At 4 to 5 hours, arterial pH may increase above 7.4 from hyperventilation and intravenous (IV) bicarbonate, but normalization of cerebrospinal fluid (CSF) acidosis often lags significantly behind. Brain lactate levels of about 20 times normal seem to define the critical limits of tolerance in terms of brain recovery ( 11,12 and 13). With further passage of time, arterial pH continues to rise, and at 24 hours metabolic alkalemia may be seen (arterial pH above 7.4 and increased base excess). Postresuscitative hypoxemia on breathing air is common, particularly in subjects with preexisting cardiopulmonary disease or after prolonged periods of arrest and resuscitation, and occurs as a result of ventilation-perfusion mismatching with shunting, primarily from pulmonary edema and contusion (external heart compressions) and atelectasis. Controlled ventilation with 50 to 100% oxygen should, therefore, be continued long into the recovery period ( 60). PEEP should be used only as much as necessary to achieve a PaO 2 of about 100 mm Hg because the resulting increase in venous and intracranial pressures may hurt the already injured brain. Hepatic and renal functions halt immediately on cessation of circulation. The liver thus fails in its vital role of detoxification, and noxious metabolites are no longer cleared from the circulation. Such metabolites may contribute to cerebral dysfunction because exchange transfusion, plasmapheresis, and liver perfusion used during the resuscitative period have all been shown to somewhat increase the tolerance of the CNS to the ischemic-anoxic insult ( 3,4,37,41). The kidneys also cease functioning immediately on arrest and show subtle changes in function for several weeks after ischemia; anuria, however, is less likely to occur after total cessation of circulation of several minutes than after hypovolemic shock of 1 hour or more. The role of endocrine function in dying and resuscitation involves increased production of glucocorticoids and adrenocorticotropic hormone (ACTH) in the terminal state is believed to exert a protective effect. The value of steroid medication in the postischemic phase is not established, however.

FUNDAMENTAL MECHANISMS OF RAPID DYING AND RESUSCITATION Ventricular Fibrillation VF is “irregular continuous peristaltic quivering motion of the ventricles of the heart” ( 61) (Fig. 1–1.12 and Fig. 1–1.13). It does not pump blood and is associated with the characteristic ECG pattern of oscillations without intermittent ventricular complexes. Primary VF, in the strictest sense, is that occurring from electric shock (described later) or in patients without premonitory signs and symptoms of myocardial infarction. Generally, however, the term primary VF is used whenever this type of cardiac arrest occurs suddenly without evidence of preceding cardiovascular or pulmonary failure, in patients with or without known ischemic heart disease. Because the majority of sudden deaths in patients with preexisting myocardial ischemia seem to be caused by VF, in most cases of witnessed cardiac arrest VF should be suspected as the cause. High concentrations of adrenergic agents, either exogenously administered or endogenously released, also may trigger VF, particularly in the presence of sensitizing drugs such as cyclopropane or halothane. Catecholamine release secondary to an increase in Pa CO2 has also been cited for triggering VF during anesthesia.

Figure 1–1.12. Electrocardiographic diagnosis of cardiac arrest. Top: Relation of normal ECG to cardiac anatomy. Bottom: The three typical ECG patterns associated with pulselessness: 1. Asystole; 2. electromechanical dissociation (cardiovascular collapse, mechanical without electrical asystole); and 3. ventricular fibrillation. Electromechanical dissociation is not associated with a characteristic QRS pattern. (Reproduced with permission from the American Heart Association, Dallas, Texas.)

Figure 1–1.13. ECG fibrillation patterns. 1. Coarse ventricular fibrillation (pulselessness); 2. fine ventricular fibrillation (pulselessness); 3. artifact from patient movement with QRS complexes and with pulse; 4. atrial flutter (includes QRS complexes). (Reproduced with permission from the American Heart Association, Dallas, Texas.)

Secondary VF may occur spontaneously or be provided by stimuli such as heart massage in the weakly beating or arrested heart with bizarre ECG complexes or asystole; for instance, in asphyxia, exsanguination, or other causes of rapid dying. Secondary VF is more likely to occur in the anoxic (acidotic) heart and in the presence of high catecholamine levels ( 62). The larger and more diseased the heart, the more likely it is to fibrillate. Sudden VF in the conscious person produces unconsciousness within about 10 to 15 seconds ( 63). Terminal gasping may continue for 20 to 30 seconds during VF, which may produce minimal arterial pulse waves (probably without significant blood flow) because of the intrathoracic pressure fluctuations of gasping. VF can be proved as the cause of pulselessness only by ECG or direct visualization of the heart. Inspection and palpation of the fibrillating heart reveal wormlike movements all over the myocardium. The fibrillating heart is at first pink, and the ECG shows strong, rhythmic sinusoidal patterns with high amplitude. Later, the quivering motions become weaker, the heart grows cyanotic, and the ECG shows arrhythmic, polymorphous patterns with low amplitude. In the unanesthetized dog, electrically induced VF fades into cardiac electrical silence in about 10 to 20 minutes. After 10 to 15 minutes or more of VF in dogs, the ECG pattern is so weak and the heart so anoxic and acidotic that CPR attempts may fail to restore spontaneous circulation. In humans, VF does not ordinarily terminate spontaneously, but in most instances it can be terminated by electric defibrillation, giving way to effective cardiac contractions, provided that the myocardium is adequately oxygenated when defibrillation is attempted; however, it has been seen occasionally to stop spontaneously (64), for instance in about 50% of patients developing “runs” of VF from coronary hypoperfusion from bradycardia in heart block (Adams-Stokes syndrome). In only

rare instances have prolonged CPR efforts, including the administration of bicarbonate, led to spontaneous defibrillation. The likelihood of VF stopping spontaneously varies inversely to the size of the heart. POSSIBLE MECHANISMS OF VF 1. VF occurs secondary to excitation from many newly developed heterotopic foci that are independent of each other. 2. VF arises as a result of a circus movement, most likely triggered by an ectopic focus, creating a wave of excitation with multiple reentry of impulses circulating continuously into areas that recently depolarized. Support of the triggering role of ectopic foci derives from the fact that, in ischemic heart disease, frequent premature ventricular contractions (PVCs) or ventricular tachycardia (VT), with or without pulse, usually precedes VF. Support for the circus movement derives from the efficacy of electric defibrillation. PVCs, electric shock, or other stimuli are most likely to throw the heart into VF when they occur during late systole, specifically the vulnerable period of the ECG, i.e., the upstroke of the T wave. The triggering foci seem prone to develop when there are regional perfusion differentials in the myocardium—the “checkered, pale/pink heart” ( 65,66 and 67). The resulting electric instability is worsened by exertion, which further exaggerates the oxygen differential among regions. Autopsies conducted shortly after sudden death have shown that one–third of the patients did not have myocardial infarction or major coronary artery obstruction ( 68). These events can be explained by coronary spasm from emotion, reflexes, and other causes—a mechanism difficult to prove in humans but highly probable in view of suggestive clinical causes ( 69) and the results of coronary angiography during angina attacks. Although myocardial depressant drugs such as lidocaine, procainamide, quinidine, and potassium occasionally have some place in the patient with intractable or recurrent VF when given in sufficient doses to terminate VF during CPR, they may make restoration of effective spontaneous cardiac contractions difficult. Therefore, the most reliable method at present for defibrillating the ventricles and restoring effective spontaneous circulation is electric shock, applied either directly to the heart or externally across the chest (62,70,71,72,73 and 74). The principle of electric cardiac defibrillation is that a strong, brief shock of alternating current or capacitor discharge direct current produces synchronized depolarization of all heart muscle fibers, thereby eliminating the uncoordinated ectopic foci or circus movements of electric activity and converting all electric activity into a single contraction. This massive synchronous depolarization is followed by a refractory period and, if the heart is adequately oxygenated at the time, through early application of countershock or effective CPR, by spontaneous sinus rhythm and cardiac contractions ( 74A). There is no evidence that a manual precordial thump produces an electric impulse to the heart sufficiently strong enough to have a defibrillating effect. Occasionally, however, VT has been terminated by precordial thump (75). Unpredictably, precordial thumps can change any abnormal ECG pattern in a sick heart into VF ( 76). The likelihood of success in stopping VF with electrical countershock and restoring spontaneous circulation depends on the degree of myocardial hypoxia and acidosis, the duration of fibrillation, the size of the heart, the degree of coronary disease, and other factors. Countershock success is also increased with higher median frequency and amplitude as measured on the ECG (77). The physiologic requirements for electric defibrillation follows: 1. 2. 3. 4. 5. 6.

Reoxygenation of the myocardium (reperfusion pressure > 30 mm Hg). Arterial pH normalization (acidosis weakens the myocardium and increases its resistance to catecholamines). Enough energy to arrest fibrillation throughout the myocardium. Not as much energy as to overwhelm the pacemaker needed to initiate coordinated contractions. Resumption of function of a single pacemaker because multiple pacemakers may cause return to VF. A heart muscle capable of contracting vigorously; weak, uncoordinated contractions are prone to revert to VF ( 78).

Some of these requirements are met by CPR, plus the intravenous administration of bicarbonate and epinephrine ( 33,79,79A), as well as newer innovative advanced life support pharmacology, such as buffers, new vasopressors, and amiodorone and other antiarrhythmics ( 79B). The b-receptor (inotropic) effect of epinephrine can induce VF, but when given during VF, epinephrine makes VF more vigorous and thus promotes response to countershock and resumption of strong contractions. The a-receptor (vasoconstrictor) effect of epinephrine increases the artificially induced arterial pressure during heart compressions, and thus increases coronary perfusion and myocardial oxygenation. The greater importance of the latter mechanism is evident from the ability of primarily a-adrenergic agents (e.g., norepinephrine, phenylephrine, methoxamine) also to enhance electric defibrillation and restoration of spontaneous circulation ( 80,81). The concurrent concensus standards for advanced cardiac life support (ACLS) are recommended. It should be noted, however, that these are not universally agreed upon in all details and outcome research is lacking for many ACLS actions. (Fig. 1–1.14, Fig. 1–1.15, Fig. 1–1.16 and Fig. 1–1.17). Active compression-decompression (ACD) has also been advocated, but the benefits are not clear ( 81A).

Figure 1–1.14. Ventricular fibrillation/pulseless ventricular tachycardia (VF/VT) algorithm. *High-dose epinephrine has not been demonstrated to improve outcome (77A).

Figure 1–1.15. Bradycardia algorithm (patient is not in cardiac arrest).

Figure 1–1.16. Asystole treatment algorithm.

Figure 1–1.17. Pulseless electrical activity (PEA) algorithm (electromechanical dissociation [EMD]).

Asystole and Electromechanical Dissociation (Now termed Pulseless Electrical Activity [PEA]) The electrocardiographic definition of asystole is “pulselessness with cardiac standstill and isoelectric ECG,” i.e., electric asystole. When discussing asystole here, we include “electromechanical dissociation (EMD),” namely, pulselessness and cardiac standstill (no blood flow) (PEA), with intermittent normal or abnormal ECG complexes, i.e., mechanical asystole. Primary asystole in the strictest sense occurs only with a sudden overwhelming overdose of myocardial depressant drugs (e.g., intravenous potassium, barbiturate, inhalation anesthetic, or local anesthetic); in sustained high-energy electric shock (systolic arrest), such as used to occur in electrocutions; and in patients with progressive severe bradycardia (Adams-Stokes syndrome) and atrioventricular block, which is usually caused by focal ischemic lesions in the conduction system. In the last type of arrest, syncope may occur without chest pain or premonitory hypotension. Myocardial underperfusion from severe bradycardia may easily trigger VF or exacerbate conduction defects. More common is asystole secondary to increased vagal tone, particularly in patients with underlying heart disease or in children. Vagotonia depresses the sinus node, then the atrioventricular node, and finally the atrioventricular conduction system, which may lead in the diseased heart to idioventricular rhythm (secondary to heart block) with bradycardia of 30 to 40 beats/min. In the healthy heart, such vagotonia usually leads simply to escape beats at the nodal level. Asystole may also develop in the wake of marked sinus bradycardia. Although sinus bradycardia is considered physiologic in athletes, sinus bradycardia with a ventricular rate of less than 40 to 50 beats/min occurring in some healthy persons—or, more likely, in patients with preexisting heart disease—can occasionally result in asystole. Predisposing factors include hypercarbia, hypoxemia, hypothermia, hypothyroidism, drugs (e.g., beta receptor blockers, reserpine, narcotics, calcium entry blockers), vagal maneuvers (e.g., nausea and vomiting, oculocardiac reflex in eye surgery, pressoreceptor reflex of carotid sinus massage), hyperpotassemia (e.g., severe burns), and obstructive jaundice. Asphyxiation, exsanguination, and anesthetic overdose usually first cause pulselessness with ECG-QRS complexes continuing, i.e., “primary EMD-asystole.” This can be reversed with CPR, with or without epinephrine and volume repletion. CPR efforts rarely stimulate the weak heart into secondary VF. In contrast, VF, when countershocked, may be followed by inability of the defibrillated heart to resume effective contractions. This “secondary (postdefibrillation) EMD-asystole” is difficult to reverse; it may require high perfusion pressure as achieved only with cardiopulmonary bypass ( 45). Vasovagal syncope occurring in persons with heart disease can cause unconsciousness and airway obstruction. This is another possible mechanism of secondary asystole. In healthy young people, an emotional insult may cause a sudden reduction in heart rate and arterial pressure, leading to syncope from cerebral underperfusion. The skin becomes cold and sweaty, breathing is shallow, and the pupils are narrow and then wider. The mechanism of vasovagal syncope is not clear; it is probably partially a result of pooling of blood into capacitance vessels. Positioning the patient horizontally and raising his legs usually promptly reverses this emergency. If necessary, additional measures, if available, should include oxygen inhalation, and IV fluids and atropine; pulselessness calls for CPR. In patients with myocardial infarction (particularly diaphragmatic wall infarcts), cardiac slowing for any reason decreases cardiac contractility, cardiac output, and coronary perfusion, and predisposes to asystolic arrest, as well as to PVCs, VT, and VF. Treatment of asystole centers around CPR and abolition of the cause. The oxygenated heart with atrioventricular block and bradycardia or asystole responds to mechanical or electric stimulation with effective contractions. In severe bradycardia, atropine should be tried first to prevent asystole. Atropine is not effective, however, if the block is below the atrioventricular node, in the bundle of His, or beyond, or if the block results from structural damage to the conduction system. In such cases, isoproterenol increases the heart rate, but must be given with caution because it increases cardiac irritability and the tendency to develop VF. The definitive treatment of severe bradycardia is electric pacing. External pacing is potentially painful and unreliable, and insertion of pacing wires directly into the heart through a transcutaneous intracardiac needle is effective, but hazardous and difficult. Transvenous pacing may be difficult in the acute setting. The consensus standards for treatment are these protocols: bradycardia ( Fig. 1–1.15), asytole (Fig. 1–1.16), and electromechanical dissociation ( Fig. 1–1.17). Pediatric guidelines have stayed constant since 1992 (Table 1–1.3). A major change is the question of initial epinephrine dosage with higher doses (.1 mg/kg) that has been suggested by some investigators. Outcomes of recent studies are not conclusive.

Table 1–1.3. Changes in Guidelines for Pediatric Emergencies

Life-Threatening Dysrythmias Health professionals providing advanced CPR life support must be able to recognize the tachydysrhythmias and bradydysrhythmias ( Fig. 1–1.18, Fig. 1–1.19 and Fig. 1–1.20).

Figure 1–1.18. ECG patterns of tachydysrhythmias (All lead II). 1. One PVC with R-on-T, causing ventricular fibrillation (VF) (no pulse); 2. occasional unifocal PVCs (possibly harmless); 3. frequent multifocal PVC (dangerous); 4. PVCs causing ventricular tachycardia (can be short run, terminating spontaneously); 5. sustained ventricular tachycardia. (Adapted with permission from the American Heart Association, Dallas, Texas.)

Figure 1–1.19. ECG fibrillation patterns. 1. Coarse ventricular fibrillation (pulselessness); 2. fine ventricular fibrillation (pulselessness); 3. artifact from patient movement, with QRS complexes and with pulse. (Reproduced with permission from the American Heart Association, Dallas, Texas.)

Figure 1–1.20. ECG patterns of bradydysrhythmias (All lead II). 1. First-degree AV block (fixed prolonged P-R interval); 2. second-degree AV block (Mobitz type I-Wenckebach phenomenon) (expanding P-R and contracting R-R interval); 3. second-degree AV block (Mobitz type II) i.e., 2:1 block, evolved from 2. complete AV block with ventricular rhythm. In 3 and 4 a pacemaker is indicated. (Modified with permission from the American Heart Association, Dallas, Texas.)

PREMATURE ATRIAL CONTRACTIONS Premature atrial contractions are usually harmless, and may occur in normal persons. If they are frequent, they may indicate heart or lung disease and may initiate atrial tachycardia. They are important primarily because they must be distinguished from PVCs, which are sometimes dangerous. Therapy for premature atrial contractions consists of sedation, treatment of the underlying problem, if any, and interdiction of coffee and cigarettes. ATRIAL FIBRILLATION Atrial fibrillation results in an irregular ventricular rhythm, which is the hallmark of this dysrhythmia and makes it immediately recognizable even on palpation of the pulse (pulsus irregularis perpetuus). Atrial fibrillation is usually not life-threatening unless associated with a rapid ventricular rate. It is treated first by a calcium blocker, e.g., Verapamil. If unsuccessful and associated with hemodynamic instability, the most effective treatment is synchronized electric (low energy) direct current countershock (cardioversion) (25 to 50 J). This should be undertaken with great caution in the digitalized patient. Use sedation (e.g., IV micazolam 2 to 3 mg) ( Fig. 1–1.21). Digitalis remains the most commonly used long-term therapy and may be used in the hemodynamically stable patient for both control and conversion to sinus rhythm and may require the addition of procainamide or quinidine in difficult-to-control cases.

Figure 1–1.21. External electric defibrillation by two bimanually triggered chest paddles applied on conductive jelly or saline-soaked sponge, one paddle just below right clavicle, the other over the cardiac apex. The paddles incorporate defibrillation outlets and ECG leads. A. Wrong paddle electrode placement, too close together, current shunted away from heart. B. Correct paddle electrode placement, wider spacing, more current through heart. C. External placement of “quick ECG look”

defibrillating paddle chest electrode. (Reproduced with permission from Ewy GA. Defibrillating cardiac arrest victims. J Cardiovasc Med 1982; 7:28.)

PREMATURE VENTRICULAR CONTRACTIONS PVCs (Fig. 1–1.18A.) are wide (QRS ³ 0.12 second), bizarre, extra ECG complexes triggered by an ectopic ventricular focus. Sometimes they can be felt as extra pulse beats; often PVCs do not produce a pulse because of inadequate ventricular filling. The PVC, if followed by a compensatory pause, which the patient can sometimes feel as a momentary “fullness” in the chest. Frequent multifocal PVCs are the most common precursors of VT and VF (i.e., sudden cardiac death), and a PVC falling on a T wave (R-on-T phenomenon) may initiate VF. More than three PVCs in a row are, by definition, VT. If every other beat is preceded by a PVC, it is called “ventricular bigeminal rhythm”; if it is every third beat, it is called “trigeminal rhythm.” Single PVCs of similar configuration that do not fall on the T wave occur in otherwise healthy persons and were once thought harmless; in ischemic hearts, however, they represent an increased risk of sudden cardiac death, particularly in acute myocardial infarction (82). PVCs initially are treated with an IV bolus of lidocaine (1–1.5 mg/kg IV). VENTRICULAR TACHYCARDIA VT (Fig. 1–1.18E) is the most dangerous precursor of VF (Fig. 1–1.19). VT is a continuous sequence of PVCs. During VT, there may or may not be a palpable pulse, depending partly on the rapidity of the rate. When there is a pulse, and the patient is conscious, IV lidocaine should be administered in an attempt to terminate VT, however, VT with unconsciousness or pulselessness must be treated immediately just as VF, namely with electric countershock and CPR, as needed. It is important to differentiate between ventricular and supraventricular tachycardia because the latter is usually not immediately harmful and the former is immediately life-threatening. If the differentiation is impossible, the hemodynamic effects of the dysrhythmia, as monitored by pulse and arterial pressure, should guide therapy. Eventually, even atrial tachycardia should be treated, particularly in the elderly with coronary artery disease (Valsalva maneuver, carotid sinus massage, verapamil, adenosine, digitalis, overdrive pacing, esmolol, etc). BRADYCARDIA Bradycardia (Fig. 1–1.20) is defined as a heart rate of less than 60 beats/min. This may produce hypotension in the critically ill person when the heart rate is less than 50 to 60 beats/min, irrespective of whether it is sinus bradycardia or bradycardia of ventricular origin. One should always make an attempt to differentiate between these two. Sinus bradycardia is harmless in healthy persons and common in athletes, but can be risky in patients with myocardial disease. Bradycardia of ventricular origin is life-threatening because it is caused by complete heart block. ATRIOVENTRICULAR BLOCK Atrioventricular block may be first, second, or third degree ( Fig. 1–1.20). First-degree atrioventricular block is merely a delayed passage of the impulse through the atrioventricular node, causing a prolonged (> 0.20 second) P-R interval. It serves as a warning, but treatment is rarely needed. Second-degree atrioventricular block results in intermittently nonconducted impulses and may be one of two types, the Mobitz type I pattern (Wenckebach) and the more dangerous Mobitz type II pattern. Mobitz type I is characterized by progressively longer PR intervals and shortening R-R intervals until a beat is dropped. Mobitz type I atrioventricular block is common in myocardial infarction, usually transient, and if associated with significant bradycardia requires atropine or isoproterenol rather than a pacemaker. In inferior wall myocardial infarction, Mobitz type I block may precede Mobitz type II atrioventricular block, which occurs in large myocardial infarctions, often as a forerunner to complete atrioventricular block. The appearance of Mobitz type II atrioventricular block may indicate the need for a demand pacemaker, which may be transvenous or external. Mobitz Type II block is characterized by a constant PR interval aside from intermittently nonconducted impulses. Third-degree (complete) atrioventricular block is characterized by a complete absence of conduction of impulses from the atria to the ventricles with a slow idioventricular rate of 30 to 40 beats/min as in Stokes-Adams syndrome. The P waves are unrelated to the QRS complexes. With an extremely slow ventricular rate, blood flow may become inadequate to maintain consciousness, and reduced myocardial perfusion can result in congestive heart failure, angina, VT or VF. Treatment in the patient who tends to become unconscious or whose heart rate is considered dangerously slow should consist of external electrical pacing while an IV infusion of isoproterenol is started. With this treatment, the patient's heart rate can usually be supported adequately until an IV pacemaker is inserted. During CPR, when recurring runs of VT or even VF occur on restoration of spontaneous circulation, one should study the ECG in detail to determine whether the tachydysrhythmia is preceded by third-degree (complete) atrioventricular block. In this instance, lidocaine may be contraindicated, and seemingly paradoxic treatment with isoproterenol and pacing may keep the sinus rate high enough to prevent such recurrent ventricular tachydysrhythmias and cardiac arrest. Atropine is generally more effective for increasing the heart rate in sinus bradycardia than in ventricular bradycardia (complete heart block), when isoproterenol is more effective in the short run. Patients with acute myocardial infarction of the anterior wall (which carries a high mortality) can suddenly develop complete heart block and are usually unresponsive to atropine. In contrast, patients with acute myocardial infarction of the inferior wall (which carries a low mortality) can develop bradycardia as a result of increased vagal tone with a slow progression to Mobitz II block and finally to third-degree atrioventricular block; these conditions sometimes do respond to atropine. PACING IN CPR External electric pacing attempts ( 83), once given up because of painful muscle contractions, have recently succeeded in overcoming this complication by technical modifications. Transthoracic wire pacing is a last resort. Transvenous pacing is the method of choice in the presence of spontaneous circulation. Indications for pacing include severe sinus or ventricular bradycardia, atrioventricular blocks, atrial tachycardia and flutter, recurrent VT, and refractory asystole. The heart must be oxygenated to respond to electric or mechanical stimuli with contractions, and the pink heart without atrioventricular block beats without pacing. One should not expect refractory pulseless electrical activity to respond to pacing. For temporary transvenous pacing, a catheter electrode is inserted percutaneously under ECG guidance into the right atrium or ventricle, by way of the subclavian, internal jugular, brachial, or femoral vein. ALVEOLAR ANOXIA Anoxia means “no oxygen,” hypoxia means “less than normal oxygen” (usually referring to PO 2). “Alveolar anoxia” is rare, but active emergency departments (EDs) see occasional examples of this, namely patients who have inhaled oxygen-free gas (e.g., from laboratory, industrial, mining, or anesthetic accidents), or who have suffered rapid decompression (in a low-pressure chamber or in high-altitude flying). A sudden switch from breathing air or oxygen to breathing oxygen-free inert gas causes rapid cerebral failure, followed by cessation of breathing movements and circulation. This pattern of dying is one of pure oxygen lack because there is continued removal of C O2 and other metabolites from anoxic tissues until oxygen lack stops the heart. The resulting neuronal failure, therefore, is associated with less acidosis than in asphyxia from airway obstruction or apnea. A sudden change to breathing oxygen-free inert gas in unanesthetized dogs results instantaneously in spontaneous hyperventilation, and within 1 minute in hypotension, bradycardia, and pupillary dilation. Within 3 minutes, cardiac arrest develops in asystole. The dogs continue hyperventilating almost to the point of cardiac arrest ( 84,85). Clinical death after about 5 minutes is easily reversed with promptly initiated CPR. In unacclimatized adults dying from hypoxemia, cardiac arrest may occur at a PaO 2 of 15 to 25 mm Hg. In acclimatized adults (e.g., patients with acutely

decompensated chronic obstructive lung disease, with polycythemia and increased base excess), we have occasionally seen pulse and some cortical function continue during resuscitation attempts at a time when blood gas determinations unexpectedly revealed PaO 2 values of 15 to 20 mm Hg. Obviously, such severe degrees of hypoxemia cannot be tolerated long by the heart and brain. In acclimatized mountaineers exerting themselves at altitudes above 7000 meters (22,000 feet), hyperventilation, increased blood volume and cardiac output, and other special adaptive mechanisms that are still poorly understood seem to be more important than the altitude-induced polycythemia, to explain survival under extreme hypoxemia. To the contrary, polycythemia, with hematocrit values above about 50%, previously believed to be a positive adaptive mechanism, has been found to reduce performance capability at high altitude; indeed, physical performance at high altitudes seems enhanced by moderate hypovolemic hemodilution, probably because of its microcirculatory hemodynamic advantages ( 86). ASPHYXIA Hypoxemia denotes reduced arterial PO 2 (PaO2); hypercarbia (hypercapnia), increased arterial P CO2 (PaCO2); and “asphyxia,” a combination of both. Hypoventilation is a reduction in alveolar ventilation (minute volume minus dead-space minute ventilation). This results, in the air-breathing animal or person, in a progressive increase in Pa CO2 and an inversely related decrease of PaO 2. The extremes of hypoventilation are complete airway obstruction and apnea (no breathing movements), and these comprise the two principal causes of asphyxia ( Fig. 1–1.22).

Figure 1–1.22. Pattern of deterioration of physiologic variables in mechanical asphyxiation, using a spontaneously breathing dog as a representative example. (Reproduced with permission from Kristoffersen MB, Rattenborg CC, Holaday DA. Asphyxial death: the roles of acute anoxia, hypercarbia and acidosis. Anesthesiology 1967, 28:488.)

By far the most common cause of rapid dying from obstructive asphyxia is coma, irrespective of the cause. Coma may result in (a) upper airway soft-tissue obstruction from malpositioning (flexion) of the head or (b) airway obstruction by foreign matter (e.g., vomitus). This is treated by positioning ( Fig. 1–1.8, Fig. 1–1.9 and Fig. 1–1.10). These can be cleared as in Figure 1–1.23, Figure 1–1.24 and Figure 1–1.25 and, inhospital by suction ( Fig. 1–1.26).

Figure 1–1.23. Back blows and abdominal thrusts for foreign body obstruction in the conscious standing or sitting victim. A. For back blows, deliver a series of 3 to 5 sharp blows with the heel of your hand over the victim's spine between the shoulder blades. If possible, lower his head below his chest to utilize gravity. B. For abdominal thrusts, stand behind the victim, wrap your arms around his waist, grasp your fist or wrist of one hand with the other, place your hands against his abdomen between navel and xiphoid process (rib cage), and press your fist into his abdomen with a quick thrust upward. Repeat up to 3 to 5 times. Avoid the xyphoid process. Less potentially injurious (particularly in pregnant or obese patients) are chest thrusts over the lower sternum (not shown). (Reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation Stavanger, Norway: Asmund S. Laerdal, 1981.)

Figure 1–1.24. Back blows and abdominal thrusts for foreign body obstruction in the unconscious lying (horizontal) victim. A. For back blows, roll the victim on his side facing you, with his chest against your knees; deliver sharp blows with the heel of your hand over the victim's spine, between the shoulder blades. B. For abdominal thrusts, place the victim supine (face up) and kneel at the side of his abdomen or straddling it. Place one of your hands on top of the other, with the heel of the bottom hand in the midline between the patient's navel and xiphoid process. Lean forward so that your shoulders are over the victim's abdomen, and press toward the diaphragm with a quick thrust inward and upward. Do not press to the right or left of the midline. Repeat up to 3 to 5 times if necessary. Less potentially injurious (particularly in pregnancy or obese patients) are chest thrusts over the sternum (not shown), which are performed in the same manner as external cardiac compressions. (Reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation Stavanger, Norway: Asmund S. Laerdal, 1981.)

Figure 1–1.25. Back blows in infants and small children. Hold the child face down, supporting chin and neck with your knee and one hand, and apply gentle back blows between the shoulder blades. For chest thrusts (not shown), place the child face up on your forearm, lower his head, and apply chest thrusts gently with two or three fingers, as in external cardiac compressions. If the child's airway is only partially obstructed and he is conscious and able to breath in the upright position, do not turn him head down. Do not use abdominal thrusts in infants and in small children. (Reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation Stavanger, Norway: Asmund S. Laerdal, 1981.)

Figure 1–1.26. Suctioning by controllable wall suction or portable suction. A. Suctioning of oropharynx with rigid tonsil suction tip. B. Suctioning of nasopharynx or tracheobronchial tree with curved-tip soft catheter. (Reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation Stavanger, Norway: Asmund S. Laerdal, 1981.)

Intubation is the surest way to control the obstructed airway, requiring equipment ( Fig. 1–1.27) and a good knowledge of anatomy (Fig. 1–1.28).

Figure 1–1.27. Equipment for tracheal intubation. Left (top to bottom) tongue blade, clamp for cuff, bite block, tape to secure tracheal tube, nasopharyngeal tube, oropharyngeal tubes, curved connector, laryngoscope handle with adult curved and straight blades and child straight blade. Right (top to bottom) curved-tip tracheal suction catheter, pharyngeal rigid suction tip, lidocaine water-soluble jelly. Magill forceps, three-way stopcock and syringe for cuff inflation, assortment of tracheal tubes (sizes 12 F infant to 38 F adult), stylet. (Reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation Stavanger, Norway: Asmund S. Laerdal, 1981.)

Figure 1–1.28. Anatomic views for endotracheal intubation. A. Diagram of the anatomy of the laryngeal entrance exposed by direct laryngoscopy (Reproduced with permission from American Heart Association Advanced Life Support Slide Series, 1976). B. First direct laryngoscopic view during tracheal intubation; exposure of uvula and epiglottis. C. Second direct laryngoscopic view during tracheal intubation; exposure of arytenoids. D. Third direct laryngoscopic view during tracheal intubation; exposure of glottis. The anterior commissure is not fully seen. The posterior commissure is below. (Views B, C, and D are reproduced with permission from Hollinger PH, et al. J Thorac Surg 1948, 17:178.)

Technique The technique of intubation is illustrated in Figure 1–1.29. Knowledge of laryngoscopic blade sizes ( Table 1–1.4) and endotracheal tube sizes is essential ( Table 1–1.5). Endotracheal intubation should be performed without delay in cases of asphyxia or CPR. If equipment is not available use any available means to access the airway (e.g., cricothyroid puncture, etc.). Use of endotracheal intubation will ensure that aspiration will not occur.

Figure 1–1.29. Technique of orotracheal intubation. A. Laryngoscopy for endotracheal intubation with straight laryngoscope blade. Left. insertion of blade; right. larynx exposed. Note elevated occiput with head tilted backward (sniffing position). Note direct elevation of epiglottis with tip of blade. (Do not use teeth as fulcrum.) B. Laryngoscopy for endotracheal intubation with curved laryngoscope blade. Left. insertion of blade; right. larynx exposed. Note indirect elevation of epiglottis by tip of blade elevating base of tongue. C. Exposure of the larynx with curved blade and insertion of cuffed tube through right corner of mouth. (Reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation Stavanger, Norway: Asmund S. Laerdal, 1981.)

Table 1–1.4. Laryngoscope Blades

Table 1–1.5. Endotracheal and Tracheostomy Tubes

The following sequence should be learned and practiced to perfection, first on adult and infant intubation mannequins and then on anesthetized patients: 1. Have a competent assistant available if possible. 2. Select, prepare, and check the equipment ( Fig. 1–1.27). Do not depend on others to do this. A. Select the appropriate size of tracheal tube ( Table 1–1.5) and a spare tube one size smaller. B. Select the appropriate size and type of laryngoscope ( Table 1–1.4). Check the laryngoscope light. C. Check the cuff by inflation by means of the cuff pilot tube and deflate the cuff. 3. Have the patient in the supine position, with the occiput elevated and the head tilted backward (sniffing position) if possible, to allow alignment of the operator's line of sight, the laryngoscope blade, and the larynx ( Fig. 1–1.29). 4. Preoxygenate the patient with 100% oxygen for at least 2 minutes (e.g., with bag-valve-mask) if feasible. Apply cricoid pressure to limit regurgitation. 5. Interrupt ventilation for intubation. When intubating an apneic patient, hold your own breath and stop the intubation attempt when you become short of breath, or use a time measure (approximately 30 seconds or less). 6. For insertion of the tube: A. First, open the patient's mouth with your right hand (e.g., with the crossed finger maneuver) ( Fig. 1–1.11). B. Grasp the laryngoscope handle firmly with the left hand and insert the blade from the right corner of the patient's mouth, pushing the tongue to the left so as not to obscure the view by the tongue bulging over the open side of the laryngoscope blade ( Fig. 1–1.29). Protect the lips from being injured between teeth and blade. C. Move the laryngoscope blade toward the midline and visualize the patient's mouth, uvula, pharynx, and epiglottis ( Fig. 1–1.22B) while moving your right hand to the patient's forehead or occiput to hold his or her head tilted backward. D. Visualize the arytenoids and the midline (the most important landmarks) ( Fig. 1–1.22C), and finally the vocal cords (highly desirable but not an absolute requirement) (Fig. 1–1.22D), by lifting the epiglottis directly with the straight blade ( Fig. 1–1.29A) or indirectly with the curved blade, placing its tip at the midline against the glossoepiglottic frenulum ( Fig. 1–1.29B). E. Expose the larynx by pulling the laryngoscope handle inferiorly and anteriorly at a right angle to the blade. Do not use the upper teeth as a fulcrum. When the curved blade is used, too-deep insertion pushes the epiglottis downward, whereas a too-superficial insertion makes the base of the tongue bulge and obscures the vision of the larynx. Excessive rotation of the laryngoscope handle toward the operator lifts the larynx anteriorly out of the field of vision. With the straight blade, too-deep insertion (into the esophagus) lifts the entire larynx out of view. These mistakes can be avoided by recognition of the arytenoid cartilages (Fig. 1–1.28C). F. Insert the tracheal tube (with your right hand) through the right corner of the patient's mouth while looking through the laryngoscope blade ( Fig. 1–1.29C). Rotate the tube if necessary. Observe the tip of the tube and the cuff as they pass through the larynx, and advance the tube so that the cuff is placed just below the vocal cords. In most average adults, proper tube placement results in the tube tip being 19 to 21 cm below the incisors. G. Ask the assistant to hold the tube in place against the corner of the mouth or teeth while removing the laryngoscope blade. 7. Remove the stylet, if used, and immediately ventilate and oxygenate by a self-refilling bag-valve-oxygen unit. 8. Inflate the cuff temporarily to achieve a seal to protect against aspiration. 9. Turn ventilation and oxygenation over to your assistant. 10. Remove the laryngoscope blade and insert an oropharyngeal tube or bite block. 11. Verify tube position by auscultation of both apices and bases and epigastrium. Use capnography if available. Position the tube to avoid bronchial intubation, using one of the following steps: A. Press with one finger into the suprasternal notch and feel for the tip of the tube; advance the tube with the other hand 2 cm farther. Retain correct depth of tube insertion by marking tube length at the level of the upper teeth. B. Auscultate both lungs to rule out bronchial (usually right bronchial) intubation and to determine need for suctioning.

12. Tape the tube securely to the patient's face. When the cheeks are unshaven or moist, a dry, broad, loose tape can be placed around the neck and both cheeks first and the tube taped to it. 13. While applying continuous positive pressure, reinflate the cuff permanently, but only to the point of abolishing audible leaks, i.e., minimum occlusive pressure. (Inflate large low-pressure cuffs to 15 to 20 cm H 2O intracuff pressure between lung inflations.) 14. Suction the tracheobronchial tree if necessary. If aspiration is suspected, use a suction trap for examination of the material removed ( Fig. 1–1.26B) and to send for culture. 15. Establish nonkinking, nonslipping connections to the ventilator if it is used. 16. In a patient with multiple trauma, coma, or gastric distention, insert a gastric tube, preferably through the nose. If this is contraindicated or proves impossible, insert through the mouth. 17. Deliver oxygen by means of a heated humidifier or nebulizer and use atraumatic aseptic suctioning as needed. Rapid-Sequence Intubation All emergency intubations should be assumed to involve a full stomach, which requires rapid-sequence intubation to minimize the risk of aspiration ( 87,88). Any patient requiring neuromuscular blockade for intubation falls into this group. Be prepared with suction for regurgitation. After preoxygenation (preferably with 100% oxygen without positive pressure), close the patient's esophagus by pressure on the cricoid cartilage and paralyze the patient with succinylcholine (1.5 mg/kg) or vecuronium (0.1–0.25 mg/kg). Intubate swiftly. The convulsing, asphyxiated patient with head injury is a challenging example. He or she may have to be intubated with a muscle relaxant and thiopental because coughing and straining in the presence of brain contusion can cause additional cerebral edema and hemorrhage and lethal intracranial pressure rise. One can pretreat with lidocaine 1–1.5 mg/kg and use defasciculating doses of vecuronium or pancuronlium (0.01 mg/kg). On the other hand, rapid-sequence intubation under paralysis may be hazardous in the hands of the inexperienced. Intubating the Conscious Patient Some think that awake endotracheal intubation is indicated for patients at risk of aspiration or severe pulmonary insufficiency. Tracheal intubation of the conscious patient is difficult and requires skill, experience, and artistry. Topical anesthesia of the upper airway mucosa is provided by spraying a topical anesthetic, e.g., 4 to 10% lidocaine from a nebulizer, first onto the tongue and oropharyngeal mucosa, then under direct vision, with a partially inserted laryngoscope blade, onto the hypopharynx and supraglottic laryngeal mucosa, avoiding stimulation of the gag reflex. Under relatively elective circumstances, the tracheal mucosa is then sprayed with 2 to 3 mL of 4% lidocaine either by instillation through the glottis into the tracheal lumen using a cannula with multiple holes, or by translaryngeal injection through the cricothyroid membrane, using a thin (e.g., 22-gauge) needle. The procedure may be facilitated by a sedative or analgesic by IV titration, e.g., midazolam or fentanyl. Take care not to abolish the response to verbal command. Suction should be ready to cope with regurgitation. For intubation, the laryngoscope blade and tracheal tube must be handled securely, gently applying pressure only when and where absolutely necessary. The operator's reassuring voice is important, but complete lack of cooperation is an indication for more sedation or neuromuscular blockade. Should regurgitation or vomiting occur before the tube is inserted, suction and coach the patient to help by clearing his or her own airway by coughing. TECHNIQUE OF NASOTRACHEAL INTUBATION Nasotracheal intubation is more difficult, more time-consuming, and potentially more traumatic (with the possibility of epistaxis and laryngeal damage) than orotracheal intubation. The blind nasotracheal technique is less reliable. Furthermore, the technique carries the risk of introducing nasal bacteria into the trachea. It is not a suitable procedure for emergency airway control in the asphyxiating patient. In several circumstances in which the patient is breathing spontaneously and is not asphyxiated, however, e.g., trismus or inability to tilt the head backward (suspected or proven neck fracture), nasotracheal intubation may be indicated. Some also think it more suitable for long-term intubation because the nasal tube is better tolerated than the oral tube, although sinusitis remains a risk in the ICU setting. For elective nasotracheal intubation, select the more patent nasal passage by checking the patient's ability to sniff through each nostril separately. For intubating the conscious patient, apply a nasal vasoconstrictor (e.g., phenylephrine drops or spray) to constrict the nasal mucosa, together with a topical anesthetic, e.g., 4 to 10% lidocaine (lignocaine, xylocaine) to minimize discomfort. Alternately, cocaine 1 to 2% may be used in small amounts because it is both a potent topical vasoconstrictor and an anesthetic. If feasible, apply topical anesthesia to the hypopharynx, larynx, and trachea as described. Nasotracheal tubes should be soft, well-curved, and well-lubricated, and cuffed for adults. The tube should be 1 mm smaller in inside diameter than that for orotracheal intubation ( Table 1–1.5). Insert the tube through the more patent nostril, parallel to the palate. Ideally, the tube's bevel should face the nasal septum to avoid damaging the turbinates. Tilt the patient's head backward moderately and elevate the occiput. Gently advance the tube beyond the “give” of the nasopharyngeal angle. For blind nasotracheal intubation, maneuver the tip of the tube laterally by twisting it, and maneuver it anteriorly or posteriorly by extending or flexing the head (but not in suspected neck injury). Then advance the tube during inhalations, listening for air flow or coughing, which indicates entry into the larynx. If the patient's mouth can be opened, nasotracheal intubation can be facilitated by visualizing the larynx. In this case, hold the laryngoscope in your left hand. Direct the tube, using Magill's forceps or a large Kelly clamp in your right hand to grasp the tube, and guide it in the right direction, under direct vision while an assistant advances the tube through the nose. This technique is also recommended for nasotracheal intubation in the comatose patient whose mouth can be opened. DIFFICULT INTUBATION Intubation attempts may fail when there is inadequate muscular relaxation, poor technique, or anatomic abnormality. Difficulty with intubation can be anticipated, for example when the patient has taut neck tissues, a short thick neck, receding jaw, protruding teeth, inability to tilt the head backward, a narrow oral cavity, or a large tongue. In such patients, intubation should be attempted by the physician most skilled in airway management. Effective intubation in the spontaneously breathing, oxygenated patient, when difficulties with intubation are anticipated, may be accomplished with the use of a flexible fiberoptic laryngoscope or bronchoscope. The endotracheal tube to be used is inserted through the nose (preferable route) or mouth into the hypopharynx. The well-lubricated, flexible fiberoptic laryngoscope (with a diameter considerably smaller than the tracheal tube so that the patient can breathe around the scope) is inserted through the tube and directed under vision through the larynx into the trachea. When the tip of the flexible fiberoptic laryngoscope or bronchoscope enters the trachea, the tracheal tube is slipped over the flexible scope into the trachea, and the flexible scope is removed. This technique, however, is rarely logistically feasible, clinically wise, or technically possible in emergency intubation. TACTILE DIGITAL OROTRACHEAL INTUBATION This technique, performed without the use of a laryngoscope, was practiced widely by pediatricians during the early 1900s for choking victims of diphtheria and is now being revived ( 89). It can be practiced on cadavers. It is applied clinically (a) in the comatose patient when a laryngoscope is not available, (b) when cervical spine injury is suspected and orotracheal intubation by laryngoscope is not possible because of suboptimal head position, and (c) when orotracheal intubation fails for other technical reasons ( 90). Tactile orotracheal intubation is an alternative to blind nasotracheal intubation, which is difficult to learn, not entirely reliable, and endowed with its own complications. Use a lubricated tube with a stylet bent into a J-shaped orotracheal tube. Hold the tube in your right hand and stand at the right side of patient, facing his or her right shoulder. After preoxygenation, insert the index and middle fingers of your left hand into the mouth, and while depressing the tongue, reach with your fingertip for the epiglottis. Guide the tube along with your fingers toward the palpated epiglottis. If your fingers seem too short, go in by way of the corner of the mouth. With your fingers, pull the base of the tongue and the rim of the epiglottis forward while maneuvering with your right hand the tip of the tube into the larynx entrance. Withdraw the stylet and advance the tube farther, to 20 to 22 cm from the teeth in the average adult.

TRANSILLUMINATION OROTRACHEAL INTUBATION This technique uses a lighted stylet and was first tested for blind orotracheal intubation in the operating room. The method has been used with considerable success

even in the prehospital setting by physician-guided paramedics ( 91). Insert the flexible light into a regular orotracheal tube to illuminate its tip. Bend the tube slightly more than 90°. Grasp the patient's tongue with gauze and pull it forward. Slide the tube in, toward the larynx, and pick up the epiglottis. Observe correct passage in midline by watching light on the skin of the neck. Lateral illumination indicates wrong position into the piriform fossa; subdued light, esophageal placement; and bright light in the midline, correct position. Engage the larynx with the tip of the tube. Withdraw the stylet while pressing the tube against the tongue. Advance the tube into the proper position.

INTUBATION OF INFANTS AND SMALL CHILDREN When intubating the trachea in infants and small children, keep in mind that the infant's larynx, in relation to that of the adult, is located higher, has a floppy U-shaped epiglottis, and is funnel-shaped, with the narrowest diameter at the level of the cricoid ring ( 92). Selecting a tube with too large a diameter can cause inability to intubate, laryngeal damage, and postextubation croup from mucosa edema at the cricoid level. For intubation in infants, particularly in newborns, use of a straight blade (e.g., Miller, Wisconsin-Hipple, or Flagg blade) is more satisfactory than the curved laryngoscope blade (Table 1–1.4). Because the small dimensions of the infant make accidental bronchial intubation more likely, carefully place the tip of the tube just beyond the cords, using a tube with graduated rings near the tip to measure depth of insertion, thus preventing accidental bronchial intubation. Selecting the tube with the optimal diameter and length (Table 1–1.5), use of atraumatic techniques, and attention to details are important. Extubation Extubation is potentially hazardous, and its safe execution depends on special knowledge and skills. After using general anesthesia in the healthy person, the endotracheal tube is removed when the patient has recovered upper airway reflexes and responds to commands. This is not a sufficient condition after emergency intubation. Respiratory insufficiency (hypoxemia, hypercarbia), acute acid-base abnormalities, and circulatory derangements must be ruled out before extubation. Ideally, the patient should be conscious and able to achieve a forced vital capacity of at least 10 mL/kg upon command, to avoid progressive atelectasis after extubation. Other signs of adequate muscular power include ability to squeeze the attendant's hand and to raise the head, a negative inspiratory force of less (i.e., more negative) than 20-cm H 2O and the absence of retractions during spontaneous breathing. Also, the stomach should not be distended. In the ED and ICU setting, a minute volume of less than 10 L is a useful parameter, as is a FiO 2 requirement of 40% or less. There are no completely reliable predictors of successful weaning from mechanical ventilation and extubation, however, and deliberate loss of control of the airway must be a well-considered decision. When in doubt, leave the tube in. The recommended technique of extubation requires an assistant. First, suction the patient's mouth, oropharynx, and nasopharynx. Then allow the patient to breathe 100% oxygen for 2 to 3 minutes and suction the tracheobronchial tree with a separate, sterile, curved-tip catheter. After suctioning, again allow the patient to breathe 100% oxygen. Then, while you apply positive pressure to the trachea by means of a bag-valve device, instruct the assistant to deflate the cuff of the endotracheal tube; the positive pressure helps to exsufflate secretions (which have accumulated above and below the cuff) into the pharynx, which should be suctioned promptly. Having deflated the cuff, remove the tube gently while maintaining positive pressure with 100% oxygen in the trachea. Tracheal suction should not be continued during withdrawal of the tracheal tube because this can empty the lungs and cause severe hypoxemia. After removal of the tube, oxygenation is continued by mask, using approximately 50% oxygen. If a requirement for more than 50% oxygen is predicted by preextubation arterial blood gases, the tube should generally not be removed in the ED. Be prepared to treat postextubation laryngospasm with oxygen by positive pressure and, if necessary, with a relaxant (i.e., succinylcholine) and reintubation. For extubation of patients with upper airway problems, cricothyrotomy equipment should be ready, and expert help should be at the bedside.

Complications of Tracheal Intubation Attempts at endotracheal intubation can injure any portion of the airway. Nasotracheal intubation can cause epistaxis and, in addition, injure the nasal mucosa and the adenoids. Undetected, inadvertent intubation of the esophagus is the most dangerous complication of orotracheal and nasotracheal intubation attempts. Esophageal intubation may go unnoticed unless one listens carefully for breath sounds over both sides of the chest and the epigastrium. Capnography provides unequivocal confirmation. Other potential complications include tube obstruction by compression, kinking, obstruction secretions, biting, a bulging cuff, a too-narrow lumen, or obstructing adapters; accidental bronchial intubation; and tube dislodgement. Persistent coughing or “bucking” calls for positive pressure inflation with oxygen, and may require sedation, analgesia, or even neuromuscular blockade to facilitate oxygenation and ventilation and thus prevent asphyxia. In spite of these possible complications, correct use of tracheal intubation has become the cornerstone of emergency resuscitation and long-term airway control in the critically ill patient.

ALTERNATIVES TO TRACHEAL INTUBATION Cricothyroid membrane puncture and translaryngeal oxygen jet insufflation are two useful steps of last resort when endotracheal intubation is impossible in an asphyxiating patient and, when necessary, equipment for these techniques is immediately available ( 93). While one operator tries to oxygenate the patient by mask, the other performs cricothyrotomy, which is independent of a supply of pressurized oxygen because inhalation and exhalation are possible through the large-bore tube. It is preferable to translaryngeal jet ventilation in the spontaneously breathing patient. Translaryngeal oxygen jet ventilation, which requires compressed oxygen and the necessary connections for intratracheal insufflation, is preferred over cricothyrotomy as an elective procedure for anesthesia in patients undergoing operations on the upper airway in the presence of laryngeal or supralaryngeal obstruction. In complete upper airway obstruction, cricothyrotomy should be used, not jet ventilation, because the latter needs an open upper airway for exhalation. These two alternative measures are rarely needed, but both should be part of the therapeutic repertoire of trained professionals involved in emergency resuscitation. Cricothyrotomy This technique is used for spontaneous breathing of air or oxygen, artificial ventilation, and suction ( Fig. 1–1.30). It requires use of the largest available cannula that does not cause further injury to the trachea, i.e., in the adult a 6 mm and in the large child a 3 mm outside diameter endotracheal tube. In small children and infants, this technique requires extraordinary expertise. Merely incising the cricothyroid membrane does not establish an airway. The opening must be kept patent, and a standard adapter must permit connection of ventilation equipment. One may teach the cut-and-poke cricothyrotomy technique ( Fig. 1–1.30), which includes a skin incision and piercing of the membrane under vision. Blind (percutaneous) automatic cricothyrotomy techniques are hazardous and, therefore, not recommended.

Figure 1–1.30. Cricothyrotomy with curved cannula. The cannula can be self-made from curved endotracheal tube slip joints or stiff shortened endotracheal or tracheostomy tubes (a 6-mm outside diameter for adults; a 3-mm outside diameter for large children), with a 15-mm male adaptor to connect ventilation equipment. For small children and infants, use a 12-gauge over-the-needle catheter. A. Anatomy with cannula in place. H, hyoid cartilage; Th, thyroid cartilage; C, cricoid cartilage; TR, trachea; CTM, cricothyroid membrane; E, epiglottis; T, tongue; FC, false cords; VC, vocal cords; Es, esophagus. Beveled curved cannula. Knife blade with handle (rubber stopper), to be carried safely within a 15-mm slip joint of cannula. B. Technique of cricothyrotomy. Place the patient supine with his head tilted backward. Grasp the larynx with your thumb and middle finger, and identify cricothyroid membrane with index finger. Make an adequate horizontal skin incision. Make a stab incision through the cricothyroid membrane. Poke a blunt-tip cannula through the membrane into the tracheal lumen. During intermittent positive pressure (assisted) breathing (IPPV) minimize leakage by closing the mouth and nose by hand. (Reproduced with permission from Safar P, Penninckx J. Anaesthesiology 1967, 28:943.)

Translaryngeal Jet Insufflation This technique consists of insertion of a thin over-the-needle catheter through the cricothyroid membrane, with intermittent insufflation of oxygen ( Fig. 1–1.31) (94,95,96 and 97). A high-pressure source (30 to 60 psi, 2 to 4 atm) of oxygen is required to overcome the resistance of the system. The chest must be carefully observed, and the valve must be turned off the moment the chest rises, to prevent lung rupture.

Figure 1–1.31. Translaryngeal oxygen jet insufflation. Prepare necessary equipment assembly, consisting of 30 to 60 psi (2 to 4 atm) oxygen source, high-pressure tubing valve (three-way stopcock, or pushbutton release valve), extension tubing, and 14- to 16-gauge over-the-needle catheter. Hold the patient's head tilted backward, hold the larynx between the thumb and middle finger, and identify cricothyroid membrane with the index finger. Insert the catheter needle through the cricothyroid space into the tracheal lumen, pointing downward. Connect extension tube-equipment assembly. Inflate the lungs by turning the valve or stopcock until the chest moves; then turn the valve off and let the patient exhale passively through the mouth and nose.

Passive exhalation is achieved through the upper airway, which must be at least partially open to avoid lung rupture. In complete upper airway obstruction, a second large-bore tracheal catheter needle, perhaps with intermittent suction, should be inserted to allow exhalation. Inflation starts with some air entrainment and ends with upward leakage through the larynx. The most life-threatening complication (which can be avoided with proper technique) is interstitial oxygen insufflation from lung rupture or from accidental insertion of the catheter into tissue spaces instead of into the tracheal lumen. This tracheal insufflation technique can exsufflate upper airway secretions, but does not allow suctioning. For translaryngeal high-frequency ventilation, see the section entitled, “Emergency Artificial Ventilation and Oxygenation” (98,99).

OTHER AIRWAY CONTROL PROCEDURES Tracheotomy, bronchoscopy, bronchodilation, and pleural drainage are usually elective (though sometimes urgent) procedures, which are adjunctive to the steps of emergency airway control described so far. Tracheotomy Tracheotomy (Fig. 1–1.32) is used for long-term airway management and, ideally, should be done under conditions of optimal lighting and sterility in the operating room. In acute emergencies, the skilled operator can usually perform endotracheal intubation or cricothyrotomy more rapidly than tracheotomy. The resulting opening in the tracheal wall is called tracheotomy; the opening that results from suturing the entire lumen of the trachea into the skin after laryngectomy is called tracheostomy.

Figure 1–1.32. Technique of tracheotomy. A. Make a horizontal or vertical skin incision. B. Ligate and divide the thyroid isthmus if necessary, and expose tracheal rings 1, 2, 3, and 4. C. Ask an assistant to withdraw the translaryngeal (endotracheal) tube partially, with the tip remaining in the larynx. Place stay sutures through tracheal rings 2 and 3 on both sides of the anticipated opening for immediate access to the tracheal lumen in case of tube dislodgement later. Make a midline incision of tracheal rings 2 and 3 (oval-shaped or inverted V-shaped excision in adults). D. Quickly insert the appropriate size tracheostomy tube (9–2) with large soft cuff. Inflate the cuff to abolish audible leak. Connect by nonslip swivel adapter to ventilation-oxygenation device. Remove translaryngeal (endotracheal) tube. (Illustration © Asmund S. Laerdal, Stavanger, Norway. 1981: reproduced with permission from Safar P. Cardiopulmonary cerebral resuscitation.)

A switch from tracheal tube to tracheostomy tube should be considered when tracheal cannulation is expected to be needed longer than 3 weeks. Whenever possible, tracheotomy should be done as an elective procedure and on an oxygenated, well-ventilated patient, if necessary, with a tracheal tube in place. Bronchoscopy This procedure is needed to clear the tracheobronchial tree after aspiration of solid foreign matter or obstruction by thick mucus or blood. For emergency tracheobronchial clearing, the rigid-tube ventilation bronchoscope ( 100) is more effective than the flexible fiberoptic bronchoscope ( 101), which has only a narrow lumen for suctioning ( 102). The flexible fiberscope, however, has revolutionized diagnostic and elective therapeutic bronchoscopy. Bronchoscopy in critically ill, conscious patients with acute respiratory insufficiency should be undertaken after endotracheal intubation and with oxygenation and assisted ventilation. In massive aspiration of solid foreign matter, rigid bronchoscopy can be a lifesaving resuscitative measure if available immediately. The flexible fiberoptic bronchoscope ( 102) has advantages for examination and for removing mucus plugs from smaller bronchi, particularly in the upper lobes. Lung rupture is possible during bronchoscopy through an endotracheal tube with IPPV if the bronchoscope impedes exhalation. Ventilation with 100% oxygen during bronchoscopy is recommended with the use of a tracheal tube adaptor through which the bronchoscope passes. A wide tracheal tube and thin scope should be used to avoid lung rupture. OTHER CAUSES OF ACUTE AIRWAY OBSTRUCTION Other causes of upper airway obstruction include trauma with soft-tissue obstruction or inhalation of blood, inflammatory swelling of tissues (e.g., cellulitis of the floor of the mouth, croup, epiglottitis), and food bolus obstruction ( 103). Laryngospasm (1,104) may result in hypoxia-induced apnea, but usually the larynx relaxes before cardiac arrest.

Foreign matter usually obstructs the airway only partially; however, it may trigger reflex laryngospasm, which in turn completes the obstruction. The larynx may then relax only when severe hypoxemia ensues, which may be at a moment when breathing movements already have ceased. If started before cardiac arrest, skillfully applied positive-pressure artificial ventilation usually can revive the patient even if the foreign matter was not removed. Moderate partial airway obstruction, as in bronchospasm, first stimulates increased respiratory efforts, which can usually maintain normal or even low Pa CO2 values for some time. Hypoxemia may occur early because of ventilation-perfusion mismatching and shunting. When the patient becomes exhausted or if the obstruction worsens, asphyxia develops, with rapidly progressive hypoxemia and hypercarbia leading to secondary apnea and cardiac arrest ( Fig. 1–1.10). The events accompanying complete airway obstruction in air-breathing animals, with or without light anesthesia, were studied ( 34,42,43,84,85,106,107 and 108). Although these investigators used slightly different models, the sequence of events, not only in dogs but also in humans, is as follows: struggling and increased breathing efforts (with exaggerated intrathoracic pressure fluctuations causing intercostal and suprasternal retractions) are accompanied by a sympathetic discharge with arterial hypertension and tachycardia. Anesthesia, which mitigates the struggling and subsequent oxygen consumption, or clamping the airway at end-inspiration instead of end-expiration, which increases the alveolar oxygen reserve, retards but does not prevent this asphyxial process. Unconsciousness starts at about 2 minutes after complete airway obstruction, when PaO 2 reaches 30 mm Hg or less (arterial oxygen saturation 60%). Apnea occurs at 2 to 6 minutes, and pulselessness occurs (asystole in diastole) at 5 to 10 minutes. Hypoxia and acidosis (from accumulation of CO 2 and fixed acids) in blood and tissues combine as a cause of circulatory failure. When PaO 2 is 20 to 30 mm Hg, arterial pH (pHa) is about 6.8 to 7.0 and Pa CO2 is about 80 mm Hg, the systemic arterial pressure falls to about 30 to 50 mm Hg; further decreases in SAP below 30 mm Hg lead to pupillary dilation and the onset of an isoelectric EEG. Pulselessness occurs when the PaO2 is about 10 mm Hg or less and pHa is 6.5 to 6.8. The ECG develops nodal rhythm and, when hypotension occurs, bizarre ventricular complexes with gigantic T waves. At the time of pulselessness, the ECG shows asystole or electromechanical dissociation (i.e., some ECG complexes without pulse). Usually, toward the end of a 5-minute period of clinical death the ECG is flat. When IPPV is started before the critical arterial pressure is reached, resuscitation is prompt. When CPR is started within 2 to 5 minutes of cardiac arrest, recovery with an intact CNS is common. We have seen histologic brain damage in dogs after 5 to 7 minutes of asphyxiation and only 2 minutes of pulselessness ( 109). After up to 20 minutes of pulselessness from asphyxia in animals, restoration of spontaneous circulation by CPR is still possible, although the severe acidemia requires administration of large amounts of both epinephrine and bicarbonate. Epinephrine is less effective at such low pH values. In dogs, asphyxia-induced normothermic cardiac arrest of 5 minutes or less could be reversed to complete neurologic (not brain histologic) recovery; when it was 7 minutes or longer, it resulted invariably in permanent neurologic deficit even with special brain resuscitation measures ( 5,34,109). In some human cases of slow asphyxiation, as little as 1 to 2 minutes of arrest or even no circulatory arrest at all have resulted in permanent neurologic deficit, particularly when preexisting illness or injury caused a decrease in arterial oxygen transport before the beginning of airway obstruction. Probably the more severe brain acidosis during asphyxiation leads to more brain damage than the same period of VF-induced arrest (11,12 and 13,32,34,106,109). Sudden apnea in an air-breathing animal results in a similar pathway toward asphyxial cardiac arrest, but events proceed at a somewhat slower pace than in airway obstruction because, in apnea, less vigorous respiratory efforts and less profound struggling entail lower oxygen consumption during the terminal state ( 48). Sudden apnea may occur as a result of high-energy electric shock; intravenous injection of a paralyzing dose of muscle relaxant (anesthesia); sudden severe increase in intracranial pressure with brain herniation; and large doses of anesthetics, narcotics, or hypnotics ( Table 1–1.1). Hypercarbia without hypoxemia can be produced by inhalation of an oxygen-enriched atmosphere before hypoventilation or apnea. The rate of Pa CO2 rise in apnea is about 4 to 6 mm Hg/min. The rate of deoxygenation in apnea can be calculated from alveolar oxygen, functional residual capacity, and oxygen consumption. Preventilation with 50% oxygen can maintain PaO 2 above normal values for at least 5 minutes of apnea in persons with healthy lungs. Preventilation with 100% oxygen and complete denitrogenation, in animals or humans with healthy lungs, initially produces a PaO 2 above 75 mm Hg for over 30 minutes, provided that the oxygen-filled alveoli and airways remain connected to an oxygen reservoir without other gases ( 110). This process is called apneic diffusion oxygenation ( 111) and works through mass transport of oxygen by way of the tracheobronchial tree. Through continuous absorption of oxygen into the blood, a subatmospheric pressure in the alveoli allows flow of oxygen down into the alveoli. The PaO 2 declines below normal only when alveolar oxygen is displaced by CO 2, and right-to-left shunting occurs from absorption atelectasis of oxygen-filled alveoli. Without administration of buffers, circulatory collapse begins when pHa falls to about 6.8, and cardiac arrest occurs when pHa decreases to about 6.5. In dogs, this may occur as late as after 1½ hours of apnea, when the Pa CO2 has risen to about 340 mm Hg but the PaO2 is still above 80 mm Hg (48,108). Whereas alveolar anoxia without hypercarbia stops the heart in systole, hypercarbia alone (without hypoxemia), as well as asphyxia, produces acidemia, which stops the heart in diastole. Hypercarbia per se rarely kills; the dog, for example, can tolerate artificial ventilation with up to 70% CO 2 (30% oxygen) without circulatory embarrassment (112). But acidemia causes potassium loss from blood cells into plasma, which may produce dangerous arrhythmias in individuals with heart disease. Rapid lowering of PaCO2 from extremely high levels can precipitate sudden VT or VF, presumably as a result of reentry of potassium into cells even in healthy individuals or animals. Diffusion oxygenation may contribute to the benefit of prophylactic oxygen inhalation for patients whose respiratory sufficiency or airway patency are at risk (e.g., convulsive states). The elevation of PaO 2 is probably more important than mass transport of oxygen because true diffusion requires nearly complete denitrogenation. A clinical example of hypercarbia without hypoxemia, at least in its initial stages, is the chronic obstructive lung disease patient inhaling an enriched oxygen mixture by breathing spontaneously. Normalization of PaO 2 through abolition of hypoxemia, which ordinarily provides the predominant respiratory drive in such patients, results in moderate hypoventilation ( 113) and, rarely, apnea. At that point, however, apneic oxygenation does not occur because these patients usually have not been breathing 100% oxygen, but rather lower oxygen concentrations. Thus, at the moment of apnea, severe hypoxemia rapidly develops and asystolic arrest can occur. This problem is avoided by administering oxygen together with assisted or controlled ventilation. In alveolar anoxia, asphyxia, and hypercarbia without hypoxemia, the depletion of oxygen stores progresses ten times more rapidly than the accumulation of lethal quantities of hydrogen ions ( 108). In dogs, the lethal values are about 10 mm Hg for PaO 2 and 6.5 for pHa, irrespective of the rate of deoxygenation and accumulation of hydrogen ions. A further example of asphyxia is that which develops in neonates. Every vaginal delivery is an asphyxial experience for a baby. Before, during and/or sometimes after birth, a combination of respiratory asphyxia (hypoxemia and hypercarbia) and lactic acidosis from hypoperfusion develops. Asphyxia neonatorum can lead to brain damage and sometimes cardiac arrest. Predisposing factors include prematurity, postmaturity, prolonged labor, prolapsed cord, placental separation, placenta previa, uterine tetany (oxytoxic drugs), general anesthesia and analgesia (narcotics), and traumatic delivery.

USE OF OPEN-CHEST CPR Exsanguination This mechanism of dying (3,37) was described earlier (see Rapid Dying and Resuscitation), serving as a model for understanding the detailed dying processes and the “postresuscitation syndrome” (4,5). In such cases of exsanguination cardiac arrest in humans, open-chest CPR is indicated along with rapid fluid and blood infusion. There has been an increasing trend for more liberal use of this technique even when cardiac arrest occurs from a primary cause. Open-Chest CPR Cardiac resuscitation by thoracotomy was practiced widely in hospitals before the introduction of closed-chest CPR in 1960, and the earlier technique produced high survival rates with good brain function ( 114,115,116,117,118,119,120 and 121). Direct cardiac compressions produce better overall and cerebral blood flow than do sternal compressions because the latter increase overall intrathoracic pressure, which in turn increases venous pressure simultaneously with arterial pressure. The open-chest technique (Fig. 1–1.33) produces higher arteriovenous perfusion pressures and, when cardiac massage is necessary for prolonged periods, also a better chance for sustaining cerebral and myocardial viability and restoring spontaneous circulation ( 122,123,124,125,126,127,128,129,130,131,132 and 133). Figure 1–1.34

illustrates hand position for direct heart compression.

Figure 1–1.33. Open-chest cardiopulomary resuscitation. A. Open the chest at the fourth or fifth left intercostal space (inset). Grasp and rhythmically compress the heart as described in the text. (Reproduced with permission from Johnson, Surgery of the Chest. Chicago. Year Book Medical Publ., 1952). B. Internal direct electric defibrillation. When fibrillation is felt, apply the electrodes and countershock, first wtih the pericardium closed. (If possible, have electrodes prepared with tied-on saline soaked gauze.) Apply the internal electrodes as illlustrated wearing rubber gloves and release the shock.

Figure 1–1.34. Hand positions for open-chest CPR. Operator stands on patient's left side facing cephalad. After thoracotomy, insert left hand and pump heart (first without opening pericardium) either with thumb posteriorally over left ventricle and fingers anteriorly over right ventricle (A); or with two hands, using palm of left hand over right ventricle and fingers 2–5 of right hand over left ventricle posteriorly (B); or using fingers 2–5 of right hand posteriorly over left ventricle compressing the heart against the sternum upward. Methods shown in B and C give better blood flow and are less fatiguing and less traumatic than that shown in A. (Reproduced with permission from Barnett WM, et al: Ann Emerg Med 1984;13:397.)

In addition, open-chest CPR permits direct palpation and observation of the heart, which helps guide drug and fluid therapy and electric countershock in difficult CPR efforts. Finally, the open chest also permits direct compression of a bleeding site in intrathoracic exsanguination and, in cases of intra-abdominal hemorrhage, allows temporary compression or clamping of the thoracic aorta above the diaphragm. For most cases of cardiac arrest, closed-chest CPR has replaced open-chest CPR because the former can be started without delay and can be performed by persons not trained in surgical techniques (i.e., outside the hospital). Many physicians fear the possible complications associated with thoracotomy, such as injury to heart and great vessels, and infection. In the hands of physicians with the necessary skills, equipment, and facilities, however, the open-chest CPR approach is safe and is hemodynamically superior to the closed-chest technique (see Comments). The dismal overall CPR statistics even from in-hospital cardiac arrests (15%) ( 133A) suggest a need to use open-chest CPR. Indications for Open-Chest CPR Open-chest CPR, as reappraised in recent years through new research, is indicated in the hands of trained physicians only, in circumstances for which it may be the only effective method of restoring life: 1. When the chest is already open (in the operating room). 2. In suspected intrathoracic trauma such as uncontrollable hemorrhage associated with cardiac arrest, particularly from penetrating wounds of the chest; crushing chest injury; or after cardiothoracic surgery and in suspected cardiac tamponade. 3. In suspected intra-abdominal exanguination with pulselessness. Thoracotomy enables CPR, arterial infusions, and temporary clamping of lower thoracic aorta for controlling bleeding in the abdomen. 4. In suspected massive pulmonary embolism. In this condition, the open-chest technique permits breaking up or removing the emboli and also prompt initiation of cardiopulmonary bypass. 5. In cardiac arrest with hypothermia. In this case, the open-chest CPR technique permits direct rewarming of the heart (which is necessary for defibrillation) with warmed saline. 6. When no artificial large artery pulse is produced by standard CPR, as is occasionally the case with chest or spine deformities or severe emphysema with barrel chest. 7. In suspected long arrest time or other difficult resuscitation (e.g., potassium bolus) as in unwitnessed arrest, followed by inability of correctly performed standard advanced life support (ALS) (with CPR, epinephrine, NaHCO 3, and countershocks) to promptly restore spontaneous circulation within 5 to 10 minutes. Technique for Open-Chest CPR The procedures for performing open-chest CPR are given in Table 1–1.6. They pertain to intubated patients only.

Table 1–1.6. Technique for Open-Chest CPR a

A controlled study in dogs to evaluate hand positions, using 60 compressions per minute, revealed that perfusion pressures and common carotid blood flows were high when the heart was compressed against the sternum, equally high when squeezing it with both hands, but relatively lower with the use of one hand with the thumb posteriorly over the left ventricle ( Fig. 1–1.30, Fig. 1–1.31, Fig. 1–1.32, Fig. 1–1.33 and Fig. 1–1.34). In suspected cardiac tamponade, if time permits and the patient is not yet pulseless, rapid drainage of the pericardial sac by needle puncture (alongside the xiphoid) may obviate the need for thoracotomy. If the diagnosis is uncertain, the chest and pericardium should be opened and direct cardiac compressions started. Open-chest CPR is ALS by physicians who have performed thoracotomies and are knowledgeable about the pathophysiology of the open thorax. Nonsurgeons, however, can be trained to perform this procedure with safety and speed. Evaluation of Open-Chest CPR Although few seriously question the hemodynamic superiority of open-chest CPR over standard external CPR the question remains: When does opening the chest offer an advantage over standard CPR? We believe that the indications of open-chest CPR ought to be reevaluated clinically and its indications widened, to include cases of prolonged arrest time and failure of standard CPR with drugs and countershock to promptly restart spontaneous circulation ( 128). The physiologic superiority of open-chest CPR over all external CPR methods in terms of overall blood flow, ease of restarting spontaneous circulation, and cerebral outcome, has been convincingly established by clinical observations and experimental work ( 116,117,118 and 119,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138 and 139). Open-chest CPR, but not external CPR methods, can produce perfusion pressures adequate for cerebral and coronary blood flows of at least 20% of normal, even after several minutes of no blood flow. During open-chest CPR, suggestive evidence was found of a shift of blood flow from the face to the brain ( 122) and during external CPR, particularly SVC-CPR, a suggested blood flow shift was found from the brain to the face ( 127). In patients, lower venous and higher perfusion pressure with higher cardiac output during open-chest CPR compared with external CPR were measured ( 131). High venous and low perfusion pressures limit the efficacy of external CPR ( 130). Direct cardiac massage squeezes the ventricles and not the veins; chest compressions squeeze also the intrathoracic veins and atria. Open-chest cardiac defibrillation had been done on animals at the beginning of this century ( 140), but was used in humans only after Beck convinced his colleagues that cardiac arrest from VF often occurs in “hearts too good to die” ( 64,141,142). By 1953, Stephenson et al. (118) had accumulated 1200 cases of cardiac arrest treated with open-chest CPR; 28% went home, and 14% of the resuscitation attempts were initiated outside the operating room (inside the hospital), with a 17% survival rate. In autopsies, lacerations of the heart were seen in 10% of cases ( 142), but massage of up to 2½ hours could lead to recovery ( 143,144). Physicians of various disciplines have performed open-chest CPR, even in EDs and on wards ( 121,131,143,145,146) return of spontaneous circulation (ROSC) with drugs, fluids, and countershocks was facilitated by the visual control and touch provided. Most patients either recovered with good brain function (even after 1 to 2 hours of open-chest CPR) or died. Infection was not a problem. The infection rate in one study was only 2 of 43 patients, and the 2 cases were not lethal ( 147). Since the rediscovery of external CPR (148), open-chest CPR was almost exclusively reserved for cases with thoracic trauma ( 149,150,151,152,153) and (154). In several series, the incidences of wound infection ranged between 0.0 and 9.1% and the incidences of iatrogenic heart damage ranged between 0.1 and 1.4%. Neurologic outcome results were encouraging ( 150). In suspected exsanguinating hemorrhage into the abdomen (e.g., trauma, ruptured aortic aneurysm), immediate application of the medical antishock trousers (MAST) may restore a carotid pulse. Before removal of the MAST for emergency laparotomy, however, and in the case of pulselessness in such patients, emergency thoracotomy should be contemplated, e.g., the left chest prepared. This left-sided procedure permits not only open-chest CPR and aortic infusions in case of pulselessness but also occlusion of the lower thoracic aorta for temporary hemostasis, to permit removal of the MAST and surgical repair of the abdominal lesion. (See the indications for open-chest CPR described previously.) In conclusion, considerable evidence suggests that open-chest CPR may be more efficacious than external CPR and that the risks of thoracotomy might be acceptable as compared to near-certain death. Patients who respond to conventional ALS with resumption of adequate spontaneous circulation within the first 5 to 10 minutes of resuscitation are unlikely to have benefited from open-chest CPR. The benefit to nonresponders, however, may be great. Cardiopulmonary Bypass The heart-lung machine was originally developed for the provision of cardiopulmonary bypass, usually by venoarterial pumping of blood by an oxygenator, to enable open-heart surgery ( 108). Cardiopulmonary bypass for emergency resuscitation in addition to or instead of standard CPR has considerable potential ( 155,156,157 and 158). Patients dying from massive pulmonary thromboembolism have sometimes been resuscitated from severe shock states, occasionally even from pulselessness, with rapidly begun cardiopulmonary bypass ( 159,160,161 and 162). These applications were with closed thorax and cannulation by cutdown of femoral artery and vein, in conjunction with CPR for pulselessness, and in preparation for open-heart surgery. Other clinical trials have been for rapid reversal of hypothermia-induced cardiac arrest (163,164,165 and 165). Limitations proved to be primarily (a) the time required for inserting large-bore tubes into the venae cavae and the femoral artery of the patient with cardiac arrest, and (b) the nonavailability of a small portable emergency pump oxygenator primed with plasma substitute. Such a portable pump oxygenator is commercially available ( 166). The first experimental evaluation of cardiopulmonary bypass for cardiac arrest was by Bozhiev et al. ( 167), who reported complete recovery of dogs with use of short-term cardiopulmonary bypass after 15 minutes of normothermic complete circulatory arrest. Cardiac resuscitability in dogs after 15 to 20 minutes of normothermic total circulatory arrest is greater with cardiopulmonary bypass than with standard CPR ( 168) and cardiopulmonary bypass can restart spontaneous circulation after up to 90 minutes of ice water submersion ( 10A,169). Cardiopulmonary bypass, as compared with conventional ALS for restoration of spontaneous circulation, not only enhances cardiac resuscitation but also cerebral recovery, even when cardiopulmonary bypass was started after prolonged standard CPR, as could be the case in prehospital scenarios ( 166). The superiority of cardiopulmonary bypass over external and perhaps also over open-chest CPR in restarting infusion instantaneously, even after very prolonged cardiac arrest, is obvious. Only anecdotal data exist on how cardiopulmonary bypass, which requires several minutes of preparation to be started, should fit into the CPR-ALS sequence and whether or not short-term versus long-term cardiopulmonary bypass postarrest would enhance outcome with better cardiac and cerebral function compared with closed-chest or open-chest CPR followed by spontaneous circulation. Portions of this chapter appeared in: Schwartz GR, Cayten CG, Mangelsen MA, et al., eds. Principles and practice of emergency medicine. 3d ed. Philadelphia: Lea & Febiger, 1992 and were authored by Dr. Peter Safar and Dr. Nick Bircher. Dr. Safar has been a leader in resuscitation research and the leading American resuscitation and research center is the Safar Center for Resuscitation and Research in Pittsburgh, PA.

References 1. 2. 3. 4. 5. 6. 7. 8. 9.

Safar P, Bircher NG: Cardiopulmonary Cerebral Resuscitation. An Introduction to Resuscitation Medicine. 3rd ed. London, WB Saunders, Ltd., 1988. Safar P, Elam J, eds: Advances in Cardiopulmonary Resuscitation. First Wolf Creek Conference. New York, NY, Springer-Verlag, 1977. Negovsky VA: Introduction: Reanimatology—The Science of Resuscitation. In: Stephenson HE, ed. Cardiac Arrest and Resuscitation. 4th ed. St Louis, MO, CV Mosby Co., 1974;3–27. Negovsky VA, Gurvitch AM, Zolotokrylina ES: Post-resuscitation disease. Amsterdam, Elsevier, 1983. Safar P: Effects of the postresuscitation syndrome on cerebral recovery from cardiac arrest. Crit Care Med 1985;13(11):932–935. White RD, Asplin BR, Buglius TF, et al: High discharge survival rate after out-of-hospital VF with rapid defibrillation by police and paramedics. Ann Emerg Med 1996;28:480. Schaffer WA, Cobb LA: Recurrent ventricular fibrillation and modes of death in survivors of out-of-hospital ventricular fibrillation. N Engl J Med 1975;293:259. Safar P: Resuscitation from clinical death: pathophysiologic limits and therapeutic potentials. Crit Care Med 1988 Oct;16(10):923–941. Eisenberg MS, Horwood BT, Cummins RO, et al: Cardiac Arrest and Resuscitation: A Tale of 29 Cities. Ann Emerg Med 1990;19(2):179–186.

10. Grenvik A, Safar P, eds: Brain Failure and Resuscitation: Clinics in Critical Care Medicine Series. New York, NY, Churchill Livingstone, 1981. 10A. Walpoth BH, Walpoth-Aslan BN, Mattle HP, et al: Outcome of survivors of accidental deep hypothermia and circulatory arrest treated with extracorporeal blood warming. Med 1997;337(21):1500–1505. 11. 12. 13. 14.

N Engl J

Siesjo BK, Carlsson C, Hagerdal M, et al: Brain metabolism in the critically ill. Crit Care Med 1976;4:283. Siesjo BK: Brain Energy Metabolism. New York, NY, John Wiley & Sons, 1978. Siesjo BK: Mechanisms of ischemic brain damage. Crit Care Med 1988 Oct;16(10):954–963. Plum F: The clinical problem: how much anoxia-ischemia damages the brain? Arch Neurol 1973;29(6):359–360.

14A. Horowitz BZ, Matheny L: Health care professionals' willingness to do mouth-to-mouth resuscitation. West J Med 1997 Dec;167(6):392–397. 15. 16. 17. 18. 19. 20. 21. 22. 23.

Hossman KA, Kleihues P: Reversibility of ischemic brain damage. Arch Neurol 1973;29:375. Hossman KA: Resuscitation potentials after prolonged global cerebral ischemia in cats. Crit Care Med 1988 Oct;16(10):964–971. Hossman KA: Neuronal survival and revival during and after cerebral ischemia. Am J Emerg Med 1983;1:191. Nemoto EM, Erdmann NW, Strong E, et al: Regional brain PO 2 after global ischemia in monkeys: evidence for regional differences in critical perfusion pressures. Stroke 1979;10:44. Snyder JV, Nemoto EM, Carroll RG, et al: Global ischemia in dogs: intracranial pressures brain blood flow and metabolism. Stroke 1975;6:21. Brierley JB, Meldrum BS, Brown AW: The threshold and neuropathology of cerebral “anoxic-ischemic” cell damage. Arch Neurol 1973;29:367. Brierley JB, Meldrum BS, eds: Brain Hypoxia. Philadelphia, PA, JB Lippincott Co., 1971. Brierley JB, Prior PF, Calverley J, et al: The pathogenesis of ischemic neuronal damage along the cerebral arterial boundary zones in papio anubis. Brain 1980;103:929. Garcia JH, Kalimo H, Kamijyo Y, et al: Cellular events during partial cerebral ischemia. Part I: electron microscopy of feline cerebral cortex after middle-cerebral artery occlusion. Virchows Arch [B] Cell Pathol 1977;25:191.

23A. Kalimo H, Garcia JH, Kamijyo Y, et al: The ultrastructure of “brain death.” II. Electron microscopy of feline cortex after complete ischemia. 1977;25:207.

Virchows Arch [B] Cell Pathol

23B. Garcia JH: Morphology of global cerebral ischemia. Crit Care Med 1988 Oct;16(10):979–987. 24. 25. 26. 27.

Moossy J: Pathologic studies: an essential guide. Prehosp Disaster Med 1983;I(suppl):18. Moossy J: Morphological validation of ischemia stroke models. In: Price TR, Nelson E, eds. Cerebrovascular Diseases. Eleventh Princeton Conference. New York, NY, Raven Press, 1979. Steegman A: The neuropathology of cardiac arrest. In: Minckler J, ed. Pathology of the Nervous System. vol. 1. New York, NY, McGraw-Hill, 1968. Drewes LR, Gilboe DD, Betz AL: Metabolic alterations in brain anoxia and subsequent recovery. Arch Neurol 1973;29:385.

27. Cowley RA, Trump BF, eds: Pathophysiology of Shock, Anoxia, and Ischemia. Baltimore, MD, Williams & Wilkins, 1982. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74.

Huckabee WE: Relationships of pyruvate and lactate during anaerobic metabolism: I. Effects of infusion of pyruvate or glucose and of hyperventilation. J Clin Invest 1958;37:244. Lowry OH, Passonneau IV, Hasselberger FX: Effect of ischemia on known substrates and cofactors of the glycolytic pathway in brain. J Biol Chem 1964;239:18. Nemoto EM: Pathogenesis of cerebral ischemia-anoxia. Crit Care Med 1978;6:203. Bircher N, Safar P: Cerebral preservation during cardiopulmonary resuscitation. Crit Care Med 1985;13:185. Vaagenes P, Cantadore R, Safar P, et al: Amelioration of brain damage by lidoflazine after 10 minutes ventricular fibrillation cardiac arrest in dogs. Crit Care Med 1984;12:846. Redding JS, Pearson JW: Resuscitation from ventricular fibrillation. Drug therapy. JAMA 1968;203:255. Safar P, Gisvold SE, Vaagenes P, et al: Long-term animal models for the study of global brain ischemia. In: Wauquier A, Borgers M, Amery WK, eds. Protection of Tissues Against Hypoxia. Amsterdam, Elsevier, 1982;147–170. Kampschulte S, Morikawa S, Safar P: Recovery from anoxic encephalopathy following cardiac arrest. Fed Proc 1969;28:522 (abstract). Kouwenhoven WB, Jude JR, Knickbocker GG: Closed-chest cardiac massage. JAMA 1960;173:1064. Negovsky VA: Resuscitation and Artificial Hypothermia. New York, NY, Consultant's Bureau, 1962. Kirimli B, Safar P: Arterial versus venous transfusion in cardiac arrest from exsanguination. Anesth Analg 1965;44:819. Kirimli B, Kampschulte S, Safar P: Resuscitation from cardiac arrest due to exsanguination. Surg Gynecol Obstet 1969;129:89. Kirimli B, Kampschulte S, Safar P: Pattern of dying from exsanguinating hemorrhage in dogs. J Trauma 1970;10:393. Negovsky VA: Current Problems of Reanimatology. Moscow, Mir Publishers, 1975. Redding J, Voigt GC, Safar P: Drowning treated with intermittent positive pressure breathing. J Appl Physiol 1960;15:849. Redding JS, Pearson JW: Resuscitation from asphyxia. JAMA 1962;182:283. Safar P: Resuscitation of the ischemic brain. In: Allen MS, ed. Textbook of Neuroanaesthesia. New York, McGraw-Hill, 1997;557–595. Safar P, Abramson NS, Angelos M, et al: Emergency cardiopulmonary bypass for resuscitation from prolonged cardiac arrest. Am J Emerg Med 1990 Jan;8(1):55–67. Elam JO: Respiratory and circulatory resuscitation. Handbook of Physiology Respiration, Vol. II, American Physiologic Society, 1965;1265–1312. Safar P, Stezoski W, Nemoto EM: Amelioration of brain damage following 12 minutes of cardiac arrest in dogs. Arch Neurol 1976;33:91. Crile G, Dolley DH: An experimental research into the resuscitation of dogs killed by anesthetics and asphyxia. J Exp Med 1906;8:713. Safar P, et al: J Cereb Blood Flow Metab 1991;11(Suppl 2):S320. (abstract). Bleyaert AL, Nemoto EM, Safar P, et al: Thiopental amelioration of brain damage after global ischemia in monkeys. Anesthesiology 1978;49:390. Gisvold SE, Safar P, Rao G, et al: Prolonged immobilization and controlled ventilation after global brain ischemia in monkeys. Crit Care Med 1984;12:171. Nemoto EM, Bleyaert AL, Stezoski SW, et al: Global brain ischemia: a reproducible monkey model. Stroke 1977;8:558. Nemoto EM: Role of synaptic transmission failure without neuronal necrosis in neurological dysfunction of ischemic brain injury. Proceedings of NATO—Advanced Research Workshop on mechanisms of secondary brain damage. Mauls/Sterzing Italy, February 1984. Staub MC: Pulmonary edema: physiologic approaches to management. Chest 1978;74:559. Shoemaker WC, Ayres S, Grenvik A, et al., eds: Textbook of Critical Care. 2nd ed. Philadelphia, PA: WB Saunders Co., 1989. Trunkey DD, Lewis FR Jr, eds: Current therapy of trauma. St. Louis, MO, CV Mosby Co., 1984. Tisherman S, Chabal C, Safar P, et al: Resuscitation of dogs from cold water submersion using cardiopulmonary bypass. Ann Emerg Med 1985;14:389. Safar P: Cerebral resuscitation after cardiac arrest: a review. Circulation 1986 Dec;74(6 Pt 2):IV138–IV153. Kampschulte S, Smith J, Safar P: Sauerstofftransport nach Herz-Lungen-Wiederbelebung. Anaesthesiol Reanim 1969;30:95. Smith J, Penninckx JJ, Kampschulte S, et al: Need for oxygen enrichment in myocardial infarction shock and following cardiac arrest. Acta Anesthesiol Scand (Suppl) 1968;29:127. Vesalius A: De corporis humani fabrica. Libri Septem 1543. Gerst PH, Fleming WH, Malm JR: Increased susceptibility of the heart to ventricular fibrillation during metabolic acidosis. Circ Res 1966;19:63. Rossen R, Kabat H, Anderson JP: Acute arrest of cerebral circulation in man. Arch Neurol Psychiatr 1943;50:510. Harben K, MacKenzie IL, Ledingham IM: Spontaneous reversion of ventricular fibrillation. Lancet 1963;2:1140. Beck CS, Pritchard H, Feil SH: Ventricular fibrillation of long duration abolished by electric shock. JAMA 1947;135:985. Beck CS, Leighninger DS: Scientific basis for the surgical treatment of coronary artery disease. JAMA 1955;159:1264. Beck CS, Leighninger DS: Death after a clean bill of health. JAMA 1960;174:133. Adelson L, Hoffman W: Sudden death from coronary artery disease. JAMA 1961;176:129. Hellstrom HR: Vasospasm in ischemic heart disease—a hypothesis. Perspect Biol Med 1973;16:427. Gurvich NL, Yuniev SG: Restoration of a regular rhythm in the mammalian fibrillating heart. Am Rev Soc Med 1946;3:236. Kouwenhoven WB, Milnor WR: Treatment of ventricular fibrillation using a capacitor discharge. J Appl Physiol 1954;7:253. Prevost JL, Batelli F: On some effects of electrical discharges on the hearts of mammals. Paris, CR Acad Sci 1899;129:1267. Tacker WA, Wey GA: Emergency defibrillation dose: recommendations and rationale. Circulation 1979;60:223. Zoll PM, Linenthal AJ, Gibson W, et al: Termination of ventricular fibrillation in man by externally applied electric counter shock. N Engl J Med 1956;254:727.

74A. Walcott GP, Knisley SB, Zhou X, et al: On the mechanism of ventricular defibrillation. Pacing Clin Electrophysiol 1997;20(2 Pt 2):422–431. 75. Pennington JE, Taylor J, Lown B: Chest thump for reverting ventricular tachycardia. N Engl J Med 1970;283:1192. 76. Redding JS: Precordial thumping during cardiac resuscitation. In Safar P, ed. Advances in Cardiopulmonary Resuscitation. New York, NY, Springer-Verlag, 1977:87–93. 77. Strohmenger HV, Lindner KH, Brown CG: Analysis of the ventricular fibrillation ECG signal amplitude and frequency parameters as predictors of countershock success in humans. Chest 1997;111:584. 77A. Sherman BW, Munger MA, Foulke GE, et al: High-dose versus standard-dose epinephrine treatment of cardiac arrest after failure of standard therapy. Pharmacotherapy 1997;17(2):242-247. 78. Stephenson HE: Cardiac Arrest and Resuscitation. 4th ed. St. Louis, MO, CV Mosby Co., 1974. 79. Stewart JS: Management of cardiac arrest with special reference to metabolic acidosis. Br Med J 1964;1:476. 79A. Higginson I, Montgomery D, Tuck R: The use of high doses of adrenaline in pediatric cardiac resuscitation. J Pediatr Child Health. 1996;32:1. 79B. Brown C, Wiklund L, Bar-Joseph G, et al: Future direction for resuscitation research. Innovative life support pharmacology. Resuscitation 1996;33:163. 80. Redding JS, Pearson JW: Evaluation of drugs for cardiac resuscitation. Anesthesiology 1963;24:203.

81. Pearson JW, Redding JS: Influence of peripheral vascular tone on cardiac resuscitation. Anesth Analg 1965;44:746. 81A. Panzer W, Bretthaver M, Klingler H, et al: ACD vs. standard CPR in a prehospital setting Resuscitation 1996;33:117. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133.

Gunnar RM, Bourdillion PDV, Dixon DW, et al: ACC/AHA guidelines for the early management of patients with acute myocardial infarction. Circulation 1990;82:664. Zoll PM, Linenthal AJ, Norman LR, et al: Treatment of unexpected cardiac arrest by external stimulation of the heart. N Engl J Med 1956;254:727. Swann HG, Brucer M: The cardiorespiratory and biochemical events during rapid anoxic death. Tex Rep Biol Med 1949;7:511. Swann HG: Resuscitation in semi-drowning. In: Whittenberger JF, ed. Artificial Respiration. New York, NY: Harper & Row, 1962;202–224. Sutton JR, Houston CS, Jones NL, eds: Hypoxia exercise and altitude. Proceedings of the Third Banff International Hypoxia Symposium. New York, NY, Liss, A.R., 1983. Sellick BA: Cricoid pressure to control regurgitation of stomach contents during induction of anesthesia. Lancet 1961;ii:404. Stept WF, Safar P: Rapid induction/intubation for prevention of gastric-content aspiration. Anesth Analg 1970;49:633. Stewart RD: Tactile orotracheal intubation. Ann Emerg Med 1984;13:175. Stewart RD, Paris PM, Stoy WA, et al: Field endotracheal intubation by paramedical personnel: success rates and complications. Chest 1984;85:341. Vollmer TP, Stewart RD, Paris PM, et al: Guided orotracheal intubation using a lighted stylet. Ann Emerg Med 1984;13:404. Eckenhoff JE: Some anatomic considerations of the infant larynx influencing endotracheal anesthesia. Anesthesiology 1951;12:401. Crile G, Dolley DH: An experimental research into the resuscitation of dogs killed by anesthetics and asphyxia. J Exp Med 1906;8:713. Jacobs HG: Emergency percutaneous transtracheal catheter and ventilator. J Trauma 1972;12:50. Jacoby JJ, Hamelberg W, Ziegler CH, et al: Transtracheal resuscitation. JAMA 1956;162:625. Singh NP: Transtracheal jet ventilation as a new technique and experiences with ketamine and propanidid in India. In: Miyazaki M, ed. Anesthesiology. (WSFA Congress, Kyoto, 1972). Amsterdam: Excerpta Medica, 1973; 160. Spoerel WE, Narayanan PS, Singh NP: Transtracheal ventilation. Br J Anaesth 1971;43:932. Klain M, Smith RB: High frequency percutaneous transtracheal jet ventilation. Crit Care Med 1977;5:280. Klain M: High frequency ventilation. In: Shoemaker WC, Ayres S, Grenvik A, et al: Textbook of Critical Care. 2nd ed. Philadelphia, PA: WB Saunders Co., 1989;641–696. Safar P: Ventilating bronchoscope. Anesthesiology 1958;19:407. Marini JJ, Pierson DJ, Hudson LD: Acute lobar atelectasis: a prospective comparison of fiberoptic bronchoscopy and respiratory therapy. Am Rev Respir Dis 1979;119:971. Ikeda S, Yanai N, Ischikawa S: Flexible bronchofiber scope. Kei J Med 1968;17:1. Haugen RK: The cafe coronary. Sudden death in restaurants. JAMA 1963;186:142. Fink BR: The etiology and treatment of laryngeal spasm. Anesthesiology 1956;17:569. Redding J, Cozine RA, Voigt GC, Safar P: Resuscitation from drowning. JAMA 1951;178:1136. Vaagenes P, Safar P, Diven W, et al: Brain enzyme levels in CSF after cardiac arrest and resuscitation in dogs: markers of damage and predictors of outcome. J Cereb Blood Flow Metab 1988;8:262. Hendricks HH, Rao GR, Safar P, et al: Asphyxia, cardiac arrest and resuscitation in rats. I. Short term recovery. Resuscitation 1984;12(2):97–116. Kristoffersen MB, Rattenborg CC, Holaday DA: Asphyxial death: the roles of acute anoxia, hypercarbia and acidosis. Anesthesiology 1967;28:488. Vaagenes P, Cantadore R, Safar P, et al: Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs. Crit Care Med 1984;12(10):846–855. Roth LW, Whitehead RW, Draper WB: Studies on diffusion respiration: II. Survival of the dog following a prolonged period of respiratory arrest. Anesthesiology 1947;8:294. Holmdahl MD: Pulmonary uptake of oxygen, acid-base metabolism, and circulation during prolonged apnea. Acta Chir Scand (Suppl) 1956;212:1. Graham GR, Hill DW, Nunn JF: The effect of high concentrations of carbon dioxide on the circulation and respiration. Anaesthetist 1960;9:70. Aubier M, Murciano D, Fournier M, et al: Central respiratory drive in acute respiratory failure of patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1980;122:191. Schiff M: Uber direkte Reizung der Herzoberflache. Arch Ges Physiol 1882;28:200. Beck CS, Pritchard H, Feil SH: Ventricular fibrillation of long duration abolished by electric shock. JAMA 1947;135:985. Boehm R: Uber Wiederbelebung nach Vergiftungen and Asphyxie. Arch Exp Pathol Pharmakol 1878;8:68. Zoll PM, Linenthal AJ, Gibson W, et al: Termination of ventricular fibrillation in man by externally applied electric countershock. N Engl J Med 1956;254:727. Stephenson HE, Reid LC, Hinton JW: Some common denominators in 1200 cases of cardiac arrest. Ann Surg 1953;137:731. Leighninger DS: Contributions of Claude Beck. In: Safar P, ed. Advances in CPR. New York, NY, Springer-Verlag, 1977;259–262. Stephenson HE: Cardiac Arrest and Resuscitation. St. Louis, MO: CV Mosby Co., 1974. Dripps RD, Kirby CK, Johnson J, et al: Cardiac resuscitation. Ann Surg 1948;127:592. Stajduhar K, Steinberg R, Sotosky M, et al: Cerebral blood flow and common carotid artery blood flow during open chest cardiopulmonary resuscitation in dogs. Anesthesiology 1983;59:A117. Lee SK, Vaagenes P, Safar P, et al: Effect of cardiac arrest time on cortical cerebral blood flow during subsequent standard external cardiopulmonary resuscitation in rabbits. Resuscitation 1989;17:105. Alifimoff JK, Safar P, Bircher N, et al: Cerebral recovery after prolonged closed-chest, MAST-augmented and open-chest cardiopulmonary resuscitation (CPR). Anesthesiology 1980;53:S147. Alifimoff JK, Safar P, Bircher N, et al: Cardiac resuscitability after closed-chest, MAST augmented and open-chest CPR. Anesthesiology 1980;53:S151. Bircher NG, Safar P, Stewart RD: A comparison of standard, “MAST”-augmented, and open-chest CPR in dogs. Crit Care Med 1980;8:147. Bircher N, Safar P: Comparison of standard and “new” closed-chest CPR and open-chest CPR in dogs. Crit Care Med 1981;9:384. Bircher N, Safar P: Open-chest cardiopulmonary resuscitation: an old method whose time has returned. Am J Emerg Med 1989;2:568. Bircher NG, Safar P: Cerebral preservation during cardiopulmonary resuscitation. Crit Care Med 1985;13:185. MacKenzie GJ, Taylor SH, McDonald AH, et al: Hemodynamic effects of external cardiac compression. Lancet 1964;i:1342. Del Guercio LRM, Feins NR, Cohn JD, et al: Comparison of blood flow during external and internal cardiac massage in man. Circulation 1965;31/32:I171. Bircher NG, Safar P: Manual open-chest cardiopulmonary resuscitation. Ann Emerg Med 1984;13:770. Redding J, Cozine R: A comparison of open chest and closed-chest cardiac massage in dogs. Anesthesiology 1961;22:280.

133A. Schneider AP 2d, Nelson DJ, Brown DD: In-hospital cardiopulmonary resuscitation: a 30-year review. J Am Board Fam Pract 1993 Mar;6(2):91–101. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169.

Barnett WM, Alifimoff JK, Paris PM, et al: Comparison of open-chest cardiac massage techniques in dogs. Ann Emerg Med 1984;13:397 (abstract). Wiggers CJ: The physiological bases for cardiac resuscitation from ventricular fibrillation: method for serial defibrillation. Am Heart J 1940;20:413. Byrne D, Pass HL, Neely WA, et al: External vs. internal cardiac massage in normal and chronic ischemic dogs. Am Surg 1980;46:657. Weiser FM, Adler LN, Kuhn LA: Hemodynamic effects of closed and open chest cardiac resuscitation in normal dogs and those with myocardial infarction. Am J Cardiol 1962;10:555. Weale FE, Rothwell-Jackson RL: The efficiency of cardiac massage. Lancet 1962;1:990. Sanders AB, Kern K, Ewy GA, et al: Improved survival from cardiac arrest with open-chest massage. Ann Emerg Med 1984;13:672. Prevost JL, Battelli F: On some effects of electrical discharges on the hearts of mammals. Paris, CR Acad Sci 1899;129:1267. Adelson L, Hoffman W: Sudden death from coronary artery disease: a statistical study. JAMA 1961;176:129. Adelson L: A clinicopathologic study of the anatomic changes in the heart resulting from cardiac massage. Surg Gynecol Obstet 1957;104:513. Ravitch M, Lane R, Safar P, et al: Lightning stroke. Recovery following cardiac massage and prolonged artificial respiration. N Engl J Med 1961;264:36. Shocket E, Rosenblum R: Successful open cardiac massage after 75 minutes of closed massage. JAMA 1967;200:333. Safar P, Bircher NG: Cardiopulmonary cerebral resuscitation. An introduction to resuscitation medicine. Stavanger, Norway (Laerdal); London, W.B. Campbell TP, Stewart RD, Kaplan RM, et al: Oxygen enrichment of bag-valve-mask units during positive-pressure ventilation: a comparison of various techniques. Ann Emerg Med 1988;17:232. Altemeier WA, Todd J: Studies on the incidence of infection following open-chest cardiac massage for cardiac arrest. Ann Surg 1963;158:596. Kouwenhoven WB, Jude JR, Knickerbocker GG: Closed-chest cardiac massage. JAMA 1960;173:1064. Mattox KL, Espada R, Beall AC, et al: Performing thoracotomy in the emergency center. JACEP 1974;3:13. Baker CC, Thomas AN, Trunkey DD: The role of emergency room thoracotomy in trauma. J Trauma 1980;20:848. Ivatury RR, Shag PM, Ito K, et al: Emergency room thoracotomy for the resuscitation of patients with “fatal” penetrating injuries of the heart. Ann Thorac Surg 1981;32:377. Moore EE, Moore JB, Galloway AC, et al: Post-injury thoracotomy in the emergency room: a critical evaluation. Surgery 1979;86:590. Eldor J, Frankel DZN, Davidson JT: Open chest cardiac massage: a review. Resuscitation 1988;16:155. Heller MB. Open-chest cardiac massage. The possible rebirth of an old procedure. Postgrad Med 1990;87:189. Gibbon JH: Application of a mechanical heart and lung apparatus to cardiac surgery. Minn Med 1954;37:171. Mair P, Hoermann C, Moertl M: Percutaneous veno-arterial extracorpreal membrane oxygenation for emergency mechanical circulatory support. Resuscitation 1996;33:29. Karmy-Jones R, et al: Cardiopulmonary bypass for resuscitation after penetrating cardiac trauma. Ann Thorac Surg 1996;61:1244. Bircher N, Otto C, Safar P, et al: Future directions for resuscitation research. II External cardiopulmonary resuscitation basic life support. Resuscitation 1996;32:63. Reul GL, Beall AC: Emergency pulmonary embolectomy for massive pulmonary embolism. Circulation 1974;49:II-236. Mattox KL, Beall AC: Resuscitation of the moribund patient using portable cardiopulmonary bypass. Ann Thorac Surg 1976;22:436. Stuckey JH, Neumann MM, Dennis C, et al: The use of the heart-lung machine in selected cases of acute myocardial infarction. Surg Forum 1947;8:342. Safar P, Abramson NS, Angelos M, et al: Emergency cardiopulmonary bypass for resuscitation from prolonged cardiac arrest. Am J Emerg Med 1990;8:55. Ledingham I, Douglas IH, Routh GS, et al: Central rewarming system for treatment of hypothermia. Lancet 1980;1:1168–1169. Husby P, Andersen KS, Owen-Falkenberg O, et al: Accidental hypothermia with cardiac arrest: complete recovery after prolonged resuscitation and rewarming by extracorporeal circulation. Intensive Care Med 1990;16:69. Saltiel A, Kopf GS, Elefteriades J, et al: Resuscitation of cold water immersion victims with cardiopulmonary bypass. J Crit Care 1989;4:54. Levine R, Pretto E, Gorayeb M, et al: Improved outcome after cardiac arrest in dogs using emergency cardiopulmonary bypass. Am J Emerg Med 1986;4:419. Bozhiev AA, Tolova SV, Trubina IE, et al: Peculiar features of resuscitation with the use of extracorporeal circulation. Kardiologiia 1974;14:101. Cantadore R, Vaagenes P, Safar P, et al: Cardiopulmonary bypass for resuscitation after prolonged cardiac arrest in dogs. Ann Emerg Med 1984;13:398. (abstract). Tisherman S, Chabal C, Safar P, et al: Resuscitation of dogs from cold-water submersion using cardiopulmonary bypass. Ann Emerg Med 1985;14:389.

Chapter 1.2 Post Intubation: Airway and Ventilator Management Principles and Practice of Emergency Medicine

CHAPTER 1 MECHANISMS OF DYING AND TECHNIQUES OF RESUSCITATION

2 Post Intubation: Airway and Ventilator Management George J. Rubeiz, Georges S. Yacoub, Basim A. Dubaybo Indications Techniques Legal and Ethical Considerations

INDICATIONS The indications for mechanical ventilation include respiratory and nonrespiratory conditions as listed in Table 1–2.1 and Table 1–2.2

Table 1–2.1. Indications for Endotracheal Intubation

Table 1–2.2. Criteria for Initiation of Mechanical Ventilation

TECHNIQUES Classification of Ventilators The three basic types of ventilators are negative pressure, positive pressure, and high frequency. NEGATIVE PRESSURE VENTILATORS These are rarely used and are mentioned for historic reasons. They produce negative pressure around the thorax and abdomen, lowering the alveolar pressure and producing inspiratory air flow. The iron lung, which is fitted around the entire body up to the neck, and the cuirass, which fits over the chest and upper abdomen, are examples of these devices. They are occasionally used in home treatment of patients with neuromuscular or musculoskeletal disorders or severe chronic obstructive lung disease who are not candidates for intubation. These inefficient and uncomfortable ventilators transmit negative pressure to the abdomen resulting in blood pooling, diminished venous return, and decreased cardiac output. POSITIVE PRESSURE VENTILATORS These devices cause inspiratory air flow by raising airway pressure. Depending on the mechanisms that terminate inspiration, they are divided into three categories: pressure cycled, volume cycled, and time cycled. Pressure-cycled ventilators are triggered by the patient's inspiratory effort to deliver air until a specific preset airway pressure is reached. Once this is attained, the inspiratory flow stops and passive exhalation starts. The delivered tidal volume, therefore, varies with changes in compliance and resistance of the patient-ventilator system. Volume-cycled ventilators are the most frequently used systems. These ventilators are designed to deliver a set volume of gas. Expiration follows passively. These respirators provide a consistent tidal volume despite changes in airway resistance or compliance. Time-cycled ventilators deliver air for a preset period. Consequently, they deliver a consistent tidal volume in spite of changes in the airway resistance or the lung compliance. HIGH-FREQUENCY VENTILATORS These include high-frequency positive pressure ventilation (HFPPV), high-frequency jet ventilation (HFJV), and high-frequency oscillation (HFO). They deliver smaller tidal volumes and do not require a cuffed endotracheal tube. HFPPV uses a respiratory frequency of 40 to 100 breaths/min, and tidal volumes approaching the calculated dead space volume, achieving minute ventilation of about 30 L/min. HFJV uses a respiratory frequency between 100 and 300 breaths/min, and tidal volume less than dead space. Minute ventilation is usually greater than 20 L/min but is difficult to quantitate exactly. The tidal volume of a single breath is unknown because it depends on the amount of air entrained from the ambiant air with each jet of gas. HFO uses a respiratory frequency of 300 to 3000 breaths/min, and tidal volumes of 10 to 100 mL. Indications for this modality include the management of bronchopleural fistula, the ventilation of some patients during bronchoscopy, and airway control during abdominal, thoracic, and brain surgery. It has also been used during resuscitation, for weaning of ventilator-dependent patients, and for treating patients with adult respiratory distress syndrome (ARDS). Several mechanisms have been proposed to explain how high-frequency ventilation maintains adequate alveolar

ventilation. These include direct convective ventilation of the alveoli closest to the mouth, turbulent mixing, convective dispersion from asymmetrical airway velocity profile, pendelluft, and Taylor dispersion. Modes of Ventilation CONTINUOUS MANDATORY VENTILATION (CMV) In this setting, the ventilator delivers a preset tidal volume at a preset rate. It is the best ventilatory mode to achieve a maximum decrease in the work of breathing and has generally been reserved for patients with severe respiratory failure or apnea, drug overdose, severe central nervous system dysfunction, neuromuscular disorders, chest injuries, and general anesthesia. Because this mode operates irrespective of the patient's needs, it can cause hypoventilation or hyperventilation, especially if the patient's respiratory or metabolic status changes. In this situation, the patient appears to fight or be out of synchrony with the ventilator. This increases the work of breathing and the demand for oxygen, and decreases the efficiency of breathing. ASSISTED MECHANICAL VENTILATION (AMV) In this mode, the ventilator delivers a preset tidal volume in response to the patient's inspiratory effort. Theoretically, the ventilator provides the work necessary to complete the work of breathing while the patient controls the amount of ventilation. Studies have confirmed, however, that the patients can still perform a significant fraction of the work of breathing. If excessive patient effort is used, abnormal inspiratory pressure curves will be observed. Because this mode is patient-triggered, it is usually combined with minimal CMV backup that functions if the patient's respiratory rate falls below a preset rate. This is commonly referred to as assist/control (A/C) mode. INTERMITTENT MECHANICAL VENTILATION (IMV) AND SYNCHRONIZED IMV (SIMV) In this setting, the ventilator provides a preset minimal minute ventilation. The patient ventilates spontaneously between the preset tidal breaths and can, therefore, respond to changes in the metabolic or respiratory needs. In SIMV, the preset tidal volumes are synchronized with the patient's spontaneous breathing, resulting in a decrease in bucking of the ventilator. Compared to CMV, IMV allows the continued use of the respiratory muscles. Acid-base maintenance is easier to achieve and airway pressure is lower. There is also greater patient comfort and less need for sedation. On the other hand, IMV support in some patients may result in diaphragmatic muscle fatigue. Spontaneous breaths may result in small tidal volumes that do not participate significantly in gas exchange and serve only to increase the work of breathing. PRESSURE SUPPORT VENTILATION (PSV) In this mode, a patient's inspiratory effort triggers a preset amount of positive pressure to the airway from the ventilator. This preset inspiratory pressure is maintained throughout inspiration, and the tidal volume remains dependent on the patient's effort. This positive pressure is intended to overcome the ventilator's valve and tubings resistance. The pressure support mode does not provide for adequate ventilation without the patient's spontaneous effort. As with CMV, IMV, or A/C ventilation and unlike continuous positive airway pressure, (CPAP), the ventilator returns to baseline pressure at the end of inspiration. PSV can be coupled with IMV, in which pressure support is given only with the spontaneous breath, or with CPAP for adequate ventilation. PSV has recently become more popular, especially for weaning patients from mechanical ventilation. PRESSURE-CONTROLLED VENTILATION (PcV) On a pressure-cycled ventilator, a specific pressure is set and the machine delivers a preset flow until that pressure is reached, at which point inspiration ends and exhalation begins. A backup rate can be set for the hypoventilating patient. In this mode there is no guaranteed minute ventilation. If the patient fights the breath, the inspiration ends prematurely, resulting in insufficient tidal volumes. Similarly, decreased lung compliance or increased airway resistance also reduce the tidal volume. PCV is often combined with inverse ratio ventilation (IRV), and the resultant PCIRV is used primarily in patients with ARDS. The potential effects of PCV are a more even gas distribution and perfusion match, greater response to patient's flow demand, and a decreased peak inspiratory pressure. This mode of ventilation is labor intensive and requires frequent monitoring, that is best achieved in an intensive care setting. POSITIVE END-EXPIRATORY PRESSURE (PEEP) Ventilation to fluid-filled or atelectatic small airways and alveoli can be restored by the establishment of a back pressure in the airway during expiration. This causes an increase in the functional residual capacity and the available alveolar surface area, thereby improving ventilation-perfusion relationships and improving arterial oxygen tension. Furthermore, the increase in alveolar volume results in a greater surface area exposure between the alveolar epithelium and the juxta-alveolar capillaries. Additionally, when hypoxemia is secondary to alveolar flooding from pulmonary edema, PEEP-induced increase in alveolar diameters may cause thinning of the alveolar fluid film, and gas exchange may improve. Selection of the optimal level of PEEP may be accomplished by measuring and following the effect of PEEP on several physiologic parameters. These include optimal oxygenation as determined by FIO 2, PO2, oxygen saturation, or oxygen transport, and improved lung compliance, pulmonary vascular resistance, pulmonary dead space, and physiologic shunt. The principal advantage of PEEP is that it often allows the reduction of the FIO2 required to achieve oxygenation of the arterial blood. Disadvantages include increased incidence of barotrauma, which correlates with peak airway pressure. Additionally, PEEP may cause a decrease in cardiac output, a decrease in venous return, and may also increase the work of breathing. Maintaining the lowest pressure for oxygenation and accepting modest hypercapnia may reduce risk of barotrauma ( 1). CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) and BiPAP In this mode of ventilation, airway pressure is maintained at a pressure greater than ambient pressure throughout the breathing cycle. It may be delivered through a ventilator or a sealed face mask. This kind of therapy may provide an alternative to endotracheal intubation and alleviate the need for mechanical ventilation in several patients. It is effective in the management of hypoxemia in the setting of ARDS and in the treatment of cardiogenic pulmonary edema. A nose mask with an air-tight seal can also be used (BiPAP) and may reduce the need for intubation ( 2). Initial Settings In most cases, mechanical ventilation is delivered using volume-cycled ventilators. Several parameters should be set on the ventilator after intubation, including the mode of ventilation, tidal volume, FIO 2, ventilatory rate, PEEP, I:E ratio (the ratio of the duration of inspiration to the duration of expiration), flow rate, and waveform (Table 1–2.3). In addition, various alarm limits should be set on the ventilator. A/C mode is the safest initial choice because it allows the patient to supplement preset mandatory ventilation with minimal respiratory effort. Tidal volumes of about 10 to 15 mL/kg are reasonable in most patients. Because in many critically ill patients a high degree of ventilation-perfusion mismatch is present with a varying degree of shunt, an FIO 2 of 100% should be used first. A rate of 10 to 12 breaths/min is recommended for most patients unless an unusually high minute ventilation is expected in a patient who is too weak or lethargic to trigger the assist mode of the ventilator. Flow rates of 40 to 80 L/min are commonly used, with 60 L/min a good starting point. Patients with high inspiratory demands clinically do better with high flow rates, which have been associated with a decrease in the inspiratory work of breathing. A flow rate of 40 L/min generally allows an I:E ratio of 1:3. This may need to be altered in patients with chronic obstructive lung disease and prolonged expiratory phase. A pressure alarm system usually set at 10 cm of water above the peak airway pressure, and another used to monitor the exhaled volume, which is usually set at 50 mL lower than the delivered tidal volume, should be set on the ventilator. Newer ventilators have other sophisticated alarm systems with which the physician should be familiar.

Table 1–2.3. Mechanical Ventilation: Initial Settings

Modification of Ventilator Settings The initial settings previously described are rules of thumb that allow the initiation of mechanical ventilation. This therapy, however, should be modulated according to the patient's response to assisted ventilation using the previously mentioned parameters. When treating respiratory failure, it is essential to avoid overcompensation because prolonged use of high oxygen concentrations may result in pulmonary oxygen toxicity and inappropriately high and sustained minute ventilation may precipitate pulmonary edema and cerebral vasoconstriction. In contrast, undercompensation delays the reversal of the physiologic impairment and causes hypoxemia, hypercarbia, or acidosis. This results in prolongation of hospitalization and predisposes to local and systemic complications. The parameters that need continuous monitoring and alteration include the FIO 2, the respiratory rate, the tidal volume, dead space, and PEEP or PSV, if used. Changes in the concentration of inhaled oxygen and the need for airway pressure support are determined by evaluation of the PO 2 while alterations in the respiratory rate and tidal volume are dictated by measuring the PCO2 and pH of arterial blood. In general, modification of PO 2 or oxygen saturation can be accomplished by altering the FIO 2 5% at a time, or changing the level of the PEEP or PS by 2 to 5 cm H 2O at a time. When PEEP values exceed 15-cm H2O, the physician should consider bilateral prophylactic chest tube insertion in anticipation of barotrauma. The PCO 2 and pH can be modified by altering the respiratory rate, usually by 2 breaths/min at a time, or the tidal volume by 50to 100-mL increments. Patients with chronic obstructive lung disease may benefit from prolongation of the expiratory phase (I:E ratio < 1:3) and from adding dead space at 50-mL increments. It is recommended that only one parameter be changed at a time and that arterial blood gases be checked within 30 minutes of any alteration. In patients with chronic obstructive lung disease, a waiting period of 1 hour is recommended before arterial blood gases are checked. Although these are useful rules of thumb, different patients require individual attention and ventilator changes should be tailored to their specific needs. Care of the Ventilated Patient Most patients requiring mechanical ventilation should be admitted for observation and management in an intensive care setting. Occasionally, however, the intubated patient may spend a short time in the emergency department while awaiting the availability of a monitored bed. In such instances, basic airway care has to be provided in the holding area. The intubated patient is incapacitated by bypassing the upper airways. The resultant loss of humidification and gag and cough reflexes predisposes the patient to retention of secretions, atelectasis, and nosocomial pneumonias. These can be ameliorated by frequent suctioning under sterile conditions. Before suctioning, oxygenation should be optimized through the use of higher FIO 2 or larger tidal volumes for a few breaths. Patients on PEEP can be suctioned without compromising airway pressure by the use of a connector with a self-sealing orifice. The procedure should be sterile, the catheter passed quickly through the endotracheal tube with suctioning applied only on the way out from the airway. The instillation of 5 to 10 mL of normal saline into the trachea improves the results of suctioning. Although some patients with thick and viscous secretions may benefit from the instillation of intratracheal N-acetylcysteine (2%), this should be reserved only for the extremely difficult patient. A key factor in preventing long-term complications of mechanical ventilation is ensuring proper inflation of the cuff of the endotracheal tube. Several methods can be used to evaluate cuff inflation such as the minimal leak technique in which the balloon is first inflated to provide a complete seal of the trachea. Subsequently, the balloon is gradually deflated by small decrements until an air leak is audible at the end of inspiration. Adding a small volume of air at this point results in full occlusion. Another technique requires actual measurement of cuff pressures using simple manometers. The limits of cuff pressure have been set at a level of 20 to 25 mm Hg, lower than the transcapillary pressure and allowing adequate mucosal perfusion. Complications of Mechanical Ventilation Many of the complications of mechanical ventilation are related to the presence of the endotracheal tube and were discussed previously ( Table 1–2.4). Other complications have been described and are summarized in Table 1–2.5.

Table 1–2.4. Complications of Endotracheal Intubation

Table 1–2.5. Complications of Mechanical Ventilation

LEGAL AND ETHICAL CONSIDERATIONS The advent of critical care medicine and the development of new and sophisticated techniques for airway and ventilator management have enabled physicians to alter the clinical course of patients in respiratory distress and prolong their lives. Unfortunately, these extraordinary techniques are occasionally used to prolong the lives of patients in chronic vegetative states who are not expected to recover and lead functional lives. Some patients may refuse such interventions on the basis of personal, religious, or social factors. It is, therefore, imperative for the physician to determine the need for the implementation and the potential benefits (or lack thereof) of these techniques and weigh these against the potential financial and psychologic harm that may be inflicted on the patient's family. Before initiating mechanical ventilation, the physician should document unequivocal evidence of an indication for mechanical ventilation. Frequently, a competent patient may have expressed a desire not to be maintained on artificial means to prolong life. Under these circumstances, the patient's will should be respected because it supersedes that of the next of kin or the physician. Initiation of mechanical ventilation could result in legal action and should not be attempted without a court order. More commonly, patients are considered for mechanical ventilation when the treating physician has established lack of potential benefit from such procedures. This situation may be encountered in comatose patients with no known written or verbal will whose relatives are unwilling or unable to make a determination on withholding life support. In these cases, it is the duty of the physician to educate the patient's family about the prognosis. Because making the decision to withhold life support may provoke guilt feelings, the physician should take the initiative and advise the patient's relatives about what is in the best interest of the patient. Such compassionate advice may mitigate the guilt feeling and help ambivalent individuals reach a final decision. If such a decision cannot be reached, the physician may obtain the opinions of two colleagues and the ethics committee in the hospital before obtaining a court order to withhold artificial ventilation. Because different regulations may apply in different states, the emergency department staff should be aware of the laws enforced in the particular area where they practice. References 1. Amato MB, Barbas CS, Medeiros DM, et al: Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998;338(6):347–354. 2. Poponick JM, Renston JP, Emerman CL: Successful use of nasal BiPAP in three patients previously requiring intubation and mechanical ventilation. J Emerg Med 1997;15(6):785–788.

Suggested Readings Ajian P, Tsai A, et al: Endotracheal intubation of pediatric patients paramedics. Ann Emerg Med 1989;18:489. Boysen PG, McGough E: Pressure-control and pressure-support ventilation: flow patterns, inspiratory time and gas distribution. Resp Care 1988;33:126. Carrero R, Wayne M: Chest trauma. Emerg Med Clin North Am 1989;7:389. Deem S, Bishop MJ: Evaluation and management of the difficult airway. Crit Care Clin 1995;11:1. Goldman JM: Hemoptysis: emergency assessment and management. Emerg Med Clin North Am 1989;7:325. Grum CM, Chauncey JB: Conventional mechanical ventilation. Clin Chest Med 1988;9:37. Kharasch M, Graff J: Emergency management of the airway. Crit Care Clin 1995;11:53. MacIntyre NR: New forms of mechanical ventilation in the adult. Clin Chest Med 1988;9:47. Morris IR: Functional anatomy of the upper airway. Emerg Med Clin North Am 1988;6:639. O'Connor BS, Vender JS: Oxygen therapy. Crit Care Clin 1995;11:67. Ovassapian A, Randel GI: The role of the fiberscope in the critically ill patient. Crit Care Clin 1995;11:29. Piotrowski JJ, Moore EE: Emergency department tracheostomy. Emerg Med Clin North Am 1988;6:737. Stone DJ, Gal TJ: Airway management. In: Miller, ed. Anesthesia. 4th ed. New York, 1994.

Chapter 2.1 Shock Principles and Practice of Emergency Medicine

CHAPTER 2 CARDIOVASCULAR SYSTEM FAILURE AND SHOCK

1 Shock Max Harry Weil and Eric C. Rackow Introduction Hemodynamic Mechanisms of Shock

INTRODUCTION Shock is a clinical syndrome characterized by protracted prostration, pallor, coolness and moistness of the skin, collapse of the superficial veins, alteration of mental status, and suppression of urine formation. The basic defect that underlies shock is a reduction in effective perfusion of tissues with decreased oxygen delivery to the capillary bed. The systolic arterial pressure is usually less than 90 mm Hg or has declined by more than 50 mm Hg from a previous hypertensive level. A “normal” blood pressure may reflect excessive vasoconstriction even when blood flow is critically reduced. Shock may be regarded as a hemodynamic defect of such severity that delivery of oxygen is not adequate to meet the metabolic needs of the tissues ( 1). Biochemical disturbances follow ischemic injury to tissues. These include the liberation of lysosomal enzymes, histamine, serotonin, kallikrein, and prostaglandins; alterations in blood clotting with consumption coagulopathies and disseminated intravascular coagulation; reduction in reticuloendothelial activity; and the release of protein breakdown products, especially uric acid, urea, and creatinine. Acidemia from an excess of these acids, as well as lactic and pyruvic acid, fatty acids, ketones, and amino acids, ensues. Signs of diffuse injury appear, including increases in serum transaminase and lactic dehydrogenase. Indocyanine green clearance by the liver is impaired, reflecting a decrease in hepatocellular function. When intracellular oxygen is critically reduced, mitochondrial function and the regeneration of high-energy phosphate compounds are impaired ( 2). Cellular membrane permeability is increased, and the sodium-potassium pump is damaged. Accordingly, intracellular potassium is reduced, sodium concentration is increased, and the cell swells. Intracellular acidosis and lysosomal lysis with release of lysosomal hydrolases initiate autodigestion of cell parenchyma with ultimate cell death (3). Impairment of aerobic metabolism triggers a less efficient anaerobic pathway of energy production with accumulation of lactic acid, which has been correlated with severity and survival ( 4,5,6,7 and 8) (Fig. 2–1.1).

Figure 2–1.1. The probability curve indicating the likelihood of survival based on a given value of arterial blood lactate in patients with circulatory shock. (Reproduced with permission from Weil MH, Afifi AA: Circulation 1970;41:989.)

We believe that the lactate concentration currently serves as the best single measurement of the presence and the severity of shock states ( 9).

HEMODYNAMIC MECHANISMS OF SHOCK The hemodynamic mechanisms of shock are best viewed in relationship to the functional components of the cardiovascular system. The first component is the total volume of blood contained within the vascular compartment. The second component is the heart, which serves as the pump providing hydraulic power for circulation. The third component is the resistance circuit, which includes arteries and arterioles, through which blood travels to the capillary exchange beds. The fourth component is the capillary bed, which is the site of nutrient exchange and fluid filtration between the intravascular and interstitial fluid compartments. Blood flow and fluid filtration through these capillary beds are regulated by humoral and neurogenic controls on the precapillary arterioles and postcapillary venules. The postcapillary venules are the fifth component, serving as a site for venous pooling. The sixth component is the venous capacitance bed, which is the primary storage reservoir, accommodating up to 80% of the total blood volume. Changes in venous capacitance serve to increase or decrease the circulating blood volume and, therefore, the preload, which may be represented as the venous return of blood to the heart. The metarterioles are the seventh component. These vessels bridge the resistance vessels and the postcapillary venous beds, bypassing the capillary circuit, and serve as “shunts.” The mainstream channels are the eighth component, conducting blood to and from the heart. Hemodynamic mechanisms of shock are related to the dysfunction of one or more components of the system (Table 2–1.1).

Table 2–1.1. Hemodynamic Mechanisms of Shock

Although a single hemodynamic abnormality may initiate the low-flow state, the progression of shock is typically related to the combined effect of several causes. For instance, a critical reduction in intravascular volume accounts for hypovolemic shock, but progression of the shock state is also related to increased arterial and venular resistance, venous pooling, cardiac failure, and intravascular coagulation with vascular obstruction. In cardiogenic shock, factors that may account for the progression of shock include hypovolemia, distributive defects associated with increased arteriolar and venular resistance, and even obstructive defects from thrombosis and embolization. Circulatory competence and oxygen delivery to the tissues is maintained by an integrated functioning of the cardiovascular system, including ( 10) the heart, which serves as a pump; (11) the arterial tree, as the resistance bed, which serves as the conduit that delivers blood to the capillaries through which metabolites are exchanged; (12) the low-pressure veins as the return system, which also serves as the capacitance bed; and ( 13) the blood volume. Shock is classified as: (a) hypovolemic, (b) cardiogenic, (c) obstructive, (d) or distributive ( Table 2–1.2). The primary defect underlying all acute circulatory failure is reduction of effective blood flow with inadequate tissue perfusion. Lactic acid accumulates because of anaerobic metabolism and can provide a quantitative measure of perfusion failure and oxygen deficit. Pulmonary hydrostatic pressure and colloid osmotic pressure are important in the production of pulmonary edema. When caused by left ventricular failure, pulmonary edema represents a form of shock that may even require fluid repletion to restore the effectiveness of inotropic and vasodilator drugs.

Table 2–1.2. Classification of Shock

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Rackow EC, Astiz ME, Weil MH: Cellular oxygen metabolism during sepsis and shock. The relationship of oxygen consumption to oxygen delivery. JAMA 1988;259:1988. Crowell JW, Smith EE: O 2 deficit and irreversible hemorrhagic shock. Am J Physiol 1964;206:313. DeDuve C, Wattiaux R: Function of lysosomes. Annu Rev Physiol 1966;28:435. Afifi KA, Chang PC, Liu VY, et al: Prognostic indices in acute myocardial infarction complicated by shock. Am J Cardiol 1974;33:826. Schweizer O, Howland WS: Prognostic significance of high lactate levels. Anesth Analg 1968;47:363. Blair E, Cowley RA, Tait MK: Refractory septic shock in man: role of lactate and pyruvate metabolism and acid-base balance in prognosis. Am Surg 1965;31:537. Peretz DI, McGregor M, Dosseter JB: Lactic acidosis: a clinically significant aspect of shock. Can Med Assoc J 1964;90:673. Broder G, Weil MH: Excess lactate: an index of reversibility of shock in human patients. Science 1964;143:1457. Henning RJ, Wiener F, Weil MH: Blood lactate as a prognostic indicator of survival. Circ Shock 1982;9:307. Braunwald E, Swan HJC. Cooperative study on cardiac catheterization. Circulation 1968;37:27. Chien S. Role of the sympathetic nervous system in hemorrhage. Physiol Rev 1967;47:214. Rothe CF: Reflex control of the veins and vascular capacitance. Physiol Rev 1983;63:1281. Rothe CF: Physiology of venous return. Arch Intern Med 1986;146:977.

Suggested Readings Peitzman AB, Billiar TR, Harbrecht BG, et al: Hemorrhagic shock. Curr Probl Surg 1995;32:925. Shoemaker WC, Peitzman AB, Bellamy R, et al: Resuscitation from severe hemorrhage. Crit Care Med 1996;24(2):312. Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med 1996;334:1448.

Chapter 2.2 Shock: Clinical Treatment Principles and Practice of Emergency Medicine

CHAPTER 2 CARDIOVASCULAR SYSTEM FAILURE AND SHOCK

2 Shock: Clinical Treatment George R. Schwartz* Hypovolemic Shock Specific Organ Involvement in Shock and Treatment to Reduce Ischemic Damage Prehospital Assessment and Stabilization Clinical Presentations of Shock Causes and Classification Hypovolemic Shock Cardiogenic Shock Septic Shock Obstructive Shock Anaphylactic Shock Initial Management of Shock Laboratory and Other Procedures Therapeutic Regimens Miscellaneous Treatments

HYPOVOLEMIC SHOCK Neurohumoral Responses The response to hypovolemic hypotension in an otherwise healthy person is reproducible ( Fig. 2–2.1). A fall in blood volume initiates increased activity from the carotid and aortic arch baroreceptors, and from mechanoreceptors within the right atrium. A neurohumoral response is initiated that includes increased sympathetic nervous system activity with direct cardiac stimulation and peripheral vasoconstriction, increased pituitary release of adrenocorticotropic hormone (ACTH) and antidiuretic hormone (ADH), increased adrenocortical release of epinephrine and cortisol, and increased renin-angiotensin-aldosterone secretion. The net effect is an integrated response to maintain blood pressure and blood volume. With severe hypovolemia, however, these compensatory mechanisms are ineffective and organ function deteriorates. Other hormones besides catecholamines have vasoactive properties and are released into the circulation during shock. Immune system factors producing inflammation are also released ( 1). The result alters myocardial function, clotting mechanisms, and increase inflammatory response to name just a few. A loss of more than 30% of plasma volume threatens immediate survival and elicits a profound body reaction as described previously.

Figure 2–2.1. Expected neurohumoral response to hypovolemia.

Causes of shock determine body response. For example, infarcted myocardium is largely unresponsive to adrenergic stimulation, and cardiac stimulation is thereby limited as an early compensatory mechanism during cardiogenic shock. Peripheral vasoconstriction, which may be useful during hypovolemic shock, can be counterproductive during cardiac shock, especially in the presence of an already weakened myocardium, by increasing cardiac afterload. Alternatively, during septic shock, peripheral vasoconstriction is often absent or ineffective, and myocardial dysfunction is the result of coronary hypoperfusion or circulating depressant factors.

SPECIFIC ORGAN INVOLVEMENT IN SHOCK AND TREATMENT TO REDUCE ISCHEMIC DAMAGE When coronary perfusion is compromised, as it is during systemic hypotension, especially with underlying coronary disease, cardiac function suffers. Myocardial depressant factors may also be present in some forms of shock (2,3), and cardiac output can be compromised by dysrhythmias caused by coronary ischemia, hypoxemia, adrenergic stimulation, drug toxicities, hypoxemia, or acidosis. In the absence of coronary stenosis, myocardial necrosis per se (as evidenced by release of the MB fraction of creatine kinase, troponin I, or electrocardiographic ST-segment elevation and Q wave development) is unusual in shock. Rather, unless shock is of cardiac origin, the heart usually plays a participatory role in which it is unable to compensate fully for arterial hypotension caused by hypovolemia, vasodilation, or other factors. Ordinarily, cerebral perfusion is kept relatively constant over a wide range of perfusion pressures. Eventually, however, cerebral perfusion decreases if perfusion pressure falls below about 60 to 70 mm Hg. Brain function can also be significantly affected by regional decreases in perfusion imposed by underlying cerebrovascular disease. Renal Function and Tubular Necrosis Oliguria is a cardinal manifestation of shock. In fact, the diagnosis should be seriously questioned if oliguria is not present. Nevertheless, the pathogenesis of shock-related oliguria is complex. It is not simply caused by renal hypoperfusion. Reduced cardiac output, sympathetic stimulation, circulating catecholamines, angiotensin, and locally produced prostaglandins all contribute to renal afferent arteriolar vasoconstriction and to the redistribution of blood flow away from cortical glomeruli toward the medulla. The net effect of these changes is a decrease in glomerular filtration rate. These reflex responses, all of which cause oliguria can also be altered by therapy (e.g., the use of vasoconstricting catecholamines) and by injury to the nephron. Three pathologic changes are frequently observed: tubular necrosis with back-diffusion of glomerular infiltrate, tubular obstruction by casts or other cellular debris, and tubular epithelial damage with consequent interstitial edema and tubular collapse. This mixture of reflex responses and primary ischemic damage may explain the variable response to therapy for oliguria. When afferent arteriolar vasoconstriction predominates, dopamine, in low doses, may help to preserve urine output by opposing vasoconstriction. As pathologic changes occur, intravascular volume expansion combined with a loop diuretic or mannitol may diminish tubular obstruction by maintaining urine flow. Once obstruction or tubular necrosis is present, treatment becomes basically conservative, supported by dialysis, while cellular repair and recovery take place. Urine that is produced during shock often reflects these pathophysiologic changes in the kidney. When reflex vasoconstricting mechanisms predominate (hypovolemic and cardiogenic shock), the urine is largely free of salt and highly concentrated. In contrast, when ischemic damage is prominent, tubular function, salt retention, and urine osmolality decrease. Even so, urine chemistries are not highly specific, and caution must be used to avoid overinterpretation. Osmotic agents (e.g., mannitol or diuretics [furosemide]) have been used based on animal experiments showing protection against ischemic injury. While proof of outcome improvement is still lacking

we suggest the use of osmotic agents to increase urine flow. Other Organ Systems: Heart, Lungs, Liver, Gut Other organ systems are affected by shock. Pulmonary edema is common during shock, and may be the result of cardiac failure, overly aggressive intravascular volume expansion, or increased pulmonary vascular permeability ( 4). With hepatic ischemia (“shock liver”), characteristic enzymes (serum glutamic-oxaloacetic transaminase [ALT] and serum glutamic-pyruvate transaminase [AST]) are released. Occasionally, an obstructive picture with elevated bilirubin and alkaline phosphatase predominates. Ischemic injury to the gut is manifested primarily by interstitial fluid sequestration, hemorrhage, or necrosis of the mucosal lining. Ulcer formation with exsanguinating hemorrhage can occur, often several days after normal hemodynamic function has been restored. The ischemic lesions that develop in the gut usually are most prominent in the stomach, with the rest of the gastrointestinal tract less frequently affected. Breakdown of the gut epithelium also creates a portal for entry of bacteria or other deleterious bacterial products.

PREHOSPITAL ASSESSMENT AND STABILIZATION The most important obligation of field personnel is to recognize that shock or a preshock state is present. Invariably, this assessment begins with accurate vital signs. A combination of systolic blood pressure less than 90 mm Hg, combined with either bradycardia or tachycardia and an altered mental status, should be considered shock until proven otherwise. Although virtually all patients in shock have an impaired level of consciousness, in preshock states these changes can be subtle. When shock is associated with peripheral vasoconstriction, the skin will feel cool and clammy, and capillary refill will be prolonged (>2 seconds). With fever or sepsis, this sign may not be present. With hypoxemia, cyanosis may be apparent, but only if sufficient reduced hemoglobin is present. Once shock is recognized, treatment depends greatly on severity and the underlying cause. Severity can best be judged in the field by the effects on cardiac and brain function. If mental status is reasonably normal and electrocardiographic manifestations of ischemia are absent, aggressive therapy can usually be deferred until arrival at the hospital. Otherwise, some form of resuscitation should be attempted immediately, if possible, as indicated by the most likely cause. Certain measures are relevant to any patient. 1. Ensure adequate gas exchange 2. All patients should receive supplemental oxygen. 3. Those in respiratory distress or with inadequate ventilatory effort should be intubated through the trachea, if possible or otherwise aided with ventilation until ED arrival. 4. Venous access should be attempted. Place one or two large-bore (18 gauge or larger) peripheral intravenous catheters if transport will not be delayed. If cardiogenic shock can be excluded with confidence (for instance, when trauma or hemorrhage is the obvious cause), start intravenous fluids, especially if the neck veins are flat. A balanced isotonic salt solution should be infused at a rapid rate. A current controversy involves whether rapid infusions may increase bleeding (4A). After arrival in the emergency department, these rates can be adjusted as appropriate. The patient should be kept warm with blankets, especially if ambient temperatures are low or the patient is shivering. Obviously, gross external hemorrhage should be stopped if possible. The time spent in the field, however, should be kept to a minimum. Do not persist in prolonged unsuccessful attempts at intubation or intravenous catheterization. Usually two or three attempts at either procedure determine the likely feasibility of additional effort.

CLINICAL PRESENTATIONS OF SHOCK Because perfusion is directly related to pressure, a fall in systemic blood pressure is a cardinal manifestation of shock ( Table 2–2.1). Changes in regional vascular resistance can, however, compensate for modest decreases in perfusion pressure, thereby maintaining perfusion to vital organs. Thus, a fall in arterial pressure can be a harbinger of potential shock, as well as a common manifestation of shock itself, but a “normal” blood pressure is still possible during the early phases of compensated shock (“preshock”). Indeed arterial hypotension can often be treated before vital organ dysfunction is clinically obvious. This presumably prevents irreversible organ dysfunction or at least ameliorates its severity.

Table 2–2.1. Distinguishing Clinical Features in the Initial Presentation of Shock

An accurate blood pressure is necessary when treatment is initiated, especially to avoid false low readings. Peripheral vascular disease, tachycardia with a small pulse pressure, and irregular rhythms such as atrial fibrillation can cause the auscultatory blood pressure to be underestimated. Doppler devices often, but not always, improve pressure detection. Postural Changes in Blood Pressure Postural changes in blood pressure and heart rate can be helpful in detecting mild to moderate degrees of hypovolemia ( 5). Orthostasis normally causes the systolic pressure to decrease slightly, the diastolic pressure to increase or stay unchanged, and the pulse rate to increase by less than 10 to 20 beats per minute. With hypovolemia, a fall in diastolic blood pressure greater than 15 to 20 mm Hg when the patient is sitting or standing is almost always abnormal, especially if accompanied by an increase in pulse rate greater than 20 to 30 beats per minute. Significant dizziness or lightheadedness on sitting or standing, even in the absence of significant pulse and blood pressure changes, is still consistent with hypovolemia, because some patients maintain blood pressure at the expense of cardiac output. Changes in systolic blood pressure are more variable and thus less helpful in evaluating orthostasis. In contrast, dangerous hypovolemia is essentially excluded if significant dizziness or changes in blood pressure or pulse fail to occur on the patient's assuming the standing position. Shock Affecting Brain, Heart, and Kidney The brain, heart, and kidneys are the vital organs most often affected by shock. Therefore, reducing the effect of shock on these organs is the key to treatment. The severity of organ dysfunction and clinical presentation, however, varies with previous levels of organ function, compensatory mechanisms, and cause. The most common clinical manifestation of cerebral dysfunction is an acute change in mental state, varying from mild changes in mental acuity to frank coma. Focal neurologic deficits are not expected. When they are present, an associated primary neurologic problem should be assumed. The most common presentation of cardiac dysfunction is tachycardia. The pulse is frequently “thready,” indicating a low cardiac stroke volume. With coronary ischemia, more complex rhythm disturbances may occur, and these can also impair cardiac function. As the heart fails, left ventricular end-diastolic pressure rises,

ultimately causing pulmonary edema and respiratory failure. The most common clinical symptoms of coronary hypoperfusion are chest pain and dyspnea; physical signs include the appearance of a dyskinetic apical cardiac impulse, a new third or fourth heart sound, a new murmur of mitral regurgitation (representing papillary muscle dysfunction), and pulmonary crackles. Electrocardiographic signs (ST-T wave changes) of myocardial ischemia can also be expected. Occasionally, shock can result from mitral valvular dysfunction or papillary muscle rupture ( 6). Skin Changes When the skin is poorly perfused, its temperature falls and its color changes. Often skin color is pale and dusky, representing oligemia and venous pooling of blood desaturated of oxygen. With concomitant hypoxemia, frank cyanosis can be present. Sympathetic nervous system stimulation, a compensation for hypotension, causes sweat gland hypersecretion. The result is the frequently observed cool, clammy skin of shock. In addition, other skin manifestations can occur. For instance, diffuse erythroderma in a menstruating woman suggests the toxic shock syndrome. Cellulitis, erysipelas, or fasciitis may be both the cause or result of sepsis. Urticaria or angioneurotic edema may signify anaphylactic shock. The presence of petechial hemorrhages or ecchymoses may indicate disseminated intravascular coagulation (DIC) or, more rarely, meningococcemia. Embolic lesions may indicate endocarditis. Pulmonary dysfunction is common and usually represents pulmonary edema from either increased hydrostatic pressures (e.g., cardiac shock) or increased vascular permeability (e.g., septic shock). During anaphylactic shock, upper airway obstruction may result from swelling of the tongue or larynx (manifested by stridor) and lower airway obstruction from bronchospasm (manifested by wheezing). Wheezing can also occur in pulmonary edema. Liver failure is occasionally prominent, as evidenced by either hyperbilirubinemia or the release of liver enzymes. When shock is caused by infection hyperglycemia and fever are usually present; paradoxically, hypothermia can also occur. Metabolic (lactic) acidosis is caused by tissue hypoxia and anaerobic metabolism, often complicated by hepatic dysfunction and inadequate lactate metabolism. The severity of acidosis varies greatly and is poorly correlated with outcome when all forms of shock are considered. In summary, confusion, tachycardia, arterial hypotension, and oliguria are the most common early manifestations of brain, cardiac, and kidney dysfunction, respectively, during shock. More severe degrees of shock result in coma, myocardial ischemia, and pulmonary edema. Metabolic acidosis and arterial hypotension are frequent, especially when shock is severe, but are not prerequisites for diagnosis. Other physical signs depend on the underlying cause, the level of organ function before the onset of shock, and the effectiveness of compensatory mechanisms.

CAUSES AND CLASSIFICATION A useful way to classify shock (Table 2–2.2) is by the primary cause of the circulatory disturbance producing arterial hypotension and the effects ( Table 2–2.3). Many cases of shock overlap more than one category. In other cases, the circulatory disturbance is complex, uncertain, or unknown. This outline is a variant of the terms hypovolemic, cardiogenic, obstructive, or distributive.

Table 2–2.2. Classification of Shock

Table 2–2.3. Some Common Hemodynamic Patterns in Shock

HYPOVOLEMIC SHOCK Hypovolemic shock produces the prototypical hemodynamic picture of shock. It is characterized by marked decreases in cardiac filling pressures and a consequent decrease in stroke volume. Cardiac output is partially maintained by a compensatory tachycardia. Reflex increases in peripheral vascular resistance and myocardial contractility initially maintain perfusion to the brain and heart. When blood loss exceeds 20 to 25% of the intravascular volume (about 1 L), however, these compensatory mechanisms are no longer effective. The decrease in cardiac output causes decreased oxygen transport to peripheral tissues. The arteriovenous oxygen content difference widens as oxygen extraction increases, but eventually tissue hypoxia and lactic acidosis supervene. Treatment must focus on restoring volume, red cells, and perfusion.

CARDIOGENIC SHOCK Cardiogenic shock occurs if more than 40% of the left ventricle is involved in acute infarction ( 7). Clinically, signs of peripheral vasoconstriction are prominent, pulmonary congestion is frequent, and oliguria is virtually always present. The complications of myocardial infarction also produce characteristic signs. Cardiac rupture into the pericardial sac can produce classic signs of tamponade. Septal rupture can produce the classic murmur and thrill of a ventricular septal defect. Papillary muscle or chordae tendineae rupture can produce fulminant mitral regurgitation and pulmonary edema. Emergency echocardiography can confirm poor left ventricular function and can help exclude surgically correctable mechanical lesions, which may be contributing to the picture of shock ( 6). Thrombyolytics are useful if myocardial infarction is the cause. Various bypass adjuncts are experimental. Medications to improve heart failure are not usually effective. Mortality is still high, regardless of treatment. Right Ventricular Infarction and Shock An important variant of cardiogenic shock is that due to right ventricular (usually inferior wall) myocardial infarction, since treatment differs markedly from that indicated for left ventricular infarction ( 8). Clinically, the lungs are clear despite the presence of jugular venous distention. Occasionally, Kussmaul's sign (jugular

venous distention during inspiration) may be observed. Hemodynamic findings are variable, but frequently include elevated right atrial pressure compared with the wedge pressure, elevated right ventricular diastolic pressure, and decreased pulmonary artery pressure. The cardiac output is decreased and, not infrequently, equalization of vascular and ventricular end-diastolic pressures is present. In this case, pericardial tamponade must be excluded. Again, emergency echocardiography can help with this determination, while also demonstrating decreased right ventricular function. Left ventricular contractility may be normal or abnormal, depending on whether it is affected by ischemia, too. When right ventricular dysfunction is present, a pulmonary perfusion or ventilation perfusion scan may be necessary to exclude pulmonary embolus. With pulmonary embolization, however, pulmonary hypertension almost invariably accompanies shock. The main focus in treating hypotension accompanying right ventricular infarction is to maintain right ventricular filling pressure and preload with intravascular volume expansion. Left ventricular filling pressure should be used along with measurements of cardiac output as an end point for further fluid administration. Because the dilated right ventricle may cause the septum to bulge into the left ventricle and, therefore, change left ventricular diastolic compliance (“ventricular interdependence”), however, little change in cardiac output may occur despite an increase in the pulmonary artery wedge pressure. If volume infusion is not sufficient to restore hemodynamic function to normal, inotropic therapy should be used. The inotropic agents of choice, such as dobutamine or dopamine, do not increase pulmonary vascular resistance.

SEPTIC SHOCK Septic shock is caused by the presence of infectious agents or their products in the blood stream. Gram-negative organisms are responsible for the majority of cases. Gram-positive bacteria, fungi, and viruses, however, are all capable of producing a clinical syndrome indistinguishable from that due to Gram-negative bacteria. A useful definition of septic shock is: sepsis-induced hypotension despite adequate fluid challenge with systolic blood pressure less than 90 mm Hg or reduction of more than 40 mm from baseline along with organ perfusion abnormalities ( 9,10). Sepsis and septic shock are not identical. Sepsis is best considered as the host response to bacteremia, endotoxemia, or other byproducts of bacteria in the blood. This host response is characterized by clinical features such as fever, tachycardia, tachypnea, and respiratory alkalosis. Metabolic abnormalities (e.g., both hypoglycemia and hyperglycemia, as well as acidosis and hypocalcemia) are also common in sepsis ( 6). Bacteremia or a localized infectious site (e.g., an abscess) are common, but toxic shock syndrome may not demonstrate source (11,12,13 and 14), although careful search is usually rewarding. Beware of unusual causes such as postsplenectomy sepsis, sepsis in sickle cell disease patients and pseudomonas sepsis with or without the skin changes of ecthyma gangrenosum (usually teeming with bacteria). Meningococcal sepsis is particularly aggressive and requires rapid treatment. Septic shock is often described, in its initial phases, as a hyperdynamic state with a high cardiac output, normal to low cardiac filling pressures, and decreased systemic vascular resistance (15,16). Indeed, a hyperdynamic circulation in a patient with shock is sufficiently characteristic of sepsis in which an empirical broad spectrum antibiotic therapy should be immediately initiated along with fluid resuscitation and occult sources of infection excluded. Occasionally, a hyperdynamic picture is associated with other causes of shock, including severe hepatic dysfunction, hyperthyroidism, and trauma. In the terminal stages of septic shock, cardiac function deteriorates and the hemodynamic pattern often resembles that of cardiogenic shock ( 17). Even when cardiac output is elevated during septic shock, cardiac function and peripheral perfusion are still abnormal ( 2,3,18,19). Abnormalities in systolic function are characterized by decreases in stroke volume and ejection fraction. Experimentally, abnormalities in myocardial contractility have been demonstrated. These abnormalities may be caused by the presence of “myocardial depressant factors,” or coronary ischemia. Because contractility may sometimes be abnormal, increasing preload (e.g., with intravascular volume expansion) may not always increase stroke volume but may instead exacerbate pulmonary edema. Abnormalities in ventricular compliance (diastolic dysfunction) also occur in septic shock. A significant decrease in systemic vascular resistance, often out of proportion to any increase in cardiac output, is common in septic shock and may be responsible for refractory hypotension in many patients. In general, in most forms of shock, tissue oxygen consumption remains independent of oxygen delivery as tissue oxygen extraction increases. In septic shock, however, oxygen consumption appears to be directly proportional to oxygen delivery. The clinical implications of this oft-repeated finding, however, are still uncertain.

OBSTRUCTIVE SHOCK Several causes of shock present with signs of elevated right-sided cardiac filling pressures but no evidence of pulmonary edema, suggesting normal left-sided filling pressures. These include right ventricular infarction (see previous description), pulmonary embolus, tamponade, and tension pneumothorax. Pulmonary embolus is usually characterized by the sudden onset of chest pain, tachypnea, tachycardia, elevated jugular venous pressure, hypoxia, and at times hemoptysis. In severe cases, pulmonary artery obstruction results in pulmonary hypertension and even acute right heart failure. In patients with otherwise normal cardiopulmonary systems, shock caused by pulmonary emboli only occurs when at least 60 to 75% of the pulmonary circulation is obstructed. With underlying cardiopulmonary disease, lesser degrees of obstruction can cause shock. Cardiac tamponade can occur acutely as the result of blunt or penetrating trauma, or develop chronically in a more subtle fashion, as the result of pericarditis, renal failure, or a malignant pericardial effusion. Symptoms depend largely on the primary disease process. With chest trauma, acute cardiac tamponade is suspected in any patient who presents with Beck's triad: elevated neck veins, shock, and muffled or distant heart sounds. In the more chronic evolution of cardiac tamponade, a frequently present sign is pulsus paradoxus. The patient also develops symptoms of right heart failure with peripheral edema, dyspnea, venous congestion, and tachycardia. The chest radiograph demonstrates cardiomegaly with a widened transverse diameter and a globular appearance of the cardiac silhouette. An echocardiogram confirms the diagnosis of pericardial effusion and can suggest the possibility of hemodynamic embarrassment. Periocardiocentesis is the required treatment. Tension pneumothorax (often associated with assisted ventilation) can also cause shock with distended neck veins. In tension pneumothorax, however, there are no breath sounds on the affected side, and the mediastinum is shifted, with displacement of the trachea away from that side. Tension pneumothorax causes shock by decreasing blood return to the right heart. Treatment can range from rapid needle decompression to tube thoracostomy.

ANAPHYLACTIC SHOCK Anaphylactic shock can occur when a previously sensitized individual is exposed to a specific antigen. Atopic persons are particularly at risk. Parenterally administered drugs, especially penicillins, cephalosporins, and iodinated contrast media, are common offenders. The hemodynamic manifestations of anaphylactic shock include decreased blood pressure, cardiac output, preload (primarily from venodilation), and occasionally systemic vascular resistance. The latter may not be apparent until after fluid resuscitation. When systemic vascular resistance is decreased, the hemodynamic picture may be confused with sepsis. The cause is unclear, but is usually attributed to vasoactive mediators. In contrast to other forms of hypovolemic shock, vasodilation produces warm skin, and increased permeability produces peripheral edema. Rapid reversal requires adrenaline, fluid support, corticosteroids, and antihistamines.

INITIAL MANAGEMENT OF SHOCK Most patients with fully developed shock require tracheal intubation and mechanical ventilatory support, even if acute respiratory failure per se (diagnosed with arterial blood gases) is not yet present. Tracheal intubation is also indicated if mental status changes makes protection of the airway uncertain, or if inadequate respiratory compensation for a metabolic acidosis is life-threatening ( Fig. 2–2.2).

Figure 2–2.2. Clinical algorithm for the initial approach to the presentation of a patient with possible shock. (Reprinted with permission from Emergency Decisions, Physicians World Communications Group, 1987;3(87):32–43.)

Theoretically, tilting a patient into the head-down (Trendelenburg) position diverts blood volume into the central circulation, increasing cardiac filling and augmenting stroke volume. Recent studies, however, have failed to demonstrate significant redistribution of blood volume centrally. For this reason, and because the head-down position can cause worsened gas exchange and even worsened cardiac function, use of the Trendelenburg position in the emergency management of shock can no longer be routinely recommended. If any such measure is desirable, it is sufficient to simply raise the patient's legs above the level of the heart. When blood pressure requires immediate treatment ( Fig. 2–2.3), one must choose either a vasopressor agent (e.g., levarterenol, dopamine) or intravascular volume expansion (with blood, blood substitutes such as albumin-containing solutions or hetastarch, or isotonic crystalloid solutions). Often, a combination of a vasopressor with a trial of volume expansion is appropriate. The consequences of inadequate cerebral and coronary perfusion are potentially so disastrous that every effort must be made to rapidly restore perfusion pressure to at least 90 mm Hg systolic or 60 mm Hg mean. This goal can be achieved rapidly with a vasopressor, even if shock is caused by hemorrhage, as long as fluids are also given simultaneously. Although vasoactive agents are least effective when intravascular volume is depleted, their use can be justified by the lethal consequences of prolonged systemic arterial hypotension, namely, irreversible cerebral and cardiac injury. Levarterenol is the best initial choice for raising blood pressure. Subsequently, every attempt must be made to rapidly decrease the infusion rate of the vasopressor, to switch to a lower (and less vasoconstrictive) effective dose of dopamine, or to discontinue vasoactive agents altogether ( 20).

Figure 2–2.3. Clinical algorithm for the initial approach to the presentation of a patient with possible shock. (Reprinted with permission from Emergency Decisions, Physicians World Communications Group, 1987;3(87):32–43.

With noncardiogenic forms of shock, especially in the absence of pulmonary edema, intravascular volume expansion should be attempted. The actual choice of fluid frequently represents a compromise between what is readily available and what is required, based on estimated or observed losses. If blood is the obvious choice for hemorrhage, but is not immediately available, a blood substitute or isotonic crystalloid solutions should be given initially. The outcome from shock is probably not affected by the type of solution given during the first hours of resuscitation. On the other hand, the rate of administration can critically affect outcome. If it is too slow, arterial hypotension or vasopressor use is unnecessarily prolonged; if too fast, the risk of pulmonary edema increases rapidly. No arbitrary formula should be adhered to dogmatically, but a reasonable approach is to administer 500 to 750 mL of a blood substitute or 2000 mL of a crystalloid solution (normal saline or Ringer's lactate) during the first hour (not counting ongoing losses). In hemorrhagic shock, even more rapid administration may be necessary such as a rapid 500 mL bolus (the “ATLS” challenge). Blood losses can also be occult (e.g., from internal bleeding after trauma or leaking aortic aneurysm). Blood administration may be used to supplement fluid administration in other forms of shock when anemia is present. At all times, the rate of administration should be adjusted frequently, using changes in blood pressure, urine output, or evidence of emerging pulmonary edema as important clinical end points. Additional fluid administration is dictated by the clinical response to this initial fluid challenge, or eventually by new information from hemodynamic monitoring ( 21). After this initial period, during which maintenance of a minimally acceptable mean systemic blood pressure, organ perfusion, and a trial of intravascular volume expansion are emphasized, attention must be directed toward acquiring additional data, defining the cause, and implementing appropriate further specific management.

LABORATORY AND OTHER PROCEDURES Initial laboratory investigations should include serum electrolytes, creatinine, and blood urea nitrogen; a complete blood count and differential; a platelet count, prothrombin time, and activated partial thromboplastin time; and, arterial blood gases if indicated by oximetry. Further cardiac enzymes should be taken if there is a chance of cardiogenic shock. A pregnancy test should be performed in all women of childbearing age. An electrocardiogram and chest radiograph are always indicated. Other studies (e.g., cultures, additional radiographic studies) depend on the circumstances and likely diagnosis. Monitoring the patient in shock initially includes noninvasive determination of vital signs, pulse oximetry cardiac rhythm, and urinary output. Noninvasive monitoring are easy to apply, and are more useful in the emergency setting ( 13,13A). When hypotension is profound and/or unresponsive to initial resuscitative measures, invasive hemodynamic monitoring (arterial and pulmonary arterial catheterization) is indicated, but should be deferred until the patient has been admitted to an intensive care unit.

THERAPEUTIC REGIMENS Choice of Fluid for Volume Expansion The type of fluid to be administered is a matter of considerable controversy. Despite numerous studies, no consistent evidence indicates that any fluid regimen reliably affects outcome more favorably than any other, particularly if patients are closely monitored for improvement or complications of therapy. Thus, fluid replacement should include (although not necessarily be limited to) the kind of fluid being lost (e.g., blood or packed red cells in the case of hemorrhage, crystalloid solutions in the case of diarrhea or excessive diuretic therapy). Blood and colloid-containing solutions are more efficient and often more effective in rapidly expanding intravascular volume than are isotonic crystalloid solutions. Short-term use of blood or colloid-containing solutions is sensible for rapid expansion of intravascular volume (as is often the case in shock) when oxygen delivery is compromised ( 21A). In practice, patients for whom a trial of volume expansion is indicated should receive 1 to 2 L of isotonic crystalloid solution or 500 to 1000 mL of a colloid-containing solution (or equivalent), followed by blood transfusions if anemia or hemorrhage is present. Subsequently, colloid is rarely justified because of the expense and the risk of precipitating pulmonary edema. Additional fluid administration can be handled with any combination of blood and crystalloid solutions.

Serum albumin is available in 5 and 25% solutions. The former is the form usually used to expand volume. Albumin solutions are stabilized and heat-treated to kill hepatitis virus. Albumin has no deleterious effect upon hemostasis. RAPID USE OF BLOOD Typing and cross matching of blood cannot always be achieved before blood needs to be administered, especially if exsanguination is imminent. The best choice in this situation is type-specific blood, which is preferable to O negative (universal donor) blood because transfusing large amounts of type O blood can make subsequent typing and cross matching of the patient's blood difficult. However, if there is to be any delay in a hemorrhagic patient, it is better to use the O negative. If an additional 15 minutes are available, saline cross matching can be carried out in addition to typing. This permits determination of the Rh factor and detects strong antibodies of the minor blood groups (e.g., anti-Kell), avoiding severe reactions. With massive transfusion, a blood warmer can help protect the patient's core temperature and the heat-sensitive coagulation mechanism. A microwave oven or incubator can be used for this purpose with crystalloids (Ringer's lactate can be maintained at 40ºC in the emergency department). Blood, however, must be warmed using blood warmers. Two units of fresh frozen plasma and 3 to 4 units of platelets may be necessary after every 8 units of packed cells. Current practice requires administration only for demonstrated coagulopathy or laboratory confirmation. Calcium gluconate is rarely needed unless the infusion rate of blood is more than 75 to 100 mL/min for more than several units. Pharmacologic Support of Blood Pressure Levarterenol is the best choice in hemorrhagic shock, although dopamine and dobutamine are the most commonly used inotropic agents in the treatment of cardiogenic shock (22). Dopamine is an endogenous precursor of norepinephrine, and has multiple dose-related effects. At low doses, b 2 and dopaminergic effects are evident, and enhanced blood flow to renal and splanchnic beds is prominent. At higher doses, cardiac inotropy is seen; at still higher doses, vasoconstriction predominates. Dobutamine is a synthetic congener of isoproterenol with primarily b 1 (cardiac) but also b 2 (vasodilatory) stimulating properties. It has little independent vasoconstrictive or renal vasodilating effect ( Table 2–2.4).

Table 2–2.4. Suggested Indications and Dosages for Vasoactive Agents in the Treatment of Shock

When shock involves heart failure, dobutamine can often be used to advantage. Cardiac output is usually increased without marked increases in heart rate, and the pulmonary artery wedge pressure usually falls. A simultaneous infusion of low-dose dopamine (5.5 mEq/L) is the most important electrolyte disturbance of ARF, particularly in patients with oliguria. Because cardiac and skeletal muscle contractility and nerve conduction potentials are affected markedly by serum potassium levels, hyperkalemia can lead rapidly to cardiac arrhythmia and standstill. Hyperkalemia in ARF can be aggravated by tissue injury, infection, metabolic acidemia, hypoxemia, or hemolysis. Moreover, the adverse effects of hyperkalemia are enhanced in the presence of hypocalcemia and hypomagnesemia and the concomitant use of digitalis. When serum potassium exceeds 6 mEq/L after the correction of severe metabolic acidemia, sodium polystyrene sulfonate resin (Kayexalate) may be given as a high colonic retention enema. The resin may be given orally but is less effective. Each dose of 1 g/kg body weight in 70% sorbitol may reduce serum potassium by 1 mEq/L. It should be noted that this resin works by exchanging sodium for potassium, and repetitive use may contribute to salt retention and blood volume expansion. The administration of insulin and glucose (1 U insulin/5 g glucose) may be effective in managing hyperkalemia, but the volume of fluid required to administer such doses cannot be tolerated by most patients with ARF. Calcium gluconate (10% solution given at 0.5 mL/kg body weight per dose) can be a helpful adjunct in treating the patient with hyperkalemia because calcium reduces the risk for potassium-induced cardiac arrhythmias through direct stabilization of myocardial conduction. When plasma potassium falls below 3 mEq/L, particularly if the patient is administered digitalis, 20 to 40 mEq of potassium may be added to each liter of the intravenous solution. In addition, many patients with nonoliguric ARF may still secrete potassium into the distal tubules and, thus, are at less risk for hyperkalemia. These patients frequently require potassium replacement. Often, hypocalcemia is present early in the course of ARF and may result in, or potentiate, neuromuscular disturbances. Among the factors implicated as causes of hypocalcemia are hyperphosphatemia—particularly after severe muscle injury or neoplasm lysis—the use of oxalated blood products, lack of calcium intake, reduction in serum proteins, diminished renal activation of vitamin D, and increased clearance of 25-hydroxyvitamin D 3. Under many circumstances, little, if any, salt replacement is needed unless fluid losses through the skin (burns) or chest and nasogastric drains are excessive. When this occurs, replacement with 0.2 or 0.45 normal saline usually suffices. Metabolic acidemia can occur rapidly in ARF. This is directly attributable to an inadequate renal tubular excretion of titratable acids and to the impaired renal tubular recovery of bicarbonate due to diminished tubular availability of ammonia. The hypercatabolic state of the patient, the administration of oxalated blood, and the reduction in tissue perfusion may worsen metabolic acidemia. Improved nutrition may limit metabolic acidemia, by decreasing catabolism and tissue breakdown, by combating infections, and by restoring tissue perfusion. The correction of metabolic acidemia by alkali treatment should take place slowly; rapid correction may result

in seizures and other cerebral disturbances through alterations in the blood-brain acid-base equilibrium. Moreover, aggressive alkali therapy lowers serum-ionized calcium levels, diminishes oxygen unloading, and may contribute to tissue hypoxia. Sodium bicarbonate at a dose of 2 mEq/kg body weight is recommended as an intravenous bolus for a blood pH £7.1. Subsequent doses of sodium bicarbonate may be given to correct as much as half the total base deficit over the subsequent 12 to 24 hours, using the following formula: total body weight × 0.5 (distribution space of bicarbonate) × 0.5 base deficit

ANEMIA Anemia and bleeding diathesis are seen frequently and may occur early in the course of ARF. In most instances, there is no laboratory confirmation of disseminated intravascular coagulation, and it appears that these abnormalities are related to ARF, although satisfactory mechanisms explaining their pathogenesis are lacking. Superficial ecchymoses may be caused by increased vessel fragility found in subjects with azotemia or secondary to thrombocytopenia and platelet dysfunction. A deficient production of platelet factor III and decreased platelet adhesiveness have been demonstrated in azotemia. Anemia in patients with ARF must be corrected regardless of the cause. The level of hemoglobin needed varies with the specific illness and usually is dictated by the patient's level of hypoxemia and respiratory effort. More important, efforts should be directed at detecting and correcting specific abnormalities such as infection, disseminated intravascular coagulation, hepatic dysfunction, and blood loss from wounds. Vitamin K, platelets, and fresh frozen plasma may be given to treat specific situations. Erythropoietin (Epogen) has gained a useful role in stimulating blood production, but it is of no use in the ED.

GASTROINTESTINAL HEMORRHAGE The incidence of gastrointestinal hemorrhage in patients with ARF is in the range of 22 to 40%. In addition to the aforementioned coagulation difficulties, gastritis and ulcer formation occur frequently. Hyperchlorhydria is more common in postsurgical patients, in patients with head injury or serious trauma, and in most patients in stressful environments. Moreover, gastric acid production may be stimulated by circulating gastrin, the level of which is often raised in patients with renal failure. An aggressive antihistamine and antacid regimen should be used to reduce the acidity and volume of gastric secretions. A maximum intravenous dose of 5 mg/kg of cimetidine every 8 hours or 25 to 50 mg of ranitidine every 12 to 24 hours appears to be effective for this application. Aluminum-based antacids with a low sodium content such as magaldrate (Riopan) or aluminum hydroxide (Amphogel) also may be effective and should be used in place of preparations containing magnesium to avoid magnesium toxicity. Omeprazole, a specific inhibitor of gastric acid secretion, may be useful in certain patients at 20 mg per day.

INFECTION Infection occurs in 35 to 40% of patients with ARF, with the more serious infections contributing significantly to the already high morbidity and mortality rates. Common sites of infection include the lungs, urinary tract, wounds, peritoneum, and intravenous and other sites of catheterization. Factors that predispose patients to serious infections include the interruption of the integrity of the skin and mucosa by burns, surgical incisions, or pressure wounds; the use of indwelling catheters; the performance of invasive procedures; and the use of prophylactic antibiotics. Although chronic renal failure and chronic malnutrition, alone or together, may impair immunologic defenses and predispose a patient to infection, there are no data showing that humoral or cellular immunity are affected directly by the acute hypercatabolic state associated with ARF. Antibiotics usually should not be given prophylactically, even when Foley catheters are in place for prolonged periods of time. Antibiotics may be used, however, if an infection is strongly suspected on the basis of leukocytosis and/or a positive Gram-stain examination of serum buffy coat, urine, peritoneal fluid, or other drainage fluids. Blood, cerebrospinal fluid, and other cultures should be obtained before antibiotics are prescribed. As a general rule, a full loading dose of the antibiotic is given initially; thereafter, it is imperative to modify the dose based on the level of GFR and dialyzability of these drugs in patients with renal failure managed by dialysis (Table 49.18). Whenever possible, it is recommended that peak and through blood levels of specific medications be obtained to avoid drug toxicity while effectively treating the infection. Drug or dosages must be modified in patients with renal failure because of the effects of dialysis ( Fig. 49.1).

Table 49.18. Drug Therapy in Renal Failure

Figure 49.1. Pathogenesis of acute renal failure. According to this scheme, renal ischemia is the central event, but bidirectional arrows indicate important interaction among tubular obstruction, tubular injury, and renal ischemia in the development of renal insufficiency and oliguria. Renal ischemia may continue despite correction of prerenal events that initiated acute renal failure, owing to the persistence of tubular damage, tubular obstruction, or altered intrarenal hemodynamics. Undernutrition (not shown) may prolong the oliguric phase by contributing to hypoperfusion and delayed healing of damaged tissue. See text for evidence in support of these mechanisms. (Adapted with permission from Ellis D, Gartner JC, Galvis AG. Acute renal failure in infants and children: diagnosis, complications and treatment. Crit Care Med 1981;9:607.)

DIALYSIS MODALITIES IN ACUTE RENAL FAILURE If less invasive measures have failed to control many of the complications associated with ARF, the application of one of several dialytic modalities constitutes an important adjunct in its treatment. In the ICU or ED observation unit, there is usually ample time to observe the patient's clinical course and to involve the nephrologist

early in the care of the patient so that well-timed intervention with dialysis can be effected. Dialysis is most successful during the early stages of ARF, and it has been reported to reduce the incidence of gastrointestinal hemorrhage and of infection. This early or “prophylactic” dialysis is aimed at preventing, rather than treating, uremic complications such as central nervous system disturbances, gastrointestinal hemorrhage, and pericarditis, and at treating fluid overload and hyperkalemia, which are the two other major indications for dialysis. Though the value of early dialysis has not been established, patients who are dialyzed when the level of BUN is between 50 and 100 mg/dL appear to have a better overall prognosis than those treated at higher BUN levels.

PROGNOSIS OF ACUTE RENAL FAILURE The mortality rate associated with ARF ranges from 9 to 72%. The lower mortality rates are those found in ARF that complicate pregnancy; the higher rates are applicable to ARF associated with major trauma or surgery. In general, patients with nonoliguric ARF have better prognoses. The most important determinant of outcome in patients with ARF, however, is the course of the primary condition itself.

CHRONIC RENAL IMPAIRMENT A patient with chronic renal disease passes through four stages of progressive renal impairment. Initially, with the reduction of renal function from 100 to 50% of normal, there is a stage of decreased renal reserve. Excretory and regulatory functions of the kidney are well preserved, and symptoms are absent. With the reduction of renal function from 50 to 20% of normal, the stage of renal insufficiency supervenes. It is manifested by mild azotemia, impaired ability to concentrate the urine, and mild anemia. This stage is characterized chiefly by a marked loss of flexibility of renal homeostatic function. Major alterations in body fluid composition and symptomatology are absent except during times of unusual dietary or metabolic stress. The third stage of progressive renal disease is renal failure, which occurs when renal function is reduced from 20 to 5% of normal. This loss of function is sufficiently severe to cause alterations in the composition of body fluids with normal metabolic demands. Advancing anemia, hypocalcemia, hyperphosphatemia, metabolic acidosis, and isosthenuria are characteristically present. Although hyponatremia and hyperchloremia may occur at this stage, hyperkalemia is uncommon. The final stage of progressive renal disease is symptomatic uremia, which occurs when renal function is less than 5% of normal. At this stage, the failure of renal excretory function leads to retention of water and solutes, including a number of putative uremic toxins. Symptomatic uremia includes a constellation of symptoms most commonly referable to the gastrointestinal tract, cardiovascular system, central nervous system, skin, and hematopoietic systems (Table 49.19). The causes are myriad (Table 49.20).

Table 49.20. Causes of Chronic Renal Failure

CARDIOVASCULAR ABNORMALITIES Four major categories of cardiovascular abnormalities are seen in patients with chronic renal failure (CRF): pericardial disease, hypertension, myocardial dysfunction, and carbohydrate and lipid abnormalities associated with accelerated atherosclerosis. Echocardiographic studies have shown a 30 to 50% incidence of pericardial effusion in patients with CRF before the initiation of dialysis. The mechanism by which uremia causes pericardial disease is unknown; however, the pathology of pericardial inflammation is well described and consists of fibrinous exudative changes associated with a serous effusion. Though generally asymptomatic and clinically undetectable, such changes may produce acute symptomatic pericarditis, pericardial tamponade, or chronic pericardial constriction secondary to collagenization of the pericardial exudate. The symptoms of pericarditis and the development of hemodynamic compromise or tamponade depend on multiple factors that include the amount of fluid in the pericardium, the rate of accumulation of fluid, and the nature of the effusion (serous versus hemorrhagic). Intensive dialysis therapy may improve symptomatic pericarditis rapidly in the patient with uremia, and control of total body volume status appears to be important in the resolution or prevention of pericardial effusion in patients who are dialyzed. Before the initiation of specific treatment in any patient with uremia, it is critical to determine that the pericarditis has no other cause. Infectious, neoplastic, and autoimmune causes must be excluded. The major treatment for uremic pericarditis is initiation of dialysis therapy. The initial treatment of patients in whom pericarditis develops while they are on dialysis therapy is the intensification of such therapy or a change from hemodialysis to peritoneal dialysis. In patients with chest pain and systemic symptomatology (fever and malaise), symptomatic relief may be obtained with the use of indomethacin. In approximately 5% of patients with symptomatic uremic pericardial disease, the life-threatening complication of cardiac tamponade develops, and they will require more aggressive therapy. Tamponade is rare in patients with asymptomatic pericardial effusion. Acute tamponade is a medical emergency that may require acute pericardiocentesis. Because the effusion recurrence rate is high, even with repeat pericardiocentesis, the use of an indwelling pericardial catheter for drainage, with periodic instillation of nonabsorbable steroids, has been successful in controlling effusion. The definitive surgical approach for recurrent or intractable effusions or constrictive pericarditis is total pericardiectomy. More than 50% of patients with CRF have hypertension. In patients with underlying glomerular lesions or renal damage with systemic vasculitis, hypertension may be a prominent clinical feature, even with minimal decreases in GFR. The frequent association of hypertension with atherosclerosis, left ventricular dysfunction, and accelerated renal failure indicates its important contribution to the cardiovascular morbidity and mortality rates from CRF. Although many different mechanisms predispose the patient with CRF to hypertension, the major cause is volume overload. Additional factors, such as elevated plasma renin activity, an increase in sympathetically mediated vasoconstriction, and absence of renal-produced vasodepressor substances (such as prostaglandins and kinins) may be important factors contributing to hypertension in certain patients. Hypertension is associated strongly with cardiac and cerebrovascular disease, and aggressive therapy for hypertension is indicated in all patients. The treatment of hypertension reduces the cardiovascular morbidity and mortality rates in the general population, and an even greater salutary effect may be expected in patients with CRF already at major risk for death from cardiovascular disease. The specific drug therapy for hypertension in patients with CRF is similar to the treatment for hypertension in patients with normal renal function and will not be considered here in additional detail. Myocardial dysfunction occurs commonly in patients with CRF. The prevalence of left ventricular dysfunction assessed by echocardiography in such patients ranges from 25 to 40%. The increased cardiac workload of such patients is a function of increased preload secondary to fluid overload, increased afterload secondary to hypertension, and a high output state induced by anemia. In addition, hemodialysis patients with arteriovenous fistulas have an even greater demand on cardiac output. A chronic increase in cardiac workload leads to hypertrophy and to a permanent alteration of ventricular contractility and compliance. In any given patient, the uremic metabolic abnormalities of hyperkalemia, hypocalcemia, and acidemia may induce a state of negative inotropy and further diminish cardiac function. In addition to these factors, increased atherogenesis of the coronary arteries seen in the population with uremia may cause the increasing mismatch of myocardial oxygen delivery with myocardial oxygen demand and further compromise cardiac function. The net result of all these factors, in addition to putative uremic myocardial toxins, is an increased incidence of clinical congestive heart failure and ischemic heart disease in patients with CRF. The major goals in the management of myocardial dysfunction are to optimize afterload, preload, and heart rate and to improve overall cardiac contractility. Sodium restriction and diuresis or dialysis decrease both preload and afterload, and frequently improve ventricular performance. The control of blood pressure will decrease afterload and improve left ventricular function. If volume reduction is unsuccessful, inotropic agents may improve ventricular performance. In the acute situation, dopamine, dobutamine, or isoproterenol may increase myocardial contractility, decrease heart size, and increase cardiac output. Additional benefits may be obtained by using vasodilator therapy, which may further lower arteriolar resistance and afterload and increase cardiac output. The primary goal in the management of

symptomatic coronary artery disease is to maintain a balance between myocardial oxygen supply and demand. When hematocrit falls below 20%, the transfusion of packed red blood cells may provide additional benefits by increasing the oxygen-carrying capacity and decreasing the high output cardiac workload as long as significant volume expansion and hypertension are avoided. Despite control of these factors, many patients with CRF and coronary artery disease require further medical management. Chronic medication regimens of oral nitrates, nitroglycerin ointment, and b-blocking agents chronically decrease myocardial oxygen consumption. If significant angina persists despite adequate medical management, cardiac catheterization and subsequent coronary artery bypass surgery should be considered. A high prevalence of atherosclerotic cardiovascular disease has been noted in patients with CRF. In addition to the risk factors of hypertension, hyperparathyroidism, hyperuricemia, and abnormal carbohydrate metabolism, patients with CRF have significant abnormalities of lipoprotein metabolism.

NEUROLOGIC ABNORMALITIES IN RENAL FAILURE The neurologic disorders seen in patients with CRF include encephalopathy and neuropathy. As GFR falls below 10% of normal, early signs of uremic encephalopathy, which include malaise, apathy, and fatigue, become evident. Episodic and transient alterations in attention span become prominent and, as renal function decreases, become constant. Most patients show multiple defects in intellectual function that include abnormalities of short- and long-term memory and an overall clouding of consciousness. Tremor, most evident during the movement of limbs or the fixed extension of the hands, is an early and sensitive index of encephalopathy. Asterixis is a sensitive but nonspecific early indicator of progressive encephalopathy. With continuing renal deterioration, uremic delirium with delusional behavior and hallucinations may occur. Finally, stupor and coma with the motor manifestations of myoclonus and seizure activity supervene. Uremic seizures usually are generalized and are of the major motor type, although focal motor seizures may occur. Because seizures are relatively uncommon in other metabolic encephalopathies, the unusual mixture of signs of cerebral depression and excitation is distinctive of uremic encephalopathy. The pathogenesis of uremic encephalopathy remains unclear. Suspected uremic neurotoxins accumulate with progressive renal failure, and recent evidence suggests that such toxins may decrease cerebral glycolysis and metabolic rate, decrease brain cortical ATPase, and markedly alter the permeability of brain cell membranes. Pathologic findings include the degeneration of neurons with relative preservation of glial elements, which are preferentially located in the sensory nuclei of the brain stem, the reticular formation, and the cerebral cortex. Neuropathy occurs in most patients who have reached the stage of uremia. Uremic neuropathy is a distal symmetric mixed sensory-motor polyneuropathy that affects the lower limbs to a greater extent than the upper limbs. The severity, the prominence of either motor or sensory signs, and the rate of progression are variable. In many patients, peripheral nerve involvement in uremia is heralded by the restless leg syndrome. This syndrome consists of unpleasant creeping, crawling, and pruritic sensations deep in the muscles of the leg. Such sensations are worse in the evening and are relieved by movement of the limbs. The pathogenesis of uremic neuropathy, including the restless leg syndrome, is unclear. Pathologically, a primary axonal degeneration is followed by secondary segmental demyelination. Uremic encephalopathy and the sensory components of uremic neuropathy are reversible with adequate dialysis treatment. The motor components of uremic nephropathy appear to be largely irreversible; however, effective dialysis can prevent progression. From the clinical standpoint, the appearance of uremic neurologic abnormalities is an indication for regular dialysis therapy. The course of uremic neurologic disease is generally slow and progressive. Abrupt changes in neurologic status in a patient with slowly declining renal function should mandate a thorough evaluation for reversible metabolic or structural problems. Indeed, in clinical studies, the abrupt appearance of uremic convulsions has been associated with hyponatremia and other electrolyte imbalances. The anticonvulsant treatment of acute and chronic seizures in patients with uremia does not differ significantly from such management in patients without uremia. References 1. Silix DH, McDonald FD: Acute renal failure. Crit Care Clin 1987;5:909. 1A. DuBose TD, Warnock DG, Mehta RL, et al: Acute renal failure in the 21st century. Recommendations for management and outcomes assessment. Am J Kidney Dis 1997;29:793–799. 2. Goldstein MB: Acute renal failure. Med Clin North Am 1983;67:1325. 3. Gas PW, Iwatsuki S: Acute and chronic renal failure. Surg Clin North Am 1989;57:1263. 3A. Knuppel RA, Montenegro R, O'Brien WF: Acute renal failure in pregnancy. Clin Obstet Gynecol 1985;28:288. 3B. Engle WD: Evaluation of renal function and acute renal failure in the neonate. Pediatr Clin North Am 1986;33:129. 3C. Brezis M, Rosen S, Silva P, et al: Renal ischemia: a new perspective. Kidney Int 1984;26:375–383. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Pine RW, Wertz MJ, Lennard ES, et al: Determinants of organ malfunctions or death in patients with intra-abdominal sepsis: a discriminant analysis. Arch Surg 1983;118:242. Gaudio KM, Ardito TA, Reilly H, et al: Accelerated cellular recovery after an ischemic renal injury. Am J Pathol 1983;112:338. Myers BD, Moran SM: Hemodynamically mediated acute renal failure. N Engl J Med 1986;314:97. Olsen S, Solez K: Acute renal failure in man: pathogenesis in light of new morphological data. Clin Nephrol 1987;27:271. Parekh N, Esslinger H, Steinhausen M: Glomerular filtration and tubular reabsorption during anuria in post-ischemic acute renal failure. Kidney Int 1984;25:33. Olbricht CJ, Fink M, Gutjahr E: Alterations in lysosomal enzymes of the proximal tubule in gentamicin nephrotoxicity. Kidney Int 1991;39:639. Bennett WM: Aminoglycoside nephrotoxicity. Nephron 1983;35:73. Mela–Riker LM, Widener LL, Houghton DC, et al: Renal mitochondrial integrity during continuous gentamicin treatment. Biochem Pharmacol 1986;35:979. Clive DM, Stoff JS: Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1984;310:563. Kleinknecht D, Landais P, Goldfarb B: Analgesic and non-steroidal anti-inflammatory drug-associated acute renal failure: a prospective collaborative study. Clin Nephrol 1986;25:275.

13A. DeBroe ME, Elseviers MM: Analgesic nephropathy. N Engl J Med 1998;338:447–452. 14. Hou SH, Bushinsky DA, Wish JB, et al: Hospital-acquired renal insufficiency: a prospective study. Am J Med 1983;74:243. 14A. Barret B, Partly PS: Prevention of nephrotoxicity induced by contrast agents. N Engl J Med 1994;331:1449–1450. 14B. Solomon R, Werner C, Mann D, et al: Effects of saline mannitol and furosemide on acute decreases in renal function induced by radio-contrast agents. N Engl J Med 1994;331:1416–1430. 15. 16. 17. 18. 19. 20. 21.

Russell JD, Churchill DN: Calcium antagonists and acute renal failure. Am J Med 1989;87:306. Lieberthal W, Levinsky NG: Treatment of acute tubular necrosis. Semin Nephrol 1990;10:571. Livio M, Manucci P, Vigano G, et al: Conjugated estrogens for the management of bleeding associated with renal failure. N Engl J Med 1986;315:731. Hull RW, Hasbargen JA: No clinical evidence for protective effects of calcium-channel blockers against acute renal failure (letter). N Engl J Med 1985;313:1477. Letter. Zucchelli P, Zvccala A, Gaggi R: Calcium channel blockers: effects on progressive renal disease. Am J Kid Dis 1991;17 (Suppl 1):94. Zoja C, Perico N, Remvzzi G: Antiplatelet agents: effects on progressive renal disease. Am J Kid Dis 1991;17(Suppl 1):98. Allgren RL, Marbury TC, Rahman SN, et al: Anaritide in acute tubular necrosis. N Engl J Med 1997;336:828–834.

21A. Klahr S, Miller SB: Acute oliguria. N Engl J Med 1998;338:671–675. 21. Maxwell LG, Fivush BA, McLean RH: Renal failure. In: Rogers MC, ed. Textbook of pediatric intensive care. Baltimore: Williams & Wilkins, 1987:1001. 22. Schaer GL, Fink MP, Parrillo JE: Norepinephrine alone versus norepinephrine plus low-dose dopamine: enhanced renal blood flow with combination pressor therapy. Crit Care Med 1985;13:492. 23A. Denton MD, Chertow GM, Brady HR: “Renal-dose” dopamine for the treatment of acute renal failure: scientific rationale, experimental studies and clinical trials. Kidney Int 1996;50:4–14. 23B. Flanebaum E, Chopan PS, Dasta JF: Quantitative effects of low dose dopamine on urine output in oliguric SICU patients. Crit Care Med 1994;22:61–68. 24. Thadhani R, Pascual M, Bonventre JV: Medical progress: acute renal failure. N Engl J Med 1996;334:1448–1460. 25. Pascual J, Liano F, Ortuno J: The elderly patient with acute renal failure. J Am Soc Nephrol 1995;6:144–153. 26. Feest TG, Round A, Hamad S: Incidence of severe acute renal failure in adults: results of a community based study. Br Med J 1993;306:481–483.

27. 28. 29. 30. 31.

Rudnick MR, Goldfarb S, Wexler L, et al: Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: a randomized trial: the Iohexol Cooperative Study. Kidney Int 1995;47:254–261. Baldwin L, Henderson A, Hickman P: Effect of postoperative low-dose dopamine on renal function after elective major vascular surgery. Ann Intern Med 1994;120:744–747. Conger JD: Interventions in clinical acute renal failure: what are the data? Am J Kidney Dis 1995;26:565–576. Thompson BT, Cockrill BA: Renal-dose dopamine: a siren song? Lancet 1994;334:7–8. Humes HD: Application of cell and gene therapies in tissue engineering of renal replacement devices. In: Lanza RP, Langer R, Chick WL, eds. Principles of tissue engineering. New York: Academic Press, 1997:577.

31A. Forni LG, Hilton PJ: Current concepts: continuous hemofiltration in the treatment of acute renal failure. N Engl J Med 1997;336:1303–1311. 32. Sieberth HG, Mann H, eds. Continuous arteriovenous hemofiltration (CAVH). New York: Karger, 1985. 33. Houston MC: Pathophysiology, clinical aspects, and treatment of hypertensive crises. Prog Cardiovasc Dis 1989;32:99.

Suggested Readings Griffin KA, Bidani A: Guidelines for determining the causes of acute renal failure. J Critical Illness 1989;4:32. Grunfeld JP, Pertuiset N: Acute renal failure in pregnancy, 1987. Am J Kidney Dis 1987;9:359. Kuhn JA: Acute renal failure in the outpatient setting. Emerg Med Primary Care Physician 1986;13:169. Mathew A, Schrier R: Pharmacological therapy of acute renal failure: current practices and future horizons. IM Intern Med Specialist 1989;10:101.

CHAPTER 50 URINARY TRACT INFECTIONS, CYSTITIS, PYELONEPHRITIS Principles and Practice of Emergency Medicine

CHAPTER 50 URINARY TRACT INFECTIONS, CYSTITIS, PYELONEPHRITIS Mike Kozminski and George R. Schwartz Introduction Pathophysiology Localization of Infection of the Urinary Tract Clinical Presentation Laboratory and other Procedures Urine Culture Management and Indications for Hospital Admission Antibiotic Treatment Oral Agents for Urinary Tract Infections

INTRODUCTION Many patients come to the emergency department (ED) with irritative voiding complaints. Although the symptoms are not usually immediately life threatening, they can be signals of underlying disease. Patients with frequency, fever, urgency, dysuria, and pain require thorough urologic evaluation. It is important to ascertain the onset and duration of symptoms and their relationship to voiding patterns. A carefully obtained urinalysis is vital. Pyuria and bacteriuria may indicate inflammation and infection. If fever and flank pain are present, pyelonephritis, stone disease, and obstruction must be considered. If casts and proteinuria are found, nephrologic causes should be investigated. Any abnormalities noted on the ED evaluation should be followed up with a urologic referral. Differential diagnosis is given in Table 50.1.

Table 50.1. Differential Diagnosis of Urinary Symptoms

PATHOPHYSIOLOGY Urinary tract infections (UTI) usually are caused by Gram-negative organisms. Gram-negative bacteria have a natural reservoir source in the gastrointestinal tract flora. Certain of these bacteria have an efficient mechanism to attach to the adjacent vaginal epithelium. These bacteria, with greater adherence factors, multiply and invade the lower urinary tract ( 1). If the patient does not adequately empty the bladder, or if a nidus (i.e., stone, indwelling catheter) is present, the bacteria multiply and cause a symptomatic infection. Various underlying disease states are associated with an increased UTI frequency, including diabetes and sickle cell trait. More common in females, it is thought that sexual activity and pregnancy are important precipitating factors of UTI. Recent urologic instrumentation or catheterization also increases the risk of a urinary tract infection, as does use of a diaphragm with spermicide ( 2). Bacterial adherence to mucosal surfaces is important for colonization of the urinary tract and initiation of the infection, and studies suggest that women with susceptibility to UTI have an increased binding of the bacteria to epithelial surfaces ( 1). These women may have an increased number of cell surface receptors for specific bacterial adhesions. Deficiencies in the urethral lining layer, which prevents bacterial adherence, and a poorly emptying bladder increase the chances for a urinary tract infection ( 3). Certain cell surface antigens also may affect the bacterial adherence. Surface blood group antigens of women who are resistant to urinary tract infections have a greater secretor phenotype. These specific antigens may block adhesion sites on epithelial cells. Conversely, women without these surface antigens have been shown to have recurrent urinary tract infections ( 4). Persistent abnormalities in the vaginal bacterial flora may predispose to UTI ( 5). Once the infective organism is present in the lower urinary tract, the risk for upper tract infection increases. Most cases of pyelonephritis are secondary to the ascending spread of the pathogen; rarely does renal infection have a hematogenous source. Patients with vesicoureteral reflux, bladder outlet obstruction (e.g., prostatic hypertrophy), hypertonic bladder, or urinary reservoir may be at a higher risk for upper tract infection ( 1). These patients may have elevated reservoir pressures, deficient ureterovesical junctions, or both, that enable the ascent of bacteria. The pathophysiology of the urethral syndrome is less clear ( 6,7 and 8). This is a syndrome of exclusion. The symptoms suggest UTI; however, the urine specimen is sterile for aerobes and anaerobes. These irritative syndromes can result from such dietary supplements as aspartame (Nutrasweet) and some red dyes. The difficulty in separating these two groups of patients becomes clear because in 80% of women with acute UTI, the urine spontaneously clears within a few weeks of infection. The urine of a woman who was symptomatic for several days may become sterile by the time she arrives in the doctor's office or the ED. Gynecologic abnormalities such as cervical erosion, cervicitis, uterine prolapse, and vaginal discharge usually do not contribute to the urethral syndrome ( 7).

LOCALIZATION OF INFECTION OF THE URINARY TRACT Clinicians generally believe that infections of the lower urinary tract have less clinical significance than do infections of the renal unit itself. Most upper UTI start as ascending infections from the lower urinary tract. It is, therefore, important that a lower UTI be treated appropriately and aggressively to prevent any damage to the upper collecting system. Certain serologic and immunologic markers can be identified to help diagnose whether the infection is located in the upper or lower urinary tract. Antibody titers to certain Gram-negative organisms commonly associated with urinary tract infections may become elevated during episodes of pyelonephritis. Enzyme-linked immunosorbent assay testing for 0 antigens of the Enterobacteriaceae have been used for those studies. Measurement of immunoglobulin (IgM) and IgG antibodies follows the course of recurrent parenchymal infections. C-reactive protein and erythrocyte sedimentation rates may be elevated; however, these are less specific for episodes of pyelonephritis. With the bladder-washout method, antibody-coated bacteria may be identified in the urine. These specific immunoglobulins can be detected on the bacterial surfaces, which will reflect the presence of IgG-, IgA-, and IgM-antibody coatings. These particular antibodies may be in the urine of patients with cystitis; however, they usually do not coat the bacteria. If bacteria are coated with these antibody markers, it strongly suggests that the UTI is located in the renal unit. Evidence of a lower UTI or bacteriuria in a patient with vesicoureteral reflux is worrisome. Those patients should be followed closely to make sure they do not have subsequent upper tract damage or infection. For ED use, these tests are not suitable due to time constraints, and unless previously done, the ED physician must rely on clinical grounds.

CLINICAL PRESENTATION Patients who complain of irritative voiding may have a UTI or the urethral syndrome. They may have frequency, urgency, dysuria, suprapubic pain, or postvoid

fullness and report a history of hematuria, incontinence, or dyspareunia. Chills, fever, and flank pain raise the suspicion of UTI or obstruction.

LABORATORY AND OTHER PROCEDURES After the history and physical examination, evaluation of an adequately obtained urine specimen is critical ( 8). A midstream-voided urine sample after appropriate preparation is usually satisfactory for urinalysis and culture techniques. If there is any doubt about the adequacy of the collection (e.g., if a large number of epithelial cells has been noted), a suprapubic aspiration or sterile catheterization can be performed. These latter techniques give the most accurate results for the evaluation of microbial growth. Urinalysis, culture, and sensitivity identify UTI. Other testing modalities are available to diagnose active infection. Several companies have made quick dipstick tests to check for bacteriuria. A microscope examination can show evidence of bacteriuria on centrifuged specimens. White blood cells identified on a microscopic high-powered field examination are also significant. The clinician has a multitude of devices to choose from to determine whether a UTI is present. Various test dipstick products and rapid culture medium devices are available. Many of these are costly. Relying on a simple centrifuged urine specimen and evaluating the high-powered field examination gives good results. The various dipstick chemical methods available include the Griess test, a simple screening test that checks for the presence of nitrites. The principle behind it is that bacteria reduce nitrate in the urine to nitrite. A less specific dipstick test is the glucose oxidase urine test. A small amount of glucose is present in normal urine (approximately 2 to 10 mg/100 mL) and is usually metabolized by bacteria. In the absence of this small amount of glucose, bacteriuria may be suspected. These two tests for nitrite and glucose oxidase rely on bladder incubation; therefore, an early morning specimen gives the most valid results. The latter test often yields false-positive results and must be confirmed by a formal culture and sensitivity. Unfortunately, the results of the nitrite test also may be inaccurate because it is not designed for random urine specimens. Bladder intubation and the first morning specimen help to raise the accuracy of nitrite screening test results. In any case, if there is doubt, a standard culture should be taken. Occasionally, the nitrite test has been used in conjunction with a leukocyte esterase test on a specific dipstick. The leukocyte esterase test is a screening method to identify the presence of pyuria. If nitrite and leukocyte esterase test results are positive, the sensitivity and accuracy of a presumed UTI is improved. These tests have limitations. As stated before, the nitrite test should be obtained on a first morning incubated voided specimen. In addition, the presence of pyuria alone does not confirm the presence of a bacterial infection. Leukocytes may be signs of other types of inflammatory processes. In women, white cells can be discharged from the vagina and contaminate the urine. In addition, pyuria may be secondary to the presence of a tumor or a foreign body, or it may occur with sterile urine, tuberculosis, or other unusual organisms. The dipstick tests are quick and easy to use, but their accuracy must be weighed against the knowledge of their limitations. These tests are generally useful for negative urine results, but microscopic examination should be performed if the patient is acutely symptomatic.

URINE CULTURE Uncomplicated UTI do not necessarily require culture and sensitivity ( 9). In complicated UTI, culture and sensitivity clearly are indicated, as are possible blood cultures and/or other serum tests, such as a complete blood count and serum creatinine. A urine culture and sensitivity should be used for patients at high risk, among them those in whom treatment has failed, the elderly or immunosuppressed, children, adult men, those with recurrent renal infections, the severely or chronically ill, those with evidence of anatomic renal abnormalities or obstruction, and pregnant women. If several days later a patient returns with repeat symptoms after having been “cured” of a simple UTI, a culture and sensitivity should be obtained. The organisms may be different or resistant to the initial antimicrobial agent given to the patient. Classically, a count of 10 5 bacteria/mL is consistent with UTI. Unfortunately, patients may have symptomatic infections with lower colony counts. The consensus definition by the Infectious Disease Society of America (IDSA) suggests bacterial levels of 10 3 and above (9A). In women, the difficulty arises in relying solely on the colony count with sterile urine and a large number of pathogenic bacteria on the perineum. Are these colony counts accurate assessments of the urinary tract or simply contamination problems with poor collection techniques? Many times, when cultures are obtained, not only is the organism identified, but sensitivity discs are placed in the culture media to determine the appropriate antimicrobial agent. The antimicrobial agents that should be selected are those that cover the most common Gram-negative enteric bacteria as well as staphylococci and enterococci. Most of the penicillins and first-generation oral cephalosporins are effective. In addition, trimethoprim and sulfa agents give broad-spectrum coverage for UTI. The newer agents—noroxin, ofloxacin, and ciprofloxacin (fluoroquinolones)—are also good oral agent choices. Urethral cultures for Neisseria and Chlamydia should be considered in dysuria, pyuria, or urethral discharge. If the patient has pelvic pressure or postvoid fullness or is noted to have some suprapubic distension, catheterization to assess residual urine volume is indicated. Other tests that may be indicated by the urologist include cystometrogram and cystourethroscopy (7). If hematuria and flank or colicky pain are present, an upper tract evaluation (intravenous pyelogram or ultrasound) should be considered. Pyelography is usually not required during the first few days of therapy unless an acute obstruction is suspected. For hematuria, urinary cytology should be performed.

MANAGEMENT AND INDICATIONS FOR HOSPITAL ADMISSION If a UTI is diagnosed, antibiotics such as trimethoprim–sulfamethoxazole, nitrofurantoin, cephalexin, or a fluroquinolone should be used until culture and sensitivity results have been obtained. These patients need office follow-up to check laboratory or radiograph test results and to follow clinical improvement. If they have high fever or severe pain or are unable to keep down adequate fluids, admission is indicated. Seriously ill patients cannot be evaluated and treated adequately as outpatients. Admission should be considered in diabetic or immunosuppressed patients, patients who are pregnant, and patients with poor social situations. Acute Pyelonephritis Acute pyelonephritis is identified clinically by flank pain and fever, which may be accompanied by systemic symptoms of nausea, vomiting, and malaise. Bacteremia may be present, accompanied by chills or fever. With the clinical findings, the IDSA has suggested that 10 4 organisms/mL or higher may be the diagnostic criterion for bacteriuria in acute pyelonephritis ( 11). In the most severe cases, the patient appears ill, white blood cell count is high with a left-shift, and there may be nausea and vomiting, with dehydration and inability to take oral antibiotics. In such cases, hospitalization is essential even for a short stay. The newer “Emergency Department Observation Units” tend to be useful in this situation. To being hydration, use antinauseants and begin parenteral antibiotics. Intravenous antibiotic choices for inpatients include third-generation cephalosporins (e.g., ceftriaxone) or a first-generation cephalosporin with an aminoglycoside, pending the results of the urine culture and sensitivity. Ampicillin is no longer recommended as first-line therapy. Pyridium may be given for the first few days for symptomatic treatment. Occasionally, selected outpatients can receive parenteral medication (begin with Ceftriaxone intramuscularly and then oral medications). However, in one study almost 10% of the outpatients returned for admission, and the need for close follow-up was emphasized ( 10). Patients who do not respond quickly should be evaluated for obstruction, stone, or perinephric abscess with CT scan, ultrasound, and IUP.

ANTIBIOTIC TREATMENT Much has been written about the usefulness of single-dose antimicrobial therapy for the treatment of UTI. The use of a high-dose single-agent antimicrobial for a simple UTI can be appropriate, especially in women with no upper tract symptoms (fever, flank pain) who are not pregnant or nursing. Several studies have shown that single-dose therapy is an effective way to treat bacterial cystitis (dysuria, frequency, and abnormal urinalysis). Ampicillin, amoxicillin, and trimethoprim–sulfa combinations have been shown effective, with 80 to 100% success in simple bacterial cystitis. Three grams of ampicillin or two double-strength tablets of the trimethoprim–sulfa agents have been shown to be effective. However, with growing ampicillin resistance, the first choice should be TMP-SMZ. The quinolones are equally effective, but more costly. Patients do not require culture and sensitivity, but they must be reexamined with repeat urinalysis within the first week. If the infection does not clear, culture and sensitivity are indicated, as are additional diagnostic studies. All other bacterial infections except for this limited group require several days of therapy. There is no clear-cut answer to whether 3 days is better than 10 days of treatment; it is simply a matter of clinical judgment. If any

concern exists regarding upper tract symptoms, such as fever, obstruction or flank pain, a longer course of therapy is required and parenteral dosing should be considered. Single-dose therapy for UTI in infants and adult men is not recommended. In neonates and infants younger than 2 years, UTI should be treated with a minimum of 10 to 14 days of antimicrobial therapy. When symptoms are severe or causes are complicated, longer doses of antimicrobial agents may be indicated because these children must be protected from upper tract scarring. In school-age children, short-term antibiotic treatment can be considered that lasts from several days to 1 or 2 weeks. Adequate information is not available to consider single-dose therapy for children. Pediatric patients need follow-up evaluation with a urologist to make sure there are no anatomic abnormalities, velicoureteral reflex, and/or obstruction. In men, urinary tract infection is less common and usually is related to an anatomic or other structural defect such as prostatism, calculus disease, or tumor. These patients need several days of antimicrobial therapy. Follow-up should be arranged with a urologist or the patient's local physician to evaluate the urinary tract.

ORAL AGENTS FOR URINARY TRACT INFECTIONS Trimethoprim–Sulfamethoxazole Combination Trimethoprim with sulfamethoxazole is a rapidly absorbed agent that can be given orally or intravenously ( Table 50.2). Both components are effective against most enteric bacteria that commonly produce UTI. It should be noted that this is not a single-dose agent to be used against Pseudomonas. Occasionally, resistance to either one of these components may be encountered, and this can be noted for patients with resistant UTI based on culture and sensitivity reports. These medications may be used for long-term prophylactic use in combination, or trimethoprim may be used alone.

Table 50.2. Antibiotic Options

DOSE Children: Not to be used in children younger than 2 months; 8 mg/kg trimethoprim and 40 mg/kg sulfamethoxazole in two divided doses daily. Adults: Should not be used during pregnancy or nursing. One double-strength tablet twice a day for 3 to 10 days is adequate for simple urinary tract infection. Prophylactic doses consist of one-half to one tablet at bedtime. Penicillin Ampicillin and amoxicillin are good for urinary infections, but amoxicillin has better gastrointestinal tract absorption. Certain penicillinase-resistant penicillins, such as oxacillin, nafcillin, cloxacillin, and dicloxacillin, are more specific for Staphylococcus aureus infections; however, their use for uncomplicated UTI is limited. There is a higher frequency of treatment failures from resistant bacteria rendering these medications less effective as a first-line treatment. AMPICILLIN DOSE Children: 100 mg/kg body weight in four equally divided doses. Adults: 250 to 500 mg three to four times daily. AMOXICILLIN DOSE Children: 40 mg/kg body weight in three equally divided doses. Adults: 250 mg three to four times daily. Nitrofurantoin Nitrofurantoin is also a good choice for an oral antimicrobial agent. There are fewer resistance problems with nitrofurantoin than with penicillin. Long-term use can have some pulmonary and hepatic complications. These should be watched closely if the patient is on Macrodantin for a prolonged period of time. Overall, it is a good therapeutic and prophylactic agent for UTI. DOSE Children: 5 to 7 mg/kg in four divided doses. Adults: 50 to 100 mg three to four times per day. Prophylactic use for recurrent infections can be 50 to 100 mg at bedtime. Cephalosporins First-generation cephalexin has good broad-spectrum coverage for most enteric UTI. Tetracyclines Tetracycline is another antimicrobial agent that can be used as an alternative medication for UTI. They are contraindicated in children because they stain forming teeth. They are a good choice for some sexually transmitted diseases. DOSE Adults: 250 to 500 mg three to four times a day. Quinolones Some of the quinolone agents such as ciprofloxacin, ofloxacin, and noroxin are available. They give broad-spectrum coverage with a unique mechanism of action different from that of the previously mentioned antimicrobial agents. They are effective in most UTI, including those caused by Pseudomonas. They have a broader spectrum of antimicrobial activity and are far more active than some of the older medications. Some early resistance has been identified in these agents, and their specific use should be reviewed to decrease the resistance.

DOSE Noroxin is supplied in 400 mg tablets, one tablet twice a day for adult dosage. Ciprofloxacin is supplied in 250, 500, and 750 mg tablets. Ofloxacin is supplied in 200, 300, and 400 mg tablets for dosing twice a day. Their dosage should be adjusted for renal insufficiency. Quinolones are contraindicated in children and pregnant women. Antifungal Microbials Candiduria develops in many patients who are immunocompromised or have been on long-term antibacterial agents. They may have systemic deep-tissue fungal infections. For the latter, amphotericin B is clearly the standard treatment. It must be used with great care on an inpatient basis with observation of the total dose and of high amount of toxicity related to its use. Diflucan (flucytosine) is a fairly new antifungal agent with excellent renal excretion. Its toxicity profile is less than that of amphotericin B, and it is a good alternative agent for candiduria. The simplest thing to determine about candiduria is its cause. Consider foreign bodies, underlying diabetes mellitus, and prolonged use of antibacterial agents before using any antifungal agent. If any of these can be removed or diminished in their severity, patients have a good chance of clearing the funguria on their own. References 1. 2. 3. 4. 5. 6. 7. 8. 9.

Uehling DT, Hopkins WJ, Jensen J, et al: Vaginal immunization against induced cystitis in monkeys. J Urol 1987;137:327. Hooton TM, Scholes D, Hughes JP, et al: A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med 1996;335:468. Parsons CL, Boychuk D, Jones S, et al: Bladder surface glycosaminglycans. J Urol 1990;143:139. Sheinfeld J, Schaeffer AJ, Cordon-Cordo C, et al: Association of the Lewis blood-group phenotype with recurrent urinary tract infections in women. N Engl J Med 1989;320:773. Hooton TM, Stamm WE: The vaginal flora and UTI. In: Urinary tract infections: molecular pathogenesis and clinical management. Mobley HLT, Warren JW, eds. Am Soc Micro 1996:67. Ledger WJ: Infection in the female. Philadelphia: Lea & Febiger, 1986:140. Scotti RJ: Urethral syndrome and urethral infections: I. patient evaluation and infectious causes. Infect Surg 1989;8:102. Scotti RJ: The urethral syndrome: noninfectious causes. Infect Surg 1989;8:178. McMurray BR, Wrenn KD, Wright SW: Usefulness of blood cultures in pyelonephritis. Am J Emerg Med 1997;15:137–140.

9A. Warren JW: Management of urinary tract infections. Resident and Staff Physician 1998;44:33–40. 10. Pinson AG, Philbrick JT, Lindbeck GH, et al: ED Management of acute pyelonephritis in women: a cohort study. Am J Emerg Med 1994;12:271. 11. Rubin RH, Shapiro ED: Evaluation of new anti-infection drugs for UTI. Clin Infect Dis 1992;15:5216–5227.

CHAPTER 51 HEMATURIA Principles and Practice of Emergency Medicine

CHAPTER 51 Hematuria Patricia L. Lamb Capsule Introduction Pathophysiology Clinical Presentation Hematuria in Children and Adults The Diagnostic Approach Evaluation of Hematuria in the Child

CAPSULE Hematuria is a common clinical problem with an extensive differential diagnosis. The age and sex of the patient and the initial visit determine the extent of the workup in the ambulatory care setting. Knowledge and an adequate framework of reference for the various causes and available diagnostic modalities is necessary for the appropriate referral and follow-up. A brief overview of the various disease states causing hematuria and an expedient diagnostic approach are discussed here.

INTRODUCTION The discovery of bright red urine naturally is cause for alarm. The goal of the clinician is to begin an evaluation that is well thought through and that will prevent morbidity and hospitalization. Treatment depends on the natural history of the intrinsic disease or the structural defect precipitating the symptoms. By definition, hematuria is three red blood cells per high-power field ( 1). Gross hematuria generally prompts a patient to seek immediate medical attention. Microscopic hematuria may be an incidental finding but should be investigated to rule out cancer or progressive diseases ( 2). Red urine does not always mean blood in the urine. Dye, drugs, and various pigments may mimic red cells in the urine. A positive dipstick with a negative urine sediment is the cue to pigmenturia.

PATHOPHYSIOLOGY The causes of hematuria, including false hematuria, are generally classified by an anatomic relationship within the genitourinary tract. Nonurinary tract causes also exist (Table 51.1). Generally, four categories encompass the majority of anatomic and physiologic expression of diseases that often accompany hematuria: renal-glomerular, renal-nonglomerular, postrenal, and miscellaneous disorders.

Table 51.1. Hematuria in the Ambulatory Care Setting: Usual Pathophysiology

Infection and glomerular disease are the most common disorders in young adults and children. Nephrolithiasis, diseases of the prostate, and malignancies become more prominent in middle-aged and mature adults. The most common cause of hematuria worldwide is schistosomiasis. Although not endemic to the United States, it must be considered in patients such as military personnel, diplomats, or tourists returning from the Middle East and Africa ( 3). Vascular disorders and bleeding anomalies comprise a smaller number of cases. The obvious disorder seen in sickle-cell disease or coagulopathies is readily diagnosed. Vascular disorders such as bladder hemangioma in children or peculiar anomalies such as the loin pain hematuria syndrome in women represent a greater clinical challenge ( Table 51.2).

Table 51.2. False Hematuria

CLINICAL PRESENTATION In hematuria, it is important to delineate age and sex and to distinguish the presentation as gross or microscopic. Generally, in men and boys of any age, gross or microscopic hematuria merits a complete urologic workup. Cystitis in a man or a boy follows predisposing conditions that obstruct the flow of urine or seed bacteria into the bladder. The history and physical examinations elicit clues regarding prostate enlargement or prostatitis, outlet obstructions, stones, or possible malignancies. Some studies have suggested that the degree of hematuria in relation to age is not significant. Case reviews at the Mayo Clinic, in which the degree of hematuria was provided by red cell number per high-power field (HPF), noted an increased incidence of disease in these persons who had more than 8 red blood cells (RBC) per HPF. In men 55 years and older, uroepithelial and prostate cancer were more prevalent. Neoplastic disease should always be considered early in the differential diagnosis, and cytologic studies should be ordered before contrast studies are obtained. Hematuria in adult women differs in that infection is more prominent in younger women because of the correlation between acute bacterial cystitis and intercourse. In women between 20 and 40 years of age, hematuria with painful urination generally reveals a lower urinary tract infection. In patients in which classic cystitis later reveals low bacterial colony counts, acute urethral syndrome should be considered and the appropriate tests for chlamydia trachomatis initiated. Pain other than that experienced with micturition in association with hematuria may herald

other underlying conditions. Nephrolithiasis remains the second most common cause of hematuria associated with somatic pain ( 4). Gross hematuria associated with anterior or lower abdominal pain may be caused by endometriosis. Transvaginal ultrasound may detect a mass. However, it is often a negative test (4A). The symptoms generally persist over several months and are cyclic in nature. The nonspecific presentation frequently is confused with that of a ureteral tumor. Distal obstruction is common. Numerous physical findings accompany this entity, the most common of which is a pelvic mass. The mass generally lies in the rectovaginal vault or adnexa or against the uterosacral ligament. Menses are concurrent in fewer than 15% of the patients. Menstrual dysfunction, however, is present in more than 60% of them, particularly with intrinsic ureteral involvement. A key factor in a woman who has had a hysterectomy for endometriosis is to ascertain whether an intravenous pyelogram (IVP) was taken before surgery ( 5). A small vessel occlusive vascular disease known as loin pain hematuria syndrome may develop in women taking estrogen (6). It occurs chiefly in young women, although incidences in older women are reported. Clues are recurrent loin pain and hematuria. The diagnosis is confirmed by arteriogram, which demonstrates small vessel disease, usually in the lower poles. Treatment consists of antiplatelet therapy and discontinuation of estrogen. Painless hematuria in young women elicits consideration of other diagnoses such as polycystic kidney, staghorn kidney, or a solitary renal cyst. Glomerulonephritis, because of its prevalence in young adults, is always part of the early differential diagnosis. Intermittent painless hematuria may be an early sign of carcinoma. Renal lesions are more prevalent in younger women than bladder or lower tract tumors. After age 60, bladder carcinoma is more common. The evaluation of asymptomatic hematuria in older women parallels that in men. Common mismanagement of hematuria concerns the patient on anticoagulants or the patient with an underlying bleeding disorder. The former often have predisposing factors that facilitate a bleeding diathesis. A patient with a diagnosed disease that has known bleeding tendencies frequently has spontaneous transient hematuria that is dismissed. Later investigations often reveal independent urologic disease. The astute clinician should consider the root cause of hematuria at the first visit. To do otherwise would delay diagnosis and subsequent in-depth management of a potentially serious disease ( 7). More remote causes of hematuria are usually apparent by history. Occupational exposure to chemicals such as carbon tetrachloride and naphthalene occasionally may cause hematuria (8). The additional finding of hematuria after heavy exercise has been observed in athletes. The condition is generally seen in male runners, although the phenomenon has been observed in other competitive sports such as swimming and rowing. Aviators also demonstrate microscopic hematuria ( 9).

HEMATURIA IN CHILDREN AND ADULTS Hematuria in children differs in cause and manifestation from that in adults. Glomerulonephritis is the most common cause, followed by cystitis and posterior urethritis (10). The significance of hematuria is often overstated, and the child is subjected to unnecessary invasive procedures. A good understanding of the pathophysiology and the disease processes found in the pediatric patient help the clinician to establish a working differential diagnosis. The extent of the evaluation in the ambulatory care setting is defined by the age and sex of the child, the degree of illness, and the presence or absence of infection. Toxic causes should not be overlooked. The general classification of hematuria, including false hematuria ( Table 51.3), applies. The gamut ranges from mild urethral irritation to life-threatening glomerulonephritis. The most common form of glomerulonephritis, however, is acute poststreptococcal glomerulonephritis. This is easy to diagnose. It appears in children 3 to 7 years of age (rarely in children younger than 2) 7 to 21 days after skin (e.g., impetigo) or throat infection with group A b-hemolytic streptococcus. Diagnosis can be confirmed in the acute phase by demonstrating a decrease in the C 3 complement level and positive streptozyme test results. The latter demonstrate antibodies to five different streptococcal antigens. It is a study preferred over the traditional antistreptolysin-O titer, which does not rise after skin infections.

Table 51.3. Classification of Hematuria

Gross hematuria 1 to 3 days after an upper respiratory tract infection or recurrent hematuria during a subsequent upper respiratory infection typifies a form of glomerulonephritis classified as I gA–IgG nephropathy. C3 complement levels are normal and, other than a low-grade proteinuria, renal function is generally normal. The average age in one study was 9.5 years, with a male predominance ( 10). Although the course of disease carries a good prognosis, progression to chronic renal failure does occur. The other forms of glomerulonephritis, such as anaphylactoid purpura and systemic lupus erythematosis, are characterized by distinct physical complaints. The presenting features, among them purpuric skin lesions on the lower extremities and gastrointestinal bleeding in the first entity and the more typical manifestations of SLE in the second, are described in Table 51.4. The nephritis of chronic infection may be more subtle, depending on the cause of the disease and the time of presentation.

Table 51.4. Glomerulonephritis: Pertinent Distinguishing Features

The nephrotic syndrome is seen in membranoproliferative glomerulonephritis; hypertension is often an early sign. This manifestation, as well as antiglomerular basement membrane disease, is found in young adults and teenagers. There is a male predominance in the latter. When accompanied by hemoptysis, it is designated as Goodpasture syndrome. Both progress to renal failure. It is important to have a grasp of the manifestations and long-term sequelae of the various forms of glomerulonephritis. Generally, the disease resolves in asymptomatic patients. The restriction of activity that is recommended is simply not warranted. In general, if glomerulonephritis is not accompanied by hypertension,

edema, and renal insufficiency, the disease process is self-limited. The diagnosis can be made at the initial visit on the basis of the clinical features ( 11). A small percentage of patients with hematuria has a systemic disease with a genetic cause. Early detection of the various familial diseases in the ambulatory care setting is facilitated by a thorough history. Microscopic or intermittent episodes of gross hematuria, coupled with sensory-neural hearing loss, are indicative of Alport syndrome. Progression to renal failure, although gradual, is common in men. Similarly, gross and microscopic hematuria, with the concomitant finding of bilateral flank masses, usually elicits a family history of polycystic kidney disease, with renal failure occurring in the fifth and sixth decades. Yet a third genetic phenomenon is that of benign familial hematuria. Renal function is normal, but episodic gross hematuria or persistent microscopic hematuria is common. Hematuria secondary to coagulopathy is more typically present with other expressions of the underlying disorder. Sickle-cell anomalies may accompany isolated episodes of gross hematuria. This phenomenon also is seen in thrombocytopenia. If it occurs in a critically ill infant or child younger than 3 years who has had recent respiratory or gastrointestinal illness, it should alert the clinician to hemolytic uremic syndrome ( 12). Severe dehydration after gastrointestinal illness or angiography in an infant may precipitate a renal vein thrombosis ( 13). Extrarenal lesions secondary to trauma, including blows to the abdomen, drug reactions, and congenital disorders may produce gross or microscopic hematuria. Malignancies and renal stones in children are rare. A palpable renal mass may suggest a Wilm's tumor, and in the ill, anemic patient with intermittent gross hematuria, a bladder hemangioma should be considered. Percutaneous lesions in the lower abdomen, pelvis, and thighs usually are noted ( 14). An uncommon cause of hematuria, but one associated with voiding dysfunction, is that of a congenital polyp of the posterior urethra ( 15). Reflux nephropathy and posterior urethritis are more common extrarenal causes. The former is seen from infancy through middle childhood. The latter, which is characterized by gross hematuria, dysuria, underwear spotting, pyuria, and negative urine cultures, often resolves without treatment. The differences in the manifestations and causes of hematuria in pediatric patients must be considered while obtaining the history and performing the physical examination. The parameters initially established determine the causes for further diagnostic interventions and followup. The workup in the child differs from that in the adult because cystoscopy rarely is indicated and certain laboratory studies, such as the C 3 complement levels, are more commonly ordered (10).

THE DIAGNOSTIC APPROACH As noted in the previous discussion, the causes of hematuria are extensive. Localization of the source ( Table 51.5) is helpful. When weighing the evaluation, one must use a workup designed to detect intrinsic renal disease and structural abnormalities. Detection of serious disease is often possible with a minimum of invasive tests.

Table 51.5. Localization of Source of Hematuria

Bearing in mind that hematuria in the adult is related to sex and age, the clinician must separate the presentation parameters and proceed with the workup accordingly. In women younger than 40, hematuria generally is related to infection, and the onset of symptoms often can be related to sexual intercourse. In the absence of such a history, a bladder tumor must be considered. Urine cytology, cystoscopy, and an intravenous pyelogram are all warranted ( 16). Between ages 40 and 60 in both sexes, carcinoma plays a more prominent role. After age 60, the possibility of cancer is predominant in the differential diagnosis ( Table 51.6). The history and physical examination can reveal most of the underlying disease previously described ( 16). Color, character, and timing of the urine are important clues. Previously mentioned pertinent facts such as medication, travel, recent respiratory infections, and appropriate medical history help to focus the physical examination and to direct the selection of the appropriate studies ( 16). The presence or absence of protein, red cell casts, and dysmorphically shaped red cells microscopically denote glomerular or intrinsic renal disease. Proteinuria secondary to hematuria in the presence of a negative urine culture can be assessed by a urine protein electrophoresis. If obtained with a 24-hour urine protein collection, the detection of protein from lysed RBCs is more easily ascertained ( 17). And as stated before, urine cytology must be obtained in a first-void speciment on all persons older than 40 before contrast dyes are used ( 13).

Table 51.6. Age-Related Causes of Hematuria

Structural studies of the kidney are sequenced in relationship to age and the patient's medical history. In general, persons older than 40 require intravenous pyelogram with tomograms. If the study is negative, cystoscopy is performed. If the IVP demonstrates a parenchymal mass, ultrasonography is conducted, leading to cyst aspiration or definition of a solid tumor, which is then evaluated by arteriography. Some would choose computerized tomography or nuclear magnetic resonance imaging for additional evaluation after a negative cystoscopy. Should cystoscopy denote blood in a urethral orifice, one must consider a tumor, vascular abnormality, or glomerulonephritis. Arteriography is indicated. The decision to proceed to renal biopsy depends on the need to make a definitive diagnosis in the face of other negative studies. The discovery of treatable disease is rare ( 13). The diagnostic challenge is asymptomatic hematuria. A well-thought-out evaluation can decrease costs, which are estimated between $75,000 to $86,000 per patient and include significant morbidity during diagnostic procedures ( 18). Studies vary but significant lesions, including neoplasms, range from 2 to 13% of the cases reviewed (18). The higher prevalence of serious urologic disease in the referral-based studies has been reevaluated by the Mayo Clinic study mentioned previously. The actual incidence of neoplasm was found to be significantly lower. The relationships among the degrees of hematuria were noted to be 3.6% in persons with more than 8 RBC/HPF, 0.5% in patients with 1–8 RBC/HPF, and 0.2% of control patients. More significant differences were observed in what the author categorized as moderately serious disease (17). These findings are helpful in choosing the definitive study to evaluate the asymptomatic patient. Infection, systemic disease, and the possibility of intrinsic renal disease must be eliminated by history and physical and basic laboratory studies. Microscopic hematuria then can be classified as

asymptomatic hematuria. The evaluation begins with cystoscopy and proceeds, according to findings, to ultrasonography and then computerized tomography or angiography (Fig. 51.1) (19).

Figure 51.1. Strategy for evaluation of patients with asymptomatic microscopic hematuria. CYSTO, cystoscopy; US, ultrasound; CT, computed tomography; ANGIO, angiography; ASPIRATE, cyst aspiration; +, positive test results; –, negative test results. (Reprinted with permission from Corwin HL, Silverstein MD. The diagnosis of neoplasia in patients with asymptomatic microscopic hematuria: a decision analysis. J Urol 1988;139:1002–1006.)

EVALUATION OF HEMATURIA IN THE CHILD The key to the diagnostic approach in a child ( Fig. 51.2) is to remember that the usual cause of hematuria is either glomerulonephritis or infection. The problem is defined in terms of cause rather than the anatomic reference used in the adult. After the initial evaluation and treatment, these children usually are referred for additional study.

Figure 51.2. Hematuria in childhood: diagnostic strategy overview.

The workup should be appropriate for the degree of illness. Generally, the initial study is a urinalysis and culture. If positive, antibiotic treatment ensues, with a subsequent follow-up urinalysis. In all infants, all boys, children small in stature, or girls with repeated urinary tract infections, an IVP and a voiding cystourethrogram (VCUG) are obtained. These studies identify congenital anomalies, foreign bodies, strictures, and stones that may be a nidus for infection and precipitate a concomitant hematuria. A urine culture negative for infection, the age and sex of the child, the medical history, and physical examination define subsequent studies (Table 51.7). The multiplicity of causes discussed in the previous section must be considered. The history often reveals familial disease, underlying systemic illnesses, medication, trauma, or a history of recent infection. The physical examination may reveal a simple cause such as an external lesion or more ominous signs such as hypertension, edema, and abdominal masses. As in adults, false hematuria must be differentiated from true hematuria ( Table 51.2). All heme-positive dipstick urines should be differentiated and screened for RBC. If the history reveals a drug-related cause ( Table 51.2) and hematuria persists after the medication is discontinued, a serum creatinine is ordered. Other laboratory tests are determined by the medical history data ( Table 51.7). Proteinuria generally suggests renal parenchymal disease and may occur with gross or microscopic hematuria.

Table 51.7. Laboratory Evaluation of Hematuria in Children

Microscopic hematuria in the absence of infection often is presumed to be glomerulonephritis or a focal nephritis. Invasive studies including renal biopsy are indicated in certain forms of glomerulonephritis ( Table 51.4). An IVP and possibly a VCUG are indicated when the screening laboratory study results are negative. By contrast, gross hematuria mandates an IVP. As noted previously, cystoscopy rarely is indicated in children. An exception are patients in whom the history implies a lower track bleeding site or the persistence or recurrence of bright red hematuria with a previously normal IVP ( 13). Bleeding from a ureteral orifice is evaluated by angiography to rule out an arteriovenous malformation. A point of clarification in children with gross hematuria and the classic symptoms of posterior urethritis is that cystoscopy does not alter the management or prognosis. In addition, red urine in the neonate has myriad causes such as porphyrins, urate, hemoglobin, or bile pigments. In older children or adults, foods such as beets and blackberries can cause red urine. Paroxysmal hemoglobinuria has a genetic cause. True hematuria in this age group heralds more serious disease such as Wilm tumor, obstructive uropathy, infection, congenital nephrosis, or polycystic kidney disease and renal vein or artery thrombosis. A urinalysis must be obtained on a fresh voided specimen ( 13). References 1. 2. 3. 4.

Kanarvogel LE: Hematuria. In: Saunders manual of medical practice. Philadelphia: WB Saunders, 1996;518. Yasumasu T, Koikawa Y, Uozumi J, et al: Clinical study of asymptomatic microscopic hematuria. Int Urol Nephrol 1994;26:1. Smith LH, Christie JD. The pathobiology of schistosoma haematobium infection in humans. Hum Pathol 1986;17:333. Stewart C: Nephrolithiasis. Emerg Med Clin North Am 1988;6:617.

4A. Langer RD, Pierce JJ, O'Hanlan KA, et al: Trans-vaginal ultrasound vs endometrial biopsy for the detection of endometrial disease. N Engl J Med 1997;337:1792–1798.

5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.

Klien R: Uretheral endometriosis. J Urol 1979;8:477. Reifsteck J, Holder J, Liu G, et al: Loin pain hematuria syndrome. Urol Radiol 1987;9:155. Walker AM, Jich H: Predictors of bleeding during anti-coagulant therapy. JAMA 1980;244:1209. Sutton JM: Evaluation of hematuria in adults. JAMA 1990;263:2475–2480. Voge VM, Salmond R: IgA nephropathy in a student aviator. Aviat Space Environ Med 1988;54:655. Wyatt R, et al: Hematuria in childhood: significance and management. J Urol 1977;117:36. Andrioli SP, Bergstein JM: Hematuria in childhood. J Indiana State Med Soc 1980;Aug: 523. Giantonio CA, et al: The hemolytic–uremic syndrome. Nephron 1973;11:174. Brewer ED, Benson G: Hematuria algorithms for diagnosis. JAMA 1981;246:877. Leonard MP, Nickel JC, Morales A: Cavernous hemangiomas of the bladder in the pediatric age group. J Urol 1988;140:1503. Aragona F: Congenital polyps of prostesic urethra. Urol Int 1988;43:113. Benson G, Brewer E: Hematuria: algorithm for diagnosis. JAMA 1981;246:993. Mohr D, et al: Isolated microscopic hematuria. J Clin Intern Med 1987;2:318. Froom P, Gross M, et al: The effect of age on the prevalence of asymptomatic microscopic hematuria. Am J Clin Pathol 1986;86:656. Corvin H: Diagnosis of neoplasm in patients with asymptomatic hematuria a decision analysis. J Urol 1988;138:1002.

Suggested Readings Alyea EP, Panish HH: Renal responses to exercise and urinary findings. JAMA 1958;167:807. Bloom K: An algorithm for hematuria. Clin Intern Med 1988;8:577. Copley JB: Idiopathic hematuria. Arch Intern Med 1987;147:434. Fred HL, Matelson EA: Grossly bloody urine of runners. South Med J 1977;70:1394. Mohr DW, Offand KP: Asymptomatic microhematuria and urologic disease: a population-based study. JAMA 1986;256:224.

CHAPTER 52 MALE GENITAL PROBLEMS Principles and Practice of Emergency Medicine

CHAPTER 52 MALE GENITAL PROBLEMS Scott B. Freeman Capsule Torsion of the Spermatic Cord and other Scrotal Masses Anatomy and Pathophysiology Prehospital Assessment and Stabilization Clinical Presentation and Examination Differential Diagnosis Procedures and Laboratory Testing Manual Detorsion Disorders of the Penile Shaft Anatomy and Pathophysiology Clinical Presentation and Examination Procedures and Laboratory Testing Management and Admission Medicolegal Pearls

CAPSULE Diseases of the male genitalia are rarely life-threatening but may be associated with significant morbidity. The relationship of the genitalia to sexual function causes anxiety in patients and physicians when dysfunction or pain develops. Sophisticated tools for the accurate diagnosis of diseases of the male genitalia are often unavailable to the emergency physician. Consequently, the importance of the anatomy and pathophysiology of the male genitalia is amplified. This presentation concentrates on torsion of the spermatic cord, the differential diagnosis of scrotal masses, and problems related to the penile shaft, and briefly describes prostatitis.

TORSION OF THE SPERMATIC CORD AND OTHER SCROTAL MASSES Diseases beginning inside and outside of the scrotum may present as acute scrotal pain. Of those originating within the scrotum, the most important to manage correctly and promptly is torsion of the spermatic cord. Improper management of torsion of the spermatic cord is likely to cause infarction and functional loss of the affected testicle. Torsion of the spermatic cord may be confused with the frequently seen infection of the epididymis. To avoid making this mistake, one must maintain a high index of suspicion and recognize the limitations of history and physical examination.

ANATOMY AND PATHOPHYSIOLOGY Subcutaneous tissue of the scrotum is continuous with the fasciae of the abdominal wall and perineum, and this may become clinically relevant when collections of blood or urine deep to this plane begin to pool in the scrotum. The interior is incompletely divided into right and left compartments, and fluid may traverse from one side to the other. The testes is surrounded almost completely by a thick, invaginated fibrous capsule, the tunica vaginalis. The epididymis and the ductus deferens are attached posteriorly, with the former lateral and the latter in a medial position. Together with the neurovascular supply of the testes, they comprise the spermatic cord. Both the testis and epididymis bear a pedicled appendix, which are embryonal remnants. The testes itself is attached to the posterior scrotal wall as depicted in Figure 52.1. Variations in the positioning and attachment of the testes may promote twisting on the pedicle created by the spermatic cord as depicted in Figure 52.2. The common anomaly associated with torsion is the “bell-clapper” deformity. When variations in the attachment of the testes are present they are frequently bilateral.

Figure 52.1. Transverse section of testes.

Figure 52.2. (A) normal testes; (B) loose epididymal attachment; (C) torsed testis with transverse line; ( D) “bell-clapper” deformity. (Adapted with permission from Ransler C, Allen T. Torsion of the spermatic cord. Urol Clin North Am 1982;9:248.)

In torsion of the spermatic cord, a twist develops, as depicted in Figure 52.2C. This leads to ischemia and eventual infarction of the testes if not corrected in a timely manner. The salvage rate for testicles affected by torsion is time-dependent and appears to decrease after 6 hours. The appendages of the testes or epididymis may also turn on their stalks and become ischemic. Because these appendages have no significant function, their torsion is important in that its occurrence appears like that of torsion of the spermatic cord.

PREHOSPITAL ASSESSMENT AND STABILIZATION As anticipated, little specific therapy can be rendered in the prehospital setting other than local cooling and scrotal elevation. The rare exception to this could be the presence of infection that has resulted in the systemic signs of sepsis such as functional hypovolemia.

CLINICAL PRESENTATION AND EXAMINATION Although torsion of the spermatic cord has been reported in a wide age range, it occurs predominantly near the age of puberty. An increased incidence is also observed in the first year of life, and torsion after age 30 can be considered a rare event. The incidence has been estimated at 1 case per 4000 males under age 25

by Williamson ( 1). The clinical history is nonspecific in comparison with the presentation of epididymitis, as demonstrated in Table 52.1. Typically, the onset of pain in torsion is sudden and severe, and a history of similar pain that has resolved spontaneously is often elicited. Beware of abdominal pain which can mislead the examiner. In some cases, complete abdominal workup has occurred before testicular examination.

Table 52.1. Clinical History of 75 Patients with Acute Scrotal Emergency

Testicular torsion may well occur during physical exertion but does not have to be associated with such activity. There is some nausea and frequently vomiting but no preceding urethral discharge or fever. Physical examination is also limited in its ability to differentiate between torsion of the testicle and epidydimitis ( Table 52.2). Diagnosis of torsion is suggested by examination of a tense swollen mass in the scrotum in which the epididymis cannot be outlined. The testicle usually is riding high in the upper part of the scrotum. The cord, if palpable, is edematous. Relief of pain on elevation of the affected testicle (Prehn's sign) was felt to suggest epididymitis rather than torsion but is not reliable. The presence of the cremasteric reflex suggests that acute torsion of the spermatic cord is not present.

Table 52.2. Physical and Laboratory Findings

Torsion of the Appendices of the Testis and Epididymis Instead of torsion of the entire spermatic cord, twisting of the appendices can occur. This usually occurs in children and is noted by the sudden onset of severe testicular pain. On examination, a small, tender lump may be felt in the upper anterior pole of the testicle or epididymis. Later in the disease, however, the entire testicle is swollen and tender. Surgical exploration is usually done to make the diagnosis and relieve the torsion. The use of Doppler may make operations unnecessary in certain cases. The ability to differentiate torsion of the spermatic cord from other entities through history and physical examination is limited. Because of this and the time-related nature of testicular viability when torsion is present, it is no surprise that Williamson reported a salvage rate of 55% ( 1). Higher salvage rates have been reported by those who advocate rapid exploration of the scrotum, but this results in the exploration of a significant number of patients with epididymitis ( 2,2A). Magnetic resonance imaging (MRI) exam has emerged as an accurate test, but may require excessive delay ( 3). Doppler ultrasonography has offered a rapid bedside test ( 3).

DIFFERENTIAL DIAGNOSIS In addition to torsion of the spermatic cord or appendages and epididymitis, the differential diagnosis of scrotal masses should include hernia, testicular tumor, scrotal fat necrosis, idiopathic scrotal edema, Henoch-Schönlein purpura, intra-abdominal hemorrhage or infection, spermatic vein thrombosis, orchitis, Fournier's gangrene, hydrocele, varicocele, spermatocele, and cryptorchidism. Epididymitis, a common problem, typically causes pain in the scrotum that gradually becomes worse over several hours or days. Epididymitis An epididymitis usually presents as a painful mass on one side of the scrotum. If examined early, the enlarged tender epididymis can be palpated, but later there is a tender scrotal mass. It usually lies in the bottom half of the scrotum, and the patient can sometimes be made more comfortable by scrotal elevation. A history of previous urethral dilatation, catheterization, operation, or urethral discharge is often present. The inflammation may be associated with a high fever and generalized sepsis. The differential diagnosis between torsion and tumor can be difficult. The overlying skin is red and edematous, and may be bilateral at times. Acute Orchitis Mumps orchitis can occur in association with mumps parotitis. The clinical findings are approximately the same as those seen with epididymitis. The treatment includes antibiotics, bed rest, and testicular support. Orchitis may occur as an extension of epididymitis or as an unusual isolated infection, most often of viral cause. Hydrocele A hydrocele is a collection of fluid within the tunica vaginalis. Approximately 15% of testicular neoplasms present as hydroceles, but most often no cause is found or the hydrocele is found secondary to inflammatory disease or trauma. Many infants are born with hydroceles, and these disappear during the first or second year of life. Most hydroceles occur in men over 40 years. If a hydrocele changes in size, as it frequently does in children, there may well be a patent processus vaginalis and an associated hernia. There is no pain involved, and the patient presents with a mass, occasionally large. Examination reveals a round intrascrotal mass that is not tender and in which the testicle is usually not palpable. Transillumination is easily performed but may not be practicable in patients with pigmented skin. Occasionally, if the testicle is not palpable, it is important to make a urology referral to aspirate the fluid and make sure that the testicle itself is normal. Management is usually nonoperative unless the patient believes that a large hydrocele is causing him a great deal of difficulty because of its size. We do not believe

in aspirating a hydrocele routinely because complications can outweigh the beneficial effects. Hydrocele fluid is clear. Varicocele This condition is common in young, sexually active men and is actually a dilation of the pampiniform plexus of the spermatic cord. It is usually seen on the left side but can occur on the right. A symptomatic varicocele is one that develops secondary to a renal tumor invading the renal vein and does not disappear on recumbence. Diagnosis is made by examination of the scrotum, where a mass of veins is felt above the testicle. On recumbency, the mass disappears. The only indication for surgical correction is an infertility problem. Hematospermia can result from this condition. Hernia A scrotal mass may be a hernia. This is important to determine before needling any scrotal mass. Peristalsis can be heard on auscultation, and the mass does not transilluminate. The mass is frequently reducible, and a normal testicle can be felt below. Tumor of the Testicle This disease usually occurs in men in their twenties and thirties and presents as a painless mass in the scrotum. There may be hemorrhage into the tumor, however, and the patient may present with typical painful sudden swelling that mimics an inflammatory testicle. Examination reveals a hard mass involving the testicle and a normal epididymis. The association of trauma is incidental and probably the event that draws the patient's attention to a mass already present. This should be treated as an emergency, with admission to the hospital, followed as soon as possible by surgical exploration of the mass. Spermatocele This is a painless cystic mass containing sperm. It lies above and posterior to the testis but is separated from it. The testicle is easily palpable, as is the epididymis. On examination, these masses are small and nontender, and no correction is necessary unless the patient insists. Scrotal and Penile Edema In congestive heart failure, massive swelling of the entire scrotum and penis can occur. This is easily differentiated because the swelling is in the scrotal skin and there is pitting edema. Sometimes the penis disappears within the mass, and it may be difficult to catheterize the patient. Cryptorchidism An undescended testis sometimes presents as a mass in the inguinal region with an absence of a testicle in the scrotum. Diagnosis is made by history and by palpation of the inguinal testicle. Torsion of the spermatic cord or appendages and epididymitis are most likely to be confused with each other, and their differentiation may be difficult.

PROCEDURES AND LABORATORY TESTING Evaluation of the patient's white blood cell count and a urinalysis are appropriate diagnostic procedures in patients with acute scrotal pain. Unfortunately, neither test clearly produces a reliable diagnostic result ( Table 52.2). As can be expected, there appears to be a higher incidence of leukocytosis and abnormalities seen on urinalysis with epididymitis. Doppler ultrasound evaluation of the spermatic cord to assess blood flow to the testes has been advocated. It is available, painless, and inexpensive to perform. Unfortunately, it is not a reliable way to exclude torsion of the spermatic cord because false-negative examinations clearly occur. Color Doppler ultrasound has emerged as a more accurate test with close to 100% sensitivity ( 3). The most accurate technique capable of demonstrating normal blood flow to the testicle, and thus excluding torsion of the testes, is technetium pertechnetate blood flow scanning. A normal and abnormal scan resulting from torsion of the spermatic cord are demonstrated in Figure 52.3. Accuracy approaches 100% and has caused Doppler ultrasound examination to be characterized as “useless” ( 4). The drawbacks associated with radionuclide scanning include its cost and a significant delay in availability. The alternative reliable way to exclude the diagnosis of torsion of the spermatic cord is exploration of the scrotum. If radionuclide scanning is not available and the clinical presentation is consistent with torsion of the spermatic cord, rapid exploration of the scrotum by a urologist is indicated.

Figure 52.3. (A) Normal 5-minute Tc-99m-pertechnetate scan of the scrotum. (B) Early torsion of the testes. There is no reactive hyperemia surrounding the photopenic area (arrows). (Reprinted with permission from Walker JM, Margouleff D, eds. A clinical manual of nuclear medicine. East Norwalk, CT: Appleton-Century-Crofts, 1984:243–244.)

MANUAL DETORSION Torsion of the spermatic cord requires operative intervention and eventual admission to the hospital. While waiting for an evaluation by a urologist, attempt to correct the torsion manually through the intact scrotum. Torsion usually occurs with the anterior portion of the testes rotating from its lateral aspect to its medial aspect. When viewed from above, manual detorsion should attempt to turn the right testicle clockwise and the left counterclockwise. Adequate attempts at manual detorsion may be precluded by tenderness of the involved testicle. Relief of pain suggests a successful attempt to detorse the testicle manually. Evaluation by a urologist is indicated regardless of the outcome of attempts to detorse the testicle manually. This evaluation is necessary to assess the viability of the testicle and fix the affected and unaffected testicle in position, by performing an orchiopexy, to prevent additional episodes of torsion. In contrast, the treatment of epididymitis usually occurs on an outpatient basis. It should include the administration of a broad-spectrum antimicrobial, bed rest with elevation of the scrotum, analgesia, and scrotal support when the patient is ambulatory. The possibility of concurrent gonorrheal infection should be kept in mind when initiating antibiotic therapy. Relief is usually seen in 48 hours. The reported poor salvage rates for testicles affected by torsion of the spermatic cord suggest that delays in presentation, diagnosis, or misdiagnosis are common. It is important to realize that, if the treatment for epididymitis is inappropriately rendered for torsion of the spermatic cord, the result is most likely to be loss of the affected testicle. Radionuclide scanning may accurately confirm the diagnosis. When radionuclide scans are not available urgent consultation with a urologist is recommended.

DISORDERS OF THE PENILE SHAFT Priapism, phimosis, paraphimosis, and balanitis may all precipitate visits to the emergency department (ED). As with torsion of the spermatic cord, anxiety in the patient and health care providers may lead to delays in management. Priapism is prolonged involuntary erection of the penis. Phimosis, a condition in which the foreskin cannot be retracted over the glans, may be caused by inflammation of the glans, which is called balanitis. Paraphimosis is the condition that exists when the foreskin remains retracted and results in edema and obstruction of venous outflow of the glans.

ANATOMY AND PATHOPHYSIOLOGY The shaft or corpus of the penis is comprised of three elongated masses of erectile tissue. The lateral and superior pair of corpora cavernosa form the greater part of the body of the penis. The neurovascular bundle runs over the superior aspect in the midline. Inferiorly is the corpus spongiosum, which contains the urethra. Erection of the penis is the result of neural stimuli and vascular phenomena. In a normal erection, the corpus spongiosum is engorged; in priapism, this is not the case. The corpora cavernosa share vascular supply and drainage, and the corpus spongiosum remains separate. Normal erection begins with a rise in the rate of inflow of blood. Pathologic erection occurs when the inflow exceeds the outflow capacity. Persistence of priapism may result in impotence and fibrosis of the corpora. The causes of priapism include a variety of drugs, trauma, nervous system lesions, tumors, and common hematologic disorders, especially sickle cell disease. Idiopathic and neonatal episodes have also been described.

CLINICAL PRESENTATION AND EXAMINATION The diagnosis of priapism is elementary after history and physical examination. The patient presents because of failure for an erection to resolve and may or may not have pain. The glans, which is part of the corpus spongiosum, is not involved. Likewise, phimosis, paraphimosis, and balanitis are readily apparent on physical examination.

PROCEDURES AND LABORATORY TESTING Laboratory assessment for patients with priapism should assess possible underlying causes that can be reversed. At a minimum, a complete blood count, coagulation studies, and urinalysis should be performed. If an underlying medical condition exists or a recent traumatic event has occurred, it should be evaluated from the perspective that the episode of priapism is possibly the result of the other illness. No specific evaluation can be recommended for phimosis, paraphimosis, or balanitis, with the exception of considering the extent of infection when balanitis exists.

MANAGEMENT AND ADMISSION The goal in therapy for episodes of priapism is to improve venous drainage and prevent ischemia, fibrosis, and impotence. Correcting the underlying condition may be possible, as in the case of sickle cell disease, which may respond to oxygen, hydration, alkalinization, and possibly transfusion. Urologic consultation is indicated and should be considered early in the patient's course. Hydration, oxygen administration, and sedative and analgesic use should be considered conservative supportive measures. Local anesthesia at the base of the penis may be attempted with plain lidocaine. If urinary retention is present, a bladder catheter should be placed. Surgical treatment is indicated if conservative measures fail. The corpora may be directly irrigated with plain or heparinized saline by means of large-bore needles. General anesthesia, ketamine, and shunting procedures may be pursued in the appropriate setting. Impotence may result from an episode of priapism and the patient should be advised. Balanitis and Paraphimosis Balanitis may precipitate an episode of phimosis because of swelling of the foreskin and glans. The infection requires treatment with a broad-spectrum antibiotic and local cleansing by the use of soaks or sitz baths. Circumcision should be considered as a means to prevent recurrences, but should be delayed until the infection has resolved. Rarely, a dorsal slit is needed in the foreskin to help resolve the infection or allow a bladder catheter to be placed. Paraphimosis with resulting edema of the glans warrants reduction. The glans may be manually compressed before or after local anesthesia at the superior aspect of the base of the corpus. Consultation should be provided by a urologist if this is unsuccessful. Arrangements for later circumcision should be arranged if the episode is resolved. Otherwise, onsite consultation is required due to compression with ischemia, future ulceration, and even gangrene. Fournier's Gangrene This is a rapidly progressive gangrenous infection usually originating in the scrotum. The mixed infection ( Bacteroides and streptococcus) can cause rapid necrosis. Broad-spectrum antibiotic therapy must be initiated rapidly. A gram stain can be useful since cultures take too much time to be useful. Surgical debridement is often needed (5). Peyronie's Disease This is a fibrous plaque of the corpora cavernosa that produces chordee and pain on erection, the so-called “bent spike” syndrome. The patient may present in the ED because of difficulty in intercourse because of the bent erection. The important thing to remember is that there is considerable psychologic overlay with this problem. Patients require reassurance and support and avoidance of operative intervention. No medication is effective. Through examination and discussion of the mechanism of the curvature, the problem is usually managed satisfactorily. Tumor of the Penis This occurs only in uncircumcised men and boys and presents as a mass that is usually palpable underneath the foreskin. If the prepuce cannot be pulled back and a mass is felt, biopsy is indicated. Occasionally, a patient waits too long, and a completely eroding ulcerative lesion of the penis can be seen. This must be considered carcinoma until proved otherwise by biopsy. Any lesion of the penis not of a specific cause should be biopsied. Precancerous skin lesions, such as Queyrat's erythroplasia Bowen's disease, and leukoplakia may occur and must be treated, and are best referred from the ED. Hematospermia Many middle-aged men present with blood in their semen. Often a female partner also complains of bleeding, but then the couple realizes that the blood is coming from the man. It must be ascertained whether the semen was bloody or the blood was coming from scrotal varices. Management in the ED involves only reassurance. If the condition recurs or is ongoing, urologic investigation is indicated. The cause is usually non-neoplastic and probably arises from varicosities near the verumontanum. Occasionally, hematospermia can herald a testicular or prostatic tumor. Prostatitis Acute and chronic bacterial prostatitis and prostatodynia are all associated with pain in the prostate region. In the latter two, rectal exam may not be associated with tenderness. Acute bacterial prostatitis usually presents as an illness with an abrupt onset, associated with systemic signs of infection. The history, physical, and laboratory evaluation of acute prostatitis suggest the presence of a lower urinary tract infection. Manipulation of the acutely infected prostate during rectal examination is painful and may result in bacteria being dispersed into the systemic circulation. When sepsis from an infected prostate occurs, hospitalization and parenteral antibiotics are necessary. When acute bacterial prostatitis is associated with urinary retention or systemic signs of infection, or is complicated by underlying chronic or debilitating disease, hospitalization and parenteral antibiotic therapy are warranted. Particularly in the elderly, prostatitis may be accompanied by obstructive symptoms and

bacteremia—leading to a septic state. Parenteral antibiotics with antipseudomonas coverage included are necessary (e.g., an aminoglycoside and third-generation cephalosporin). Outpatient treatment with oral antibiotics, usually a sulfa combination or a quinolone (e.g., ciprofloxacin 500 mg twice daily for 2 weeks), may be considered in those less severely ill. Tetracycline or doxycycline are secondary choices, but can be used in cases where the patient is taking H-2 blockers because the quinolones are poorly absorbed from the stomach if the pH is greater than 5.0. Oral antibiotics, which usually have poor penetration into the prostate, may be effective in acute prostatitis because of increased permeability as a result of inflammation. A therapeutic plan should be developed in conjunction with a urologist so that appropriate continuing care can be arranged. The chronic, recurrent, or nonbacterial forms of prostatitis or prostatic symptoms of unclear cause warrant the involvement of a urologist. Attention should be directed toward assessment of the patient's ability to void and renal function.

MEDICOLEGAL PEARLS Many cases have resulted from delays in treatment of a torsion with resultant loss of a testicle. Abdominal pain can cause mistaken emphasis and result in delay. Beware of bite infections of the penis or scrotum, which can rapidly progress. References 1. Williamson R: Torsion of the testis and allied conditions. Br J Surg 1976;63:465. 2. Cass A, Cass B, Verraraghavan K: Immediate exploration of the unilateral acute scrotum in young male subjects. J Urol 1980;124:829. 2A. Kass EJ, Stone KT, Cacciorelli AA, et al: Do all children with an acute scrotum require exploration? J Urol 1993;150P2:667–669. 3. Wilbert DM, Schaerfe CW, Stern WD, et al: Evaluation of the acute scrotum by color-coded Doppler ultrasonography. J Urol 1993;149:1475. 4. Ransler C, Allen T: Torsion of the spermatic cord. Urol Clin North Am 1982;9:245. 5. Saluino C, Hartford FJ, Dobrin PB. Necrotizing infection of the perineum. South Med J 1993;86:908.

CHAPTER 53 ACUTE URINARY RETENTION AND BLADDER DRAINAGE Principles and Practice of Emergency Medicine

CHAPTER 53 ACUTE URINARY RETENTION AND BLADDER DRAINAGE Lester Karafin and A. Richard Kendall Capsule Introduction Diagnosis Management

CAPSULE The physiologic act of micturition is taken for granted by all human beings until there is some disturbance in function. The actual inability to void is most often the final event but is preceded by years of symptoms such as hesitancy, dribbling, and poor stream. Men, women, and children, however, can present in the emergency department (ED) with a complete inability to void, usually accompanied by abdominal discomfort, or the condition may be of the “silent” variety, so that the individual gives a history of not voiding only over the past 12 to 24 hours.

INTRODUCTION A detailed history helps to delineate the actual cause. In the case of the adult male, a history of a previous urethral stricture with passage of sounds is a good clue that the retention may be caused by a urethral stricture. The patient may state that he had prostate gland trouble for some time with such signs and symptoms of obstruction as hesitancy and dribbling. He may state that he had a growth in his prostate resulting in hormone therapy and an operation on his scrotum (bilateral orchiectomy for carcinoma of the prostate). Clot retention may occur with hematuria secondary to a bladder tumor, prostatism, or upper tract disease. Neurogenic bladder disease is usually apparent and associated with such other significant neurologic abnormalities as a cerebral vascular accident or chronic neurologic disease. We have, however, seen acute urinary retention as the only presenting sign of multiple sclerosis and early in the course of herpes zoster affecting the lower nerve roots of the spinal cord. Medications (antihistamines) or parasympatholytic drugs may produce acute urinary retention, as can others. In children, such congenital anomalies as a urethral valve or a meatal stenosis can actually produce complete urinary retention. Finally, in the differential diagnosis, hysterical retention may be seen in young women. Foreign bodies (self-inserted) or bladder calculi that obstruct the vesical neck are much rarer causes of this problem.

DIAGNOSIS Physical examination usually reveals a large globular mass above the symphysis extending up to the umbilicus. Amazingly, many times an abdominal mass can disappear on simple insertion of a urethral catheter. Rectal examination may reveal a benign enlarged prostate or the typical stony-hard, irregular enlargement of carcinoma of the prostate. A normal feeling prostate on rectal examination does not preclude prostatism as a cause of urinary retention. The absolute diagnosis, as well as part of the initial management, is made by passage of a small No. 16 or 18 urethral catheter. If the instrument passes easily through the urethra, stricture is ruled out, and if a large amount of urine is obtained, the diagnosis of urinary retention is made. Emptying the bladder by means of catheter and evacuating more than several hundred mililiters of urine, followed by disappearance of the abdominal mass, confirm diagnosis of urinary retention.

MANAGEMENT Nonsurgical management involves the use of urethral catheters. There are many factors to be considered in instrumentation. Initially, use an aseptic technique, since the obstructed bladder provides a fertile field for bacterial growth. The genitalia should be washed thoroughly with soap and water or hexachlorophene (pHisoHex) solution and an antiseptic sponge placed on the urethra, on either the glans or the vulva. Bacteria are always present in the urethra, and external cleansing does not preclude the possibility of introduction of bacteria. Catheter and urethra should be adequately lubricated. Ordinarily, it is sufficient to lubricate the catheter with water-soluble jelly. Urethral catheterization should be performed gently, without force. Discomfort experienced in a urethral catheterization is similar to that felt in a rectal examination when the examiner attempts to force his finger through the anal sphincter. Therefore, if the physician forces a catheter through the urethral sphincter, it will cause a great deal of discomfort. Instilling lubricant directly into the penis is helpful. The physician will find that asking the patient to attempt to urinate on catheterization can be an aid, and, in a patient with an enlarged prostate, that simply inserting the finger in the rectum and directing the tip over the median lobe while someone else inserts the catheter can be helpful. A soft rubber catheter should be used routinely. A 30F sound has a diameter of 10 mm. A 16 or 18F soft rubber catheter is used most often for diagnostic purposes, as this size should pass in the absence of a stricture. It is a mistake to attempt to pass anything smaller than a 16F catheter in adult men because smaller sizes frequently lack the necessary stiffness and are apt to coil in the urethra. A No. 18 Foley is probably the best catheter to choose when urinary retention is suspected because it obviates the need to catheterize an individual twice. If the physician is unable to pass the catheter and the area of holdup is not the urethra but back at the prostate, insert a finger into the rectum, as described previously, or select a catheter coudé, which has a curved tip at the end that allows the catheter to slide over the median lobe of the prostate. If this approach is unsuccessful, a lubricated catheter stylet placed within the lumen of the catheter before insertion can be used if it is a familiar instrument to the operator and if they are careful during insertion. The technique is similar to that used in passing a sound, but it should be done only by those experienced in its use. Use of a filiform and following sound might be a safer method in this situation. The catheter is inserted like a sound, the stylet is removed, and the catheter remains in the bladder. The danger is perforation of the urethra or the bladder by the rigid instrument. If a Foley cannot be inserted, a straight rubber catheter can be placed and taped to the penis. It is important to allow expansion of the penis and not to use tape around its entire circumference. In the presence of a urethral stricture, filiforms and following sounds are indicated. The filiforms are made of woven silk-plastic material and come in sizes 3 to 6F. Various types of tips are available, with a corkscrew or coudé being useful. The other end of the filiform is equipped with a female thread so that a following metal or woven catheter measuring from sizes 8 to 30 can be used. These catheters can be solid or hollow so that drainage can occur. Filiforms are inserted into the bladder; two or three are used because some go into the false passages. It takes some experience to be certain that the filiform is completely within the bladder. Then the following sound is screwed on and dilation of the urethral stricture is done in a progressive manner. Regular metal sounds without these filiforms are commonly used, chiefly in large caliber strictures. Sounds are curved at the end and are available in sizes ranging from 8 to 30 F. The size of the initial sound should be approximately 20 so that the broad tip will not perforate the urethral wall. If necessary to use a size smaller than No. 20, it is better to use a filiform. Once the sound is introduced and reaches the external sphincter, the handle is brought down to a vertical position, which enables the sound to pass. Occasionally, the physician uses a panendoscope to find the way into a tortuous urethra that resists all forms of catheterization. Surgical management is required when the urethra cannot be traversed and retention is not relieved. A suprapubic catheter can be inserted under local or field-block anesthesia by direct visualization of the bladder and insertion of a large mushroom or Foley catheter from above. The Campbell punch cystotomy instrument can be used in the ED only if the bladder is definitely palpable. This allows the insertion of a No. 18 Foley catheter through a trocar. With the advent of the cystocath, suprapubic insertion by the needle puncture has eliminated the need for the Campbell punch. A No. 16 to 18 Foley catheter can be inserted following gradual dilation of the suprapubic tract after several days.

CHAPTER 54 NEUROGENIC BLADDER: CAUSES AND EVALUATION Principles and Practice of Emergency Medicine

CHAPTER 54 NEUROGENIC BLADDER: CAUSES AND EVALUATION Scott B. Freeman Capsule Anatomy and Pathophysiology Clinical Presentation Differential Diagnosis Procedures and Laboratory Testing Management and Admission Medicolegal Pearls

CAPSULE The loss of normal innervation of the urinary bladder may result in the retention of urine. The onset of the disturbance may be rapid or slow in onset. The origins may be divided into lesions of the upper or lower motor neurons and those of the motor or sensory nerves of the bladder. Urinary retention commonly results from obstructive lesions rather than denervation of the bladder. Other neurogenic causes include myriad drugs that can cause retention of urine ( Table 54.1).

Table 54.1. Pharmacologic Agents Associated with Urinary

ANATOMY AND PATHOPHYSIOLOGY In the normal adult, the bladder is behind the pubic symphysis. In childhood or when chronically distended, the bladder rises superiorly above the symphysis. Posteriorly, the bladder is adjacent to the rectum in men and the vas deferens and seminal vesicles are on this surface. In women, the posterior surface is adjacent to the vagina and cervix. The bladder is surrounded laterally by the levator ani and obturator internal muscles. The bladder fuses to the prostate in men, and in women it lies directly on the pelvic fascia. The muscular coat component of the bladder is a crisscross arrangement of fibers. These condense in a circular manner to form the internal sphincter near the internal orifice. The nerves supplying the bladder comprise the vesical plexus, which arises from the anterior part of the inferior hypogastric plexus. It is comprised of sympathetic and parasympathetic components, and branches are sent to the seminal vesicles and deferent ducts. The sympathetic efferent fibers arise from the last two thoracic and first two lumbar spinal cord segments. The parasympathetic efferent fibers arise from the second through fourth sacral segments of the spinal cord. The parasympathetic efferent fibers innervate the detrusor muscle and the inhibitory fibers to the internal sphincter. The external sphincter is supplied by the pudendal nerve and is under voluntary control. Pain fibers, which are stimulated by distension of the bladder, run in the sympathetic and parasympathetic nerves. These fibers then lie in the anterolateral white columns of the spinal cord. The posterior columns contain fibers that transmit the awareness of filling of the bladder and the desire to micturate. Until micturition starts, voluntary restraint is exercised by coincident inhibition of the detrusor and contraction of the external sphincter and perineal muscles. The internal sphincter is not under voluntary control, and an increase in tone occurs as the detrusor is relaxed during filling of the bladder. The first stage of micturition is a relaxation of the perineal muscles, except for the external sphincter, and contraction of the muscles of the abdominal wall. Next, the detrusor contracts and the internal sphincter relaxes. The flow of urine begins with the relaxation of the external sphincter and is assisted by the contraction of the abdominal wall musculature. Upper motor neuron lesions or lesions above the T-11 spinal level can be conceptualized as creating a urinary bladder that fails to store urine. Lower motor neuron lesions or lesions that involve the conus medullaris and cauda equina can create a urinary bladder that fails to empty. Mixed lesions occur from injuries between these cord levels.

CLINICAL PRESENTATION Urinary dysfunction is rarely the sole presenting symptom for patients with a neurogenic bladder. This is in opposition to urinary retention that is the result of an obstructive lesion in which the resulting urinary dysfunction is the primary reason for seeking treatment. The individual with a neurogenic bladder caused by denervation of the sensory pathways may not have pain as part of the presentation. As urine is retained in the bladder, stasis promotes infection and hydrostatic injury to the ureters and kidneys begins to develop. Upper motor neuron lesions may be caused by spinal cord trauma, tumors, or multiple sclerosis. Lesions in the cerebral cortex or pyramidal tracts lead to a loss of inhibitory control of micturition. Cortical lesions may be the result of stroke, head injury, Parkinson's disease, or intracerebral tumors. Lower motor neuron lesions may result from spinal cord trauma, tumors involving the spinal cord, herniated nucleus pulposus, and multiple sclerosis. This is by no means an exhaustive list, and other entities that affect neurologic function, such as tabes dorsalis, may also create a neurogenic bladder. Early in the course of herpes zoster, urinary retention may be the only presenting sign. Disruption of either the afferent or efferent nerves to the urinary bladder by diabetes mellitus or herpetic infections may cause a peripheral neuropathy. Neuropathies of these nerves may then result in a loss of control of micturition.

DIFFERENTIAL DIAGNOSIS Urinary retention is likely to be the presenting symptom of a neurogenic bladder. Most episodes of acute urinary retention result from an obstructive lesion rather than the loss of neurologic control of the bladder. Because the outflow tract for urine is greater in length and complexity in men, most obstructive lesions occur in this group. Urinary retention may also be precipitated by medications and psychologic stress. The most frequently encountered obstructive lesion is the result of benign prostatic hypertrophy. The resulting obstruction is generally progressive in onset and associated with symptoms that suggest a gradually decreasing caliber of the urinary outflow tract. Acute obstruction in this setting may be precipitated by infection or medications. Other entities that may cause obstructive lesions are: Prostatic cancers and infections

Strictures of the urethra Bladder neck contractures Phimosis Paraphimosis Foreign bodies Obstructive lesions are rare in women because of the short length of the urethra. Abnormalities that cause enlargement of the uterus or pelvic masses may cause urinary outlet obstruction by exerting pressure on the bladder neck or urethra. Numerous medications may precipitate an episode of urinary retention ( Table 54.1). Medications may interfere with micturition by affecting neurologic functioning at any nervous system level from the cortical to the effects they can exert on the tone of the musculature of the bladder or sphincter.

PROCEDURES AND LABORATORY TESTING Although urinary retention is rarely life-threatening, it may be associated with significant pain. Immediate drainage of obstructed urine may be indicated before a diagnostic evaluation is begun (see Chapter 53). The minimum laboratory evaluation should include a urine analysis and culture and an assessment of renal function. The evaluation may be extended to include a complete blood count, electrolytes, and a plain radiograph of the abdomen when the cause of the episode is not apparent. Blood cultures may be needed if sepsis is suspected. Additional urologic evaluation may include dynamic studies of bladder functioning, cystoscopy, and electromyography. These types of studies are appropriately done by a specialist in the functioning of the bladder, usually on an inpatient basis. Procedures in the emergency setting usually have as their goal the drainage of urine and basic evaluation for the cause. In most cases this can be accomplished by the use of urethral catheters. In uncommon cases, catheterization is not possible, and more invasive maneuvers must be pursued to drain urine from the bladder (see Chapter 12-1 and Chapter 12-2).

MANAGEMENT AND ADMISSION The drainage of retained urine is the initial phase of management. Subsequent treatment and evaluation should be directed toward determining the cause of the urinary retention. Otherwise healthy patients in whom the origin of the episode is clearly understood and not complicated by infection or renal dysfunction, and in whom drainage is accomplished by simple means, without likelihood of recurrence in the time span required for the patients to see a urologist, may be managed as outpatients with subsequent care provided by a urologist and other appropriate specialists. There is controversy over how rapidly an obstructed bladder should be drained. It is possible for rapid drainage of large amounts of urine from the bladder to cause hemorrhage and the recurrence of urinary obstruction from clot formation. This is an uncommon event, but it is prudent to drain volumes of urine that are greater than a liter at a controlled rate. Also, rapid drainage of large volumes can lead to syncope. Another uncommon complication associated with urinary retention and subsequent drainage is the development of a postobstructive diuresis. When this occurs, voluminous amounts of urine may be produced. The rate at which urine is produced may exceed a liter per hour and result in life-threatening fluid and electrolyte imbalances. The occurrence of a postobstructive diuresis warrants admission to a monitored setting. Clearly, patients in whom urinary obstruction has been relieved should be observed for several hours to exclude the occurrence of this unusual complication. Life-threatening hypertension may result from the syndrome called autonomic dysreflexia. This syndrome is the result of generalized sympathetic discharge, from distention of the bladder, in patients with high spinal cord lesions. It is associated with hypertension, diaphoresis, vasodilation and bradycardia.

MEDICOLEGAL PEARLS A patient with neurogenic bladder disease has some neurologic deficit and the cause must be established. This generally requires an inpatient evaluation. The relief of urinary obstruction by using transurethral catheters is contraindicated if the integrity of the urethra is in doubt. After urinary obstruction has been relieved, a period of observation is indicated to exclude the development of a postobstructive diuresis. In the unusual setting of autonomic dysreflexia, drainage of urine from the bladder may be life-saving. Suggested Readings Fontanarosa PB, Roush WR: Acute urinary retention. Emerg Med Clin North Am 1988;6:419–437. Fuselier HA: Etiology and management of acute urinary retention. Compr Ther 1993;19:31–36. O'Donnell W: Urologic management in the patient with acute spinal cord injury. Crit Care Clin 1987;3:612.

CHAPTER 55 RENAL CALCULI (KIDNEY STONES) Principles and Practice of Emergency Medicine

CHAPTER 55 RENAL CALCULI (KIDNEY STONES) John J. Pahira Capsule Epidemiology Causes Composition of Urinary Calculi Clinical Presentation Evaluation Early Management and Treatment Indications for Hospitalization New Treatment Options for Surgical Stones Pitfalls and Medicolegal Pearls

CAPSULE Advances in fiberoptic endoscopes, introduction of extracorporeal shock wave lithotripsy (ESWL), and significant improvements in the evaluation and treatment of recurrent nephrolithiasis have contributed to an improved quality of life for the patient with a urinary stone. The prevalence of stone disease is 10 times higher today, however, than it was at the beginning of the century. Obstruction of the urinary tract secondary to a calculus with the associated symptoms of acute onset of flank pain, nausea and vomiting, hematuria or fever remains a common cause of emergency department (ED) visits.

EPIDEMIOLOGY Formation of a stone within the urinary tract does not usually represent a specific disease but rather a complication of various disorders. It is a common affliction of the urinary tract, exceeded in incidence only by urinary tract infection and prostatic disease. According to one estimate, a white American male has about a one in eight chance of forming a stone by age 70 ( 1). Because not all patients with renal or ureteral stones are hospitalized, the exact prevalence of urinary calculus disease is difficult to estimate from data provided by hospital admissions. Epidemiologic studies indicate the frequency of urolithiasis in the United States has been increasing over the past 25 years. The current incidence of urinary tract calculi is 16 to 24 cases per 10,000 population per year ( 2). More than 350,000 Americans develop urinary tract stones yearly, and the overall hospitalization rate is about 20% of those affected ( 3). One possible explanation is the overall higher standard of living, which is associated with increased dietary protein and decreased fiber intake, shown to increase urinary levels of calcium, uric acid, and inorganic phosphate ( 4).

CAUSES The potential for forming urinary calculi in a given individual depends on various risk factors that may be classified as intrinsic and extrinsic ( 5) (Table 55.1).

Table 55.1. Intrinsic and Extrinsic Risk Factors

Intrinsic Risk Factors Intrinsic risks factors are related to anatomic, biochemical, and inherited characteristics of the individual. A family history of renal calculi suggests a heritable disorder such as cystinuria, primary hyperoxaluria, or renal tubular acidosis. Stone formation tends to be familial, and a brother of a stone former may have as great as a 50% chance of forming a stone during his lifetime. Coincident illnesses, such as inflammatory bowel disease, chronic diarrheal states, chronic pancreatitis, hyperparathyroidism, medullary sponge kidney, and recurrent urinary tract infections may be associated with an increased incidence of urinary stones. Age and sex are also important factors. A sharp increase in the incidence of stones begins at age 20, with the highest incidence occurring in patients between the ages of 30 and 50. Men are more commonly affected than women, with a male:female ratio for calcium oxalate stones of 3:1. Lower serum testosterone levels may explain the lower incidence in women and children ( 3). Stones associated with urinary tract infection (struvite, or magnesium-ammonium-phosphate stones) are seen twice as often in women as in men (5). Extrinsic Risk Factors Extrinsic risk factors that may play a role in calculi formation include climate, availability of drinking water, type of diet, type and amount of trace elements in drinking water/food, and occupation. The frequency of stones is increased in certain geographic areas. In the United States, the areas of highest incidence are the northwestern, southeastern, and southwestern regions. Hot weather seems to be directly related to an increased frequency of urolithiasis. In addition to the influence of heat on hydration status and, therefore, on urine concentration, another important factor is the exposure to sunlight, which increases the production of vitamin D, leading to increased intestinal absorption of calcium and a higher filtered load in the urine ( 6). Although most studies have shown that increased water intake is essential to reduce the likelihood of calculus formation, the issue of whether water hardness or softness contributes more to stone frequency remains controversial. Ingestion of foods high in calcium, purine, oxalate, or phosphate contributes to stone formation. Dairy products are the main source of daily calcium intake. Excessive calcium, however, can be present in the diet in the form of supplements such as bone meal, vitamin D, multiple vitamins high in calcium, enriched calcium foods, and calcium-containing antacids (TUMS, Rolaids). Excessive salt in the diet accentuates intestinal absorption of calcium. Purine, found in protein-rich foods (meat, fish, poultry), is important because of its metabolite, uric acid. Foods containing large amounts of oxalate include spinach, cranberry juice, tea, cola, cocoa, beets, raspberries, chocolate, and nuts. Vitamin C supplements more than 1000 mg/day can increase urinary oxalate levels. Occupation may be significant because it determines the ambient temperature in which an individual works. It may also be a factor in the availability of drinking water and the types of food in the diet. As previously mentioned, persons in higher socioeconomic groups tend to ingest more animal protein and less fiber, causing higher urinary levels of calcium, oxalate, and uric acid.

COMPOSITION OF URINARY CALCULI Pure calcium oxalate stones and stones that are combinations of calcium oxalate and calcium phosphate usually originate in the upper urinary tract and account for two-thirds of stones in the North American population ( Fig. 55.1). Calcium stone disease has many causes. Hypercalciuria and hyperuricosuria, alone or in combination, are the two metabolic disorders commonly identified. Hypercalciuria is typically defined as a daily urinary calcium excretion of more than 300 mg in men and 250 mg in women; however, it is more appropriately defined as more than 4 mg/kg of body weight per day. Three major mechanisms have been defined as accounting for hypercalciuria (resorptive, absorptive, and renal leak).

Figure 55.1. Composition of urinary calculi in the North American population.

Hypercalciuria can be secondary to a variety of diseases that cause hypercalcemia and elevated urinary calcium ( Table 55.2). Primary hyperparathyroidism is the common hypercalcemic state associated with urolithiasis and is seen in about 5% of patients ( 7). Parathyroid hormone (PTH) causes hypercalciuria directly, by increasing bone resorption and, therefore, increasing the filtered load of calcium, and indirectly by stimulating renal synthesis of dihydroxy-vitamin D and, therefore, increasing intestinal absorption of calcium.

Table 55.2. Diseases Associated with Hypercalcemia and Hypercalciuria

Pure calcium phosphate stones are uncommon, but are often associated with distal renal tubular acidosis (RTA). Patients with distal RTA are unable to excrete hydrogen ions from the distal tubule. There is an associated renal loss of sodium, potassium, and calcium. The resulting hypercalciuria eventually leads to nephrolithiasis or nephrocalcinosis. Patients also have hypokalemia, hyperchloremia, metabolic acidosis (with serum CO 2 less than 20), alkaline urine (fasting urinary pH always exceeds 5.5), and hypocitraturia. Most calcium oxalate stone formers have normocalcemic hypercalciuria or “idiopathic hypercalciuria.” Idiopathic hypercalciuria occurs in 2 to 4% of all adults but only 0.5% develop calcium stones (8). Absorptive hypercalciuria is the common cause of normocalcemic hypercalciuria. Sustained increase in intestinal absorption of calcium leads to suppression of PTH and an increased filtered load of calcium, causing hypercalciuria. Renal leak is a less common form of normocalcemic hypercalciuria that results from renal tubular leak of calcium, causing increased PTH and increased dihydroxy-vitamin D production and secondary increased intestinal absorption ( 9,10). Magnesium ammonium phosphate stones constitute about 15% of all stones. Their predominance is higher in women than in men (2:1), and all patients are or have been infected with urease-producing bacteria, usually Proteus, Pseudomonas, or Klebsiella. Hyperuricosuria is defined as more than 800 mg/day in men and more than 750 mg/day in women. Pure uric acid stones may occur when the urine uric acid concentration exceeds the saturation point. These account for approximately 8% of all stones. About 10 to 20% of patients with calcium oxalate stones excrete excess amounts of uric acid (11). Monosodium urate crystals can enhance calcium oxalate stone formation by acting as a nidus on which calcium oxalate crystals can grow or may lower the concentration of calcium oxalate crystal inhibitory substances such as glycosaminoglycans ( 12). Hyperuricosuria usually results from excessive dietary intake of purine-rich foods such as meats (especially organ meats such as liver and kidney), fish, and poultry. Approximately 25% of patients with symptomatic gout form uric acid stones, and similarly, 25% of patients with uric acid stones have gout. Most patients have a history of poor hydration and persistently acidic urine. Cystine stones are associated with a rare hereditary disorder, cystinuria, in which excessive amounts of the amino acids cystine, arginine, ornithine, and lysine are excreted in the urine because of a failure of reabsorption of the renal tubule. Cystine excretion is less than 100 mg/day in normal individuals, between 150 and 300 mg in individuals who are heterozygotes, and more than 400 mg in homozygotes.

CLINICAL PRESENTATION Most calculi are formed in the upper urinary tract adjacent to the renal papilla. After reaching a certain size, they pass progressively into the calyx, renal pelvis, ureter, and bladder. Urinary tract calculi may not produce symptoms and may be uncovered as an incidental radiographic finding, in the presence of microscopic hematuria, or when the urinary tract becomes infected or obstructed. The typical pain associated with urinary calculi develops only with obstruction, either partial or complete, and the pain pattern depends on the site of obstruction. A stone may obstruct the urinary system in five areas: the renal calyx, the ureteropelvic junction, the pelvic brim, the posterior pelvis, and the ureterovesical junction (Fig. 55.2). Proximal site is in a calyx or a calyceal diverticulum, obstruction causes abdominal distention, pain, and hematuria. The next place where a stone may lodge is at the ureteropelvic junction. The luminal diameter at the ureteropelvic junction is 2 to 3 mm, compared with 1 cm in the renal pelvis.

Figure 55.2. The most common areas where calculi obstruct the urinary system are shown, along with treatment approaches to patients with urinary tract stones. ESWL = extracorporeal shock wave lithotripsy.

A stone impacted in a calyx or at the ureteropelvic junction may produce excruciating pain localized to the flank or the costovertebral angle ( Fig. 55.3). Pain generated in the upper urinary tract often radiates from the back and laterally around the flank and into the abdomen. It may even radiate into the groin and testicle in men and the labia majora in women. The pain is frequently not typical and can simulate that of biliary colic, appendicitis, diverticulitis, or even perforated viscus. However, occasionally abdominal aortic aneurysm (AAA) is mistakenly thought to be due to renal colic, particularly in the presence of hematuria.

Figure 55.3. Renal colic may produce pain localized to the flank that may radiate laterally into the abdomen and even into the groin and genital region.

EVALUATION History Patients should be questioned about the character (rate of onset, severity and location) of pain and a history of previous calculi. A family history of nephrolithiasis or identification of one or more of the risk factors for stones ( Table 55.1) may suggest a urinary stone as the source of the patient's pain. Physical Examination The characteristic physical sign of renal calculus disease is the patient's perpetual motion. Unlike the patient with peritonitis, who lies quietly, often with legs drawn up in a fetal position, the patient with renal colic finds that no position brings relief from the pain. The patient alternatively sits, stands, paces, and reclines in an effort to find a comfortable position. The pain is colicky in nature and may wax and wane, but the absence of pain does not necessarily mean that the stone has passed. Tachycardia, diaphoresis, and tachypnea owing to the severity of the pain occur frequently. Hypertension secondary to a sympathetic response to pain may also be present. Nausea and vomiting may accompany renal colic because the celiac ganglion serves the kidneys and the stomach. Abdominal distention secondary to an ileus is associated with retroperitoneal irritation and may suggest other problems. Any intra-abdominal pathology can produce pain that simulates renal colic ( Table 55.3).

Table 55.3. Differential Diagnosis in Intra-Abdominal Pathology that can Mimic Renal Colic

Fever is usually not present unless the patient has a urinary tract infection. When infection accompanies obstruction, the patient may present with pyelonephritis or gram-negative sepsis. Careful examination of the abdomen is essential to distinguish renal colic from an acute surgical abdomen. With renal colic, the patient's abdomen is generally soft, without rebound, or guarding on palpation. Moderate tenderness may be elicited with palpation over the flank and the lower abdominal quadrant. Bowel sounds may be normal to diminished. The bladder should also be palpated because urinary retention occasionally accompanies acute ureteral colic. Rectal and vaginal examinations are generally unremarkable. It may be possible to palpate distal ureteral calculi on vaginal examination in some women. Laboratory Tests Urinalysis is the most important test in the diagnosis and management of renal colic. Gross hematuria occurs in 5 to 10% of cases and microscopic hematuria in 90% (13). With complete ureteral obstruction, hematuria may be absent. Because the normal urinary pH fluctuates throughout the day from 4.8 to 7.0, an isolated urinary pH in the ED setting may not have significant value. An acid pH less than 5.5, however, rules out renal tubular acidosis. Uric acid and cystine calculi form in acid urine, whereas calcium phosphate and magnesium ammonium phosphate calculi form in relatively alkaline urine. Alkaline urine implies the possibility of urea-splitting bacterial infection. Pyuria suggests the presence of urinary tract infection but may also be secondary to inflammation with mucosal irritation. Urine culture should be done in all patients suspected of having urinary stones. Crystals in the urinary sediment are of no diagnostic importance unless they are cystine crystals ( Fig. 55.4). Cystine crystals are not seen in normal urine, and their presence is diagnostic of cystinuria. Adding a few drops of vinegar or acetic acid to a urine sample may facilitate identification of cystine crystals.

Figure 55.4. Characteristic six-sided or “benzene ring” appearance of cystine crystals.

White blood cell (WBC) count may be slightly elevated during urinary colic but more than 15,000 WBCs per cubic millimeter suggests active infection. Radiographic Studies KUB At least 90% of urinary stones are radiopaque and visible on plain radiographs of the abdomen (KUB) ( 14). Calcifications on the KUB that can be confused with urinary calculi include calcified mesenteric lymph nodes, phleboliths in pelvic veins, gallstones, vascular calcifications, and calcified costal cartilage. Also, if the ureteral stone overlies the spine or bony pelvis, it may not be visualized. INTRAVENOUS PYELOGRAM The intravenous pyelogram (IVP) is the imaging study of choice for determining stone location and degree of obstruction and for evaluating renal function ( 15,16). In acute colic, the IVP shows a dense nephrogram on the affected side with a delay in excretion of contrast. The study should be continued long enough to allow contrast to fill the ureter to the point of obstruction. While the patient is in the x-ray department, be sure to have them strain their urine. Often, in response to the diuresis associated with the intravenous contrast, distal ureteral calculi pass spontaneously and may be lost if the patient is not instructed to strain their urine. Also associated with the increased intrapelvic pressure are forniceal rupture and urinary extravasation. This is usually self-limiting and is not a problem unless associated with infection. It does necessitate closer observation of the patient, and antibiotic therapy should be initiated if infection is suspected ( Fig. 55.5).

Figure 55.5. Forniceal rupture and urinary extravasation seen on IVP in this patient with a distal right ureteral stone.

ULTRASOUND IVP is more sensitive than ultrasound in detecting acute hydronephrosis and in delineating the location of renal or ureteral calculi. When an IVP cannot be obtained, as in patients with a history of contrast allergy or chronic renal failure, or in pregnancy, in which it may be appropriate to limit radiation exposure, ultrasound may demonstrate the presence of hydronephrosis or the presence of an echogenic focus with an acoustic shadow characteristic of a calculus. CT scan is useful if there is kidney disease. RETROGRADE UROGRAPHY Cystoscopy and retrograde ureteropyelogram are indicated if visualization of the stone or cause of obstruction is inadequate on IVP. In patients with a history of contrast allergy, if KUB and ultrasound are nondiagnostic, then retrograde pyelography may be indicated. A renal scan or unenhanced abdominal CT scan are also options to evaluate for stone and/or obstruction in the face of concerns relating to the use of intravenous contrast ( 16A).

EARLY MANAGEMENT AND TREATMENT Pain Control When a patient presents with signs and symptoms highly suggestive of renal or ureteral colic, appropriate pain relief while obtaining additional diagnostic studies is indicated. Before sending a patient to the X-ray department, intramuscular injection of 50- to 100-mg meperidine, 10- to 15-mg morphine, or 60-mg IM Toradol (the injectable NSAID), which is often an effective medication ( 17) depending on body size and severity of pain, should be given. Toradol can also be given at half dose (30 mg) intravenously. The use of ancillary medications for the management of colic such as antispasmodics, anti-inflammatory agents, glucagon, and diuretics, has not proven effective in reducing pain or speeding the process of stone passage and in general are not recommended ( 3,18). An occasional drug-seeking patient may present with the classic symptoms of renal colic. Be wary of the individual who has too “perfect” a history, especially when associated with a known intravenous contrast allergy. The urine sample in these individuals should be obtained in front of the physician or staff to avoid contamination with blood from other sources. If the patient is unable to produce urine in this manner, it may be necessary to catheterize the patient for a sample. In the patient with possible “drug-seeking” behavior and contrast allergy, a KUB with renal sonogram or renal scan may help to define a stone or associated relative hydronephrosis. Hydration Aggressive intravenous hydration during the acute phase of renal colic may aggravate the degree of obstruction and increase the patient's discomfort. Unless the patient appears dehydrated from vomiting or diarrhea, oral hydration is usually adequate. Maintain adequate oral hydration to keep the urine colorless. Recommend the patient drink one 8-ounce glass of liquid per hour while awake; about one-half of the liquid should be plain water. Outpatient Management Most healthy patients are able to pass their stones spontaneously and can be managed on an outpatient basis with oral analgesics and increased fluid intake ( 18A).

The probability of spontaneous passage depends on both the length and width of the stone. Stones less than 4 mm in diameter have a 75% probability of passing, whereas those with diameters of over 8 mm have only a 10% chance of passing ( 19). Instruct the patient to strain the urine until the stone passes. Analysis of the stone, especially in a patient's first stone, is important to begin evaluation of the cause of stone formation. If the patient is not admitted to the hospital for observation, instruct them to seek appropriate urologic follow-up within a short period of time. The patient must understand that simply because the pain has disappeared it may not mean that the stone has passed. The stone may still be causing partial obstruction that, if left untreated, can lead to renal damage. Also, a calculus that remains stationary within the ureter for a long time can lead to increased inflammation and possible secondary stricture formation. Urologic follow-up is important to determine how likely the patient is to form a recurrent stone. Patients at high risks for recurrent formation should undergo a metabolic evaluation to determine the cause of their calculus disease and appropriate treatment to prevent recurrence.

INDICATIONS FOR HOSPITALIZATION Patients require hospitalization if oral analgesics are not adequate for pain control and parenteral medications are necessary. If persistent nausea and vomiting prevent the patient from maintaining oral hydration, admission for intravenous hydration and parenteral pain control may be indicated. The presence of pyuria and/or bacteriuria on urinalysis, elevated temperature, WBC count greater than 15,000, or a history of urinary infection should suggest the possibility of associated urinary tract infection. This can rapidly lead to a life-threatening urosepsis and requires immediate urologic consultation plus observation and broad-spectrum intravenous antibiotic therapy. A large calculus (more than 8 mm) is unlikely to pass spontaneously, and if it is associated with high-grade obstruction, urologic consultation to determine treatment is advised. The patient with a solitary kidney or with renal insufficiency and obstruction warrants hospitalization and observation. If the diagnosis is uncertain, hospitalization is necessary for additional testing. In many instances, abdominal aortic aneurysm may present with pain and hematuria thought to be secondary to a renal stone.

NEW TREATMENT OPTIONS FOR SURGICAL STONES When a calculus is associated with persistent pain, obstruction, or infection because of size or location, surgical removal must be considered. Indications for surgical intervention in urinary stone disease are outlined in Table 55.4.

Table 55.4. Indications for Surgical Intervention in Renal Calculus Disease

Previously, the only choice for surgical management of stone disease was a standard open operation. The tissue disruption and postoperative pain, coupled with an average convalescence of 4 to 6 weeks, make such surgery for stone removal an extremely traumatic experience. Technologic advances in the field of urology have begun to revolutionize the management of “surgical” calculi. Several nonsurgical alternatives for stone removal are available, including percutaneous nephrolithotomy, urethroscopy, and ESWL ( 20). Which technique is appropriate for an individual stone depends on the patient as well as the size and the location of the stone ( Fig. 55.2). In general, stones in the lower third of the ureter are removed with the urethroscope. Stones in the middle and upper thirds of the ureter are probably best treated with manipulation of the stones into the renal pelvis, where they are more easily treated with ESWL. Stones that cannot be pushed into the renal pelvis can be treated in the ureter with ESWL. The placement of a stent preoperatively may increase the success rate. Another option for upper ureteral calculi is the use of flexible ureteroscopy and laser lithotripsy. When renal pelvic stones are smaller than 2 to 3 cm, ESWL is the optimal approach because it is the least invasive. For larger renal stones and staghorn calculi, a combination of percutaneous nephrolithotripsy and ESWL appears to be the best approach. Nephrolithotripsy is initially performed to debulk the stone and ESWL is later used to fragment the remaining pieces. Unfortunately, these therapeutic advances are applicable to only 20 to 25% of all urinary calculi. The majority of patients must still undergo the discomfort and cost (direct and indirect) associated with spontaneous passage of the stone. Therefore, the goals of medical management are ideally to prevent the formation of new stones and inhibit the growth or reduce the size of existing stones ( 21).

PITFALLS AND MEDICOLEGAL PEARLS 1. Misdiagnosing AAA as renal colic. 2. Absence of follow-up with retained stone. 3. Failure to admit to hospital when nausea, vomiting, or severe infection is present. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

Johnson CM, Wilson DM, O'Fallon WM, et al: Renal stone epidemiology: a 25-patient study in Rochester, Minnesota. Kidney Int 1979;16:624. Sierakowski R, Finlayson B, Landes RR, et al: The frequency of urolithiasis in hospital discharge diagnosis in the United States. Invest Urol 1978;15:438. Drach GW: Urinary lithiasis. In: Walsh PC, ed. Campbell's urology. 5th ed. Philadelphia: WB Saunders Co., 1986, 1094–1190. Robertson WG: Epidemiology of urinary stone disease. Urol Res 1990;18(Suppl):S3–S8. Coe FL, Keck J, Norton ER: The natural history of calcium urolithiasis. JAMA 1977;238:1519. Lee PH, Menon M: Etiology of renal stones. AUA Update Series 1986;5:34. Coe FL, Parks JH: Pathophysiology of kidney stones and strategies for treatment. Hosp Pract 1988;123:145. Coe FL: Nephrolithiasis: causes, classification and management. Hosp Pract 1981;116:33. Menon M, Krishman CS: Evaluation and medical management of the patient with calcium stone disease. Urol Clin North Am 1983;14:595. Pahira JJ: Nephrolithiasis: current concepts in medical management. Urol Radiol 1984;6:74. Pak CY, Kaplan R, Bone H, et al: A simple test for the diagnosis of absorptive, resorptive and renal hypercalciurias. N Engl J Med 1977;292:497. Preminger GM: Cost and time effective out-patient metabolic stone evaluation. Probl Urol 1987;1:569. Wyker AW Jr: Renal calculi. In: Wyker AW, Gillenwater JY, eds. Methods of urology. Philadelphia: Williams and Wilkens, 1975. Johnson RD: Renal calculus disease. In: Lapides J, ed. Fundamentals of urology. Philadelphia: WB Saunders Co., 1976. Bush WH, Gibson PA: Case for the IVP: risks and indications. AUA Update Series 1986;5:2. Labreque M, Dostaler LP, Rousselle R, et al: Efficacy of NSAIDS in the treatment of renal colic. Arch Int Med 1995;154:1381.

16A. Barret B, Partey PS: Prevention of nephrotoxicity induced by contrast agents. N Engl J Med 1994;331:1449–1450. 17. Wrenn K: Emergency intravenous pyelography in the setting of possible renal colic: is it indicated? Ann Emerg Med 1995;26:304.

18. Thuroff JW: Pain with upper tract urinary stones. Probl Urol 1989;3:196. 18A. Morse RM, Resnick MI: Ureteral calculi. J Urol 1991;145:263–267. 19. Ueno A, Kawamura T, Ogawa A, et al: Relation of spontaneous passage of ureteral calculi to size. Urology 1977;10:544. 20. O'Brien WM, Rotolo JE, Pahira JJ: New approaches in the treatment of renal calculi. Am Fam Physician 1987;36:181. 21. Sutton RL: Causes and prevention of calcium-containing renal calculi. West J Med 1991;155:249.

Chapter 56.1 Emergency Delivery Principles and Practice of Emergency Medicine

CHAPTER 56 OBSTETRIC EMERGENCIES

1 Emergency Delivery Stephen D. Higgins Capsule High-Risk Pregnancy Pathophysiology of Labor Physical Examination Prehospital Assessment and Stabilization Management Prehospital Delivery Perimortem Salvage

CAPSULE A significant number of pregnant women in labor presenting to the prehospital emergency medical service (EMS) system and the emergency department (ED) are at high risk, with a greater chance of death and disability for mother and fetus. Proper triage, conduct of delivery, and recognition and treatment of life-threatening emergencies increase the likelihood of a good outcome. Be prepared for the unusual possibility and need for perimortem cesarean section to save the fetus, and possibly also the mother, during cardiorespiratory arrest.

HIGH-RISK PREGNANCY A high-risk pregnancy is one in which the mother or the fetus has a significantly increased chance of death or disability, compared to a low-risk pregnancy in which optimal outcome is expected (Table 56–1.1). For high-risk pregnancies, the perinatal infant mortality rate is as great as 3.5 to 14.5%, whereas in low-risk pregnancies, the perinatal infant mortality rate is as little as 0.04%. In a study of 738 patients, Hobel et al. ( 1) showed that, in the prenatal period, approximately 34% of pregnant patients can be categorized as high risk. When labor begins, an additional 20% are added to this category. Study by Brunette and Sterner ( 2) confirms the increased mortality and morbidity of patients delivering in the prehospital care setting or the ED. A study of 80 patients delivering in the field or the ED, showed an infant mortality rate of 9%. There was an increased incidence of shoulder dystocia, postpartum hemorrhage, prolapsed cord, and meconium staining. Because of the significant and yet unpredictable number of high-risk pregnancies in the field and the ED, as well as the predictable increased incidence of complications associated with these high-risk pregnancies, it is important to strongly discourage prehospital deliveries whenever possible and to encourage transfer to the appropriate facility. The type of facility also has an effect on outcome. Paneth et al. ( 3) showed that patients with high-risk pregnancies have a 24% higher risk of death if birth occurred outside of a level III perinatal center. A high-risk pregnancy was easily determined in this study as either preterm (less than 37 weeks) or low birth weight (less than 2251 g). A level III perinatal center is one in which all types of perinatal care are provided, including obstetric and neonatal intensive care as well as a broad range of subspecialty consultative services.

Table 56–1.1. Glossary of Obstetric Terms

PATHOPHYSIOLOGY OF LABOR True labor is defined as pain that occurs at regular intervals, which progressively shorten while the intensity of the pain gradually increases ( Table 56–1.2). The pain can occur in the back as well as in the abdomen and can be interpreted also as mere discomfort. This is especially true in early or preterm labor. For a diagnosis of true labor, however, there must not only be pain, but also progress, i.e., documented progressive cervical dilatation and effacement. Two or more serial examinations may be necessary to properly document progress in early labor. In contrast to true labor, false labor is characterized by pain occurring at irregular intervals with the intervals remaining long and the intensity remaining unchanged or diminishing. More importantly, on repeated examinations, there is no cervical dilatation or effacement.

Table 56–1.2. Characteristics of True Versus False Labor

There are three stages of labor ( Fig. 56–1.1). The first stage of labor starts with pain and cervical dilation and effacement and ends when the cervix is fully dilated. The second stage begins with full dilation and effacement of the cervix and is completed with delivery of the infant. This is the stage during which the mother is actively pushing. The third stage begins with the delivery of the infant and ends with the delivery of the placenta and fetal membranes.

Figure 56–1.1. Progress of labor.

The first stage of labor has commonly been divided into two distinct phases, latent and active. The latent phase can be anywhere from a few hours to as long as 20 hours in nulliparas and 14 hours in multiparas. This phase is characterized by uterine contractions of milder intensity and shorter duration. The cervical dilation and effacement occur at a slower rate. During the active phase, in contrast, the cervix dilates rapidly at 1 to 2 cm/h. The active phase begins at about 4-cm dilation. During the active phase of labor, dilation occurs in nulliparas at a minimum of 1.2 cm/h and in multiparas at a minimum of 1.5 cm/h. Mothers with a higher gravidity and parity have a faster labor. It must be assumed, however, when trying to anticipate these patterns that obstetrics is predictably unpredictable. The rapid nature of the second phase of labor is probably one of the factors that results in delivery in the field or the ED; a few of these mothers are likely to have precipitate labor. Precipitate labor and delivery are those that are extremely rapid. A rapid, uncontrolled delivery with the mother pushing vigorously can cause rupture of the uterus or extensive lacerations of the cervix, vagina, vulva, or perineum. In addition, the fetus is subjected to an increased mortality and morbidity, as a result of poor uterine blood flow and oxygenation of the fetal blood during the vigorous labor, as well as direct trauma to the intracranial contents of the fetus as it is expelled explosively through the introitus. It is vitally important, therefore, for the EMS personnel or ED physician to be available to control the delivery and prevent injury to the mother and fetus as well as be available for any needed resuscitation after the delivery.

PHYSICAL EXAMINATION The basic documentation of the initial physical examination should always include a reference to amniotic fluid, cervical dilation and effacement, presenting part, and station. If the membranes have ruptured, the character of the fluid should be noted. Presence of vernix indicates a mature fetus and presence of meconium suggests fetal distress and mandates the need to prevent meconium aspiration during delivery. The amount of cervical dilation is determined by estimating the diameter of the cervical opening with two fingers in the vagina. The cervix is said to be maximally dilated when the diameter is 10 cm across or it can no longer be palpated. Cervical effacement is the length of the cervix compared to that of an uneffaced cervix. On the basis of previous experience, the examiner has a general idea of the normal length of a cervix, which is approximately 2 cm. When this cervix is reduced by one-half, it is said to be 50% effaced. A cervix is 100% effaced when it becomes almost paper-thin, i.e., has no thickness. Presenting part refers to either cephalic or breech presentation. It is important for later management to be absolutely sure of the presenting part as ascertained in the first examination. Station is the level of the presenting fetal part in the birth canal. The ischial spines felt as bony prominences in the vagina are about halfway between the pelvic inlet at the top of the birth canal and the pelvic outlet at the introitus. Stations represent centimeters above and below the ischial spine. If the fetal head is 5 cm above the ischial spine (at the pelvic inlet), it is represented as a –5/5 station. If the head is below 0 station (the ischial spines), its degree of descent is also measured in centimeters such as +1/5 or +2/5, or if the head is visible at the introitus, it is +5/5 station.

PREHOSPITAL ASSESSMENT AND STABILIZATION The minimum amount of history to be obtained by the EMS or ED personnel includes: Gravidity, parity, and abortion Last normal menstrual period Estimated date of confinement Presence or absence of ruptured membranes History of bleeding Pregnancy or medical problems The gravidity, parity, and abortion give some idea as to the rapidity with which delivery will occur. A primigravida (woman with her first pregnancy) has a slower labor than a multigravida (woman with several pregnancies). The last normal menstrual period is important to know to estimate where the mother is in the course of this pregnancy. (Note that the last normal menstrual period is defined as the first day of the last menstrual period.) A “pregnancy wheel” is most convenient for measuring the mother's gestational age. In general, fetuses with less than 26 weeks gestation are considered previable. In pregnancies of 26 to 37 weeks, fetuses are obviously premature and at higher risk. In pregnancies after 37 weeks and up to 42 weeks, fetuses are considered term. In pregnancies after 42 weeks, fetuses are postterm and again are at high risk. It is also important to ask the due date or estimated date of confinement (EDC). This might be different from the calculated date because her obstetrician might have changed it, based on earlier examination, an ultrasound, or other information. Documentation of ruptured membranes is important because it may alert you to increased risk of infection if the membranes have been ruptured for a prolonged period of time (longer than 24 hours) and guides examinations, which should be sterile once membranes have ruptured. The presence of vernix may indicate a term fetus and the presence of meconium may indicate a distressed fetus with the need for measures to prevent meconium aspiration at delivery. The presence of bleeding may indicate serious complications such as placenta previa and placental abruption. A small amount of blood mixed with mucus indicates a bloody “show,” and represents expulsion of the mucus plug from the cervix. If the mother states that a small amount of blood was mixed with mucus, it can be safely presumed that this is bloody show. If the mother states, however, that there has been bleeding without the presence of mucus and/or that the bleeding has been “more than a menstrual period,” it must be presumed that there is a placenta previa until proven otherwise with ultrasound. It is important also for ED personnel to ask the obvious question as to whether or not there have been any problems with the pregnancy. This may include not only problems with the pregnancy itself, but also any preexisting medical problems. Concomitant with the taking of the history, the physical examination is being performed and should consist of a minimum of: Vital signs Abdominal examination and monitoring of uterine contractions Examination of the perineum Among the vital signs, blood pressure is especially important because, by definition, a blood pressure of more than 140/90 mm Hg is preeclampsia, a cause of increased maternal and fetal morbidity and mortality. A brief inspection of the abdomen gives some idea of gestational age. If the top of the fundus is more than halfway between the umbilicus and the xiphoid process, the fetus is likely to be older than 26 weeks and, therefore, viable. During the history taking and physical examination, the examiner should have their hand on the patient's abdomen, monitoring for uterine contractions. The absence of frequent uterine contractions is somewhat reassuring in the prehospital or ED setting because imminent delivery is not likely. Frequent and vigorous uterine contractions, however, may be predictive of imminent delivery, precipitate delivery, or placental abruption. If there is any possibility of imminent delivery, personnel should examine the perineum for perineal

bulging, rectal bulging, and crowning of the fetal head.

PREHOSPITAL DELIVERY Imminent delivery is characterized by uncontrollable pushing by the mother, often accompanied by crowning ( Fig. 56–1.2). At this time, the basic principle must turn away from rapid transport of the mother to the hospital and instead change to immediate preparation for delivery in the field. Any attempt to restrain or delay delivery at this point by holding the baby's head back or crossing the mother's legs are absolutely contraindicated. Preparation should be made for a safe delivery with special emphasis on preventing trauma to the birth canal and fetus. In preparing for an imminent delivery, if time permits, a large-bore intravenous line is started to administer 5% dextrose and a crystalloid solution (normal saline or Ringers lactate) approximately 100 mL/h. A clean sheet is placed under the mother and the EMS personnel should allow her to assume whatever position is most comfortable. This may be on her back with her knees flexed and her thighs separated, or perhaps on her side. When she is lying in the supine position, a pillow or firm pad can be placed under the buttocks to allow room for delivery of the fetal and shoulders. The EMS personnel, as time permits, should put on mask and eye protection, wash their hands, and put on sterile gloves. The EMS personnel should be instructed now to control the delivery of the presenting head. The palm of the hand is placed on the fetal head, and gentle pressure is exerted to provide a slow, controlled delivery. The mother is instructed to “pant” and not to push between contractions. Many times the uterine contractions alone deliver the head. If not, the mother can be asked to perform controlled pushing on command when the uterine contractions commence. After the uterine contraction is over, again the mother should be asked not to push.

Figure 56–1.2. Crowning.

As the head is delivered, it rotates to one side ( Fig. 56–1.3). At this time, wipe dry the face and suction the infant's nose and mouth with bulb suction. When meconium is present, special attention should be directed to removing the meconium to prevent its aspiration by the infant during or after delivery, which can cause significant and possibly fatal lung damage. After suctioning of the fetus, the EMS personnel should palpate the top of the neck for loops of cord. If loops of cord are around the neck, gentle traction with the index finger will slip the cord down over the head ( Fig. 56–1.4). After delivery of the fetal head and suctioning of the nose and mouth, gentle downward traction on the head and neck delivers the anterior shoulder first. Following delivery of the anterior shoulder, upward traction delivers the posterior shoulder, followed by the rest of the infant. A firm grip is maintained on the infant, holding it along the length of the operator's arm with the head slightly lower than the feet.

Figure 56–1.3. Rotation of head.

Figure 56–1.4. Remove cord from neck and slip over head.

After completion of the delivery, an Apgar score should be assigned to the infant at 1 minute and 5 minutes after birth ( Table 56–1.3). The 1-minute Apgar score indicates need for immediate resuscitation, and the 5-minute Apgar score indicates increased risk of infant mortality and morbidity later on in the nursery. A score of less than 5 indicates severe neonatal depression at 1 minute, and a high-risk neonatal course at 5 minutes.

Table 56–1.3. Apgar Score

After delivery and suctioning, while the child is being vigorously dried, the umbilical cord should be cut by placing two clamps approximately 6 cm from the fetal abdomen. Cut between these two clamps, which have been placed approximately 2 cm apart. If the baby has a lusty cry, a heart rate more than 100 beats/min, and good muscle tone after wrapping, it should be presented to the mother. The placenta need not be delivered in the field but can be left in situ while transported to the nearest ED. It is important for EMS personnel during a field delivery to document: Precise time of birth (the time after the infant is completely delivered) Apgar score Child's gender

MANAGEMENT Triage All women who are pregnant and complaining of pain or bleeding are of highest priority and should be seen immediately. It is imperative to rule out in any pregnant woman the possibility of labor, abnormal presentation such as breech, or other complications such as a prolapsed cord. Any pregnant woman after rupture of her membranes should have a sterile vaginal examination to rule out prolapsed cord. Vaginal bleeding may indicate placenta previa or placental abruption, and there is always a possibility of ongoing fetal distress, which may occur in a woman who is postterm or has preeclampsia, or a fetus with cord complications. The woman who is relatively comfortable in her second trimester, but is complaining of mild abdominal pain, may actually be in active labor with a premature fetus and is in need of immediate tocolysis to stop labor and save the baby. Many pregnancy complications requiring emergency intervention might not be evident in the average pregnant patient waiting for care. Therefore, because of the occult nature of these emergencies, these patients should be seen as a highest priority in the ED. Once a diagnosis of active labor is made, it should be understood that the best place for delivery is in the labor and delivery suite. In most situations, the ED is a difficult place to keep a dedicated space available for deliveries with the capability of maintaining aseptic technique and all the equipment and personnel available to help in a delivery. More importantly, there is no capability in the ED to perform a cesarean section. Therefore, after the patient has been properly evaluated in the ED, transport rapidly to the labor and delivery suite, where she may be monitored by trained obstetric nurses, who are more comfortable with this type of patient. Even if the obstetrician or gynecologist is not available at the time, it is still safer to deliver in the labor and delivery suite, where there are perinatal nurses and neonatologists and warmers, airway equipment, umbilical lines, and other equipment. When the delivery is imminent, however, preparations for delivery in the ED must be made and there should be policies and procedures and adequate equipment in place to facilitate the emergency delivery. Delivery Delivery of the patient in active labor in the ED department should proceed the same as in the labor and delivery suite. A brief history and physical examination are done while the patient is receiving a large-bore intravenous line to instill a crystalloid solution. In the history, special attention is, of course, aimed at gravidity, parity, EDC, problems with this pregnancy, and whether or not the patient has had ruptured membranes, bloody show, or vaginal bleeding. If there is a history of ruptured membranes and delivery is not imminent, this should be confirmed using nitrazine paper. The method is to insert a sterile speculum into the vagina. A cotton-tipped applicator is used to retrieve secretions from the vaginal vault. The cotton-tipped applicator is then pressed against a strip of nitrazine paper, and if the nitrazine strip turns blue, indicating a basic pH, the membranes are likely to be ruptured. Normally, the vagina is acidic and the paper stays yellow or green. Amniotic fluid is more basic and, therefore, turns the nitrazine paper blue. Contamination with blood, however, is also basic and confuses the test by also turning the nitrazine paper blue. If the patient states that she had vaginal bleeding, determine whether this is simply bloody show or an actual episode of pathologic bleeding . The differentiation is critical. Bloody show occurs early in labor and is result of expulsion of the mucus plug from the cervix along with a little blood. Bloody show is characterized by a small amount of bleeding mixed with mucus. This is common, and when there is a clear history of a bloody show, the physician can go ahead and perform a pelvic examination without worry. If there is a significant amount of blood with no mucus mixed with it, however, one must consider the possibility of third-trimester bleeding. An important cause of third-trimester bleeding is placenta previa, and if an examination is performed on a patient with placenta previa, trauma to the placenta by the physician's fingers causes disruption of the placental vessels and resultant immediate catastrophic exsanguination of the mother on the examining table. It is, therefore, vitally important to defer pelvic examination on any pregnant woman having third-trimester bleeding. Patients with third-trimester bleeding should be immediately taken to the labor and delivery suite where the routine procedure is to institute large-bore intravenous lines, external fetal monitoring, appropriate blood studies including type and cross match, and emergency ultrasound to obtain a definitive diagnosis. If the history confirms that there has been no significant vaginal bleeding, a vaginal examination can be done. The first vaginal examination should be done with a clean glove, using sterile lubricant if the membranes have not ruptured. After the membranes have ruptured, a betadine solution may be used as a lubricant. The reason why the betadine solution is not used initially is that it may discolor the vaginal secretions, and when the membranes do rupture, the dark color of the betadine solution will be confused with meconium. The vaginal examination should determine the effacement and dilation of the cervix, the presenting part, and its station. It is vitally important to be definitely sure of the presenting part because it is dangerous to allow a breech, shoulder, or cord presentation to labor benignly without appropriate preparations for delivery. MONITORING FETAL HEART TONES Recommendations for monitoring fetal heart tones have been outlined in ( Table 56–1.4). Low-risk patients are monitored by auscultation of the fetal heart every 30 minutes after a contraction in the active phase of the first stage of labor and at least every 15 minutes in the second stage of labor. High-risk patients are monitored by either continuous electronic fetal monitoring or by more diligent auscultation at intervals of 15 minutes during the active phase of the first stage of labor and 5 minutes during the second stage of labor. Auscultation should be done immediately after a uterine contraction. When electronic fetal monitoring is used, the tracing should be monitored and initialed at comparable times during the first and second stages of labor.

Table 56–1.4. Recommended Fetal Heart Rate Monitoring

PREPARATION FOR DELIVERY In preparation for the delivery, the mother is placed in a position that is comfortable for her as well as effective for the physician who will be involved in administering analgesia and controlling the delivery. In the United States, the lithotomy position is generally used for vaginal delivery; however, many physicians have experience with and prefer the lateral or partial sitting position. The vulva and perineum are cleansed and sterile drapes applied. The physician dons scrub suit, mask, headgear, and protective eyewear; scrubs hands and forearms; and puts on water-repellant gown and gloves. The major goal now is to prevent a precipitous delivery, which would cause maternal or fetal trauma. EPISIOTOMY An episiotomy is an incision of the perineum and vaginal mucosa made just before delivery of the fetal head to avoid tearing of this area and prevention of later pelvic relaxation to avoid cystocele, rectocele, and urinary incontinence ( Fig. 56–1.5). The procedure is simply performed by taking a straight scissors and, just before the fetal head is delivered, cutting down the perineum as well as up into the vaginal mucosa. (This same incision can be actually extended into the rectum for emergency situations such as shoulder dystocia and breech delivery.) There has been much debate recently, however, regarding whether or not the attributes of episiotomy are merely theoretic. In general, the episiotomy can be avoided in multiparous patients with a controlled delivery of the fetal head. In primiparous patients, when a laceration is considered likely, a midline episiotomy should be performed. Episiotomy is contraindicated in only a few conditions. These include cases of inflammatory bowel disease, lymphogranuloma venereum, severe perianal scarring and malformation, and perhaps coagulation disorders such as idiopathic thrombocytopenic purpura. A method of repair for episiotomy is found in Figure 56–1.6.

Figure 56–1.5. Lateral episiotomy is shown. A midline episiotomy is usually used in normal birth presentations.

Figure 56–1.6. Repair of median episiotomy. A. Chromic catgut 00, or preferably 000, is used as a continuous suture to close the vaginal mucosa and submucosa. B. After closing the vaginal incision and reapproximating the cut margins of the hymenal ring, the suture is tied and cut. Next, three or four interrupted sutures of 00 or 000 catgut are placed in the fascia and muscle of the incised perineum. C. A continuous suture is now carried downward to unite the superficial fascia. D. Completion of repair. The continuous suture is carried upward as a subcuticular stitch. (An alternative method of closure of skin and subcutaneous fascia is illustrated in E.) E. Completion of repair of median episiotomy. A few interrupted sutures of 000 chromic catgut are placed through the skin and subcutaneous fascia and loosely tied. This closure avoids burying two layers of catgut in the more superficial layers of the perineum. Some physicians are preferring synthetic absorbable sutures (e.g., vicryl), which is a matter of preference rather than outcome. (Reprinted with permission from Cunningham FG, MacDonald PC, Gant NF. Williams obstetrics. 18th ed. Norwalk, CT: Appleton and Lange, 1989:324.)

NORMAL DELIVERY As delivery proceeds, the goal is to prevent a precipitous delivery that would cause maternal or fetal trauma. This can be done by gently applying guidance to the fetal head and slight pressure on the perineum of the mother, and asking her to control her pushing by intermittently panting or blowing. The normal expulsive forces of the uterus, combined with the controlled pushing of the mother, result in a controlled delivery of the fetal head, slow and progressive and not quick and explosive. After the fetal head is delivered, external rotation of the head to the side occurs and the mouth and nose are suctioned with a bulb aspirator. The neck should be checked for loops of umbilical cord, (see previous text) next, the anterior shoulder is delivered by gently pulling the head by the neck in downward position, then the posterior shoulder, and finally the body. PLACENTAL DELIVERY The third stage of labor, or delivery of the placenta, takes place after placental separation. Signs of placental separation include the following: 1. 2. 3. 4.

The earliest sign is the uterus becomes globular and more firm. A sudden gush of blood. The uterus rises into the abdomen as the placenta passes into the vagina, where its bulk pushes the uterus upward. The umbilical cord protrudes 2 or 3 inches farther out of the vagina, an indication that the placenta is descending.

Placental separation usually occurs anywhere from 1 to 20 minutes after delivery of the baby. If the physician is not sure if there has been placental separation or not, the gloved examination hand can be placed up into the vagina to confirm that the placenta is actually sitting in the vagina, away and distinct from the cervix and uterus. Gentle traction on the cord then delivers the placenta, which should be checked for its integrity. If parts of the placenta are missing, retained products of conception should be considered and the obstetrician/gynecologist should be so informed. MECONIUM STAINING MANAGEMENT Special mention should be made of proper airway management in the fetus with meconium staining. Meconium is the greenish-black contents of the fetal bowel; it consists of undigested debris from swallowed amniotic fluid as well as desquamated gastrointestinal cells and other products of secretion and excretion from the bowel. Its greenish-black color is produced by biliverdin. Normally, there is no evacuation of the bowel while the fetus is in utero. The presence of meconium staining has a strong correlation with fetal distress. Meconium staining of the amniotic fluid occurs in approximately 20% of all pregnant patients at delivery. It may occur in 44% of postdate pregnancies. If the meconium is aspirated by the fetus, meconium aspiration syndrome occurs. This syndrome has a mortality rate as high as 28%, and, therefore, the ideal method of care is to prevent the aspiration. The infant should be suctioned immediately after delivery of the head, before the fetus has a

chance to expand its lungs. The nose and then the mouth and oropharynx are suctioned using a 10F or larger suction catheter. While the body is still in the birth canal, the chest is compressed and there is no chance of the fetus expanding its lungs to take a breath and aspirating the meconium. After thorough suctioning of the nose, mouth, and oropharynx, the rest of the delivery proceeds. After delivery, the infant is placed on the examination table and laryngoscopy is used to visualize the cords. If meconium is present in the hypopharynx or on the cords, then endotracheal intubation is done and additional suctioning below the cords is performed. HEMOSTASIS AFTER PLACENTA DELIVERY After the placenta is delivered, the primary mechanism by which hemostasis is achieved is the contraction of the myometrium, which compresses the uterine vessels and, therefore, stops bleeding. Agents used to assist in this myometrial contraction include oxytocin, ergonovine, and methylergonovine. Because of the tendency for ergonovine and methylergonovine to cause a precipitous rise in blood pressure, oxytocin is the drug of choice because it is much easier and safer to use. The route of administration is 20 units of oxytocin in one liter of crystalloid solution to run in at approximately 100 mL/h. Oxytocin can be given in 10 units intramuscularly, but should never be given as an intravenous bolus because this latter route can result in episodes of hypotension. Also, oxytocin should always be given in a crystalloid solution (lactated Ringer's or normal saline) because of its antidiuretic effect. If it is given in a dextrose and water solution, the antidiuretic effect may cause water intoxication with hyponatremia and seizures in the mother. CHECK FOR CERVICAL OR VAGINAL TRAUMA The final, most important step in completing delivery is to check for genitourinary trauma. Immediately after delivery of the placenta, when the vagina has been stretched to its maximum, the best examination can be done with the least discomfort to the mother. The physician should be vigorous in putting four fingers of the left hand well into the vagina, thus pushing down the posterior floor of the vagina to reveal the cervix. Ring forceps are then used to grasp the anterior lip of the cervix and traction is applied in a downward and then upward motion to expose the entire cervical os. Only in this way can the physician be 100% assured that there are no actively bleeding tears on the cervix. When this has been ascertained, the ring forceps are disengaged, and several 4 × 4 gauze sponges are placed in the ring forceps. This bulky probe is then placed back into the vagina to push the cervix up and out of the way of the posterior vaginal wall. By continued pressure with the left hand pushing the floor of the vagina down and now pushing the cervix out of the way with the gauze bandages on the end of the forceps, the posterior wall of the vagina over the ischial spines can be visualized. It is not uncommon for a tear to occur over the ischial spines, i.e., the inferolateral wall of the vagina. These tears can be deep and not necessarily extend out into the introitus, and, therefore, can be missed if not checked. This is the ideal time to diagnose this lesion, not several hours later when the mother is hemorrhaging. Next, the vulva should be examined, including the periurethral structures. Minor periurethral tears can be ignored, but any periurethral tears involving subcutaneous tissues or those with active bleeding should be reapproximated with absorbable suture. Whenever suturing around the urethra, a Foley catheter should always be in place to ensure proper localization of the urethra so that no sutures can be placed through this structure. The most common site of tears, however, are the lacerations that occur in the perineal areas. These are labeled first-, second-, third-, and fourth-degree lacerations ( Table 56–1.5) and are repaired as illustrated ( Fig. 56–1.7).

Table 56–1.5. Classification of Lacerations of the Vagina and Perineum

Figure 56–1.7. Repair of complete perineal tear. The rectal mucosa has been repaired with interrupted, fine chromic catgut sutures. The torn ends of the sphincter ani are next approximated with two or three interrupted chromic catgut sutures. The wound is then repaired, as in a second-degree laceration or an episiotomy. (Reprinted with permission from Cunningham FG, MacDonald PC, Gant NF. Williams obstetrics. 18th ed. Norwalk, CT: Appleton and Lange, 1989:325.)

Complications of Delivery A detailed analysis and understanding of all obstetric emergencies is beyond the scope of practice of emergency physicians for several reasons. First of all, the management for many obstetric emergencies is cesarean section, which can be done neither in the field nor in the ED except as a “last-ditch” measure. In a study by Cavanagh (4), almost 90% of the obstetric emergencies occurring in a prehospital setting are related to hemorrhage. Therefore, most obstetric emergencies cannot be definitively cared for in the field or in the ED. Second, many obstetric complications are extremely rare. For example, acute uterine inversion occurs in 1 in 5,000 to 1 in 20,000 cases. When the emergency physician does see such a complication, it is vitally important to know what to do to save the life of the mother or fetus. Certain complications should be recognized and immediately referred to the labor and delivery suite for definitive care. These include breech presentation, which is likely to need cesarean section or at least delivery by an experienced obstetrician/gynecologist. Patients with third-trimester bleeding should also be immediately referred to rule out the possibility of placenta previa or placental abruption. After placenta previa is diagnosed by emergency ultrasound, the patient must have a cesarean section. And finally, of course, fetal distress, when there is no chance of imminent delivery, must be referred to labor and delivery for immediate cesarean section. Prolapsed Cord Other complications also need definitive care in the labor and delivery suite, but certain antecedent maneuvers can be undertaken to stabilize the situation. For example, prolapsed cord, when identified, is handled by placing the mother in the Trendelenburg or knee-chest position, and elevating the fetal part to prevent compression of the cord between the fetal presenting part and the pelvic bones of the mother. If compression of the cord can be prevented in this manner, the mother is rapidly transferred to the labor and delivery suite for emergency cesarean section. Uterine Inversion Another entity that can occur in the prehospital setting or the ED after delivery is acute uterine inversion. This occurs when the umbilical cord is tugged too vigorously

in an attempt to deliver the placenta and the placenta and uterus, in an inside-out fashion, prolapse out of the vagina. This presents as a large, bleeding mass the exact size of a postpartum uterus but inverted on the outside of the vagina, often with the mother in shock. The treatment is to replace the uterus back in the vagina immediately by applying pressure to the inverted tip of the uterus and folding it back inside itself, as if turning a sock inside out ( Fig. 56–1.8). After the uterus is placed back into the vagina, the physician's hand, in the form of a fist, should be held up into the now normally placed uterus inside the mother until the uterus has a chance to clamp down around the fist and hemostasis is accomplished.

Figure 56–1.8. To reposition an inverted uterus, first push it gently toward the back of the vagina (top left). Once the organ is inside, aim it with steady pressure upward toward the umbilicus (bottom left). When the organ is back in place and the placenta has been detached, put your hand back inside the uterus to make sure that it is not reinverting (bottom right).

Postpartum Hemorrhage Another complication that can be stabilized in the ED before transfer is early postpartum hemorrhage, defined as the loss of 500 mL or more of blood after delivery. As noted earlier, a thorough examination most often delineates the cause of a potential postpartum hemorrhage before it occurs. After the placenta is delivered, it is carefully examined for any missing cotyledons. If parts of the placenta are missing, retained products of conception are likely to be the cause of bleeding. A thorough examination of the vagina as described previously reveals whether or not the bleeding source is from laceration of the cervix, vagina, or vulva. If these have all been checked beforehand and postpartum hemorrhage does occur, the most likely cause is uterine atony or an inability of the uterus to contract down, compress its vessels, and, therefore, control its hemorrhage. The immediate therapy is to massage the uterus vigorously through the abdominal wall, encouraging uterine contractions and, therefore, hemostasis. At the same time, the mother is receiving oxytocin in a crystalloid infusion, approximately 20 U/L at 200 mL/h. If this does not work, methylergonovine (Methergine), 0.2 mg, is administered intramuscularly or intravenously. Great care should be taken when giving methylergonovine because it may cause hypertension and exacerbate preeclampsia. Prostaglandin F-2 alpha (Prostin/15 M) has been approved by the Food and Drug Administration (FDA) for the treatment of postpartum hemorrhage from uterine atony. If this is available in the ED, it should be given as a 250 µg (0.25 mg) dose intramuscularly. This is repeated, if necessary, at 15- and 90-minute intervals up to a maximum of 8 doses. Again, prostaglandin F-2 alpha should be monitored carefully because it may cause precipitous hypertension. If none of these rapid sequence measures seem to help, bimanual uterine compression can be used to control hemorrhage until help arrives (Fig. 56–1.9). Help consists of ensuring additional intravenous lines for fluid resuscitation, appropriate blood studies including clotting studies, type, and cross match, and calling the obstetrician for possible surgical intervention including emergency curettage as well as exploratory laparotomy, which may entail uterine artery ligation, hypogastric artery ligation, and/or emergency hysterectomy.

Figure 56–1.9. Bimanual compression of the uterus and massage with the abdominal hand usually controls hemorrhage effectively.

Late postpartum hemorrhage occurs after the first 24 hours postpartum, in the puerperium. It is most often caused by subinvolution of the placental site. Nuchal Cord Some obstetric emergencies can be handled adequately in the ED if occurring there. The first of these is nuchal cord, or cord wrapped tightly around the neck noticed after delivery of the fetal head. Most times, an index finger can be placed over the top of the fetal neck and the cord pulled down over the head ( Fig. 56–1.2). At other times, despite a nuchal cord, the fetus is delivered without any maneuvers to correct it. Often, however, a tight nuchal cord prevents delivery, and cannot be pulled down over the fetal head by the index finger. Rarely, when this happens, the cord can be clamped in two places, approximately 2 to 3 cm apart, and the cord cut between two clamps and unwound around the fetal head. The rest of the delivery should take place rapidly. Other complications handled adequately in the ED have been discussed previously and include management of meconium staining and repair of vulvar and perineal lacerations. Shoulder Dystocia One of the most serious complications of delivery, which must be handled immediately regardless of where the delivery occurs, is shoulder dystocia, which occurs after the delivery of the fetal head and is a result of the shoulders being too large for the birth canal and the anterior shoulder impacting itself against the symphysis pubis. The fetus is essentially stuck in this position, with its cord already drawn into the pelvis and compressed between the fetus and the bony parts of the pelvis. If delivery does not ensue after downward traction on the fetal head during a contraction: 1. 2. 3. 4. 5.

Call for help: Nurse assistance/obstetrician. Drain bladder if it is distended. Cut a generous episiotomy (episioproctotomy). Have assistant apply suprapubic pressure while continuing to apply downard traction on the fetal head. The two assistants initiate McRoberts maneuver: each assistant graps the mother's legs and flexes them back against the abdomen ( Fig. 56–1.10). With hips in full flexion, the pelvis is rotated and the shoulder will more likely slide under the symphysis pubis.

Figure 56–1.10. McRoberts maneuver. The maneuver consists of removing the legs from the stirups and sharply flexing the thighs upon the abdomen as shown by the horizontal arrow. The assistant is also providing suprapubic pressure simultaneously (vertical arrow). (Reprinted with permission from Cunningham FG, MacDonald PC, Gant NF, et al. Williams obstetrics. 20th ed. Stamford, CT: Appleton and Lange, 1997.)

6. If still unsuccessful, next try Rubins maneuver. Reach in and push the most accessible fetal shoulder toward the fetal chest. This decreases the shoulder-to-shoulder diameter to allow the anterior shoulder to disimpact ( Fig. 56–1.11).

Figure 56–1.11. Rubin's (second) maneuver. A. The shoulder-to-shoulder diameter is shown as the distance between the two small arrows. B. The most easily accessible fetal shoulder (the anterior is shown here) is pushed toward the anterior chest wall of the fetus. Most often, this results in abduction of both shoulders, reducing the shoulder-to-shoulder diameter and freeing the impacted anterior shoulder. (Reprinted with permission from Cunningham FG, MacDonald PC, Gant NF. Williams obstetrics. 18th ed. Norwalk, CT: Appleton and Lange, 1989:369.)

7. If still not successful, delivery of the posterior shoulder is attempted. The physician should place the examining hand into the vagina along the fetus' posterior humerus. The humerus is grasped and flipped across the chest of the fetus. The hand is then grasped and the arm and the shoulder are pulled out of the vagina. Delivering the posterior arm and shoulder will then disimpact the anterior shoulder. 8. Finally, if success is still not obtained and obstetrical help and intervention are still remote, the chances of survival are dwindling. The Zavanelli maneuver might be the last opportunity for survival, prior to emergency cesarean section. Give terbutaline 250 µ subcutaneously to relax the uterus. Position the head in its original position (occiput anterior or posterior). Now flex the head and gently apply pressure to push it back into the vagina. This may in some instances buy time to allow for a cesarean delivery. Pressure above the symphysis may occasionally bring the shoulder into the pelvis. Immediate delivery must ensue or the fetus will die in a matter of minutes. If pressure does not work, the quickest, easiest method to relieve this situation is to make a proctoepisiotomy by cutting the episiotomy all the way into the rectum to achieve the greatest opening possible. The physician should then try to rotate the shoulders one way or the other in a “corkscrew” maneuver ( Fig. 56–1.10). By taking two fingers of the examining hand, putting them into the vagina, and pushing the most easily accessible shoulder toward the chest, the physician reduces the shoulder-to-shoulder diameter, which may free the impacted anterior shoulder. If this does not work by pushing the shoulder away from the chest, rotation of the entire thorax can also result in dislodgment. If this is not successful, a final attempt is now made to grasp the posterior hand and deliver the posterior shoulder to relieve the obstruction. The physician should place the examining hand into the vagina along the fetus's posterior humerus. When this is identified, the humerus is then swept across the chest of the fetus; the hand is then grasped and the arm and shoulder are pulled out of the vagina. Delivering the posterior arm and, therefore, the shoulder disimpacts the anterior shoulder and delivery can ensue ( Fig. 56–1.12).

Figure 56–1.12. Shoulder dystocia with impacted anterior shoulder of the fetus. A. The operator's hand is introduced into the vagina along the fetal posterior humerus, which is splinted as the arm is swept across the chest, keeping the arm flexed at the elbow. B. The fetal hand is grasped and the arm extended along the side of the face. C. The posterior arm is delivered from the vagina. (Reprinted with permission from Cunningham FG, MacDonald PC, Gant NF. Williams obstetrics. 18th ed. Norwalk, CT: Appleton and Lange, 1989.)

PERIMORTEM SALVAGE Perimortem/Postmortem Cesarean Section Postmortem cesarean sections have been performed since antiquity. There are many reports in the literature of the survival of the infant after a postmortem cesarean section done because of the sudden, unexpected death of the mother from trauma or other catastrophic medical complication. The fear has always been of performing a cesarean section too soon when the mother is actually not yet dead. Several cases from the literature (5,6), however, have indicated that a postmortem cesarean section not only is an opportunity for saving the fetus, but also may result in greater likelihood for maternal survival. Several cases have now been reported in which a postmortem cesarean section has resulted in survival of the mother, which might not have occurred if the postmortem cesarean section had not been immediately done (5,6). Because these postmortem cesarean sections are done not only to save the fetus but also possibly to save the mother, they should properly be called perimortem cesarean sections. Katz et al. ( 7) has pointed out that the chances of fetal survival are greatest if the perimortem cesarean delivery is completed within 5 minutes after cardiac arrest. Cardiopulmonary resuscitation (CPR) is not an efficient method for blood flow dynamics for the mother, let alone the fetus, who quickly becomes anoxic. Therefore, if after vigorous CPR (including intubation, external cardiac compressions with leftward uterine displacement, and advanced cardiac life support drugs) there is no response, a perimortem cesarean delivery should be done. It is a relatively easy procedure and requires minimum

equipment and, preferably, a neonatal team standing by for neonatal resuscitation. The procedure is performed as follows: 1. CPR is continued. 2. A scalpel is used to incise the abdominal wall in a vertical midline incision down to the uterus ( Fig. 56–1.13).

Figure 56–1.13. Location of incision for perimortem cesarean section.

3. 4. 5. 6.

The uterus is also incised by a vertical midline incision. The fetus is extracted, the cord is clamped, and the fetus is handed to the team in attendance. The placenta is removed next. The uterine cavity and abdominal wall can be temporarily reapproximated with towel clips to control hemostasis. Continue CPR; plan open-chest CPR if possible. If survival occurs, the mother is taken to the operating suite for definite repair of her cesarean section incision. Although survival is greatest up to 5 minutes after cardiac arrest, reported cases have been documented for longer times, and it is not unreasonable to attempt a perimortem cesarean section up to 25 minutes after cardiac arrest.

The perimortem cesarean section, in view of these guidelines, is truly an emergency procedure in which seconds and minutes may decide whether the mother and fetus will live or die. Therefore, whether to obtain consent for a perimortem cesarean section from the family is a moot point. It is well established in the medical and legal literature that emergency situations involving life and death circumstances imply that the right thing should be done at the right time in the interest of the mother and fetus. There is little potential for legal liability in this strategy. References 1. 2. 3. 4. 5. 6. 7.

Hobel CJ, Hyvarinen MA, Okada DM: Prenatal and intrapartum high risk screening. Am J Obstet Gynecol 1973;117:1–9. Brunette DD, Sterner SP: Prehospital and emergency department delivery: a review of eight years' experience. Ann Emerg Med 1989;18:1116–1118. Paneth N, Kiely J, Wallenstein S, et al: The choice of place of delivery. Am J Dis Child 1986;141:60–64. Cavanagh D: Obstetric emergencies. New York: Harper & Row Publishers, 1982. DePace NL, Betesh JS, Kotle MN: Post-mortem cesarean section recovery of both mother and offspring. JAMA 1982;248:971–973. Marx GF: Cardiopulmonary resuscitation of late pregnant women. J Anesthesiol 1982;56:156. Katz VL, Dotters DJ, Druegemueller W: Perimortem cesarean delivery. Obstet Gynecol 1986;68:571–576.

Suggested Readings American Academy of Pediatrics and American Heart Association. Neonatal resuscitation. American Heart Association, 1994. Cunningham SG, MacDonald PC, Gant NF: Williams obstetrics. 20th ed. Norwalk, CT:, Appleton and Lange, 1997. Frigoletto FD, Little GA, eds: Guideline for perinatal care. 2nd ed. American Academy of Pediatrics and the American Academy of Obstetrics and Gynecology, 1988. Granopoulos JG: Emergency complications of labor and delivery. Emerg Med Clin North Am 1994;12:201. Rosenfield JA: Episiotomy and vaginal laceration repair. In: Kersey R, ed. Saunders manual of medical practice (Rakel). Philadelphia, PA: W. B. Saunders, 1996:485.

Chapter 56.2 Ectopic Pregnancy Principles and Practice of Emergency Medicine

CHAPTER 56 OBSTETRIC EMERGENCIES

2 Ectopic Pregnancy Russell J. Carlisle and Barbara Hanke Capsule General Considerations Anatomy and Physiology Clinical Presentation Initial Stabilization Diagnostic Testing: Laboratory and other Procedures Differential Diagnosis Management Pitfalls and Medicolegal Pearls

CAPSULE Ectopic pregnancy remains a leading cause of maternal mortality. Despite a decrease in the overall mortality from this disorder, the incidence continues to rise because of epidemic increases in sexually transmitted diseases (STDs), pelvic surgery and instrumentation, and changing patterns of contraception, especially the use of intrauterine devices (IUDs). In the United States, it remains the leading cause of first-trimester death and the third leading cause of nontraumatic maternal death overall. Improved rates of diagnosis will certainly result from increased clinical suspicion and the prompt use of improved pregnancy tests in reproductive age women who present with gynecologic, obstetric, and gastrointestinal complaints. Because serum human chorionic gonadotrophin (hCG) levels in ectopic pregnancy are often lower than in normal pregnancy, tests for the beta subunit or intact molecule of hCG must be sensitive to less than 10 mIU/mL to detect at least 99% of ectopic pregnancies. Such tests are now widely available and rapidly performed. Ultrasonography, now of higher resolution and availability, can then be used in most instances to establish an intrauterine or extrauterine location of the pregnancy. Traditional diagnostic tests such as culdocentesis, laparoscopy, or laparotomy can supplement or replace sonography in more urgent or less optimal situations. Observation, stabilization, and consultation with the gynecologist remain essential. Women with possible ectopic pregnancy should not leave the emergency department (ED) until pregnancy has been excluded, intrauterine pregnancy (IUP) has been confirmed, or gynecologic consultation and definite follow-up have been arranged.

GENERAL CONSIDERATIONS The incidence of ectopic pregnancy continues to increase dramatically, but despite improved diagnostic techniques and a decrease in the death rate, ectopic pregnancy remains the leading cause of maternal death in early pregnancy ( 1). Many preventable deaths still occur among women with early presentation of the disorder and those seeking health care late in the course of the disorder when rapid intervention may still not be lifesaving. Prompt diagnosis at any stage of the disorder is essential to ensure maternal survival, decrease disability, and conserve reproductive ability. Treatment without surgery makes early diagnosis imperative (2). Definition Pregnancy is defined as ectopic when the fertilized ovum implants elsewhere than the endometrial cavity of the uterus. Tubal pregnancies constitute more than 95% of all ectopic pregnancies. These occur primarily in the ampulla and isthmus and, less commonly, in the infundibulum (or fimbria) and interstitium. Nontubal ectopic pregnancy may occur in the uterine cornua or cervix, or be attached to the ovary or elsewhere in the abdomen (attached to the broad ligament or peritoneal lining) (Fig. 56–2.1).

Figure 56–2.1. Sites of ectopic implantation.

Epidemiology The incidence of ectopic pregnancy has increased dramatically in the last two decades ( 1,2,3,4,5,6 and 7). In the United States, from 1970 to 1992, the rate of ectopic pregnancy increased 4.4 times from 4.5 to 19.7 per 1000 reported pregnancies and the absolute annual number of ectopic pregnancies increased over 6 times from 17,800 to 108,800 (4) (Fig. 56–2.2). The rate of ectopic pregnancy for the same time period was consistently higher for nonwhite women. In either group, the rate is increased with maternal age.

Figure 56–2.2. Number of ectopic pregnancies in the United States, 1970–1992. *National Hospital Discharge Survey. +National Hospital Ambulatory Care Survey.

The rising incidence of ectopic pregnancy has increased its importance as a cause of maternal death despite a fall in the mortality rate ( 3). Ectopic pregnancy is the major cause of maternal death in the first trimester of pregnancy and one of three leading nontraumatic causes of maternal death overall ( 1,4,8) (Table 56–2.1). Nonwhites have the highest mortality rates, with an overall 3.5 times increased risk of death. As a result, black women have a greater than five times risk of dying of

ectopic pregnancy than white women when the net effect of the increased mortality rate and incidence rate for black women are considered together. Teenagers in any racial group have the highest age-dependent risk of death.

Table 56–2.1. Maternal Deaths, Mortality Ratios, and Relative Risks* Maternal Mortality Collaborative, 1980-1985, U.S., 19 Areas

The increased incidence of ectopic pregnancy has been noted in association with certain predisposing factors, which include: 1. Sexually transmitted diseases (STDs). The increased incidence of ectopic pregnancy closely parallels the dramatic increase in STDs. Numerous studies have associated a history of previous STD with ectopic pregnancy or found evidence of previous tubal infection on pathology following surgery for ectopic pregnancy (5,7,8,9,10,11,12,13 and 14). The association appears much stronger with upper tract disease, especially chlamydial and gonococcal salpingitis and pelvic inflammatory disease (PID). 2. Intrauterine device (IUD) use. Despite the contraceptive effectiveness of the IUD, pregnancies occur with IUD use and have an increased incidence of ectopy. The greatest risk has been noted for current IUD users with a continued risk for at least 1 year after removal ( 5,13,14). 3. Pelvic surgery. Ectopic pregnancy occurs commonly after instrumentation of the upper pelvic tract, especially tubal surgery for treatment of infertility, prevention of fertility (tubal sterilization), and treatment of previous ectopic pregnancy. Ectopic pregnancy occurs in 15 to 20% of pregnancies that follow tubal sterilization and the rate of occurrence varies widely with the method of sterilization ( 7,17). Ectopic pregnancy recurs in approximately 25% of pregnancies following previous ectopic pregnancy and in higher numbers following multiple previous ectopic pregnancies ( 7,15). One study of ectopic pregnancy following previous ectopic pregnancy or tubal infertility surgery found preexistent salpingitis to be the predominant causative factor for ectopic implantation ( 14). Previous nontubal abdominal surgery does not appear to increase the risk of ectopic pregnancy. Because tubal sterilization is the second most common ob/gyn procedure and the frequency of tubal reconstructive surgery has more than doubled in the United States, the increased incidence of ectopic pregnancy is expected to continue ( 11). Previous caesarian section is not linked to increased ectopic pregnancy risk ( 16). 4. Changes in contraceptive use. The decreased use of traditional oral contraceptives, which prevent ectopic pregnancy by depressing ovulation, may increase the incidence of ectopic pregnancy. Additionally, the use of tubal surgery, IUDs, and low-dose progestagen contraceptives in place of traditional estrogen/progestogen contraceptives may also have led to an increase in ectopic pregnancy incidence. Low-dose progestogens are felt to alter tubal motility, thereby leading to ectopic implantation. 5. Other. Use of ovulatory agents, fetal diethylstilbestrol (DES) exposure, induced abortion, and postponed timing of first pregnancy have also been noted to be associated with an increase in ectopic pregnancy incidence in some studies, although their independent contribution is less certain. Additionally, an increased suspicion and rate of detection of ectopic pregnancy may have contributed to the observed increase in incidence. Earlier detection may now include some of the 10 to 50% of ectopic pregnancies that resorb spontaneously and previously went uncounted. Risk of Tubal Pregnancy after Tubal Sterilization Although tubal sterilization decreases the incidence of pregnancy and ectopic pregnancy dramatically, as many as 15 to 20% of women who become pregnant after tubal sterilization will have an ectopic pregnancy even many years after the procedure ( 7,17). Ectopic risk was increased 27 times in women receiving bipolar electrocautery when compared with partial salpingectomy. The emergency physician should therefore treat women with previous tubal sterilization as potential candidates for ectopic pregnancy.

ANATOMY AND PHYSIOLOGY In the normal sequence leading to pregnancy, a mature ovarian follicle ruptures, releasing the ovum into the abdominal cavity. The ovum is picked up by the fimbriated ends of the fallopian tube, fertilized by the spermatozoon in the ampulla, and transported for 3 days through the fallopian tube as the resultant zygote develops into the blastocyst. Roughly 6 days after ovulation, the blastocyst implants, first adhering and then eroding through the endometrial epithelium, and becomes buried in the endometrium. Human chorionic gonadotropin (hCG) production by the fetal trophoblast begins immediately with or just before implantation and is detectable in maternal blood within the first day of implantation. The maximum level of hCG is reached at 10 to 12 weeks of pregnancy, after which it declines. In response to stimulation from hCG, the corpus luteum produces the estrogens and progesterone to maintain the pregnancy for the first 6 weeks until placental production of estrogens, progesterone, and human placental lactogen (hPL) takes over. In ectopic pregnancy, this sequence is altered drastically by the aberrant implantation. Ectopic implantation may result from anatomic or functional factors that delay or prevent passage of the fertilized ovum into the uterus or from embryonic abnormalities. These factors may include alterations of ciliary function, tubal morphology or patency as a consequence of salpingitis, tubal surgery, IUD use, or hormonal manipulation, as noted earlier. Ectopic implantation is tubal, most often in the ampulla, less often in the isthmus, and rarely in the interstitium or fimbria. Nontubal sites of ectopic pregnancy are felt to result from a primary tubal implantation and subsequent tubal rupture or abortion with secondary implantation in the nontubal site. The blastocyst, once adherent to the tubal lumen, burrows through the epithelium and into the muscular wall. Trophoblastic invasion of maternal blood vessels follows, most often with intraluminal spread of trophoblast, intraluminal hemorrhage, and often subsequent leakage of blood out the abdominal end of the tube. Growth of the embryo is limited by the musculature and vasculature of the wall and does not always correspond with gestational age. Human chorionic gonadotropin is formed by the ectopic embryo and released into the maternal circulation at levels detectable with sensitive tests in nearly 100% of cases. Maternal serum hCG levels correlate best with trophoblast mass, only roughly with degree of development of the embryo, and poorly with its age ( 18). Corpus luteum production of estrogen and progestogens is usually sufficient to produce some degree of early uterine changes, including formation of decidua, softening of the cervix and isthmus, and an increase in uterine size. External bleeding associated with ectopic pregnancy is usually secondary to degeneration and sloughing of the uterine decidua. Course of Tubal Pregnancy Tubal pregnancy may terminate in several ways, depending partly on the initial site of implantation: abortion, resorption, rupture and reimplantation, and surgical termination. Tubal abortion, common with ampullary implantation, occurs when the products of conception separate from the tubal wall and are extruded through the fimbria and into the peritoneal cavity, where they are absorbed. Partial tubal abortion may result in hematosalpinx or placental polyp in the tube and cause pain for weeks. Tubal resorption occurs with in situ death of the products of conception. Tubal abortion and resorption are estimated to occur in from 10 to 50% of ectopic pregnancies. Tubal rupture usually occurs spontaneously but may result from trauma suffered accidentally or during sexual activity or pelvic examination. Isthmic pregnancies rupture earlier and more frequently. Although rupture is less commonly preceded by bleeding or hemoperitoneum, it is usually accompanied by greater hemorrhage. Ampullary pregnancies are less prone to rupture, and their rupture is often preceded by hemorrhage ( 18,19). Profuse hemorrhage following tubal rupture results in circulatory collapse and maternal death in the absence of surgical intervention. Tubal rupture with limited hemorrhage results commonly in resorption of conceptual products. In rare instances, an abdominal pregnancy occurs when the undamaged early zygote is delivered whole into the peritoneal cavity after tubal rupture and reimplants elsewhere. Alternatively, an intact gestational sac may be freed by tubal rupture with its placenta still attached to the ruptured tube. Interstitial pregnancy is less common (3 to 4%) and generally ruptures later (eighth to sixteenth menstrual week) than ampullary or isthmic pregnancies (fourth to twelfth menstrual week), is accompanied by more profuse bleeding because of its more advanced development and proximity to uterine and ovarian arteries, and is harder to

diagnose clinically because of its easy confusion with a uterine pregnancy on examination. The incidence of simultaneous tubal and uterine pregnancies varies from 1 in 6000 to 1 in 30,000 pregnancies and is increased in patients undergoing ovulation induction. Bilateral tubal pregnancy occurs even less frequently, with an incidence of 1 in 200,000 pregnancies.

CLINICAL PRESENTATION Ectopic pregnancy may present in a multitude of ways, some more easily diagnosed than others. Classically, a young woman presents 6 to 10 weeks after her last menses with a history of amenorrhea, abnormal bleeding, and the relatively sudden onset of abdominal pain and symptoms of hypovolemia including dizziness or syncope. Examination is notable for postural or absolute hypotension, abdominal tenderness or rebound, cervical motion tenderness, and sometimes adnexal mass or culde-sac fullness. In such a classic presentation, diagnosis is relatively straightforward. Such presentations, however, are not uniform and are less common in women seeking medical attention earlier in the course of the disease. Additionally, the large number of women who had several medical visits before the diagnosis was made or who were diagnosed at time of death or postmortem testifies to the varied and atypical presentations that may occur with ectopic pregnancy. In Dorfman's 1979 study of the 86 known fatal ectopic pregnancies in the United States, 77% of the women had been previously seen by clinicians (70% of whom were gynecologists), and physician misdiagnosis or deferral of the first visit contributed to the delay in diagnosis and death in over one-half of the cases ( 12). In two larger studies of surgically diagnosed ectopic pregnancies 30 to 50% of the patients had been evaluated at least once before the correct diagnosis; 10% were evaluated three or more times (11,20). A large study of ED diagnosis of ectopic pregnancy revealed 55% were correctly diagnosed on the first visit ( 21). Symptoms Abdominal pain, amenorrhea, and abnormal vaginal bleeding are present in about two-thirds of patients ( Table 56–2.2). However, absence does not exclude no ectopic pregnancy.

Table 56–2.2. Symptoms and Signs Of Ectopic Pregnancya

PAIN Abdominal or pelvic pain is the most often experienced symptom of ectopic pregnancy, occurring in over 90% of cases. Pain may be unilateral or bilateral, localized to the lower or upper abdomen or generalized throughout the abdomen. The pain may be sharp, stabbing, cramping, dull, or aching. Pain may be referred to the shoulders or back in 10 to 20% of cases indicating diaphragmatic irritation by intraperitoneal blood. Less severe or cramplike pain may indicate tubal distention or localized bleeding; more severe, sharp, and generalized pain generally indicates rupture. Pain is most often aggravated by motion. In roughly 50% of presentations, pain is of less than 24 hours' duration but in the remainder may be of longer duration or have occurred intermittently. The reported incidence of pain is less in ectopic pregnancies diagnosed from high-risk groups by screening and when increased percentages are diagnosed before rupture ( 21). AMENORRHEA Roughly three-fourths of women presenting with ectopic pregnancy have a history of a missed menses. The other one-fourth give no history of a missed period, although on detailed questioning some say that their last period was atypical in duration or amount or may have been off by a few days representing confusion of decidual bleeding with a normal menses. Time since the last period until presentation is most often 6 to 10 weeks. Later presentations are not infrequent, especially with cornual or interstitial implantation, which present most often at 8 to 16 weeks. VAGINAL SPOTTING OR BLEEDING Roughly three-fourths of women presenting with ectopic pregnancy have a history of abnormal vaginal bleeding. Most often, the bleeding is dark brown, scanty or spotting, and intermittent. Usually it represents uterine decidual reaction from inadequate hormonal support by the ectopic trophoblast. Less often, bleeding is moderate, and even less often it is profuse. Moderate and profuse bleeding are often confused, respectively, with menstrual bleeding and threatened or incomplete abortion. Profuse bleeding may be associated with cornual or interstitial pregnancies in up to 25% of cases. SYMPTOMS OF PREGNANCY Symptoms of pregnancy, including morning sickness, breast engorgement, and production of colostrum are not common and occur in one-fourth or less of cases. Nausea may be more common but interpreted as a gastrointestinal symptom. GASTROINTESTINAL SYMPTOMS Gastrointestinal symptoms including nausea, vomiting, urge to defecate, and abdominal cramping have been noted with greatly varying incidence. In Dorfman's study of fatal ectopic pregnancies ( 12), 80% of the patients were noted to have gastrointestinal symptoms, and 25% were misdiagnosed as suffering from gastrointestinal disorders. DIZZINESS AND SYNCOPE Dizziness, weakness, or, less commonly, syncope are found in roughly one-third of cases. HISTORICAL FACTORS Inquiry should be made for a history of salpingitis, PID, tubal surgery, use of fertility agents, past or present IUD use, or previous ectopic pregnancy. Physical Examination (Signs) Findings on physical examination may vary because of differences in location or chronologic stage of the ectopic gestation. Abdominal and adnexal tenderness are most consistent. GENERAL EXAMINATION AND VITAL SIGNS Most women with ectopic pregnancy have a normal appearance and normal vital signs. Signs of hypovolemia, including diaphoresis, pale skin, tachycardia, orthostatic changes, hypotension, and shock are found in 10 to 20% of cases. In contrast, in Breen's study of 654 ectopic pregnancies from 1947 to 1967 ( 9), 80%

were ruptured at the time of surgery and 48% presented in shock. In Dorfman's study of fatal ectopic pregnancies ( 12), roughly 40% had a systolic blood pressure under 90 mm Hg and/or a pulse more than 100 beats/min. Fever, usually low grade, is also present in perhaps 5 to 10% of patients, although Breen found temperatures of 99 to 103°F in 50% ( 9). ABDOMINAL AND PELVIC EXAMINATION Abdominal tenderness is elicited in most cases. In unruptured cases, tenderness is usually less severe and better localized. It may be absent in up to 36% of ectopic pregnancies (10). Once rupture has occurred, examination is more likely to reveal generalized or rebound tenderness and rigidity, decreased or absent bowel sounds, and/or distention, all consistent with intraperitoneal bleeding. Pelvic examination reveals adnexal tenderness or cervical motion tenderness in 75 to 90% of cases. An adnexal mass is found in about one-half of cases, although in 20% of these the mass, usually the corpus luteum, is contralateral to the ectopic gestation. Cul-de-sac fullness is found in one-third to two-thirds of cases. Uterine enlargement secondary to the effect of placental hormones is commonly found, and uterine size frequently coincides with that of an IUP with a similar period of amenorrhea.

INITIAL STABILIZATION An initial assessment of diagnosis and management should be made once the history and physical examination have been completed. Once the diagnosis of ectopic pregnancy is entertained, it can be categorized into three general diagnostic and management categories: obvious and critical, probable and urgent, and possible and stable. Obvious ectopic pregnancy with hypovolemia or shock demands immediate treatment of hypovolemia; preparation for surgery including administration of cross-matched, type-specific, or universal donor blood as indicated by the situation; and surgical exploration by the gynecologist or general surgeon. Culdocentesis may be performed if time allows to confirm the diagnosis and guide laparotomy. In cases of probable ectopic pregnancy without obvious hypovolemia, gynecologic consultation should be obtained and hypovolemia protocol instituted (intravenous access and fluid administration, orthostatic testing, blood for hemoglobin and hematocrit, and type and crossmatch), coincident with blood work including serum pregnancy test and pelvic ultrasound or culdocentesis. In less probable cases, diagnostic testing may precede or obviate the need for institution of the hypovolemia protocol or gynecologic consultation.

DIAGNOSTIC TESTING: LABORATORY AND OTHER PROCEDURES Diagnostic testing includes laboratory testing of blood or urine and procedures performed while the patient is in the ED, including pelvic ultrasound and culdocentesis as well as procedures performed by the consulting surgeon/gynecologist such as laparoscopy, curettage, or laparotomy. The two principal goals of diagnostic testing in workup of suspected ectopic pregnancy are confirmation of pregnancy and, when it is confirmed, localization of the products of conception. Additional testing is performed to evaluate for anemia, infection, or other disorders coincident or confused with ectopic pregnancy. Initial blood work includes complete blood count with platelets, serum pregnancy test for hCG by a method sensitive to 5 to 10 mIU/mL such as radioimmunoassay (RIA), immunoradiometric assay (IRMA), or, in its absence, sensitive urine pregnancy test by enzyme-linked immunosorbent assay (ELISA), as well as blood typing (including Rh) electrolytes, blood urea nitrogen (BUN) and creatinine. These are frequently followed by a diagnostic procedure of pelvic ultrasonography or culdocentesis or by direct visualization by the consultant gynecologist by means of laparoscopy or laparotomy. In the clinically unstable patient in whom diagnosis is most often apparent, laboratory testing may be limited to preparation for surgery and possibly culdocentesis. Creatine kinase (CK) determinations do not appear to reliably predict ectopic pregnancy despite earlier suggestions (22). Complete Blood Count Complete blood count (CBC) does not usually contribute substantially to diagnosis. Hemoglobin and hematocrit may not reflect acute blood loss because of the time required for restoration of blood volume and resultant hemodilution. A decrease in these values usually reflects severe or chronic blood loss, and in the presence of acute bleeding the degree of hemorrhage may be underestimated. Leukocyte count is usually normal, but in a substantial percentage of cases may be elevated secondary to catechol effect from hypovolemia and, therefore, cannot reliably differentiate between pelvic infection and ectopic pregnancy. Pregnancy Tests Pregnancy testing is a pivotal point in diagnosis of ectopic pregnancy. The exclusion of pregnancy excludes ectopic pregnancy. Patient history can be remarkably inaccurate. In a study by Ramoska et al. ( 23), only 47 of 68 (63%) women with positive pregnancy tests correctly thought that they were pregnant. Twenty-eight women who thought they were pregnant were not. In women whose last menstrual period was on time, who did not believe that they were pregnant, or who stated that there was no chance of pregnancy, more than 10% were found to be pregnant. In addition, 4% of women who used birth control and had experienced a normal previous period were pregnant ( 23). In contrast, in a study of women with suspected ectopic pregnancy, only 20% had a positive pregnancy test, but of these almost one-half had an ectopic pregnancy ( 24). Understanding the limitations of pregnancy tests as well as the endocrine physiology of normal and ectopic pregnancy is critical in reaching the right diagnosis. PHYSIOLOGY Trophoblastic production of hCG begins at implantation and increases through the eighth week of conception, doubling every 1.4 to 2.1 days. Corpus luteum production of progesterone begins immediately after ovulation and, in response to hCG, continues until gradually replaced by placental production during the sixth through tenth menstrual weeks. Progesterone levels are significantly elevated by the third menstrual week, rise steadily through the fifth week, and rise gradually thereafter through the pregnancy. Because of limited space and vascular support, the production of hCG and consequent production of progesterone by the corpus luteum are significantly reduced in ectopic gestations, and the doubling time for hCG is prolonged. Serum hCG levels roughly correlate with trophoblastic mass and embryonic development but not with total ectopic size or gestational age. In rare instances ectopic pregnancy has been found with nondetectable hCG levels, but less than 1% will have an hCG level of less than 10 mIU/mL, and the great majority have levels of over 100 mIU per mL (7,11,18,19,24,25,26,27 and 28). In a study of 184 ectopic pregnancies Romero et al. ( 26) found 0.5% had a level of less than 10, 1% had a level of less than 20, 5% had a level less than 100, and 12% had a level less than 200 mIU/mL. A study of 693 ectopic pregnancies found 11% of ruptured pregnancies and 9% of unruptured pregnancies had levels of less than 100 U/L and hCG levels did not correlate with rupture ( 28). In another study of 131 ectopic gestations (hCG values converted from second IS to IRP using a factor of 1.67; see subsequent text) none had levels under 25 mIU/mL and 20 (15%) cases had levels under 167. Mean hCG levels were 6924 and 16,418 mIU/mL for ampullary and isthmic locations, respectively, and were higher when ruptured in either location (18). About 10 to 20% of ectopic gestations will have an hCG level greater than 10,000 mIU/mL. In summary, hCG level may not predict ectopic location or rupture, and hCG sensitivity to less than 5 to 10 mIU/mL is needed to detect 99% of ectopic pregnancies. HUMAN CHORIONIC GONADOTROPIN Discussion of hCG is complicated by the variety of reference standards and published discrepancies in their interconversion ( 29,30,31 and 32). Measurements of hCG in serum or urine are generally expressed as units of activity using either the older Second International Standard (2nd IS) established in 1964 or the highly purified CR 119 International Reference Preparation (IRP) established in 1974. The latter is also referred to as the Third International Standard for Chorionic Gonadotropin (WHO 3rd IS 75/537). All hCG values reported in this chapter are expressed in terms of the IRP standard. One nanogram of the IRP standard has a potency of 9.3 mIU (IRP) and about 5 mIU (2nd IS) (29,31), although a frequently cited study found it equal to 6.5 to 7.5 mIU (IRP) and 2.3 to 4.0 mIU (2nd IS) ( 32). Based on this, levels of serum measured with the IRP are roughly felt to be 100% higher than with the 2nd IS, although Fossum et al. ( 30) found the IRP to be only 34% higher. Sensitive tests for hCG use antibodies directed against the beta subunit or the intact molecule (alpha and beta subunit) because the alpha subunit is shared in common with luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). Assays sensitive to less than 5 mIU/mL are now available by various methodologies including RIA, immunoenzymetric assay (IEA), IRMA, and others, which can be performed in a matter of hours. Semiquantitative tests for serum hCG levels less than 10, between 10 and 25, and more than 25 mIU/mL can be performed by IEA or ELISA in less than 30 minutes. A qualitative urine hCG test with a sensitivity of 20 mIU/mL can be easily performed using the same methodology (Hybritech Tandem ICON II HCG) in the ED in 5 to 10 minutes. Dilute urine (specific gravity of less than 1.015) decreases the reliability of the test. Other urine tests that use hemagglutination and latex agglutination inhibition are rapidly performed but less sensitive (sensitivity of 150 to 200 and 500 to 800 mIU/mL, respectively). When both sensitivity and rapidity of diagnosis are important, a two-assay protocol can be used, with a rapid urine assay for initial testing followed by a serum assay with a more sensitive method. Or if qualitative testing only appears indicated, a sensitive urine test alone can be used. The validity of either approach was confirmed by a study comparing paired urine and blood samples for 95 ectopic and 10 intrauterine gestations analyzed by four quantitative tests and two qualitative tests. All 105 women were correctly classified as pregnant by both the

serum and urine qualitative assays (Hybritech Tandem ICON) ( 25). Quantitative tests for intact hCG showed a roughly unitary relationship between concentrations in both fluids except in the presence of dilute urine ( 25). SERIAL hCG TESTING A positive pregnancy test in a clinically stable woman, even with abdominal pain, uterine bleeding, and adnexal mass, still does not indicate ectopic pregnancy in most cases. Although the normal values for serum hCG at different conceptual ages are relatively well known for normal pregnancies, a single quantitative hCG determination cannot differentiate normal from abnormal pregnancies without the exact date of ovulation or the last period. Consequently, it has been advocated that the doubling time or slope of the increase in hCG be used to differentiate normal from abnormal pregnancies during the time when ultrasound cannot discriminate between the two. Kadar et al. (33) proposed that abnormal pregnancies were associated with less than 66% increase in hCG concentration over a 48-hour period (shorter periods were found to give too much variation). Using this criterion, 15% of normal pregnancies would be misclassified as abnormal and 13% of ectopic pregnancies misclassified as normal (33). Using a 63% increase as a cutoff, Daus et al. ( 34) found 13% of normal pregnancies to be misdiagnosed as abnormal and 6% of ectopics as normal. In an evaluation of asymptomatic women at high risk for ectopy, however, Shepherd et al. ( 35) found that 64% of ectopic gestations were misclassified as normal using the same criteria and early paired hCG measurements. With additional measurements, 85% of ectopic gestations were correctly identified (35). In the ED setting, sequential sampling may be unsuitable because of the prolonged sampling period and the unavailability of rapid quantitative hCG testing. Patients with a diagnosis of “rule out ectopic”, however, are likely to be seen more frequently because gynecologists use serial measurements to evaluate clinically stable patients with possible ectopic pregnancy. PROGESTERONE A single serum progesterone measurement has been suggested to aid in diagnosis of ectopic pregnancy ( 21,36,37 and 38). Because progesterone levels remain relatively stable from the third through eighth weeks of pregnancy, neither serial determinations nor precise knowledge of gestational age are needed to differentiate normal from abnormal pregnancies. Additionally, the short half-life of progesterone (less than 10 minutes) versus that of hCG (more than 36 hours) may reflect changes in viability more rapidly. Initial studies found serum progesterone levels of less than 15 ng/mL in patients with ectopic pregnancies and levels of more than 15 ng/mL in patients with normal pregnancies (36,37). Stovall et al. (37) screened all urine hCG-positive women presenting to the ED of a large hospital with a high observed incidence of ectopic pregnancy with quantitative serum hCG and progesterone measurements. Patients with significant risk factors or significant symptoms received additional evaluation. All those with progesterone of less than 25 ng/mL and not initially diagnosed were called back for additional evaluation and repeat quantitative hCG assay and endovaginal ultrasonography. Overall, of the 161 ectopic pregnancies found, 97% had progesterone values of less than 25, 55% were detected at first visit, and of the 45% detected on follow-up with aid of serum progesterone only one had a progesterone of more than 25. The apparent early diagnosis of ectopic pregnancy using this protocol resulted in a decrease in the rate of rupture from 79 to 39% compared with a retrospective control group ( 21,37). Shortcomings of this approach are the lack of uniformity in normal progesterone values among hospitals and the lack of availability and rapidity of testing, all of which can be expected to improve with its increased use. The urinary metabolite of progesterone, pregnanediol glucuronide (PG), is also correspondingly lower in abnormal pregnancies, and its use has also been proposed to aid in diagnosis of ectopic pregnancy ( 27). Advantages are that urine is more easily obtained than serum and a sensitive semiquantitative enzyme immunoassay is available and can be performed in less than 10 minutes without special equipment or personnel, therefore, making it suitable for ED use. Sauer et al. ( 27) found in a study of 60 ectopic and 34 intrauterine pregnancies that the urinary PG level was significantly depressed in ectopic gestations (4.8 mg/mL versus 24.5 mg/mL). PG levels of less than 9 and less than 15 mg/mL were found in 75 and 90% of ectopic pregnancies, respectively, and levels of more than 9 and more than 15 mg/mL were found in 100% and 91% of intrauterine pregnancies, respectively. With additional refinement and testing, this method may hold promise for ED use. Ultrasonography Once the existence of pregnancy has been established, pelvic ultrasonography is often used to evaluate clinically stable women suspected of having ectopic pregnancy. Its advantages are that it is noninvasive and relatively painless. Disadvantages are that it is often not available rapidly or on a 24-hour basis, it takes longer to perform, and it frequently has inadequate resolution. In fact, only 10 to 20% of ectopic pregnancies are visualized by ultrasonography, depending on ultrasonographic approach and the development and size of the ectopic gestation. Therefore, ultrasonography is often used to establish IUP and, thereby, exclude ectopic pregnancy statistically because of the extremely rare occurrence of simultaneous ectopic and intrauterine pregnancies. The resolution of ultrasonography is limited even in establishing the presence of an IUP. The range of serum hCG concentration above which an IUP can be reliably diagnosed is referred to as the discriminatory zone, a concept first advanced by Kadar et al. in 1981 ( 39). Using transabdominal ultrasound (TAUS), a normal IUP could be visualized 94% of the time with serum hCG levels above 6500 mIU/mL and that absence of visualization of a gestational sac above this level was diagnostic of an ectopic pregnancy in 86% of cases ( 40). At levels below 6000 mIU/mL, they were unable to consistently identify the gestational location. The presence of a sac below these levels was more often associated with an abnormal pregnancy—either a missed abortion or an ectopic pregnancy. The concept of discriminatory zone has become commonly recognized and found to vary with ultrasonographic method, equipment, and operator. TAUS, commonly available, requires a full bladder for visualization of pelvic structures, which many women find uncomfortable. At most institutions, the discriminatory zone for TAUS is 5500 to 6500 mIU/mL (about 6 menstrual weeks). Above this level, about 90% of IUPs can be visualized as a gestational sac (a sonolucent area surrounded by a dense echogenic rim). Absence of visualization of an IUP above this level is diagnostic of ectopic pregnancy in about 90% of cases ( 39,40 and 41). About 25 to 40% of ectopic pregnancies have hCG levels above 6,000 mIU/mL ( 39,40). Visualization of a sac below this level implies an abnormal pregnancy in over one-half of cases, most often a spontaneous abortion (SAB), but occasionally an ectopic pregnancy (representing the decidual reaction and is called a “pseudogestational” sac of ectopic pregnancy). Definitive evidence of gestational location, the presence of a fetal heartbeat, intrauterine or adnexal, is seen at even higher levels of hCG (about 17,000 mIU/mL) and later (7 to 8 menstrual weeks). Adnexal findings are, therefore, infrequently definitive but may still be helpful. Adnexal masses are visualized in up to two-thirds of ectopic pregnancies but are more often associated with SAB or IUP. Noncystic adnexal masses are found less often but are more often associated with ectopic pregnancy. The combined presence of noncystic adnexal mass and free peritoneal fluid occurs in roughly one-fourth to one-half of cases and is associated with ectopic pregnancy in over 90% of occurrences. Peritoneal fluid is visualized in up to one-half of ectopics, but in the absence of a coincidental mass is more often associated with SAB or IUP ( 42,43). Endovaginal Ultrasonography Endovaginal ultrasonography (EVUS) provides better resolution with less discomfort and increased rapidity because it does not require a full bladder and is less affected by obesity (10). Visualization of IUP, embryonic structures, and abnormal pregnancy may be made about 1 week earlier than with TAUS ( 30,44,45). EVUS allows visualization of the gestational sac at 1000 to 2000 mIU/mL (4 to 5 menstrual weeks), visualization of cardiac activity at 11,000 to 27,000 mIU/mL (5 to 6 menstrual week); differentiation between head and body may be possible at 6 to 7 menstrual weeks. Additionally, EVUS allows better visualization of adnexal structures and peritoneal fluid. An ectopic sac is found in about two-thirds of ectopic pregnancies ( 44,46,47). Cardiac activity may be seen in 10 to 25% of ectopic pregnancies. Findings of a noncystic adnexal mass imply a risk for ectopic of 85%, and with pelvic fluid the risk increases to 90% ( 47,48,49,50 and 51). Emergency physicians trained in EVUS can attain 93% agreement with radiologists ( 48) and enhance diagnostic accuracy ( 49). In review, the use of ultrasonography for diagnosis of ectopic pregnancy in the ED is limited by availability, resolution, and, in most cases, the absence of rapidly available quantitative hCG levels. Because most ectopic pregnancies present with hCG values below the discriminatory zone of TAUS and sizeable numbers with values below the discriminatory zone for EVUS, ultrasonic evidence for ectopic gestation is largely exclusionary (absence of an IUP) or based on probability or association (noncystic adnexal mass, peritoneal or cul-de-sac fluid). Definite visualization of ectopic gestation occurs in a few cases. When quantitative hCG values are available, diagnosis may be better guided. Nonvisualization of an IUP with values above the discriminatory zone of the ultrasonographic technique available makes the presence of ectopic pregnancy nearly certain. A normal ultrasonogram with hCG level below the discriminatory zone allows serial hCG monitoring or repeat ultrasonography at the time of predicted attainment of the discriminatory zone or both, as long as the patient is clinically stable. In less stable patients, nonvisualization indicates the need for a more invasive procedure such as culdocentesis or laparoscopy. Culdocentesis Culdocentesis is a simple procedure rapidly performed by the emergency physician in the ED with available equipment. Conflicting opinions have been reached by different investigators on the role and usefulness of culdocentesis despite similar findings in the probabilities and predictive values associated with the procedure. Its role has been questioned in the evaluation of the stable patient, when sensitive pregnancy testing and ultrasonography are available, have similar predictive values,

and are less painful and invasive, and in the evaluation of the less stable or more probable patient when laparoscopy has a higher predictive value and may lead to less delay in ultimate operative treatment ( 7,52,53). The continued value of culdocentesis has been argued by other investigators, especially when ultrasonography is either nondiagnostic or not rapidly available and in earlier presentations when culdocentesis has a relatively higher predictive value ( 54,55). Culdocentesis has a positive predictive value for both hemoperitoneum and ectopic pregnancy of about 85% in patients suspected of having ectopic pregnancy (7,52,53 and 54). Surprisingly, hemoperitoneum occurs in most unruptured as well as ruptured ectopics ( 53,54). As a consequence, culdocentesis does not accurately differentiate the two. The overall sensitivity of culdocentesis for ectopic pregnancy is about 70 to 90% and is slightly better for ruptured than for unruptured cases (7,52,53,54 and 55). False-negative rates of 1 to 15% (including aspiration of more than 10 mL of serous fluid) and nondiagnostic rates of 15 to 30% have been noted in association with surgically proven ectopic pregnancies. Additionally, false–positive results have been noted in similar percentages in association with SAB, IUP, ruptured ovarian cyst, retrograde menstruation, and endometriosis. Negative or nondiagnostic culdocentesis does not exclude the diagnosis of ectopic pregnancy and may occur in up to 75% of clinically suspected cases with such results. Culdocentesis is performed with the patient in the lithotomy position with the upper torso elevated. After insertion of a full-size vaginal speculum, cleansing of the vagina with antiseptic, and displacement of the cervix toward the symphysis with tenaculum, a long 16- or 18-gauge needle attached to a partially air-filled syringe is inserted through the posterior fornix. When air can be easily injected, an attempt is made to aspirate fluid. Anesthesia can be given either just before with parenteral fentanyl or coincident with needle insertion if several milliliters of 1% lidocaine is added to the syringe and injected on mucosal entry. Aspiration of more than 5 mL of nonclotting blood or bloody fluid with a hematocrit of more than 15% is considered positive, although in the presence of active bleeding larger amounts of clotting blood may be obtained. A small amount of clotting blood may indicate perforation of a local vessel by the needle at time of aspiration and is nondiagnostic. Aspiration of serous fluid is generally indicative of a ruptured ovarian cyst and a negative tap but has been reported in association with ectopic pregnancy. Failure to obtain fluid indicates failure to reach the cul-de-sac and is nondiagnostic. Other Procedures Other procedures are available to aid in diagnosis of ectopic pregnancy but are more often performed by the consultant gynecologist. Laparoscopy allows excellent visualization of adnexal structures, except in the presence of adhesions or obesity. Additionally, it can be used for treatment immediately after confirmation of the diagnosis. False-positive and false-negative rates of less than 5% occur. Dilation and curettage may also be helpful when there is no objection to pregnancy termination. Finding of evidence of an IUP grossly or on frozen section statistically excludes ectopic pregnancy, similarly to finding an IUP with ultrasonography. Laparotomy remains the definitive diagnostic as well as curative procedure, and when time is limited is the best diagnostic approach. A carefully performed early laparotomy has little morbidity if negative, and if positive may avoid a later emergent laparotomy with significant morbidity.

DIFFERENTIAL DIAGNOSIS Misdiagnosis of ectopic pregnancy may result in fatality or, with later diagnosis, serious morbidity, including a decreased chance of future successful pregnancy. A substantial percentage of women have seen a physician at least once before correct diagnosis ( 11,12,20). Perhaps one-half of the deaths from ectopic pregnancy might have been avoided if diagnosis had been made and treatment instituted more promptly ( 12). Conditions often confused with ectopic pregnancy include threatened or incomplete abortion, ruptured or torsed ovarian cyst, salpingitis, appendicitis, dysfunctional bleeding, and gastrointestinal disorder. Less commonly confused conditions include endometriosis, urinary tract infection, fibroid degeneration, ureterolithiasis, diverticulosis, and ulcer disease. Gastrointestinal disorder was the common misdiagnosis in Dorfman's study of fatal ectopic pregnancies. A sensitive pregnancy test would help to differentiate most of these conditions, except abortions and some ovarian cysts, from ectopic pregnancy ( Table 56–2.3 and Table 56–2.4).

Table 56–2.3. Conditions Confused with Ectopic Pregnancy

Table 56–2.4. Differential Diagnosis of Ectopic Pregnancy a

Threatened or incomplete abortion may be confused with ectopic pregnancy in the presence of a positive pregnancy test. Bleeding is usually more profuse, pain is crampy, midline, and less severe, and onset is usually later after the last normal period. Shock, if present, is usually proportionate to visible blood loss. The finding of products of conception is usually diagnostic (except in the rare simultaneous uterine and ectopic pregnancy). Failure to send presumed products of conception for pathologic examination can be a serious or fatal error. Patients sent home with this diagnosis should receive prompt follow-up and serial hCG testing, sonography, or curettage to confirm the diagnosis. Salpingitis may be easily differentiated from ectopic pregnancy with a sensitive pregnancy test in most cases. Treatment of salpingitis with a tetracycline antibiotic to treat possible chlamydial infection mandates such testing to avoid fetal exposure. Salpingitis is less often associated with bleeding or spotting and more often associated with fever and leukocytosis. Pain is often bilateral. Unilateral salpingitis should prompt consideration of ectopic pregnancy. A ruptured or torsed ovarian cyst may be especially difficult to differentiate from ectopic pregnancy in the presence of an IUP. Abnormal vaginal bleeding and amenorrhea may be less common. Culdocentesis or ultrasonography may not be able to differentiate the two reliably. Ultimate diagnosis may be revealed at laparoscopy or laparotomy. Pain of appendicitis may mimic a right-sided ectopic pregnancy. In appendicitis, the pain usually begins periumbilically and ultimately localizes higher. A pregnancy test is usually negative. Amenorrhea, vaginal bleeding, and adnexal mass are usually absent. Gastrointestinal disorders may be mistaken for ectopic pregnancy. The absence of diarrhea should make the diagnosis of gastroenteritis less certain. Pregnancy testing should be considered, especially because gastrointestinal complaints, including nausea, vomiting, and abdominal pain, may occur in normal as well as ectopic

pregnancies.

MANAGEMENT A woman presenting to the ED with signs and symptoms consistent with ectopic pregnancy and hemodynamic instability needs immediate gynecologic consult and preparations for surgery ( Table 56–2.5). Volume resuscitation should be instituted immediately with crystalloid through two large-bore intravenous lines while blood is obtained for hemoglobin and hematocrit and type and crossmatch. Blood and/or urine should be sent for stat pregnancy test. Cross-matched, type-specific, or universal donor blood should be given as indicated by availability and the patient's hemodynamic status. Culdocentesis may be performed at the discretion of the gynecologist or in less obvious cases. Laparotomy is diagnostic and lifesaving, and should not be delayed while waiting for other confirmatory evidence because it may prove fatal.

Table 56–2.5. Management of Possible Ectopic Pregnancy

The hemodynamically stable patient with probable or possible ectopic pregnancy can be more fully evaluated in the ED. If a question exists as to the patient's hemodynamic stability, intravenous access should be established with a large-bore intravenous line and postural blood pressures obtained. Instability revealed at this time indicates a need for a more urgent approach to diagnosis such as immediate ultrasonography, culdocentesis, or laparoscopy by the consultant gynecologist and immediate urine or serum hCG testing and blood for hematocrit and crossmatch. Approach to the still stable patient usually continues with sensitive urine or serum hCG testing and, if positive, endovaginal or transabdominal ultrasonography. If neither intrauterine nor ectopic pregnancy is found and quantitative hCG level is below the discriminatory zone for ultrasonography, arrangements should be made for prompt gynecologic consultation and follow-up. An algorithm using transvaginal ultrasound and hCG titers can definitively diagnose approximately 80% of all patients in initial evaluation ( 56). When gestational location is not found and quantitative hCG is not available or above the discriminatory zone, the patient should be admitted for additional evaluation, including possible laparoscopy. Culdocentesis can be used to evaluate a patient in the ED, but should be used only to “rule in” ectopic pregnancy and not to give a false sense of security as to its nonexistence. Serum progesterone can also be used to help in evaluation, if available, with serum values less than 25 ng/mL indicating an abnormal pregnancy and increased risk of ectopic gestation and the need for prompt re-evaluation if the patient is discharged from the ED. Discharge of the pregnant patient from the ED without firm diagnosis of IUP normal or abnormal, should be considered only after consultation with the obstetrician/gynecologist and arrangement for definite and reliable follow-up has been made. Before discharge, quantitative serum hCG measurement should be ordered and the patient given clear instructions as to her responsibility to return immediately if any signs of hemodynamic instability (e.g., weakness, dizziness, fainting) or increasing abdominal pain occur. Patients seen for re-evaluation, either scheduled or unscheduled, can be evaluated with repeat quantitative serum hCG measurement, looking for an appropriate increase in level of more than 66% per 48 hours and repeat ultrasonography, especially if hCG level is now in the discriminatory zone. Failure to find either an appropriate increase in hCG value or an IUP on ultrasonography mandates laparoscopy or other evaluation by the gynecologist. Abdominal pregnancy, usually the result of a ruptured or aborted tubal pregnancy, represents a rare and special type of ectopic gestation. The mortality is higher than for tubal pregnancies and diagnosis may be more difficult and occur much later in the course of the pregnancy. Management in the emergency room consists of prompt gynecologic consultation and admission, treatment of any hemodynamic instability, and, if any instability is present, preparation for possibly massive transfusion requirements (19,57,58). Post ED Management and Prognosis Definitive treatment of ectopic pregnancy is the responsibility of the consultant gynecologist or surgeon with the primary aim of preservation of life and the secondary aim of preservation of tubal and reproductive function. Traditionally, treatment has been surgical with salpingectomy in emergent situations and tube-conserving procedures when the situation allows such as salpingostomy (tubal incision and evacuation), salpingotomy (tubal incision, evacuation, and closure), and segmental tubal resection and anastomosis. Laparoscopic surgery has gained increasing favor and use in stable patients. Expectant management has been advocated in patients with falling hCG levels and no evidence of bleeding or tube disruption as resorption will occur in the great majority of these cases. Systemic methotrexate and direct tubal instillation of methotrexate, KCl, and other agents have also been used to induce tubal abortion and resorption. Currently, there are at least 12 reported protocols for methotrexate treatment of ectopic pregnancy ( 59). Outpatient treatment of ectopic pregnancy with methotrexate has resulted in decreased patient mortality, a preservation of reproductive capability, and when compared with inpatient surgical treatment, an estimated cost savings of $10,000 per patient (4). Persistent ectopic pregnancy has been reported after surgical tube-conserving procedures in 5 to 8% of patients and should be suspected in symptomatic patients presenting after such procedures with persistent hCG elevation. Studies show a reduction in persistent ectopic pregnancy with a single dose of methotrexate postoperatively (60), although lower doses for 5 days did not seem effective ( 61). In most patients the hCG level is undetectable by the 12th postoperative day although in some it has remained detectable for 3 weeks ( 62,63). Prognosis for additional normal reproduction has improved with earlier diagnosis and increased use of tube-conserving surgical technique. Earlier studies of women treated with either salpingectomy or salpingostomy demonstrated a subsequent IUP rate of roughly 40%. With increased use of conservative surgical technique, subsequent intrauterine pregnancy rates of 40 to 90% have been demonstrated. The rate for recurrent ectopic pregnancy has changed less and remains at about 15%, depending on preexistent tubal disease as well as time of diagnosis and surgical technique ( 7,15,31). A review of reports on laparoscopy revealed a tubal patency rate of 86%, a pregnancy rate of 66%, and a repeat ectopic pregnancy rate of 23%. Although fewer data is available in methotrexate use, reported outcomes are similar, with a tubal patency rate of 81% and a pregnancy rate of 70%, but a repeat ectopic rate of 11%, less than that seen with laparoscopy (64). Abdominal pregnancy, usually the result of a ruptured or aborted tubal pregnancy, represents a rare and special type of ectopic gestation. The mortality is higher than for tubal pregnancies, and diagnosis may be more difficult and occur much later in the course of the pregnancy. Management in the ED consists of prompt gynecologic consultation and admission, treatment of any hemodynamic instability, and, if any instability is present, preparation for possibly massive transfusion requirements ( 19,62,63).

PITFALLS AND MEDICOLEGAL PEARLS A common pitfall is failure to consider possibility of pregnancy or ectopic pregnancy in women of childbearing age in the ED. Women of reproductive age with gynecologic, gastrointestinal, or other vague symptomology should be considered pregnant and ectopic until proven otherwise. Patient self-assessment of pregnancy is relatively unreliable. Do not rely too heavily on insensitive urine or serum pregnancy tests. Urine pregnancy tests are less reliable with dilute urine (SG less than 1.015). Ectopic pregnancy can occur with serum hCG values as low as 5 to 10 mIU/mL.

Do not fail to consider ectopic or IUP when diagnosing salpingitis. Salpingitis usually occurs in reproductive-age women, and its diagnosis should indicate the need for pregnancy testing, to exclude ectopic pregnancy and to avoid fetal exposure to tetracycline antibiotics. Avoid too much reliance on a “negative ultrasound.” Ultrasonography is only definitive when intrauterine or extrauterine cardiac activity is seen. A “negative ultrasound” with an hCG value above the ultrasonographic discriminatory zone is “positive.” Do not fail to confirm IUP pathologically when diagnosing missed, incomplete, or complete SAB. Ectopic pregnancy should always be considered when diagnosing threatened abortion. Do not delay definitive diagnosis and treatment (laparoscopy or laparotomy) of unstable patients while awaiting confirmatory evidence of pregnancy or gestational location. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64.

Goldner TE, Lawson HW, Xia Z, et al: Surveillance for ectopic pregnancy—United States, 1970–1989. MMWR 1993;42:73–85. Stovall TJ, Ling FW: Ectopic pregnancy: diagnostic and therapeutic algorithms minimizing surgical intervention. J Reprod Med 1993;38:807–812. Carson SA, Buster JE: Ectopic pregnancy. N Engl J Med 1993;329:1174–1181. CDC Current trends: ectopic pregnancy-United States, 1990–1992. MMWR 1995;44:46–48. Makinen JI, Erkkola RU, Laippala PK: Causes of the increase in the incidence of ectopic pregnancy, a study on 1017 patients from 1966 to 1985 in Turku, Finland. Am J Obstet Gynecol 1989;160:642–646. Stock RJ: The changing spectrum of ectopic pregnancy. Obstet Gynecol 1988;71:885. Weckstein LN: Current perspective on ectopic pregnancy. Obstet Gynecol Surv 1985;40:259–272. Rochat RW, Koonin LM, Atrash HK, et al: Maternal mortality in the United States: report from the maternal mortality collaborative. Obstet Gynecol 1988;72:91–97. Breen JL: A 21 year survey of 654 ectopic pregnancies. Am J Obstet Gynecol 1970;106:1004–1019. Kaplan BC, Dart RG, Moskos M: Ectopic pregnancy: prospective study with improved diagnostic accuracy. Ann Emerg Med 1996;28:10–17. Brenner PF, Roy S, Mishell DR: Ectopic pregnancy: a study of 300 consecutive surgically treated cases. JAMA 1976;243:673–676. Dorfman SF, Grimes DA, Cates W: Ectopic pregnancy mortality, United States, 1979 to 1980: clinical aspects. Obstet Gynecol 1984;64:386–390. Marchbanks PA, Annegers JF, Coulam CB, et al: Risk factors for ectopic pregnancy, a population based study. JAMA 1988;259:1823–1827. Stock RJ: Histopathology of fallopian tubes with recurrent tubal pregnancy. Obstet Gynecol 1990;75:9–14. Mehta L, Young ID: Recurrence risks for common complications of pregnancy-a review. Obstet Gynecol Surv 1987;42:218–223. Kendrick JS, Tierney EF, Lawson HW, et al: Previous cesarian delivery and the risk of ectopic pregnancy. Obstet Gynecol 1996;87:297–301. Peterson HB, Xia A, Hughes JM: The risk of ectopic pregnancy after tubal sterilization N Engl J Med 1997;336:762–767. DiMarchi JM, Kosasa TS, Hale RW: What is the significance of the human chorionic gonadotropin value in ectopic pregnancy? Obstet Gynecol 1989;74:851–855. Cunningham FG, MacDonald PC, Gant NF, et al: Williams obstetrics. 20th Ed. Stamford: Appleton & Lange, 1997. Hughes GJ: The early diagnosis of ectopic pregnancy. Br J Surg 1979;66:789–792. Stovall TG, Kellerman AL, Ling FW, et al: Emergency department diagnosis of ectopic pregnancy. Ann Emerg Med 1990;19:1098–1103. Vandermolen DT, Borzelleca JF: Serum creatine kinase does not predict ectopic pregnancy. Fertil Steril 1996;65:916–921. Ramoska, EA, Sacchetti AD, Nepp M: Reliability of patient history in determining the possibility of pregnancy. Ann Emerg Med 1989;18:48–50. Schwartz RO, DiPietro DL: B-hcg as a diagnostic aid for suspected ectopic pregnancy. Obstet Gynecol 1980;56:197–203. Norman RJ, Buck RH, Rom L, et al: Blood or urine measurement of human chorionic gonadotropin for detection of ectopic pregnancy? A comparative study of quantitative and qualitative methods in both fluids. Obstet Gynecol 1988;71:315–318. Romero R, Kadar N, Copel J: The effect of different human chorionic gonadotropin assay sensitivity on screening for ectopic pregnancy. Am J Obstet Gynecol 1985;153:72–74. Sauer MV, Vermesh M, Anderson RE, et al: Rapid measurement of urinary pregnanediol glucuronide to diagnose ectopic pregnancy. Am J Obstet Gynecol 1988;159:1531–1535. Saxon D, Falcone T, Mascha EJ, et al: A study of ruptured tubal ectopic pregnancy. Obstet Gynecol 1997;90:46–49. Bangham DR, Storring PL: Standardization of human chorionic gonadotropin, HCG, subunits, and pregnancy tests (letter). Lancet 1982;1:390. Fossum GT, Davajan V, Kletzky OA: Early detection of pregnancy with transvaginal ultrasound. Fertil Steril 1988;49:788–791. Leach RE, Ory SJ: Modern management of ectopic pregnancy. J Repro Med 1989;34:324–338. Rasor JR, Farber S, Braunstein GD: An evaluation of 10 kits for the determination of human chorionic gonadotropin in serum. Clin Chem 1983;29:1828. Kadar N, Caldwell BV, Romero R: A method of screening for ectopic pregnancy and its indications. Obstet Gynecol 1981;58:162–165. Daus K, Mundy D, Graves W, et al: Ectopic pregnancy: what to do during the 20-day window. J Repro Med 1989;34:162–166. Shepherd RW, Patton PE, Novy MJ, et al: Serial B-hcg measurements in the early detection of ectopic pregnancy. Obstet Gynecol 1990;75:417–420. Matthews CP, Coulson PB, Wild R: Serum progesterone levels as an aid in the diagnosis of ectopic pregnancy. Obstet Gynecol 1986;68:390–394. Stovall TG, Ling FW, Cope BJ, et al: Preventing ruptured ectopic pregnancy with a single serum progesterone. Am J Obstet Gynecol 1989;160:1425–1431. Yeko TR, Gorill MJ, Hughes LH: Timely diagnosis of early ectopic pregnancy using a single blood progesterone measurement. Fertil Steril 1987;48:1048–1050. Kadar N, DeVore G, Romero R: Discriminatory hcg zone: its use in the sonographic evaluation for ectopic pregnancy. Obstet Gynecol 1981;58:156–161. Romero R, Kadar N, Jeanty P, et al: Diagnosis of ectopic pregnancy: value of the discriminatory human chorionic gonadotropin zone. Obstet Gynecol 1985;66:357–360. Batzer FR, Weiner S, Corson SL, et al: Landmarks during the first forty-two days of gestation demonstrated by the B-subunit of human chorionic gonadotropin and ultrasound. Am J Obstet Gynecol 1983;146:973–979. Mahony BS, Filly RA, Nyberg DA, et al: Sonographic evaluation of ectopic pregnancy. J Ultrasound Med 1985;4:221–228. Romero R, Kadar N, Castro D, et al: The value of adnexal sonographic findings in the diagnosis of ectopic pregnancy. Am J Obstet Gynecol 1988;158:52–55. Bree RL, Edwards M, Bohm-Veles M, et al: Transvaginal sonography in the evaluation of normal early pregnancy: correlation with hcg level. AJR 1989;153:75–79. Timor-Tritsch IE, Yeh MN, Peisner DB, et al: The use of transvaginal ultrasonography in the diagnosis of ectopic pregnancy. Am J Obstet Gynecol 1989;161:157–161. Cacciatore B, Stenman UH, Ylostalo P: Comparison of abdominal and vaginal sonography in suspected ectopic pregnancy. Obstet Gynecol 1989;73:770–774. Nyberg DA, Mack LA, Laing FC, et al: Early pregnancy complications: endovaginal sonographic findings correlated with human chorionic gonadotropin levels. Radiology 1988;167:619–622. Mateer JR, Aiman EJ, Brown MH, et al: Ultrasonographic examination by emergency physicians of patients at risk for ectopic pregnancy. Acad Emerg Med 1995;2:867–873. Mateer JR, Valley VT, Aiman EJ, et al: Outcome analysis of a protocol including bedside endovaginal sonography in patients at risk for ectopic pregnancy. Acad Emerg Med 1996;27:283–289. Shapiro BS, Cullen M, Taylor KJW, et al: Transvaginal ultrasonography for the diagnosis of ectopic pregnancy. Fertil Steril 1988;50:425. Bateman BG, Nunley WC, Kolp LA, et al: Vaginal sonography findings and hcg dynamics of early intrauterine and tubal pregnancies. Obstet Gynecol 1990;75:421–427. Kim DS, Chung SR, Park MI, et al: Comparative review of diagnostic accuracy in tubal pregnancy: a 14-year survey of 1040 cases. Obstet Gynecol 1987;70:547–554. Vermesh M, Graczykowski JW, Sauer MV: Reevaluation of the role of culdocentesis in the management of ectopic pregnancy. Am J Obstet Gynecol 1990;162:411–413. Romero R, Copel JA, Kadar N, et al: Value of culdocentesis in the diagnosis of ectopic pregnancy. Obstet Gynecol 1985;65:519–522. Schwab RA: Ultrasound versus culdocentesis in the evaluation of early and late ectopic pregnancy. Ann Emerg Med 1988;17:801–803. Barnhart K, Mennuti MT, Benjamin I, et al: Prompt diagnosis of ectopic pregnancy in an emergency department setting. Obstet Gynecol 1994;84:1010–1014. Martin JN, Sessums JK, Martin RW, et al: Abdominal pregnancy: current concepts of management. Obstet Gynecol 1988;71:549–557. Martin JN, McCaul JF: Emergent management of abdominal pregnancy. Clin Obstet Gynecol 1990;33:438–447. Issacs JD, McGehee RP, Cowan BD: Life-threatening neutropenia following methotrexate treatment of ectopic pregnancy. A report of two cases. Obstet Gynecol 1996;88:4–7. Graczykowski JW, Mishell DR: Methotrexate prophylaxis for persistent ectopic pregnancy after conservative treatment by salpingostomy. Obstet Gynecol 1997;89:1–5. Korhonen J, Stenman UH, Ylostalo P: Low dose oral methotrexate with expectant management of ectopic pregnancy. Obstet Gynecol 1996;88:775–778. Bell OR, Awadalla SG, Mattox JH: Persistent ectopic syndrome: a case report and literature review. Obstet Gynecol 1987;69:521–523. DiMarchi JM, Kosasa TS, Kobara TY, et al: Persistent ectopic syndrome. Obstet Gynecol 1987;70:555–558. Alexander JM, Rouse DJ, Varner E, et al: Treatment of the small unruptured ectopic pregnancy: a cost analysis of methotrexate versus laparoscopy. Obstet Gynecol 1996;88:1.

Chapter 56.3 Hypertensive Disorders of Pregnancy and Preeclampsia Principles and Practice of Emergency Medicine

CHAPTER 56 OBSTETRIC EMERGENCIES

3 Hypertensive Disorders of Pregnancy and Preeclampsia Russell J. Carlisle Capsule General Considerations Pathogenesis and Pathophysiology Clinical Presentation Management Pitfalls and Medicolegal Pearls

CAPSULE The emergency department (ED) physician's role in the care of pregnant women with associated hypertension includes: (a) recognition and diagnosis, especially in those without prenatal care or previous diagnosis; (b) obstetric consultation and hospital admission for those with preeclampsia; and (c) initiation of stabilizing treatment in those with severe preeclampsia or eclampsia coincident with obstetric consultation and hospital admission. Any pregnant woman with sustained systolic or diastolic elevation of more than 140/90 mm Hg should be questioned for history of previous hypertension, blood pressure values during previous prenatal visits, recent weight gain, edema, headache, epigastric pain, or visual disturbances. Physical examination and laboratory evaluation should be performed to ascertain the presence of edema, hyperreflexia, proteinuria, consumptive coagulopathy, or altered renal function. Hypertensive women with less than 20 weeks of gestation and without other abnormality should be referred for prompt obstetric care. Physical or laboratory abnormality indicates a need for prompt obstetric consultation. Hypertensive women with longer than 20 weeks of gestation without previous hypertension or with proteinuria, edema, consumptive coagulopathy, or altered renal function should be considered preeclamptic and admitted for obstetric care. Women with severe preeclampsia (i.e., blood pressure of more than 160/110 mm Hg, significant proteinuria, headache, visual disturbance, oliguria, or upper abdominal pain) or eclampsia (seizures) need immediate treatment with parenteral magnesium sulfate and parenteral hydralazine and prompt admission for definitive treatment. The cure for preeclampsia and eclampsia is delivery. Therefore, patients should be stabilized when necessary and admitted immediately for obstetric care.

GENERAL CONSIDERATIONS Incidence, Morbidity, and Mortality Hypertensive disease is a common complication of pregnancy. It may be of new onset or aggravated by pregnancy in previously hypertensive women. In the United States, hypertensive disease in pregnancy has an average reported incidence of 6 to 7% with significant variations, with a higher incidence in nonwhites, especially blacks, and possibly in lower socioeconomic groups ( 1). Hypertensive disorders continue to be a major cause of maternal mortality accounting for 18% of maternal deaths in two recent national maternal mortality surveys ( Table 56–3.1) and 15% of hospital admissions for severe complications of pregnancy ( 2,3 and 4). Relative risk of maternal death from hypertensive disease is increased more than twofold in women over 30 years of age and in black and other nonwhite women ( 5,6). Maternal hypertension is also an important cause of perinatal morbidity and mortality. In the Collaborative Perinatal Project, a 13 year prospective study, the fetal death rate was noted to be three times higher in association with hypertension (diastolic more than 95 mm Hg) alone and to increase with the severity of hypertension especially in the presence of proteinuria ( 7). Frequency of occurrence and perinatal mortality rates for placental infarcts, placental growth retardation, and abruptio placentae increase with increasing maternal blood pressure.

Table 56–3.1. Selected Causes of Maternal Deaths

Definitions and Classification Confusion has arisen over definitions and classification of hypertensive diseases of pregnancy. Classification by the American College of Obstetrics and Gynecology in 1986, with minor modifications by the authors of Williams Obstetrics, 20th edition, 1997 (1), is well accepted and simple (Table 56–3.2). Hypertension is diagnosed when the blood pressure is 140/90 mm Hg or when an increase of 30 mm Hg systolic or 15 mm Hg diastolic over previous values is noted on two or more occasions more than 6 hours apart. Women without a history of preexisting hypertension are considered to have pregnancy-induced hypertension (PIH). Women with preexisting hypertension that has been exacerbated by pregnancy are considered to have pregnancy-aggravated hypertension (PAH). Women with preexistent hypertension unaffected by pregnancy are considered to have coincidental or chronic hypertension. Others have advocated different blood pressure values for hypertension (e.g., more than 125/75 mm Hg with less than 32 weeks of gestation and more than 175/85 mm Hg with more than 32 weeks, or greater than 130/80 mm Hg at any time during pregnancy) based on decreased fetal survival with increasing blood pressure elevation ( 7,8). Therefore, it should be apparent that individual variations may preclude the use of any one value as an absolute indicator of hypertensive disease.

Table 56–3.2. Hypertensive Disorders of Pregnancy—Classification

Preeclampsia Preeclampsia is diagnosed when hypertension coexists with proteinuria and/or edema after 20 weeks of gestation, or earlier if there are extensive hydatiform changes in the chorionic villi (trophoblastic disease). Preeclampsia is considered severe when the blood pressure is more than 160/110 mm Hg or in the presence of headache, epigastric pain, visual disturbances, severe proteinuria, or evidence of consumptive coagulopathy such as thrombocytopenia, hemoglobinuria, or hyperbilirubinemia. Eclampsia is diagnosed in a gravid woman having convulsions with no other cause and the clinical criteria for preeclampsia. Preeclampsia and eclampsia are considered to be superimposed when they develop in a woman with preexistent hypertension. Proteinuria, defined as more than 300 mg per 24-hour period or more than 100 mg/dL in two random urine samples collected more than 6 hours apart is an important sign of preeclampsia, and some question the diagnosis in its absence. Proteinuria, however, may be late in occurrence or difficult to detect on a one-time visit with dilute urine. The presence of edema may indicate preeclampsia, but its occurrence is common in normotensive pregnant women. The edema should be pathologic, not just dependent, involve the hands and face, and not resolve with activity or upright posture. Emergent differentiation between PIH, PAH, and coincidental hypertension may be difficult. Patients may lack knowledge of previous blood pressure or hypertension or not have received prenatal care, or records may be unavailable. Additionally, in normotensive and previously hypertensive women, the blood pressure usually falls in the first two trimesters, reaching a nadir by the end of the second or early in the third trimester, and rises during the third trimester to a level above initial values. In the ED, distinction between types of hypertension may not be possible or relevant, and classification and diagnosis may be restricted to hypertension, preeclampsia, severe preeclampsia, or eclampsia. The severity of preeclampsia roughly correlates with blood pressure and degree of proteinuria ( Table 56–3.3). No one criterion, however, is entirely dependable. Convulsions may occur in the presence of mildly elevated blood pressure or with mild proteinuria, or rarely, even in their absence. Severe persistent proteinuria, however, is an indicator of severe preeclampsia, as is a significantly elevated blood pressure. Other ominous signs include severe headache or visual disturbances, right upper quadrant or epigastric pain (from stretching of the hepatic capsule secondary to edema or necrosis), and evidence of hemolysis (thrombocytopenia, hemoglobinemia or hemoglobinuria or hyperbilirubinuria). An increased risk for multiple organ failure and poor maternal and fetal outcome has been associated with a syndrome known as the HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelet count), which involves progressive disseminated intravascular coagulation (9,10). Seizures of eclampsia are generalized and may appear before, during, or up to 48-hours postpartum.

Table 56–3.3. Indicators of Severe Preeclampsia

Risk Factors The incidence of hypertensive disease of pregnancy can be related to several factors, including parity, age, race, genetics, and fetal number. Preeclampsia occurs often in nulliparous women. In nulliparous and multiparous women, the incidence of preeclampsia increases with age, with an overall twofold to fourfold increase for older women, reflecting the increased incidence of hypertension with age. Primiparas aged 25, 35, and 40 have rates of preeclampsia of 6, 9, and 15% respectively, and multiparas of the same ages rates of 3, 5, and 7%. Therefore, nulliparity and increasing age are independent risk factors for the development of preeclampsia (5,6) (Table 56–3.4). Risk is also influenced by race, adjusting for parity, with lowest incidence in whites, increasing in Hispanics, and highest in blacks. This may reflect in part the increased incidence of hypertension in blacks. Preeclampsia also appears to be inherited, with an increased risk in offspring of mothers who had preeclampsia. Multiparas who had preeclampsia with their first pregnancy have a higher risk of recurrence than multiparas without such a history, and the severity of recurrence seems to parallel the severity of disease in the first pregnancy. The overall estimated risk of recurrence is about 7.5% in women who had severe preeclampsia in their first pregnancy ( 11). Multiple gestational pregnancies are also associated with an increase in hypertensive disease.

Table 56–3.4. Risk Factors for Hypertensive Disease of Pregnancy

PATHOGENESIS AND PATHOPHYSIOLOGY The cause of preeclampsia and eclampsia involves an aberrant immunologic response to the presence of fetal trophoblastic tissue or chorionic villi. This hypothesis is supported by observations that PIH is more likely to occur with first-time exposure to chorionic villi (nulliparas), later in pregnancy (beginning and increasing in incidence after the 20th week in normal pregnancies), in women with an overabundance of chorionic villi (multiple fetal and molar pregnancies), and in pregnancies with a new antigenic identity (multiparas impregnated by new consort or donor insemination). The exact mechanisms involved are far from clear, and multiple other theories have been proposed ( 12,13,14 and 15). The basic pathophysiology of preeclampsia and eclampsia seems better elucidated. In accepted theory, altered prostaglandin metabolism is felt to cause increased vascular reactivity, with resultant widespread maternal vasospasm, endothelial damage, platelet activation, and increased endothelial damage ( 1,12,13). Vascular constricton causes increased vascular resistance and consequent arterial hypertension ( 1). This theory is felt to be supported by the finding that the normal refractoriness of pregnant women to the pressors such as angiotension II is lost in women who develop preeclampsia even before it is clinically obvious. Friedman (12) postulates that altered prostaglandin metabolism is a result of uterine hypoperfusion, caused by the unexplained inability of the spiral arteries to dilate, with fetoplacental release of lipoxygenase products and the elevation of the maternal thromboxane A 2: prostacyclin ratio. Thromboxane A 2 is a potent vasoconstrictor and platelet aggregation activator manufactured primarily by platelets. Prostacyclin is a potent vasodilator and platelet aggregation inhibitor produced by the endothelium. Supportive findings show thromboxane A 2 to be increased and prostacyclin decreased in preeclampsia ( 1,12). Additionally, studies show a possibly decreased

occurrence of preeclampsia in predisposed gravid women taking low-dose aspirin, which presumably alters the thromboxane: prostacyclin ratio ( 12,16,17). An alternative theory for the pathophysiology of preeclampsia is the hyperdynamic model in which increased cardiac output and compensatory vasodilation mediate end-organ damage. Renal hyperperfusion causes hypertension and proteinuria. Systemic vasodilation causes diffuse endothelial damage with platelet activation, altered prostaglandin metabolism, and a feedback loop of increased endothelial damage, vasospasm, and development of clinical disease with a change to a hypodynamic state (15). Maternal vasospasm causes multiple changes in maternal physiology. Maternal blood volume, which normally increases in pregnancy by 1500 mL to a total of 5000 mL, remains at 3500 mL, presumably as a result of vasoconstriction. Systemic vascular resistance (SVR) is increased, as is blood pressure, and cardiac output is decreased, while cardiac contractility and left ventricular function are usually unchanged. The preeclamptic woman is left unduly sensitive to either vigorous fluid therapy or blood loss. Maternal hematologic abnormalities are common and are characterized by a consumptive coagulopathy with thrombocytopenia, and less often by microangiopathic hemolysis and decreased levels of plasma clotting factors and elevated levels of fibrin degradation products. Endocrine changes associated with preeclampsia include an absence of elevation of renin, angiotensin II, and aldosterone levels seen in normal pregnancies. Fluid distribution is altered, with an even greater extracellular fluid volume increase than seen in normal pregnancy. Renal perfusion and glomerular filtration fail to increase as in normal pregnancy, and in severe disease may even be lower than nonpregnant levels. Proteinuria is a part of the diagnostic definition of preeclampsia, but may not occur at significant levels until late in the disease. Hepatic abnormalities, including elevated serum liver enzymes, may result from periportal hemorrhagic necrosis and indicate serious disease, usually occurring in the presence of other organ involvement. Changes seen in the brain include edema, hyperemia, focal thrombosis, and hemorrhage, and may result in seizures or coma. Visual disturbances are associated with severe preeclampsia, although blindness is uncommon. Uteroplacental vasospasm causes decreased uteroplacental perfusion, and thus is probably the major cause of perinatal morbidity and mortality associated with preeclampsia. Microscopic study of uteroplacental arteries reveals endothelial damage, myointimal proliferation, and medial necrosis.

CLINICAL PRESENTATION Most patients with hypertensive disease of pregnancy (PIH, PAH, or preeclampsia) who present to the ED are undiagnosed on their presentation. Diagnosed cases are generally already hospitalized or admitted directly to the obstetric ward. Therefore, a high index of suspicion must be maintained when seeing pregnant women in their second and third trimesters. The two most reliable criteria for preeclampsia are abnormalities of which the patient is usually unaware, hypertension and proteinuria. Edema is a common finding and less discriminative. The patient may also be unaware of recent weight gain. By the time the patient is symptomatic, the disease is advanced, and its presence is indicated by headache, abdominal pain, visual disturbance, or even seizures. Lack of prenatal care denotes a high risk for the possible presence of undetected hypertensive disease because quiescent and symptomatic abnormalities are routinely screened for during obstetric care. Other historical clues that may denote increased risk are, as noted previously, nulliparity, advanced maternal age, previous hypertension, diabetes, race, multiple fetal pregnancy, molar pregnancy, family history of preeclampsia, or previous preeclamptic pregnancy ( Table 56–3.4). Hypertension Blood pressure elevation is the only criterion for PIH or PAH, and is the most reliable indicator of preeclampsia. A confirmed elevation of blood pressure above 140/90 mm Hg, the diastolic value being more reliable, or a confirmed elevation of 30 mm Hg systolic or 15 mm Hg diastolic from a known baseline denotes probable hypertensive disease. Proteinuria Significant proteinuria (more than or equal to 1 + on the urine dipstick or more than 300 mg in 24 hours) is a later-occurring but more reliable sign of preeclampsia. In the ED, where timed collection is precluded, its reliability is decreased by normally varying urine concentration. Strongly positive urine should be regarded as indicating preeclampsia in the presence of hypertension. Edema and Weight Gain Edema may occur in pregnancy, but its occurrence may indicate preeclampsia, especially if it is nondependent, with swollen fingers or face. Onset of edema may be preceded by sudden weight gain in excess of the normally expected 1 pound per week. Headache Progressive severe headache, initially mild at onset and frontal to frontooccipital, may signify cerebral ischemia or inflammation. Headache usually precedes convulsions. Visual Disturbances Visual disturbances associated with preeclampsia may include blurring of vision, scotomata, or rarely partial or complete blindness, and indicate ischemia or inflammation of the occipital cortex, retina, or ophthalmic vasculature. Epigastric or Right Upper Quadrant Pain Epigastric or right upper quadrant pain may signify hepatic swelling or impending rupture from ischemia, edema, or hemorrhage. Convulsions Convulsions are generally tonic-clonic and may occur antepartum, intrapartum, or postpartum. The tonic phase generally lasts less than 30 seconds, followed by a clonic phase of usually less than 1 minute, followed by a postictal period. The convulsions may recur, and in untreated severe cases, recurrences may be multiple or the patient may develop status epilepticus. Preeclampsia nearly always precedes convulsions, as do severe headache and nervous system irritability. Coma may follow convulsions, but its occurrence alone is regarded as part of preeclampsia. Physical Examination In addition to checking of vital signs, the physical examination should specifically include: 1. Soft-tissue examination looking for signs of nondependent edema. 2. Chest auscultation, especially to ascertain presence of pulmonary edema, one of the most serious complications of preeclampsia. 3. Abdominal examination to elicit right upper quadrant tenderness, indicating hepatic edema or impending rupture, fundal height for estimation of gestational age, uterine tenderness to exclude abruptio placentae, and fetal heart tones to ascertain fetal viability. 4. Pelvic examination to check cervical dilation and effacement and fetal presentation and station. 5. Deep tendon reflexes to elicit hyperreflexia or clonus, indicators of central nervous system irritability or impending seizures. Laboratory Tests In the presence of suspected preeclampsia laboratory tests should include: 1. 2. 3. 4.

Complete blood count, including platelets, to look for signs of hemoconcentration, hemolysis, or disseminated intravascular coagulation (DIC). Urinalysis to ascertain presence of proteinuria, renal disease, or oliguria. Electrolytes, creatinine, and blood urea nitrogen (BUN) to ascertain electrolyte status and renal function. Coagulation studies (PT, PTT, fibrinogen) that may indicate coagulopathy or DIC, and uric acid and AST (SGOT), which may be elevated in preeclampsia.

Severity Severity of disease is generally but not reliably proportional to the degree of blood pressure elevation. Other criteria may also indicate increased severity of disease (Table 56–3.3). These include the presence of proteinuria, especially if persistent and severe, symptoms of headache, disturbed vision, abdominal pain, oliguria, and convulsions; laboratory abnormalities of azotemia, liver dysfunction, or consumptive coagulopathy; or findings of fetal growth retardation or pulmonary edema. The more diffuse or severe the abnormalities, the more severe the disease and the greater the need for emergent stabilization and pregnancy termination. Differential Diagnosis The differential diagnosis of preeclampsia includes chronic hypertension, gestational and dependent edema, and renal disease including the many types of glomerulonephritis, nephrotic syndrome, and chronic renal disease. Preeclampsia has been confused acutely and at times with resultant poor outcome with (a) ocular disorders such as retinal detachment and hemorrhage, (b) abdominal conditions such as appendicitis, cholelithiasis, hepatitis, and pancreatitis, (c) central nervous system disorders such as stroke, TIA, cerebritis, and epilepsy, and ( 4) multisystem, immunologic, or hematologic disorders such as systemic lupus erythematosus (SLE), idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and disseminated intravascular coagulation (DIC). In the acute setting, diagnosis may depend largely on history, and in the presence of elevated blood pressure, treatment of preeclampsia should be instituted along with hospitalization to the obstetric service with appropriate consultations as indicated.

MANAGEMENT Once the diagnosis of hypertensive disease of pregnancy is made, whether it is PIH, PAH, preeclampsia or eclampsia, management includes hospitalization. Pregnancy-induced and pregnancy-aggravated hypertension are sometimes managed by the obstetrician on an outpatient basis after initial hospitalization, but for the emergency physician, diagnosis of hypertensive disease of pregnancy mandates hospitalization to the service of the obstetric specialist. In suspected preeclampsia, prompt hospitalization is absolutely indicated. In severe preeclampsia ( Table 56–3.3), stabilizing treatment should be instituted immediately in conjunction with hospitalization to the obstetric service. Stabilizing treatment has two primary objectives: the termination and/or prevention of convulsions and the lowering of dangerously elevated blood pressure, which present a threat to health of the mother and fetus. Preeclampsia persists until delivery of fetus and placenta, which is the only cure. Convulsions are controlled or prevented with magnesium sulfate ( 18,19 and 20) (Table 56–3.5). The safety and efficacy of magnesium sulfate for prophylaxis in preeclampsia and treatment of eclampsia has been documented in several trials including the large-scale Collaborative Eclampsia Trial in which treatment with magnesium was superior to phenytoin or diazepam ( 18,20). If renal function is adequate, an initial loading dose of 4 to 6 g magnesium sulfate is diluted in 20 to 100 mL of D5W and given intravenously at a rate not to exceed 1 g/min, usually over 10 to 30 minutes, followed by the intravenous infusion of dilute magnesium sulfate at a rate of 1 to 3 g/h by infusion pump with regular monitoring of the patellar reflex for signs of toxicity (absent reflexes) or need for increased medication (hyperactivity or clonus). Alternatively, after the initial intravenous loading dose of 4 g, deep intramuscular administration of 10 g of magnesium sulfate (50% solution divided in two equal doses of 10 mL with 1 mL of 1 or 2% lidocaine added to the syringe to minimize discomfort) is given in the upper outer quadrants of the buttocks. At 4-hour intervals an additional 5 g of 50% magnesium sulfate is given in alternating buttocks as long as patellar reflex is present, respirations are not depressed, and urine output of at least 25 mL/h is maintained. Although less comfortable, use of the intramuscular regimen may be advantageous in situations in which the patient may have to be transferred or transported or personnel or infusion pumps are limited. In either regimen, if seizures persist, additional magnesium sulfate is given intravenously in 1- to 2-g doses at rates no faster than 1 g/min.

Table 56–3.5. Magnesium Sulfate Therapy

Plasma magnesium levels may be helpful to assess efficacy or possible toxicity of therapy but symptoms and levels do not correlate well, and toxic symptoms may occur at lower levels and dosages. The therapeutic range is 4 to 6 mEq/L. Toxic and adverse effects of magnesium include drowsiness, flushing (especially facial), diaphoresis, hyporeflexia, hypotension, hypoventilation, conduction disturbances and arrhythmias, and cardiac or respiratory arrest. Patients need constant observation. Calcium gluconate 1 g as 10 mL of 10% solution given intravenously over 5 to 10 minutes or diluted in 50 mL D5W and run in intravenous piggyback over 10 to 15 minutes usually will reverse signs of serious toxicity. Otherwise, prompt intubation and mechanical ventilation is necessary. If seizures persist despite therapeutic or elevated levels of magnesium, intravenous sodium amobarbital may be given in doses of up to 250 mg or diazepam in 5 to 10 mg doses ( 1,14,21,22 and 23). Antihypertensive Therapy Antihypertensive therapy is indicated if the diastolic blood pressure is elevated above 110 mm Hg. Hydralazine is given intravenously as a 5-mg dose and blood pressure monitored at 5-minute intervals. Hydralazine is readministered at intervals no more frequent than 15 to 20 minutes in 5- to 10-mg doses until the desired diastolic level of 100 mm Hg is reached. The initial dose should never exceed 5 mg (some advocate a 1 mg test dose). Subsequent doses should not exceed 5 to 10 mg. Increasing severity of hypertension does not predict the need for increasing dose of hydralazine. Some authors have observed that response to hydralazine correlates with severity of hypertension. An alternative is hydralazine by intravenous infusion (100 mg/250 mL NS) titrated by infusion pump to maintain a diastolic blood pressure of 100 mm Hg. While hydralazine has been the antihypertensive agent traditionally used to treat acute obstetric hypertension until recently it has not always been readily available. An alternative agent whose use has also been demonstrated is labetalol ( 1,24). Labetolol can be given intravenously as 200 mg in 200 mL of D5W infused at 1 to 2 mg (1 to 2 mL/min) until the desired blood pressure is achieved and then stopped until needed or given by incrementally increasing intravenous bolus starting with 10 mg and repeating each 10 minutes (20 mg, 40 mg, 80 mg) until blood pressure response is achieved or a total of 300 mg is administered. Overzealous lowering of blood pressure or hypotension is to be avoided to prevent decreased placental perfusion and fetal jeopardization. In the rare circumstance that hydralazine or labetalol does not effectively lower blood pressure or more precise temporal control of blood pressure is needed (such as in an eclamptic patient undergoing caesarian section under general anesthesia), nitroglycerin infusion has been advocated because of its short half-life and lack of fetal toxicity (25). In cases complicated by oliguria and/or pulmonary edema invasive monitoring may also be needed to optimize pharmacologic and fluid management (26). Use of diuretics and hyperosmotic agents is to be avoided because, although overall body fluid may be increased, the increase is in the extravascular component and the intravascular component is constricted. Excessive fluid therapy is also to be avoided because this would only exacerbate the existing maldistribution of fluid and increase the risk of pulmonary or cerebral edema ( 1,14,21,22 and 23). Complications seen with preeclampsia include pulmonary edema, intracranial bleeding, abruptio placentae and fetal distress, growth retardation, and demise. Pulmonary edema is the common cause of maternal death. Maternal mortality increases dramatically with maternal age ( 27,28).

PITFALLS AND MEDICOLEGAL PEARLS With severe preeclampsia, some maternal deaths have occurred from delays in delivery despite the fact that the infant was full-term. The emergency physician should treat this condition as possibly life-threatening. Legal cases have been settled for substantial sums because of injury or maternal death associated with administration of magnesium sulfate in excess or without constant observation. In one illustrative case, the patient was in a private room and experienced respiratory and cardiac arrest that were detected only on routine nursing assessment. Maternal and fetal deaths and serious morbidity have resulted from diagnostic confusion in obese patients presenting with right upper quadrant abdominal pain (resulting from liver distention and HELLP syndrome) and altered mental status or seizures. Obesity may represent not only an increased risk for occurrence of severe disease but also for failure to recognize pregnancy and its complications. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28.

Cunningham FG, MacDonald PC, Gant NF: Williams obstetrics, 20th ed, Stamford, CT: Appleton and Lange, 1997. Atrash HK, Koonin LM, Lawson HW, et al: Maternal mortality in the United States, 1979–1986. Obstet Gynecol 1990;76:1055–1066. Berg CJ, Atrash HK, Koonin LM, et al: Pregnancy-related mortality in the United States, 1987–1990. Obstet Gynecol 1996;88:161–167. Scott CL, Chavez GF, Atrash HK, et al: Hospitalizations for severe complications of pregnancy, 1987–1992. Obstet Gynecol 1997;90:225–229. Hanson JP: Older maternal age and pregnancy outcome: a review of the literature. Obstet Gynecol Surv 1986;41:726. Fonteyn VJ, Isada NB: Nongenetic implications of childbearing after age thirty-five. Obstet Gynecol Surv 1988;43:709–720. Friedman EA, Neff RK: Pregnancy outcome as related to hypertension, edema, and proteinuria. In Lindheimer MD, Katz AI, Zuspan FP, eds. Hypertension in pregnancy. New York: Wiley, 1976:13. Ferris TF: How should hypertension during pregnancy be managed? An internist's approach. Med Clin North Am 1984;68:491–503. Weinstein L: Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 1982;62:159–167. Van Dam PA, Renier M, Baekelandt M, et al: Disseminated intravascular coagulation and the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe pre-eclampsia. Obstet Gynecol 1989;73:97–102. Mehta L, Young ID: Recurrence risks for common complications of pregnancy—a review. Obstet Gynecol Surv 1987;42:218–223. Friedman SA: Pre-eclampsia: a review of the role of prostaglandins. Obstet Gynecol 1988;71:122–137. Gant NF, Gilstrap LC: Pharmacologic approaches to prevent pregnancy-induced hypertension. In: Cunningham FG, MacDonald PC, Gant NF, eds. Supplement No. 5 to Williams Obstetrics 18th ed. Norwalk, CT: Appleton and Lange, 1990. Doan-Wiggins L: Hypertensive disorders of pregnancy. Emerg Med Clin North Am 1987;5:495–508. Easterling TR, Benedetti TJ: Pre-eclampsia: a hyperdynamic disease model. Am J Obstet Gynecol 1989;160:1447–1453. Schiff E, Peleg E, Goldenberg M, et al: The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A 2 to prostacyclin in relatively high risk pregnancies. N Engl J Med 1989;321:351–362. Benigni A, Gregerini G, Frusca T, et al: Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension. N Engl J Med 1989;321:357. Lucas MJ, Leveno KJ, Cunningham FG: A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med 1995;333:201–205. Duley L, Johanson R: Magnesium sulphate for pre-eclampsia and eclampsia: the evidence so far. Br J Obstet Gynaecol 1994;101:565–567. Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the collaborative eclampsia trial. Lancet 1995;345:1455–1463. Cunningham FG, Pritchard SA: How should hypertension be managed? Experience at Parkland Memorial Hospital. Med Clin North Am 1984;68:505–526. Pritchard JA, Cunningham FG, Pritchard SA: The Parkland Memorial Hospital protocol for treatment of pre-eclampsia. Am J Obstet Gynecol 1984;148:951–963. Taber B: Manual of Gynecologic and Obstetric Emergencies. 2nd ed. Philadelphia: WB Saunders Co., 1989:212–229. Mabie WC, Gonzalez AR, Sibai BM, et al: A comparative trial of labetalol and hydralazine in the acute management of severe hypertension complicating pregnancy. Obstet Gynecol 1987;70:328–333. Cotton DB, Longmire S, Jones MM, et al: Cardiovascular alterations in severe pregnancy-induced hypertension: effects of intravenous nitroglycerin coupled with blood volume expansion. Am J Obstet Gynecol 1986;154:1053–1059. Clark SL, Greenspoon JS, Aldahl D, et al: Severe pre-eclampsia with persistent oliguria: management of hemodynamic subsets. Am J Obstet Gynecol 1986;154:490–494. Lehmann DK, Mabie WC, Miller JM, et al: The epidemiology and pathology of maternal mortality: Charity Hospital of Louisiana in New Orleans, 1965–1984. Obstet Gynecol 1987;69:833–840. Lopez-Llera M, Linares GR, Horta JLH: Maternal mortality rates in eclampsia. Am J Obstet Gynecol 1976;124:149–155.

Chapter 56.4 Medical Disorders of Pregnancy Principles and Practice of Emergency Medicine

CHAPTER 56 OBSTETRIC EMERGENCIES

4 Medical Disorders of Pregnancy Van H. Miller Capsule Introduction Physiology of Pregnancy Medical Complications of Pregnancy

CAPSULE Medical complications are divided into preexisting and acquired disorders by organ systems. The impact of pregnancy on disease and disease on pregnancy is evaluated and diagnosis and treatment guidelines discussed for the following conditions: congestive heart failure (CHF), coronary artery disease, arrhythmias, valvular heart disease/prosthetic heart valves, bacterial endocarditis, hypertensive disorders, obstetrical shock/third trimester bleeding, obstructive/restrictive pulmonary disease, acute respiratory failure, carbon monoxide poisoning, thromboembolic disease, diabetes mellitus, nutritional anemias, sickle cell hemoglobinopathy, consumptive and nonconsumptive coagulopathies, autoimmune disease, Rh isoimmunization, acute and chronic renal diseases, pyelonephritis, seizures, and appendicitis. Maternal and fetal/neonatal effects of viral, bacterial, and venereal infections, their basic diagnostic features and some management guidelines are discussed. Preeclampsia/eclampsia is noted to be able to masquerade as almost any acute medical problem.

INTRODUCTION Pregnant patients can be expected to present to the emergency department (ED) with routine concerns of normal pregnancy and complications of pregnancy induced by preexisting medical disorders and acquired disorders. Diagnostic and therapeutic modalities used to evaluate life-threatening medical problems in pregnancy are primarily the same as in nonpregnant patients; in general, maternal well-being ensures fetal well-being. Thorough understanding of the normal physiology of pregnancy to properly evaluate and treat pregnancy complicated by medical disorders is required. Table 56–4.1 summarizes important physiologic changes of pregnancy. Table 56–4.2 lists medical disorders by organ system and separates disease into preexisting and acquired disorders. These two tables may be used as an index to find specific medical problems that may complicate pregnancy. Expected changes in laboratory values secondary to normal pregnancy are enumerated in Table 56–4.3. Table 56–4.4,Table 56–4.5,Table 56–4.6,Table 56–4.7 and Table 56–4.8 summarize important management guidelines and clinical information.

Table 56–4.1. Physiologic Changes in Pregnancy

Table 56–4.2. Medical Complications of Pregnancy

Table 56–4.3. Laboratory Values in Pregnancy

Table 56–4.4. Hypertensive Disorders of Pregnancy

Table 56–4.5. Management of DIC in Pregnancy

Table 56–4.6. Indications for Pulmonary Angiography in the Pregnant Patient

Table 56–4.7. Management Guidelines for Seizures in Pregnancy

Table 56–4.8. Infections In Pregnancy Viral (42,43 and 44)

PHYSIOLOGY OF PREGNANCY Cardiopulmonary CARDIOVASCULAR Normal cardiovascular changes of pregnancy include an increase in cardiac output, which begins to rise during the first 10 weeks of pregnancy and peaks at the 20th week at 30 to 45% above resting cardiac output ( Table 56–4.1). Approximately 25% of maternal cardiac output goes to the uteroplacental unit, which functions as a large low-resistance arteriovenous shunt. Blood pressure is expected to fall or remain the same in relation to decreased systemic vascular resistance coupled with expanded blood volume and reduced arteriolar vasomotor tone. Dyspnea, edema, functional systolic heart murmurs, and the presence of a third heart sound are frequent occurrences in normal pregnancy. The enlarging uterus can interfere with venous and, to a lesser extent, arterial blood flow by compressing the inferior vena

cava and aortofemoral vessels when the pregnant patient is in the supine position. Changing from the supine position to the left lateral decubitus position can increase cardiac output by as much as 22%. PULMONARY The following changes increase breathing efficiency in pregnancy. Elevation of the diaphragm decreases residual volume (dead space), chest diameter is increased from thoracic wall intercostal muscle relaxation, and bronchiolar air resistance decreases from bronchiolar smooth muscle relaxation. Minute ventilation is increased up to 40% by increasing tidal volume without increasing respiratory rate. Respiratory rates above 20 breaths/min indicate pathology. The developing fetus increases maternal oxygen consumption by approximately 20%, but the increase in ventilation is more than the increase in oxygen consumption, and consequently maternal acid-base status is characterized by a mild respiratory alkalosis ( Table 56–4.2). Despite this increase in breathing efficiency, many pregnant women complain of breathlessness or feeling short of breath. Endocrine-Metabolic ENDOCRINE Early normal pregnancy has a large increase in estrogen and progesterone levels; the former stimulates insulin secretion and enhances peripheral use of glucose. The first 20 weeks of pregnancy are characterized by a decrease in fasting plasma glucose and improved glucose tolerance. The latter 20 weeks of pregnancy are characterized by a state of insulin resistance ( 1). The physiology is probably related to the insulin antagonistic effects of increased levels of human placental lactogen (hPL), prolactin, cortisol, and progesterone. Therefore, normal pregnancy is characterized by fasting hypoglycemia with exaggerated postprandial insulin and glucose levels. The placenta is impermeable to insulin and glucagon. Fetal pancreatic insulin secretion begins between 9 and 11 weeks of gestation and may be stimulated by glucose and amino acids. It is believed that fetal insulin is the major growth factor in the fetus ( 1). METABOLIC Normal pregnancy is characterized by a 2 to 3 pound weight gain in the first trimester and approximately 11 pounds of weight gain in both the second and third trimesters, for an average total weight gain of 24 to 28 pounds. Extremity edema is present in up to 80% of normal pregnancies, partly as a result of decreased serum albumin and amino acids. Because of the hormonal effects of pregnancy, the maternal response to feeding is characterized by elevated postprandial blood sugar, free fatty acids, ketones, and triglycerides. The maternal response to fasting is accelerated catabolism with a tendency for early ketosis and acidemia. The placenta regulates delivery of metabolic substrate to the fetus. Glucose is transported by facilitated diffusion, amino acids by active transport; ketones diffuse across freely, but fatty acids diffuse across in limited quantities by a gradient dependent on diffusion. The purpose is to ensure fatty fuels for maternal needs and promote carbohydrate transfer to the fetus. Maternal hyperglycemia results in fetal hyperinsulinemia ( 1,2). Hematologic-Immunologic HEMATOLOGIC Normal pregnancy produces a 45% increase in blood volume at term. The increase in circulating red blood cells is relatively less than the increase in plasma volume, leading to an approximately 15% drop in hematocrit by the second trimester. Average-term hemoglobin concentration is 12.5 g/dL, and levels below 11 g/dL should be considered abnormal. Blood leukocyte counts are generally elevated during pregnancy, and often markedly so during labor and the early puerperium. Pregnancy is frequently described as a hypercoagulable state, with a rise in most procoagulants ( 3). It is also thought that the placenta modifies fibrinolytic activity, favoring clot formation over clot lysis ( 3). IMMUNOLOGIC Maternal immune hyporesponsiveness allows maternal-fetal coexistence. The proximity of fetal and maternal circulation presents risk of isoimmunization. Renal Values of serum creatinine and blood urea nitrogen (BUN) are reduced in pregnancy. A serum creatinine and BUN more than 0.9 mg/dL and 12 mg/dL should be suspect. Ideally, glomerular filtration rate (GFR), based on the clearance of serum creatinine, is used as a measure for renal function. Normal pregnancy produces a 30 to 50% increase in GFR and an increase in renal plasma flow. These increases produce the observed lowered concentrations of serum creatinine and BUN and also increased drug clearance. As a result of increased GFR, drug dosages in pregnancy frequently have to be increased to remain therapeutic. Changes in tubular reabsorption coupled with increased glomerular filtration rate lead to glucosuria in 16% of normal pregnancies. Proteinuria is considered abnormal when urinary protein excretion exceeds 300 mg in 24 hours (4). Hormones of pregnancy also produce a physiologic hydronephrosis. Gastrointestinal The decreased peristalsis of smooth muscles of the gastrointestinal tract reduces the emptying time of the stomach, large intestines, and gallbladder, resulting in gastric reflux into the esophagus, constipation from increased water reabsorption of stool, and a propensity for gallstone formation. Musculoskeletal Low back pain and discomfort are common complaints of pregnant women. The increased incidence of nocturnal leg cramps during pregnancy remains unexplained.

MEDICAL COMPLICATIONS OF PREGNANCY Cardiovascular Preexisting Disorders CHF AND CARDIOVASCULAR DISEASE Since 1979, a clinical classification system provided by the New York Heart Association (NYHA), based on the functional status of the heart, has been widely used to determine the prognosis for successful pregnancy. In essence, this system divides all cardiac disease into four functional classes. Classes I and II are defined as having no functional limitation of activity and no cardiac symptoms with mild functional limitations and symptoms with physical activity. These patients do well during pregnancy (Table 56–4.2). Class III patients have limited ability to perform most physical activities, but are asymptomatic at rest. Severe class III patients develop symptoms with minimal physical activity. Class IV patients have severe limitation of activity with some symptoms at rest, and any physical activity produces cardiac symptoms. Management of CHF is similar in pregnant and nonpregnant patients. Functional class I and II patients may be allowed to labor and deliver with minimal intervention. Management involves close monitoring of fluid input and output, pulse rate, respiratory rate, and symptoms of dyspnea. Conventional delivery with emphasis on relief of pain and apprehension without undue depression of the infant or the mother are all that are required. Patients in the NYHA functional class III and IV categories have hemodynamically significant cardiac disease, often with accompanying pulmonary hypertension and are at much higher risk during labor and delivery. As might be expected, these patients do poorly and have a 30 to 50% chance of significant hemodynamic morbidity and a 25 to 50% chance of maternal mortality. Increases in pulse rate above 100 beats/min, respiratory rate above 24 breaths/min, particularly when associated with

dyspnea, suggest cardiac decompensation and require immediate medical intervention ( 5). Vaginal delivery is more desirable for patients with cardiac disease than cesarean section due to volume shifts, greater blood loss, and the effects of anesthesia on the cardiovascular system. Major surgical procedures are poorly tolerated by patients in heart failure, and the decision for cesarean section is reserved for the usual obstetric indications. Coronary Artery Disease and Arrhythmias Symptomatic coronary artery disease is rare in women of childbearing age. Most women with ischemic heart disease present for the first time during pregnancy. The rarity of this disease, with an estimated incidence of 1 in 10,000 pregnancies, makes low clinical suspicion a problem in making the diagnosis. The trimester in which infarction occurs has a major impact on survival. The mortality rate for third-trimester infarct is 45%, and 66% of infarctions occur during this trimester. An increased maternal mortality is seen when infarction occurs within 14 days of delivery. Management goals are the same as for the nonpregnant patient. The unique stress of labor superimposed on the ischemic or recently infarcted heart calls for intense management. In the emergency setting, the presentation and management of a tachyarrhythmia in a pregnant patient do not differ from those of the nonpregnant patient. Patients with arrhythmias resistant to medical therapy may undergo direct current cardioversion at low to moderate energy settings with little risk to the fetus, i.e. 25 to 50 joules (6). Organic Heart Disease and Prosthetic Heart Valves Septal defects, patent ductus arteriosus (left-to-right shunts), and tricuspid valve defects are low-risk organic cardiac lesions. These patients tolerate pregnancy well in the absence of pulmonary hypertension. Pregnant patients with valvular regurgitation, i.e., mitral regurgitation and aortic regurgitation, also tolerate pregnancy well. These patients are able to increase cardiac output in the face of the normal physiologic stresses of gestation and labor. Stenotic lesions, i.e., aortic stenosis and mitral stenosis, are poorly tolerated in pregnant patients. A fixed cardiac output can poorly accommodate changes in blood volume and heart rate. These patients are particularly at risk for developing acute pulmonary edema during labor, when each uterine contraction transfuses 300 to 500 mL of blood into the systemic circulation. Mitral stenosis remains one of the most dangerous cardiac complications of pregnancy. Life-threatening pulmonary edema, atrial flutter or fibrillation, and systemic embolization will often present in previously asymptomatic pregnant patients. Management does not differ from that of the nonpregnant patient, and is directed at decreasing heart rate, fluid restriction or diuretic therapy, and digitalis. Preferred delivery is vaginal, with epidural anesthesia for pain control. Patients with organic heart disease producing pulmonary hypertension, cyanotic heart disease, coarctation of the aorta, and Marfan's syndrome do poorly during pregnancy. These patients must be identified early for appropriate counseling regarding interruption of a life-threatening pregnancy versus early intensive obstetric care. The emergency physician is frequently the first to identify such patients. Pregnancy with prosthetic valves in place has significant maternal and fetal morbidity and mortality. Mechanical heart valves as well as bioprosthetic valves may have to be anticoagulated. Mechanical valves have an unacceptable risk of thrombosis/thromboembolism without anticoagulation, while bioprosthetic valves have significant accelerated deterioration from the physiologic stress of pregnancy. Optimum prophylaxis against thromboembolic disease remains unclear. Oral anticoagulants (Coumadin) cross the placenta and some studies suggest an incidence of 15 to 20% Coumadin embryopathy, others suggest the risk is much less. In the second and third trimester Coumadin is associated with abortion, stillbirth, and fetal hemorrhage ( 7). If Coumadin is used during pregnancy it is usually avoided during the first 6 to 12 weeks and in the last few weeks of pregnancy. While heparin does not cross the placental barrier it requires parental administration. Fixed subcutaneous dosages of heparin have been associated with 47% recurrence rate of venous thromboembolism and, therefore, treatment protocols require adjusted dosages (8). Low molecular weight heparin does not appear to cross the placenta and its use may reduce the risk of heparin-induced thrombocytopenia and osteoporosis but clinical experience is still limited ( 8). The American Heart Association recommends that one of the regimens shown in Table 28–6.8 (Antibiotic Prophylaxis for Infective Endocarditis), be given to high-risk pregnant patients undergoing invasive procedures to minimize the risk of bacterial endocarditis. The high-risk conditions are prosthetic heart valves, aortic valve disease, mitral insufficiency, patent ductus arteriosus, ventricular septal defect, aortic coarctation and Marfan's syndrome. Endocarditis prophylaxis is probably appropriate for all pregnant women with cardiac lesions undergoing invasive procedures or at the time of vaginal delivery in the presence of infection. Hypertensive Disorders Hypertension (HTN) is a common medical complications encountered in pregnancy. A classification scheme relating to clinical diagnosis and treatment of HTN in pregnancy is problematic. In the United States the system proposed by the American College of Obstetricians and Gynecologists (ACOG), in 1972, is widely accepted, and divides hypertensive disorders in pregnancy into three categories: chronic HTN, gestational HTN, and preeclampsia ( Table 56–4.4). Table 56–3.2 uses a modified classification of the ACOG definitions. Unfortunately no classification is adequate if etiology of HTN is unknown. It is difficult to diagnosis chronic HTN in pregnant women in whom the blood pressure before pregnancy is not known. In such cases the presence of HTN before 20 weeks gestation is accepted as evidence of chronic HTN. However, increased blood pressure before 20 weeks can be the first manifestation of preeclampsia. Chronic HTN places the pregnant women at increased risk for superimposed preeclampsia and abruptio placentae, and their infants are at increased risk for perinatal morbidity and mortality. The decision to place the HTN patient on ongoing antihypertensive therapy requires consideration of the severity of HTN, the effects of treatment on the uteroplacental blood flow, and possible effects of the drugs themselves on the developing fetus. The goal of treatment is to prevent the usual complications of HTN, i.e., intracranial hemorrhage, hypertensive CHF, and progressive renal failure. Treatment of mild to moderate HTN does not appear to change the incidence of these complications. In fact, most pregnancies do well with mild to moderate HTN, whether or not antihypertensive therapy is given. The prognosis for outcome during pregnancy is related to the severity of the disease before pregnancy. The usual standard of care is to treat with antihypertensive drugs if the blood pressure is above 150/110 mm Hg or the patient was receiving antihypertensive medication before the pregnancy and HTN is well controlled. Methyldopa is probably still the drug of first choice, with labetalol or nifedipine as reasonable but less well-studied alternatives. Diuretics are usually not effective when used alone for the treatment of HTN in pregnancy. Women with chronic HTN may need changes in their anti-HTN regimen when they become pregnant, i.e. angiotensin-converting enzyme inhibitors and atenolol have serious effects on the developing fetus and uteroplacental hemodynamics (9). Gestational HTN is defined as the development of elevated blood pressure without other symptoms of preeclampsia after 20 weeks gestation in a previously normotensive woman. It can be an early manifestation of preeclampsia or a sign of unrecognized chronic HTN. In general the outcome is good without drug therapy. Preeclampsia is a great imitator and must be differentiated from chronic HTN, gestational edema, and renal disease (see Table 57–4.9).

Table 56–4.9. The Differential Diagnosis of Preeclampsia

ACQUIRED CARDIOVASCULAR DISORDERS OBSTETRIC SHOCK AND HEMORRHAGE The normal physiology of pregnancy delays the usual clinical signs of hemorrhagic shock. By the third trimester, a 40 to 50% increase in blood volume has occurred, allowing the approximate 600 mL blood loss seen in the average normal vaginal delivery to occur without physiologic compromise ( 10). This physiologic increase in blood volume allows the pathologic loss of up to 35% of blood volume before tachycardia, hypotension, and other signs of hypovolemia are manifest. In the face of life-threatening exsanguination, mechanisms for self preservation place maternal welfare over fetal welfare. Even in relatively well-compensated hypovolemia, the fetus may be in severe jeopardy before the usual clinical signs associated with significant hypovolemia in the nonpregnant patient are manifest. In obstetric shock, the emphasis must be on early and aggressive volume replacement before the onset of the usual clinical signs of shock to avoid decreased uteroplacental blood flow. Use of vasopressors is discouraged because the uteroplacental arterioles appear to be maximally vasodilated under normal physiological conditions of pregnancy. The alpha-adrenergic activity seen in pharmacologic doses of most pressor agents can cause additional reductions in uteroplacental blood flow from direct vascular constriction and unknown effects on uterine muscle tone. If a vasopressor is needed, ephedrine has beta-adrenergic as well as alpha-adrenergic activity and, therefore, more favorable effects on uterine blood flow. THIRD-TRIMESTER BLEEDING Abruptio Placentae Premature separation of the normally implanted placenta, or abruptio placenta, has an incidence from 1 in 77 to 1 in 250 pregnancies ( 8). Its cause is unknown, but its association with maternal HTN is well documented. Abruption is equally associated with chronic maternal HTN and preeclampsia/eclampsia, and to a lesser extent with underlying renal insufficiency ( 3). In the ED, trauma, a rare cause of abruption, may be unduly represented. The most common cause of death is postpartum hemorrhage. The classic presentation is painful vaginal bleeding, often with shock out of proportion to the clinical evidence of bleeding. Most abruption affects less than 25% of the placenta area and is often not diagnosed until after delivery. Abruption of more than 50% of placental surface is severe and can lead to significant bleeding, disseminated intravascular coagulation (DIC), and intrauterine fetal demise (IUFD). Abruption severe enough to cause IUFD can be expected to have affected a 2500 mL blood loss on presentation ( 3). Treatment is immediate delivery, with vaginal delivery the preferred route. These patients often have uterine inertia and failure to progress and will be facing surgery. Attempts at stabilization of maternal hypotension with blood and crystalloid and treatment of DIC before delivery can improve their prognosis ( Table 56–4.5 and Chapter 25–1). Placenta Previa Placenta previa, low-lying placenta that encroaches on the internal cervical os, varies from partial to complete. Its cause is unknown but is associated with multiparity, advancing age, and prior uterine incisions. The incidence of placenta previa is approximately 1 in 260 pregnancies. Maternal mortality is approximately 0.1% and fetal mortality approximately 15 to 20% (11). The classic clinical presentation is painless uterine bleeding. Shock corresponds to clinical blood loss. Bleeding is generally not life threatening unless the placenta is disrupted by digital examination. Suspected diagnosis in the stable patient can be confirmed by ultrasound. No pelvic examination should be attempted unless the patient is in an operating suite with full capabilities for emergency cesarean section. Treatment is generally delivery by cesarean section. The stable patient who is not in labor, with minimal bleeding, can be admitted for observation. Eclampsia Eclampsia, a great imitator, can also present as obstetric shock. Hepatic subcapsular hematomas can rupture, producing hypovolemic shock. PERIPARTUM HEART FAILURE Obstetric patients occasionally present in the third trimester or postpartum period with CHF of no apparent cause. These patients have been labeled as having peripartum cardiomyopathy (PPCM), defined on the basis of CHF in the last month of pregnancy or within 5 months of delivery and the absence of other discernible causes of heart failure. Studies of these patients have shown a low incidence of PPCM, 1 in 15,000 deliveries. Over 75% of patients initially thought to have PPCM are later found to have CHF secondary to chronic HTN, iatrogenic volume overload, previously unrecognized valvular heart disease, morbid obesity, or prior undiagnosed viral myocarditis. The distinction between PPCM and peripartum CHF of discernible cause is important. Recognition and treatment of the underlying condition in peripartum CHF usually has a course consistent with the underlying lesion. The prognosis in PPCM corresponds to the degree of cardiomegaly persisting beyond delivery; patients with cardiomegaly beyond 6 months have a 5-year mortality more than 75% from unrelenting CHF or complications of pulmonary or systemic emboli. Patients with PPCM not responding to medical management of CHF are candidates for heart transplantation. Preexisting Pulmonary Disorders OBSTRUCTIVE AND RESTRICTIVE PULMONARY DISEASE Pulmonary diseases are commonly categorized into obstructive and restrictive disorders. Obstructive disorders include asthma, by far the most common pulmonary disease seen in with an incidence of 0.4 to 1.3% in pregnant women, chronic obstructive pulmonary disease (COPD), and emphysema. The latter two disorders are clinical amalgams of several disorders and are relatively uncommon during the childbearing years. Patients with a heavy smoking history, alpha-1 antitrypsin deficiency, or cystic fibrosis occasionally present with pregnancy complicating their management. The course of COPD is by nature variable and unpredictable, but the management does not generally differ between pregnant and nonpregnant patients. Most patients remain unchanged during pregnancy, but symptoms are more likely to get worse than to improve. Therapeutic modalities must not be harmful to mother or fetus. The symptomatic pregnant patient with COPD who does not respond to initial bronchodilator therapy should be considered for admission. Restrictive pulmonary disease, commonly kyphoscoliosis, generally has a stable course, and these patients tend to tolerate pregnancy well. A vital capacity (VC) of

less than 1 L, or 20% of predicted value represents a critical level of restrictive pulmonary disease, and these patients should be considered for therapeutic abortion or a planned cesarean section (12). Sarcoidosis is the most common interstitial lung disease to complicate pregnancy. Patients with sarcoid frequently do better during pregnancy, and the treatment is unchanged. Myasthenia gravis, a rare autoimmune disorder involving the neuromuscular endplate, can present as subtle respiratory decompensation. A low threshold for obtaining arterial blood gases (ABGs) and a measure of the VC can prevent an obstetric catastrophe. It should be remembered that any drug with a curarelike effect, e.g., magnesium sulfate, aminoglycoside antibiotics must be used with extreme caution. Dyspnea and wheezing are two common respiratory complaints in pregnancy. The sensation of dyspnea is reported in 60 to 70% of normal pregnancies. Tachypnea, a respiratory rate more than 18 to 20 breaths/min, is abnormal. Objective tachypnea should induce a search for a cause. Wheezing, the clinical hallmark of airway obstruction, does not indicate a cause and correlates poorly with the degree of obstruction and the response to therapy. Use of accessory muscles of respiration, pulsus paradoxus of 18 mm Hg or more, and tachycardia more than 120 beats/min are reliable signs of respiratory distress. ABGs give critical information and should be obtained early and often in pregnant patients with respiratory distress. Cyanosis, a late finding, should be anticipated through timely arterial blood gas measurements and avoided by appropriate interventions. Maternal arterial oxygen tension should be more than 70 mm Hg and the Pa CO2 less than 50 mm Hg. Deviations of 5 mm Hg below or above these values, respectively, is an ominous finding and should prompt immediate corrective measures, including intubation ( 12). The alveolar-arterial oxygen tension gradient, (A-a) O2, is a useful indicator of gas exchange. An elevated (A-a) O 2 gradient along with tachypnea and hypercarbia are early signs of respiratory failure. The (A-a) O2 gradient is normally increased in pregnancy, especially in the third trimester, but an (A-a) O2 gradient more than 20 mm Hg should precipitate a search for wheezing, consolidation, or pulmonary edema. Chest radiographs should be obtained when there is a change in previous pulmonary disease or new pulmonary disease. Fetal radiation exposure is a theoretic risk. There is an estimated 1 to 3% incidence of congenital anomaly with exposure to 5000 mrad. A posterior-anterior chest radiograph is 36 mrad, or the equivalent of the amount of radiation exposure in a cross-country airplane flight ( 12). When radiographs are indicated, the abdomen should be shielded to avoid emotional issues. There are no strict guidelines to determine the level of pulmonary function necessary for safe pregnancy. Despite tremendous pulmonary reserve, a forced vital capacity (FVC) or forced expiratory volume in 1 second (FEV 1) of less than 1 L can predict difficulties. Such patients breathe at more than 50% of their maximal breathing capacity at term and are dyspneic at rest. The treatment goals are unchanged in the pregnant and nonpregnant patient with pulmonary disease. Medical regimens for patients with bronchospasm usually begin with metered dose inhaler or nebulized albuterol. Terbutaline, used as a tocolytic agent in preterm labor, should be avoided in active labor. Ephedrine is an over-the-counter adrenergic agent that has not been shown to be harmful to the fetus, but should be avoided because there are better agents with fewer side effects. Corticosteroids are now routinely used for the patient with severe bronchospasm not responding to inhaled bronchodilators in the first 1 to 2 hours of treatment. For the patient with severe bronchospasm who is unresponsive to inhaled bronchodilators, the risk of fetal hypoxia is significantly greater than the potential risk of exposing the fetus to corticosteroids ( 13). The onset of action is 4 to 6 hours, and usage does not mandate chronic prednisone therapy. The dosage can be tapered over 10 to 14 days. Patients with steroid-dependent pulmonary disease must be covered with stress doses of hydrocortisone (100 mg parenterally every 8 hours). Theophylline appears less efficacious than it was once thought to be and has a narrow therapeutic to toxic dose margin. Dosage changes to avoid maternal and fetal toxicity must be anticipated as there is increased clearance of theophylline in the first and second trimester, and significantly reduced clearance in the third trimester. Mucolytic agents and any agent that contains iodine are contraindicated in pregnancy as they are concentrated in the fetal thyroid and are teratogenic. Acquired Pulmonary Disorders ACUTE RESPIRATORY FAILURE Obstetric patients develop respiratory failure from the usual causes of decompensated restrictive and obstructive pulmonary disease. In addition, many obstetric complications lead to the so-called adult respiratory distress syndrome (ARDS). Any process that results in injury to the pulmonary vascular endothelium promoting edema fluid in the lungs, with progressive hypoxemia and pulmonary infiltrates, can be defined as ARDS. This high-mortality syndrome (60 to 70% mortality) is seen in conjunction with aspiration pneumonia, hemorrhagic shock, amniotic fluid embolism, sepsis, abruptio placenta, and preeclampsia. Although the triggering mechanisms are different, management is remarkably similar. Intubation and mechanical ventilation with increased oxygen concentration and positive end-expiratory pressure (PEEP) to keep the damaged alveoli open are usually necessary while attempts to correct the underlying disorder are undertaken. In the pregnant patient with acute respiratory failure from any cause, the ED physician must realize the significance of the 20% increase in maternal oxygen consumption due to the demands of the uteroplacental unit. The fetal environment is relatively hypoxemic and hypercarbic relative to the mother (fetal umbilical vein PO 2 of 28.5 mm Hg and PCO2 of 10.0 mm Hg higher than maternal P CO2 (10). Fetal aerobic metabolism occurs because of greater affinity for oxygen by fetal hemoglobin's left-shifted oxygen dissociation curve, and other factors that allow increased oxygen extraction from the mother's blood by the fetus. Thirty seconds of apnea can produce a fall in maternal arterial P O 2 of 50 to 60 mm Hg, placing the fetus at severe risk for hypoxemic insult. Maternal respiratory embarrassment or impending respiratory arrest must be anticipated to avoid significant fetal morbidity and mortality. Management of respiratory failure in pregnancy requires an understanding of the rapidity of the development of hypoxemia, the need for rapid intubation, and knowledge of the changes in the respiratory and gastrointestinal tracts. If intubation cannot be accomplished within 30 seconds, the pregnant patient needs preoxygenation with 100% O 2 for 3 to 4 minutes or, in extreme emergency, bag-valve-mask insufflation should be administered equivalent to at least four deep breaths (12). During pregnancy, the respiratory tract has increased vascularity resulting in some level of edema to the pharynx, larynx, and vocal cords. It is often wiser to use a smaller endotracheal tube to avoid trauma or significant bleeding from the friable tissues of the hypopharynx or vocal cords. Chemical aspiration pneumonitis (Mendelson's syndrome) was originally described in postanesthesia obstetric patients. It is the common cause of maternal death associated with anesthesia. Delayed gastric emptying, decreased lower esophageal sphincter tone, increased gastric pressure from labor or uterine displacement, and the effects of magnesium sulfate or sedatives are some of the reasons for the high risk of aspiration in pregnant patients. Cricoid pressure, meaning manual application of pressure on the cricoid cartilage to compress the esophagus and prevent passage of stomach contents into the pharynx, is recommended during intubation of the pregnant patient. This pressure should be held until the proper position of the endotracheal tube is verified. Extubation of the pregnant patient should not occur until the patient is awake and competent enough to control gastric secretions. CARBON MONOXIDE POISONING Carbon monoxide (CO) is a relatively common toxic gas that produces functional tissue hypoxia by having a hemoglobin binding affinity 250 times more than oxygen. Its consequences for the fetus in pregnancy are even graver than those for the mother. Generally, maternal symptoms can be expected at a carboxyhemoglobin (COHgb) concentration of 20%. It appears that fetal COHgb levels may be 10 to 15% higher than those of the mother. COHgb concentrations that are asymptomatic for the mother may be fatal to the fetus. In addition, it appears that maternal COHgb levels at the time of clinical presentation do not correspond with the true risk of associated fetal morbidity and mortality, but that maternal COHgb levels at the site of exposure may predict more accurately the risk of fetal morbidity.

It takes five times longer to reduce an elevated fetal COHgb level using 100% normobaric oxygen to a safe level than to reduce a given elevated maternal COHgb level. Hyperbaric oxygen therapy should be strongly considered in the pregnant patient with even a low-level exposure to CO ( 14). THROMBOEMBOLIC DISEASE Thromboembolic disease (TED) is a major cause of obstetric morbidity and mortality. TED is five times more likely in the pregnant patient than in the nonpregnant patient. Hypercoagulability, vascular damage, and stasis, events that occur regularly in pregnancy, increase the risk for TED. TED includes deep venous thrombosis (DVT) of the veins of the leg and pelvis, and associated pulmonary embolization (PE). Physicians have been aware of increased risk of TED in the puerperium. Studies have shown that the majority of thromboembolic disease associated with pregnancy occurs antepartum ( 8). Because there are significant maternal and fetal complications from long-term anticoagulation, it is as important to rule out, as well as rule in these potentially fatal disorders. The clinical signs of DVT and PE are nonspecific. About one-half of patients with suspected deep venous disease do not have thrombosis by venography. A careful physical examination is necessary to exclude other disorders that may mimic DVT (e.g., ruptured Baker's cyst, muscle strain or hematoma, arterial insufficiency, neurogenic pain, superficial thrombophlebitis). PE occurs in 50% of patients with documented DVT; of these only one-half are symptomatic for PE. Classic findings of dyspnea, pleuritic pain, and hemoptysis are seen in only 25% of patients with PE. The common finding is a respiratory rate more than 16 breaths/min. The frequency of this finding in PE is so common that a respiratory rate of less than 16 breaths/min should rule against the diagnosis. The nonspecificity of clinical examination for TED makes objective tests essential for diagnosis. The diagnosis of DVT in pregnancy is achieved through a combination of clinical suspicion, noninvasive, and (if necessary) invasive testing. Doppler ultrasound/color flow ultrasound and impedance plethysmography are the primary noninvasive tests used in pregnancy. These noninvasive tests are less sensitive in detecting calf vein thrombosis than more proximal thromboses. A single noninvasive study showing evidence of thrombosis is considered sufficient to justify treatment, and therapy may be safely withheld if serial studies are negative. Beginning in the late second trimester, these procedures should be performed with the uterus displaced laterally, as compression of the iliac veins and vena cava by the enlarged uterus can produce false-positive results ( 8). A venogram is recommended by some to confirm a positive test. Venography should also be considered if noninvasive tests are equivocal or if serial noninvasive tests cannot be performed. While venography is the most definitive test available for the diagnosis of DVT, it is still subject to poor technique and errant interpretation. In addition, it is estimated to cause a 3% incidence of chemical phlebitis. Iodine 125 fibrinogen scanning is also a noninvasive study for diagnosis of DVT. It is particularly accurate for calf and lower thigh thrombosis with a sensitivity exceeding 90%. Sensitivity for proximal venous collecting system ranges between 60 and 80%. Radioactive iodine is contraindicated in pregnancy because it crosses the placenta and enters the fetal circulation, where it is concentrated in the fetal thyroid. Because it appears in breast milk, its use postpartum in the breast feeding mother is also contraindicated ( 15). The ventilation/perfusion lung (V/Q) scan is the primary tool for the diagnosis of PE in pregnant and nonpregnant patients. A large prospective multicenter trial found that 88% of patients with high probability V/Q scans had angiographic evidence of PE ( 15,16). The study also demonstrated that combining clinical assessment, that is consideration of the presence or absence of risk factors, and V/Q scan improved accuracy. A near normal scan or low probability scan in a patient with low clinical suspicion excluded the diagnosis of PE. Pulmonary angiography is necessary to rule out PE in patients with high clinical suspicion for PE and nondiagnostic V/Q scans; unfortunately this is a large percentage of patients presenting with signs and symptoms of possible PE. Pulmonary angiography is considered the “gold standard” for the diagnosis of PE. The procedure is not considered any more dangerous during pregnancy, and the fetus can be shielded to minimize radiation exposure. The morbidity and mortality are reported as less than 4% and 0.5%, respectively; deaths are principally from undiagnosed pulmonary HTN. The importance of accurately ruling out the diagnosis of PE and avoiding the risk of anticoagulation in pregnancy, with its attendant complications during labor and delivery, cannot be overstated. The decision to obtain pulmonary angiography is related to the individual and the locality. It depends on the skill of the institution in performing and reading the angiogram; there are reports of false-negative angiograms ( 15). Table 56–4.6 lists indications for obtaining an angiogram in the pregnant patient ( 17). Acute DVT or PE in pregnancy should be treated with intravenous heparin for 5 to 10 days. Subcutaneous (SQ) heparin should then be continued with an adjusted dose regimen for the remainder of the pregnancy ( 8). Anticoagulant therapy should be continued postpartum with heparin and Coumadin. When anticoagulation with Coumadin is adequate, heparin can be discontinued. Coumadin should be continued at least 6 weeks postpartum or until at least 3 months of anticoagulant therapy have been completed. Sufficient SQ heparin should be administered at 12-hour intervals to maintain the mid-interval activated partial-thromboplastin time at 1.5 times the control value or a plasma heparin level of 0.1 to 0.2 IU/mL ( 8). Pregnant patients with prior history of TED, anemia, planned operative delivery, or preeclampsia/eclampsia are at high risk for recurrent TED, and prophylactic SQ heparin is recommended by most authorities. It appears that 7500 to 10,000 IU of SQ heparin twice daily may be needed to afford adequate prophylaxis ( 8). Because long-term heparin therapy at more than 20,000 IU/day has been associated with significant osteoporosis, patients should be switched to Coumadin postpartum. Breast feeding is not contraindicated with either heparin or Coumadin therapy. Endocrine and Metabolic PREEXISTING OR OVERT DIABETES MELLITUS AND ACQUIRED GESTATIONAL DIABETES MELLITUS Diabetes mellitus can be broken down to two major classifications in regard to pregnancy gestational diabetes mellitus (GDM) and preexisting or overt diabetes mellitus. The prevalence of GDM, 0.15 to 12.3%, varies according to the blood glucose concentration used to define the disorder and the population screened. In the strictest definition, GDM is asymptomatic acquired glucose intolerance found in the latter half of pregnancy. More than one-half of the patients with GDM are ultimately found to have overt diabetes mellitus. Morbidity in GDM is primarily from complications of delivering the large infant that develops in an unchecked hyperglycemic environment. The diagnosis of overt diabetes mellitus is based on the presence of fasting hyperglycemia found on two or more occasions. The difference between noninsulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus (IDDM) is based on the degree of fasting hyperglycemia/postprandial hyperglycemia and the ability to control these values with diet. Oral hypoglycemic agents have no place in the management of pregnant diabetics. It is estimated that 1% of women of child bearing age have overt diabetes mellitus, and one-fourth of these women have IDDM. The maternal morbidity of pregnancy complicated with IDDM has largely stabilized since the introduction of insulin, remaining morbidity is primarily related to underlying vascular disease. Pregnancies with IDDM are more likely to have complications of preeclampsia/eclampsia, infection, polyhydramnios, and postpartum hemorrhage (18). Neonatal mortality approaches that of the general population, with meticulous control of diabetes starting preconceptually, intense multispecialty team care addressing obstetric, metabolic, and neonatal management, and an involved, motivated mother. Even with optimal management, infants of mothers with IDDM have a 2 to 4 times greater incidence of congenital anomalies. Poor metabolic control before and during the period of organogenesis, 3 to 8 weeks of gestational age, may result in an incidence of congenital anomalies of 22% ( 1). With poor management, pregnant diabetic women suffer IUFD, increased perinatal death, dystocia with cesarean section rates as high as 80%, newborn respiratory distress syndrome, and metabolic disturbances of the newborn exposed to prolonged hyperglycemia. These latter disturbances of the newborn are characterized by hypoglycemia, hypocalcemia, polycythemia, and hyperbilirubinemia. A tenfold increase in maternal mortality and a 17% fetal mortality rate can be expected in the pregnancy of the IDDM patient complicated by maternal neglect, poorly controlled HTN, ketoacidosis, and infection ( 18). As previously discussed, normal pregnancy is “diabetogenic.” Increasing degrees of insulin deficiency result in greater postprandial glucose fluctuations and increasing fasting hyperglycemia. The natural facility for catabolism in pregnancy lowers the threshold for ketosis and acidemia. Diabetic ketoacidosis (DKA) occurs at much lower levels of hyperglycemia and portends grave consequences, with maternal and fetal death rates reported at 10 and 50%, respectfully ( 19). With stress, as is likely to be seen with pregnant diabetic patients in the ED, insulin antagonism from catecholamines, cortisol, and glucagon, can rapidly produce hyperglycemia, resultant osmotic diuresis, and significant dehydration/tissue ischemia, if not incipient DKA. The ED physician should supply additional, crystalloid,

insulin, and carbohydrate parenterally even though the patient may be taking nothing by mouth ( 20). In these circumstances, long and intermediate acting insulin should be discontinued and insulin requirements met by sliding scale of regular (crystalline) insulin based on frequent bedside blood glucose measurements. Intravenous constant infusion insulin offers good control and is recommended ( 1,2,21). The usual constant infusion rates are 0.02 to 0.04 units of regular insulin/kg per hour ( 2). In DKA, with greater insulin antagonism from acidemia, infusion rates are 0.1 units of regular insulin/kg per hour (20,21). Intravenous solutions should contain dextrose when blood glucose reaches 150 to 250 mg/dL ( 22). Glucose requirements in the lean individual can be met by the equivalent of 5 to 10 g/h (50 to 100 mL/h of D5W 0.45, or D5W 0.9% saline) ( 2,22). The pregnant patient with IDDM has increased sensitivity to insulin during the first trimester. The evaluation of an unexplained hypoglycemic attack in an otherwise stable woman of child/bearing age should prompt a pregnancy test. After delivery, the factors causing natural insulin resistance rapidly dissipate, and insulin dosages should be reduced accordingly. Many IDDM patients require no insulin on the day after delivery. Diabetics with active retinopathy at conception can expect progression of their disease in 15 to 85% of pregnancies. When nephropathy is present, pregnancy complications are worsened. Increased HTN, proteinuria, and intrauterine growth retardation will produce an attendant increase in perinatal mortality from 2 to 10%. Although diabetic nephropathy improves after delivery, its presence heralds the inevitable downward course of diabetic renal failure. Diabetic enteropathy and gastric paresis often result in hospital admissions for correction of dehydration and acidemia secondary to nausea and vomiting ( 1). Glucosuria is present in 16% of normal pregnancies. Its presence is an indication to check blood glucose. With the development of bedside glucometers, use of urinary glucose to direct insulin dosages is outmoded and too inaccurate to be useful. Urinalysis is more valuable for the early detection of ketosis, and its presence for longer than 8 hours warrants admission. Note that finding a fasting plasma glucose more than 105 mg/dL (fasting whole venous blood glucose more than 90 mg/dL) suggests abnormal glucose tolerance and should prompt referral for a screening or formal glucose tolerance test (GTT). A screening GTT is recommended for all pregnancies between 24 and 28 weeks of gestational age. The desired “tight” metabolic control for pregnancies with IDDM is to maintain fasting serum glucose between 70 to 95 mg/dL and 2-hour postprandial glucose less than 140 mg/dL (Table 56–4.3). Although this level of control is desirable, it should not be sought in the face of frequent hypoglycemic attacks. Management of the acutely ill pregnant diabetic patient does not differ from that of her nonpregnant counterpart. Generally, well-managed pregnant diabetic patients should not present to the ED. Conversely, pregnancies complicated by diabetes showing clinical symptoms require immediate intervention and/or admission. The ED physician has a unique opportunity to counsel and/or refer the nonpregnant diabetic patient contemplating pregnancy, and this should be kept in mind when caring for diabetic patients of childbearing years. OTHER ENDOCRINE AND METABOLIC ACQUIRED DISORDERS Hyperemesis Gravidarum Nausea and vomiting are common complaints in pregnancy, usually beginning around 6 to 8 weeks of gestational age and dissipating around 14 weeks, although they can persist throughout pregnancy. Nausea and vomiting are felt to be related to the principal hormones of pregnancy, particularly HCG, but the actual relationship is unknown. When nausea and vomiting become severe enough to cause weight loss, dehydration, and starvation, the condition is termed hyperemesis gravidarum (HG). Presentation with clinical signs of dehydration, most notably evidence of ketosis/acidosis, is significant and demands immediate correction and/or admission. Other causes of nausea and vomiting in pregnancy must be considered and excluded, i.e., pyelonephritis, cholelithiasis, pancreatitis, hepatitis, and peptic ulcer disease. Laboratory studies can demonstrate varying degrees of hyponatremia, azotemia, hypokalemia, alkalosis, and acidosis. Evidence of anaerobic metabolism with ketosis is the most significant finding. HG can have low-level elevations of liver transaminases and bilirubin. These values should return to normal when the dehydration is corrected. Differentiation of HG from hyperthyroidism and can be problematic. Stabilization of HG usually allows differentiation from thyrotoxicosis but frequently requires hospital admission and consultation. Beside the obvious correction of fluid and electrolyte disorders, management includes a regimen of frequent small feedings and the exploration of emotional factors often found in association with HG. Use of promethazine, prochlorperazine, and trimethobenzamide for control of nausea is acceptable. Benign Clinical Syndromes The normal physiologic changes of pregnancy produce a number of benign clinical syndromes likely to be encountered by the ED physician. The hormonal changes that produce increased vascularity of the vagina also affect the nasal mucosa and, coupled with increased blood volume, lead to nasal stuffiness and a predisposition to epistaxis. Progesterone produces decreased peristalsis, delayed gastric emptying time, and lowered lower esophageal sphincter tone. An expanding uterus produces increased pressure on the stomach, and these two phenomena produce a 30 to 70% incidence of reflux esophagitis (i.e., heartburn) ( 22). Decreased peristalsis also predisposes to constipation and hemorrhoids. During the early middle trimester, as the uterus becomes an abdominal organ, tension is placed on the round ligaments of the uterus, causing episodic contractions that produce sharp pains in one or the other lower quadrants. Often referred to as round ligament syndrome, these pains typically last several minutes, are associated with movement, and tend to recur until the end of the second trimester. Backache is also frequently seen in normal pregnancy as the hormones of pregnancy produce relaxation of ligaments and the enlarging uterus produces a change in the center of gravity and increased lumbar sacral lordosis. Pubic symphysis separation can be seen with relatively minor trauma. Preexisting Hematologic and Immunologic Disorders ANEMIA Nutritional Anemia Anemia, the most common medical complication of pregnancy, is seen in about 50% of pregnancies in the United States. Nutritional anemia from iron or folate deficiency represents 75 and 22% of the causes of anemia, and addressing these two conditions corrects over 90% of anemias seen during the reproductive years (23). The developing fetus of the mother deficient in iron or folate does not suffer from these abnormalities because the placenta is able to absorb sufficient iron and folate from even severely depleted mothers. Because normal gestational requirements for iron and folate exceed available supply, blood loss from parturition from one pregnancy with inevitable iron and folate loss is often the cause of severe nutritional anemia in subsequent pregnancies. Vitamin B 12 deficiency in pregnancy is rare; when present in patients of child-bearing years, it is often accompanied by infertility. Although the approach to the pregnant patient with anemia is the same as in the nonpregnant patient, the clinical and laboratory diagnosis of anemia is altered by pregnancy. Symptoms suggesting anemia in a nonpregnant patient, such as pallor, malaise, and anorexia, may be present in pregnancy without actual anemia. A physiologic anemia (see, Physiology of Pregnancy) is seen because of the relatively greater increase in plasma volume over red blood cell volume. The severely iron-deficient pregnant patient shows the usual morphologic changes in serum iron, total iron-binding capacity, and serum ferritin; the moderately iron-deficient patient does not demonstrate classic laboratory findings ( Table 56–4.3). Knowledge of the increased requirements for folate and iron in pregnancy make routine supplementation during normal pregnancy rational. Mild anemia, with hemoglobin (Hgb) less than 10 to 11 g/dL and hemocrit (Hct) less than 30 vol.%, has been associated with intrauterine growth retardation, polycythemia, and other fetal complications (23). Delayed wound healing, higher incidence of infection, and prolonged hospitalization can be seen in moderately anemic patients, i.e., Hgb less than 8 g/dL and Hct less than 25 vol.%. Maternal deterioration is not usually noted until Hgb concentration is less than 4 to 6 g/dL and Hct less than 12 to 18 vol.%. The postpartum patient who is stable, no longer faces the likelihood of additional hemorrhage, can ambulate without symptoms, and is not febrile can generally

tolerate a Hgb 7 g/dL and be managed with iron supplementation rather than blood transfusion ( 24). Sickle Cell Hemoglobinopathy Sickle cell disease (SSD) is the clinical manifestation of one of a number of biochemical hereditary defects in the alpha or beta hemoglobin chains that leads to decreased red blood cell life span through sickling and hemolysis. Pregnancy is a serious burden in SSD. The maternal death rate is 125 to 150 times greater and the perinatal mortality is 5 to 13 times greater for sickle cell SS disease and SC disease, respectively, than the same rate for non-white normal pregnancies ( 24). Prenatal care and preventive treatment can reduce morbidity, mortality, and perinatal loss. Pregnancies complicated by SSD are especially at risk for covert bacteremia and its complications. Rapid diagnosis and aggressive treatment of common infections such as pneumonia and pyelonephritis is essential. Pregnant patients with SSD are often misdiagnosed as having a vaso-occlusive crisis when they are suffering from an ectopic pregnancy, placental abruption, or pyelonephritis. The stable pregnant SSD patient generally maintains and tolerates her hemoglobin concentration around 7 g/dL. These patients must be monitored closely for any factor that impairs their intense erythropoiesis, and supplemental folic acid is essential for the pregnant (and nonpregnant) patient with SSD. Critical changes in the hemoglobin/hematocrit can be seen secondary to sequestration of sickled red blood cells during a vaso-occlusive crisis or by increased hemolysis seen with infections. Exchange transfusions have been recommended for hemoglobin levels below 6 g/dL or a drop in the hemoglobin level more than 2 g per 24 hours. The issue of prophylactic red blood cell transfusions to maintain maternal Hgb concentration more than 10 g/dL and to minimize the relative concentration of Hgb SS to normal Hgb A is controversial ( 25). Although prophylactic transfusion definitely decreases maternal morbidity, studies have shown no change in perinatal outcome ( 26). Transfusion morbidity from isoimmunization, hepatitis, and risk of HIV infection make repeated pregnancies and prophylactic transfusions especially troublesome. Labor management for women with SSD is similar to that for women with cardiac disease. The woman should be kept comfortable and not over sedated, and oxygen therapy instituted. If cesarean section or complicated vaginal delivery is expected, the Hgb concentration should be elevated with consideration that these women are more prone to ventricular failure, circulatory overload, and pulmonary edema. THROMBOCYTOPENIA Idiopathic thrombocytopenia (ITP), also called autoimmune thrombocytopenia, is a syndrome that produces isolated but clinically significant thrombocytopenia by the presence of an IgG immunoglobulin that binds to platelets. Commonly seen in women of child-bearing years, it seems to be exacerbated by pregnancy ( 27). IgG antibodies cross the placenta and can cause thrombocytopenia in the fetus and neonate. Although steroids and splenectomy often produce a clinical remission, they may not produce an immunologic remission, and a mother may have a normal platelet count with continued fetal risk for bleeding, especially intracranial bleeding, during the trauma of labor and delivery ( 27). A platelet count less than 30,000/mm 2 in a term pregnancy would be considered active disease and a bleeding time would be indicated. Treatment is with corticosteroids or high-dose intravenous immune globulin. Steroid therapy appears to increase infant platelet count at birth, and it is postulated that steroid treatment can produce a safe platelet count for the infant and, therefore, avoid routine cesarean section for women with ITP ( 27). High-dose intravenous immune globulin appears to increase maternal platelet counts temporarily and benefit women with critical thrombocytopenia facing imminent surgery or vaginal delivery. The effect on neonatal platelet count cannot be determined ( 28). Unfortunately, there is no strong correlation between maternal and fetal platelet counts, nor does monitoring of platelet-associated antibody counts or levels of circulating platelet antibody correlate with the fetal level of thrombocytopenia. Intrapartum fetal scalp blood samples are used to detect significant fetal thrombocytopenia. When the fetal platelet count is less than 50,000/mm 3, an immediate cesarean section is performed (28). Thrombocytopenic patients with platelet counts between 20,000 and 50,000/mm 3 rarely have spontaneous bleeding, but the patient with a platelet count under 50,000/mm3 facing surgery or vaginal delivery is at risk for excessive bleeding ( 28). In the mother with active disease, the best route of delivery for the affected infant is unfortunately hazardous for the thrombocytopenic mother. IMMUNOLOGIC DISORDERS Rheumatoid Arthritis and Systemic Lupus Erythematosus Commonly encountered connective tissue disorders are rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). These diseases are of unknown cause but have in common the presence of autoimmune antibodies that induce inflammatory responses. They occur during child bearing years and, except in severe disease, do not affect fertility. RA generally improves in pregnancy and has no adverse effects on the fetus. Remission in one pregnancy generally implies remission in subsequent pregnancies. Nonsteroidal anti-inflammatory drugs are felt to be relatively nontoxic in early pregnancy; later in pregnancy reports are of prolonged gestation, increased antepartum and postpartum hemorrhage, and early closure of the ductus arteriosus. Steroids are used for active disease, but gold, penicillamine, azathioprine, and cyclophosphamide are to be avoided. Patients inadvertently using methotrexate during pregnancy have a 50% chance of producing an abnormal infant and should be advised to consider a therapeutic abortion ( 29). SLE patients with severe disease requiring high-dose corticosteroids, cyclophosphamid, or azothioprine regimens have a significant incidence of amenorrhea, anovulation, or premature ovarian failure, and successful pregnancy may not be possible ( 30,31). In SLE patients who are able to conceive, an exacerbation of SLE is seen in approximately 50%. These flare-ups can be expected to be seen postpartum for one-third of the patients, the remainder equally divided throughout the antepartum. Disease at the onset of gestation is associated with subsequent disease, particularly in the third trimester and postpartum. Women in remission at the time of conception have a 35% chance of flare-up. A small but significant portion of SLE patients, varying from 7 to 9%, have permanent deterioration in renal function as a complication of pregnancy ( 32,33). Thirty percent of SLE patients improve during pregnancy, but the course in one pregnancy does not predict the course in another (29). The fetal survival is 75% in women with established SLE before conception. If these women are in clinical remission before conception, the success rate is 88 to 100%. If pregnancy occurs in the presence of active disease, the survival is decreased to between 50 and 75%. Finally, the onset of SLE during pregnancy or puerperium produces the highest death rate, with fetal survival reported at 50 to 64% ( 29). Asymptomatic patients, known SLE patients, or patients with nonspecific autoimmune disorders not meeting the diagnostic criteria for SLE sometimes present with arterial or venous thrombosis, habitual miscarriage, IUFD, or neonatal lupus syndrome (congenital complete heart block, neonatal dermatitis). These patients often have one of several autoantibodies that portend poor maternal or fetal outcome and can be serologic markers for eventual overt autoimmune disease in previously asymptomatic patients (30). The stable SLE patient should continue with corticosteroids without change in dosage when pregnancy is discovered. The guideline for use of steroids in pregnancy is similar to that in nonpregnant patients: the lowest dose that controls the disease should be used. Active disease at conception requires higher doses of steroids. The adverse effect of the uncontrolled flare-up on fetal growth and development far outweighs actual or theoretic risks attributable to maternal drug therapy. Therapeutic abortion does not reduce flare-ups or change the course of remissions. Delivery is vaginal, with steroid coverage. Patients with HTN and renal disease from any cause have increased risk of developing eclampsia, and, therefore, SLE patients with nephropathy have a greater incidence of superimposed preeclampsia. The importance of differentiating maternal lupus with a flare-up from preeclampsia is underscored in the patient presenting in the third trimester with HTN, proteinuria, and edema. The treatment for eclampsia is timely delivery. The treatment for lupus nephritis is increased steroid dosage and immunosuppressive drugs if the flare-up is severe. Helpful laboratory studies are platelet counts (which tend to decrease in preeclampsia), rising titers of anti-DNA antibodies, and falling C3, C4 complement levels. Rising titers of anti-DNA antibodies and falling C3 levels can be indications of active SLE, even though the patient is clinically well. Evidence of uteroplacental compromise or decreased fetal well being require preparation for timely delivery regardless of difficulties in separating active lupus nephritis from preeclampsia ( 4,31).

Acquired Hematologic and Immunologic Disorders THROMBOCYTOPENIA Thrombotic Thrombocytopenia, Adult Hemolytic Uremia Syndrome, and Postpartum Renal Failure Thrombotic thrombocytopenia (TTP), the adult form of hemolytic uremia syndrome (HUS), and the syndrome of postpartum renal failure (PPRF) are relatively rare conditions that alter hemostasis. The pathological target is the microvasculature. These syndromes produce microangiopathic hemolytic anemia, thrombocytopenia without consumption coagulopathy (normal PT and PTT), and lead to the formation of thrombi in the microvasculature, causing arteriolar fibrinoid necrosis. The clinical expression of this process is bleeding diathesis, neurologic complications, and renal failure. The cause is unknown, but pregnancy appears to predispose to these disorders. Differentiating pregnancy complicated by TTP, HUS, or PPRF from other complications of pregnancy producing DIC is difficult. DIC is seen in association with obstetrically related acute renal failure, postpartum hemorrhage, puerperal sepsis, abruptio placentae, amniotic fluid embolism, IUFD, saline abortion, and preeclampsia/eclampsia. In addition, early presentation of TTP, HUS, or PPRF is often mild to moderate. Thrombocytopenia with or without evidence of hemolytic anemia can be confused with ITP. SLE can present with some or all of the same clinical symptoms and findings. A mother and fetus undergoing anesthesia, induction of labor, or surgery will have high mortality rates if these disorders are not promptly recognized and treated ( 34). Remember that preeclampsia/eclampsia, a far more common clinical situation, can present as progressive HTN, renal failure, and neurologic abnormalities. Treatment in this situation is prompt delivery or termination of the pregnancy to prevent maternal or fetal morbidity and mortality. Disseminated Intravascular Coagulation The placenta contains the highest concentration of thromboplastin of any tissue in the body ( 3). Clinical conditions producing exposure of the general circulation to placental material with tissue factor activity induces the phenomenon known as DIC. The severity of DIC is based on the concentration and the rapidity with which the material with tissue factor activity is discharged into the maternal circulation. Management of the pregnant patient with DIC is directed at aggressive identification and removal of the triggering insult while replacing circulatory volume and coagulation component deficits. Cardiopulmonary support is often needed in fulminant DIC. Therapeutic guidelines for blood component therapy for the patient with fulminant DIC is listed in Table 56–4.5. IMMUNOLOGIC DISORDERS Rh Iso-immunization In approximately 10% of pregnancies in Caucasian women, 5% in Black women, and 1% in Asian women, an Rh-negative woman gives birth to an Rh-positive infant. The Rh antigen is one of the most antigenic of the ABO and Rh systems and induces IgG isoantibodies in the mother if she is exposed or immunized to fetal blood with the Rh antigen. IgG immunoglobulin to Rh antigen is produced from this sensitization and can cross the placenta into the fetal circulation. Once sensitization occurs, the duration of fetal exposure and the titer of maternal anti-Rh IgG antibodies determine the prognosis for the infant. The timing of exposure is usually at delivery, miscarriage, or abortion, or possibly ectopic pregnancy. Unusually large exposure to fetal blood cells occurs with abruptio placentae, cesarean section, and traumatic vaginal delivery. When an Rh-negative mother is exposed to any of these conditions, an indirect Coombs' test should be performed to alert the physician to prior isoimmunization. The previously unsensitized Rh-negative mother exposed to small amounts of fetal blood can be prevented from Rh isoimmunization by administration of a standard dose of 300 mg of anti-Rh immune globulin (RhoGAM) within 72 hours of exposure. This dose is felt to inactivate the Rh antigen in 15 mL of red blood cells or 30 mL of fetal blood. Unusually large exposure to Rh antigen requires more than the standard dose of RhoGAM. A quantitative estimate of the amount of RhoGAM to give can be estimated based on the information from an acid elution Kleihauer-Betke test on a maternal differential count, the maternal Hct, and an estimate of maternal blood volume. Preexisting Renal Disorders IMPAIRED RENAL FUNCTION Pregnancy in women with impaired renal function is accompanied by an increase in such complications as HTN, proteinuria, fetal prematurity, and fetal loss ( 35). Maternal and fetal prognosis generally depend on the extent of renal compromise and the presence of HTN more than the specific underlying disease process ( 4,31). Pregnancy complicated by impaired renal function can be divided into mild, moderate, and severe disease on the basis of the prepregnancy serum creatinine. Mild renal dysfunction is considered to be present with a serum creatinine less than 1.4 mg/dL, with proteinuria and HTN absent before onset of pregnancy. These patients tolerate pregnancy well, and it does not appear to affect the course of their disease. Exceptions are seen in pregnancies complicated by active lupus nephritis with onset during pregnancy, polyarteritis nodosa, and scleroderma. Fortunately, the latter two are seldom seen in conjunction with pregnancy. Pregnancy is poorly tolerated and can lead to significant deterioration in renal function and unacceptable maternal and fetal mortality ( 4,30). The deterioration in renal function seen in some patients in the category of mild renal dysfunction represents the natural progression of the underlying disorder, and pregnancy does not influence that progression (4). Examples are amyloidosis, polycystic kidney disease, focal glomerulosclerosis, and some forms of glomerulonephritis. Moderate to severe renal insufficiency is considered to be present with a prepregnancy serum creatinine more than 1.4 mg/dL. Chances for successful pregnancy are generally good, but fetal death rates of approximately 76 to 80% are reported ( 4,35). Some patients with moderate renal insufficiency and pregnancy suffer irreversible damage to their renal function, but this again is felt to be part of the relentless course of the underlying disease process ( 4,35). Severe renal insufficiency is felt to be present with a prepregnancy serum creatinine level more than 3 mg/dL, and normal pregnancy is uncommon at this level. Management of the pregnant patient with impaired renal function is directed at control of HTN, maximization of existing renal function, and monitoring of fetal well-being. When a pregnant patient with evidence of deterioration in renal function is seen, reversible causes of renal deterioration should be sought. Urinary tract infection (UTI), dehydration, and fluid and electrolyte disorders are correctable causes of deteriorating renal function. Control of HTN is also of great importance. Pregnancy is allowed to continue as long as there is no evidence of relentless renal deterioration, uncontrollable HTN compromising uteroplacental function or forewarnings of preeclampsia/eclampsia. Proteinuria without a decrease in GFR or the presence of HTN does not necessarily imply renal deterioration, and the pregnancy can be allowed to continue (4). The exception to this is in SLE nephritis, where increasing proteinuria is a sign of renal deterioration and calls for increasing steroid dosage (32). If there is objective deterioration in renal function and no reversible causes, the pregnancy should be interrupted or the delivery induced. RENAL TRANSPLANT Fertility problems are seen with serum creatinine levels in the range of 2.0 mg/dL ( 30). Newer drug regimens introduced to limit the rate of lupus nephritis are also associated with impaired fertility ( 31). Dialysis patients of childbearing years seldom achieve pregnancy, and their rate for successful outcome is no more than 20 to 23% (36). Renal transplant patients can achieve pregnancy, although such pregnancies are complicated and associated with increased maternal and fetal risk. Complications include increased risk of graft deterioration and progressive HTN for the mother and increased fetal risk for prematurity, growth retardation, and infection. Continuation of immunosuppressive drugs is necessary because their withdrawal can precipitate acute rejection in a transplant patient who has otherwise been stable for years. The dosage of immunosuppressive drugs should be kept to a minimum ( 37). HTN is common and usually severe. Life-threatening HTN can occur suddenly. Its treatment does not differ from treatment of chronic HTN in pregnancy. Decisions about terminating a pregnancy or premature delivery have to be made on the basis of the difficulty in controlling HTN ( 38). Preeclampsia is seen in 30% of patients

and signs of rejection in 9%. Differentiation of acute pyelonephritis, recurrent glomerulopathy, and/or preeclampsia is difficult ( 37). Acquired Renal Disorders ACUTE RENAL FAILURE Acute renal failure (ARF) can be caused by hypovolemia or thrombotic events in the renal vasculature. In pregnancy, the most common causes are abruptio placentae, preeclampsia/eclampsia, prolonged IUFD, hemorrhagic shock, and pyelonephritis complicated by endotoxemia. Most patients recover with supportive measures appropriate for ARF. Some patients, particularly those with ARF from placental abruption, preeclampsia/eclampsia, or endotoxin-induced shock develop renal cortical necrosis and are left with varying degrees of permanent renal failure. URINARY TRACT INFECTION UTI is the most common bacterial infection in pregnancy. It can be divided into three major types; asymptomatic bacteriuria, cystitis/ urethritis, and pyelonephritis. Hormonal changes of pregnancy promote urinary stasis, diminished ureteral tone, and peristalsis. These same hormonal effects, coupled with ureteral compression by the enlarging uterus, produce hydronephrosis of pregnancy, and further predispose to UTI ( 8). Asymptomatic bacteriuria has an incidence of 2 to 12% and is typically present early in pregnancy. Twenty-five percent of patients with untreated asymptomatic bacteriuria progress to develop acute symptomatic UTI. Symptoms of cystitis/urethritis do not differ from the nonpregnant state. Forty percent of pregnant women with acute pyelonephritis had preceding symptoms of cystitis. Pyelonephritis has an incidence of 1% with the usual infecting organism being Escherichia coli. Fifty percent of cases are unilateral and right-sided, and 25% are bilateral. Symptoms must be differentiated from labor, appendicitis, and placental abruption. In pregnancy the endotoxin produced can cause septic shock on first exposure rather than requiring an initial sensitizing inoculation as in nonpregnant persons. Also, gram-negative bacteria can produce phospholipase A 2 activity that can initiate the arachidonic acid cascade to produce prostaglandins in the pregnant uterus, thereby inducing premature labor. Asymptomatic bacteriuria and cystitis can be treated with a 10- to 14-day course of antibiotics. There is a 30% recurrence rate in the eradication of asymptomatic bacteriuria, which is likely to be a relapse of the original infection. Antibiotic choices are typically nitrofurantoin, trimethoprine-sulfamethoxazole, ampicillin, or a cephalosporin. Single-dose treatment regimens have a 75% success rate. There is a 97% success rate for the 10- to 14-day treatment plan of cystitis. Return of a sterile urine culture in the symptomatic lower UTI should prompt one to consider erythromycin treatment for possible Chlamydia urethritis. Pyelonephritis is treated with hospitalization and hydration. A 10-day drug course is begun empirically with ampicillin, a cephalosporin, extended-spectrum penicillin, or a combination of gentamicin or tobramycin plus ampicillin for suspected infections caused by resistant E. coli bacteria. Serum creatinine levels and peak serum antibiotic levels should be followed for patients receiving gentamicin or tobramycin ( 38). Treatment of pyelonephritis leads to reversal of decreased GFR, dehydration, ketosis, and the risk of premature labor. Patients who fail to respond to treatment in 48 to 72 hours, i.e., prolonged fever and continued symptoms, should be evaluated for urinary obstruction, usually by renal calculi, (can be seen by abdominal flat plate radiographs in 90% of cases), and for perinephric abscess. Recurrent infection rate is 30 to 40%, necessitating frequent urinanalysis. Continued bacteriologic suppression with nitrofurantoin throughout the remainder of pregnancy can reduce relapse but can cause hemolysis for the fetus with glucose 6 phosphatase deficiency (38). Miscellaneous PREEXISTING NEUROLOGIC DISORDERS Seizure Disorders Seizures are the most common neurologic disorder seen in pregnancy. In general, 50% of pregnant patients with seizures show no change in seizure frequency, 25% a decrease, and 25% an increase in their seizure frequency. The degree of control prior to conception is probably the best predictor of seizure activity during pregnancy. Recent studies have confirmed an increase in the frequency of spontaneous abortion, prematurity, and preeclampsia for pregnant epileptic women over nonepileptic controls ( 39). The congenital malformation rate was 14% compared with 3% in the general obstetrical population ( 40). All antiepileptic drugs (AEDs) cross the placenta and so far none have been found to be free of the risk for teratogenicity ( 40). But the risk of hypoxic-ischemic encephalopathy, microcephaly, and mental retardation from untreated seizures is higher than the risk of malformations from rational use of AEDs. Polytherapy with AEDs and maternal plasma AED concentrations recently have been found to independently influence the risk of malformations ( 40). Thus monotherapy, treatment with one AED, at the smallest effective dose to control seizures, emerges as the most important goal in control of seizures in pregnancy. Compliance can be expected to improve with monotherapy and this in itself may improve seizure control. It is probably safe to say that the overall increase in obstetrical complications in epileptic women is an expression of genetics, and socio-economics as well as complications of drug therapy. The need for expeditious control of status epilepticus in a pregnant patient in the ED should be apparent as the fetus does not tolerate hypoxemia and acidemia. The treatment of status epilepticus does not differ between the pregnant and the nonpregnant patient. The prudent ED physician must differentiate eclamptic seizures from epileptic seizures. Magnesium sulfate remains the drug of choice for eclamptic seizures. Management guidelines are listed in Table 56–4.7. Trimethadione and valproic acid, used for the treatment of petit mal seizures, have unacceptable rates of birth defects and should be avoided in pregnancy. Ethosuximide is the drug of choice for petit mal seizures in pregnancy. An estimated 10% of pregnancies treated with phenobarbitol or phenytoin manifest hemorrhagic disease of the newborn, (AED-induced interference with the neonate's ability to produce vitamin K dependent clotting factors). Bleeding usually develops in the first several days of life and is treated with parenteral vitamin K ( 41). Due to changes in protein binding and relative levels of free drug, it appears that empirical increases in drug doses during pregnancy may not be warranted. Measurement of serum levels should be reserved for women who are not controlled or suspected of noncompliance. Acquired Gastrointestinal Disorders APPENDICITIS The incidence of appendicitis is about 1 in 2000 pregnancies. Pregnancy does not predispose to appendicitis but makes the diagnosis more difficult. Anorexia, nausea, and vomiting are fairly common symptoms of normal pregnancy. The physical examination is complicated by pain that is typically felt in the right middle to upper quadrant because of uterine enlargement displacing the appendix upward with advancing gestation. In addition, pregnancy is accompanied by leukocytosis. Missed appendicitis increases the likelihood of abortion or preterm labor. The fetal loss rate is about 15%. Appendiceal rupture in the third trimester is more likely to cause generalized peritonitis. Regardless of the stage of gestation, if appendicitis is suspected, surgical exploration is indicated. Infections Table 56–4.8 summarizes important aspects of pregnancy and infection. Maternal effects, fetal/neonatal effects, diagnostic features, and management points are listed in regard to the most important viral and bacterial infections. References 1. Barss VA: Diabetes and pregnancy. Med Clin North Am 1989;73:685–700. 2. Buchanan TA, Unterman TG, Metzer BE: The medical management of diabetes in pregnancy. Clin Perinatol 1985;12:625–650.

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47.

Finley BE: Acute coagulopathy in pregnancy. Med Clin North Am 1989;73:723–743. Davison JM, Katz AI, Lindheimer MD: Kidney disease and pregnancy: obstetric outcome and long-term renal prognosis. Clin Perinatol 1985;12:497–520. Gianopoulos JG: Cardiac disease in pregnancy. Med Clin North Am 1989;73:639–651. Carlson JA: The role of the medical consultant in pregnancy. Med Clin North Am 1989;73:541–555. Sullivan HJ: Valvular heart surgery during pregnancy. Surg Clin North Am 1995;75:59–75. Toglia MR, Weg JG: Venous thromboembolism during pregnancy. N Engl J Med 1996;335:108–114. Sibai BM: Treatment of hypertension in pregnant women. N Engl J Med 1996;335:257–265. Barron WM: Medical evaluation of the pregnant patient requiring nonobstetric surgery. Clin Perinatol 1985;12:481–496. Lockwood CJ: Placenta previa and related disorders. Contemp Obstet Gynecol 1990; Jan:47–65. Noble PW, Lavee AE, Jacobs MM: Respiratory diseases in pregnancy. Obstet Gynecol Clin North Am 1988;15:391–425. Roberts J: Asthma during pregnancy. Emerg Med News 1989; Dec:6–8. Koren G, Sharov T, Pastuszak A, et al: A multicenter, prospective study of fetal outcome following accidental carbon monoxide poisoning in pregnancy. Reprod Toxicology 1991;5:397–403. Haywood LB, Adam KH: Deep venous thrombosis and pulmonary embolism. Clin Ob Gyn 1996;39:87–100. Brunader RE: Diagnosis and evaluation of thromboembolic disorders. J Am Board Fam Prac 1989;2:106–117. PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis. JAMA 1990;263:2753–2754. Cousins L: Pregnancy complications among diabetic women: review 1965–1985. Obstet Gynecol Surv 1987;42:140–149. Brumfield CG, Huddleston JF: The management of diabetic ketoacidosis in pregnancy. Clin Obstet Gynecol 1984;27:50–59. Gavin LA: Management of diabetes mellitus during surgery. Clin Rev West J Med 1989;151:525–530. Nolan TE, Hess WL, Hess DB, et al: Severe medical illness complicating cesarean section. Obstet Gynecol Clin North Am 1988;15:697–717. Bjorkman DJ, Randall BW, Tolman KG: Primary care of women with gastrointestinal disorders. Clin Obstet Gynecol 1988;31:974–988. Morrison JC: Anemia associated with pregnancy. In: Sciarra JJ, ed. Gynecology and obstetrics. Hagerstown, MD: Harper & Row, 1980:3. Morrison JC: Hemoglobinopathies and pregnancy. Clin Obstet Gynecol 1979;22:819. Mclaughlin BN, Martin RW, Morrison JC: Clinical management of sickle cell hemoglobinopathies during pregnancy. Clin Perinatol 1985;12:585–597. Koshy M, Burd L, Wallace D, et al: Prophylactic red cell transfusions in pregnant patients with sickle cell disease, a randomized cooperative study. N Engl J Med 1988;319:1447–1452. George JN, Wolf SA, Raskob GE, et al: American Society of Hematology ITP Practice Guideline panel. Am Fam Physician 1996;54:2437–2447. Fellin F, Murphy S: Hematologic problems in the preoperative patient. Med Clin North Am 1987;71:477–487. Nicholas NS: Rheumatic diseases in pregnancy. Br J Hosp Med 1988; Jan:50–53. Hayslett JP, Reece AE: Systemic lupus erythematosus in pregnancy. Clin Perinatol 1985;12:539–551. Dombroski RA: Autoimmune disease in pregnancy. Med Clin North Am 1989;73:605–621. Samuels P, Pfeifer SM: Autoimmune diseases in pregnancy, the obstetrician's view. Rheum Dis Clin North Am 1989;15:307–322. Ransey-Goldman R: Pregnancy in systemic lupus erythematosus. Rheum Dis Clin North Am 1988;14:169–185. Kwaan HC: Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in pregnancy. Clin Obstet Gynecol 1985;28:101–106. Hou S: Pregnancy in women with chronic renal disease. Medical intelligence. N Engl J Med 1985;312:836–839. Jones DC, Hayslett JP: Outcome of pregnancy in women with moderate or severe renal insufficiency. N Engl J Med 1996;335:226–232. Hou S: Pregnancy in organ transplant recipients. Med Clin North Am 1989;73:667–683. Sinkinson CS, Coustan DR, Rayburn WF: How to use drugs safely and effectively for pregnant patients. Emerg Med Rep 1989;10:115–121. Wilhelm J, Mavis D: Epilepsy and pregnancy-a review of 98 pregnancies. Aust NZ J Obstet Gyn 1990;4:290–295. So EL: Update on epilepsy. Med Clin of North Am 1993;77:203–214. Patterson RM: Seizure disorders in pregnancy. Med Clin North Am 1989;73:661–665. Ellis GL, Melton J, Filkins K: Viral infections during pregnancy. A guide for the emergency physician. Ann Emerg Med 1990;19:802–811. Jenista JA, McMillan J, MacDonald N: Erythema Infectiosum and Roseola: avoiding the trap of misdiagnosis. Emerg Med Rep 1990;11:73–78. Arevalo J: Hepatitis B in pregnancy. West J Med 1989;150:668–672. Jones EM, MacGowan AP: Antimicrobial chemotherapy of human infection due to Listeria monocytogenes. Eur J Clin Microbiol Infect Dis 1995;14:165–174. Miller SK, Miller JM: Tuberculosis in pregnancy: interactions, diagnosis, and management. Clin Obstet 1996;39:120–141. The Medical Letter. Drugs for sexually transmitted diseases. 1995;37:117.

Suggested Readings Cunningham GF, MacDonald PC, Gant WF, et al., eds.: Williams Obstetrics. 20th ed. Norwalk, CT: Appleton and Lange, 1997. Hayashi RH: Emergency care of the pregnant woman. In: Schwartz GR, Bircher N, Hanke B, et al. ed. Emergency medicine, the essential update. 1st ed. Philadelphia: WB Saunders, 1989.

Chapter 56.5 Medication Use in Pregnancy Principles and Practice of Emergency Medicine

CHAPTER 56 OBSTETRIC EMERGENCIES

5 Medication Use in Pregnancy Robert R. Whipkey Capsule Introduction Categories of Medication Specific Medications Gastrointestinal Medications Anticonvulsants Respiratory Medications Cold Medications Immunizations Analgesics Substances of Abuse Cardiac Drugs Antidepressant Medications National Contacts

CAPSULE All practicing emergency physicians must be aware of the possible adverse effects of prescribed or over-the-counter medications in pregnant women and women of child-bearing age. Both mother and fetus may be affected. Potential teratogenic effects and altered physiology or drug metabolism must be taken into consideration in assessing the need for medication and the correct dosages. Prescribed and recreational drugs, along with the basic principles of prescribing, are covered in depth in this subchapter.

INTRODUCTION Increasingly, the general public and medical professionals have become concerned with the potential teratogenic effects of drugs taken during pregnancy ( 1). Altered metabolism and the possibility of drug-induced toxicity must be considered when treating pregnant patients and all women of child-bearing age. Even with widespread physician and patient education regarding devastating teratogenic effects, misuse still occurs. This was demonstrated by the exposure with isotretinoin (Accutane), introduced in 1982 to treat cystic acne. This medication carried a strong warning that it was contraindicated in women who were pregnant or were unwilling to prevent pregnancy while under treatment. Despite this warning, 62 birth defects were reported, and the FDA estimated between 900 and 1300 birth defects nationwide. In addition, 700 to 1000 spontaneous abortions and 5000 to 7000 induced abortions were reported in women who became pregnant while taking isotretinoin ( 2). As a result, Hoffman–LaRoche reemphasized the warnings, clarified the limited group of patients who actually need this drug, and recommended that only patients who can understand and carry out verbal instructions and those who give written, informed consent receive Accutane. The packaging has been redesigned so that each time a patient takes a capsule, she sees the pregnancy warning. Drugs cross the placenta by passive diffusion across a concentration gradient. A lipid-soluble, nonionized drug of low molecular weight crosses the placenta more rapidly than one that is less lipid soluble, of higher molecular weight, or in ionic form. Teratogens are agents that increase the frequency of congenital malformations or fetal damage. Neither patient nor physician may be aware of pregnancy when the rapidly differentiating organs are most susceptible to teratogens—the period spanning days 15 through 60 of gestation ( 3). The teratogenic effects of agents are influenced by the genetic susceptibility of the fetus. Teratogenicity is considered to involve gross morphologic changes, but recently more subtle physiologic, biochemical, and behavioral effects have been noted. Early in pregnancy, in the first 8 to 10 weeks of fetal life, teratogenic agents may induce more severe alterations in development, leading to gross malformations or spontaneous abortion. Drug exposure should be minimized during this period. As mentioned, however, many patients are unaware during this time that they are pregnant. Later in pregnancy, adverse effects are more likely to result from unexpected influences on the immature and sensitive fetal metabolism or from maternal physiologic changes harmful to the fetus ( 4).

CATEGORIES OF MEDICATION In 1979, the Federal Drug Administration (FDA) established five categories to which drugs would be assigned according to their potential for causing birth defects if given during the first trimester. The classification, as outlined by the FDA, includes the following: Class A medications—Controlled human studies have failed to demonstrate a risk to the fetus during the first trimester, and the possibility of fetal harm seems remote. Class B medications—Animal studies indicate no fetal risk, and there are no controlled human studies; or animal studies do show an adverse effect on the fetus, but well-controlled human studies do not. Class C medications—Teratogenic or embryocidal effects are shown in animals, but no controlled studies are available in either animals or human beings. Class D medications—Positive evidence of human fetal risks exists, but benefits may outweigh risks in certain situations. Class X medications—Studies or experience have shown fetal risk that clearly outweighs any possible benefit. Of special note is the FDA's statement that even the medications deemed safest should be used only when clearly indicated ( 5). The limitations of these classifications is exemplified additionally by the fact that animal studies failed to reveal any teratogenic effects of the drug Thalidomide before the appearance of its devastating effects on limb formation in humans. Relatively few drugs have been proven to harm the developing fetus directly. To reduce any unknown risks, a few general principles should be followed with all medications ( 6): 1. 2. 3. 4.

Decrease exposure by giving the minimum effective dose for the shortest possible time. Prescribe oral or aerosolized forms when possible. Choose well-known preparations rather than newer medications. Be aware of the potentially teratogenic components included in many combination formulations.

With some prescription drugs, the physiologic changes of pregnancy can lead to clinically important alterations in blood concentrations. Because of an increased volume of drug distribution, decreased albumin-binding sites, and increased liver metabolism and renal flow, drugs metabolized by the liver or cleared by the kidney are excreted more rapidly. For example, phenytoin and theophylline are cleared at twice the rate found in nonpregnant women. Measurement of drug concentrations can be helpful in these circumstances. Increased awareness of potential adverse effects of drug use in pregnancy among physicians and the general public has had a positive effect, with a continuous decrease in analgesic and tranquilizer use since 1964, but not in the use of antiemetics, antibiotics, or vitamins ( 7). The efficacy of alternative therapies available to treat various symptoms in pregnancy is verified by the lower levels of labor pain perceived by mothers who use natural childbirth methods of delivery. Modalities such as heat therapy, cryotherapy, massage, transcutaneous electrical nerve stimulation, and hypnosis may be safe and effective for the treatment of pregnant patients (8). Situations continue to occur, however, in which alternative methods are impractical and a thorough knowledge of the teratogenic potentials of more commonly prescribed medications must be available to allow the physician to prescribe medications with full informed consent of pregnant patients. Physicians must be aware of the risks associated with so-called recreational drugs and advise patients appropriately.

SPECIFIC MEDICATIONS

Antibiotics A prospective study of 7765 nonpregnant hospital patients, conducted by Caldwell and Cluff ( 9), showed the overall incidence of adverse side effects to be 4.4%. There have been no studies examining the incidence of pharmacologic side effects or changes in drug action in pregnant women. The hemodynamic changes of pregnancy influence the metabolism and distribution of antibiotics, as they do those of other drugs, because of increased intravascular volume, renal blood flow, and glomerular filtration rate. Pregnant patients have been shown to have lower antibiotic serum concentrations than nonpregnant patients receiving equivalent doses (10,11,12 and 13). The penicillins, including the semisynthetic forms, are considered safe for pregnant patients who do not exhibit an anaphylactic type of allergic reaction ( 14). Based on widespread use and extensive experience, the penicillins cross the placental barrier readily without teratogenicity, decreased efficacy, or adverse effects on the mother. Because of the lack of clinical experience, the newer synthetic compounds generally should not be used unless they are relatively indicated by the potential outcome of an infection inadequately treated by other agents. For patients with immediate type sensitivity to penicillin, erythromycin base is the preferred alternative therapy (15). For nonanaphylactic reactions, cephalosporins are the preferred alternative therapy ( 16). It can safely be recommended that the cephalosporin ceftriaxone (Rocephin) replace spectinomycin as the alternative therapy to penicillin for gonorrhea infections during pregnancy. Erythromycin base is safe and effective for use during pregnancy, particularly in the treatment of community-acquired pneumonias and in the management of syphilis in patients with penicillin sensitivity. Erythromycin estolate should not be used because there is evidence of an increased risk for cholestatic hepatitis in the mother ( 15). Intravenous erythromycin is needed to achieve therapeutic levels in fetal serum after 4 months of gestation ( 17). Cephalosporins (FDA class B) have no reported teratogenicity, decreased efficacy, or adverse metabolic effects in the fetus and no other reported problems ( 14). Chloramphenicol appears to be safe and has no increased incidence of adverse side effects on the fetus or mother when used during pregnancy ( 15,18). Of special interest is its association with a severe, rare, idiosyncratic toxic reaction seen especially in premature infants. The “grey syndrome” was first observed in 1959 in neonates who exhibited cardiovascular collapse after chloramphenicol therapy ( 19). Onset begins 3 to 4 days into therapy with vomiting, irregular and rapid respirations, and abdominal distension. This progresses to flaccidity, ashen grey cyanosis, and decreased body temperature. Approximately 40% of neonates survive if chloramphenicol therapy is discontinued. The incidence of this reaction is extremely low and should not deter the use of chloramphenicol when indicated in pregnant women or neonates, provided that serum drug levels are followed. The aminoglycosides cross the placenta poorly but still expose the fetus to the risk for ototoxicity ( 20). Their role in pregnancy is as backup therapy for organisms resistant to chloramphenicol. Overall, the use of aminoglycosides in pregnancy has been too infrequent to allow their unqualified recommendation, and we must rely on the proverbial risk-to-benefit ratio in clinical decision making. The sulfonamides (FDA class C), including those in combination preparations such as Bactrim and Septra, should be avoided in the third trimester, when their use is associated with an increased risk for kernicterus in the newborn ( 21). There is also theoretic concern for adverse effects on fetal development during the first trimester as a result of the antifolate activity of sulfonamides. It may be prudent to use alternative antibiotics in this period if possible, but treatment should not be withheld on this basis alone when no effective options exist. Widespread use of trimethoprim has resulted in no increase in fetal abnormalities. Tetracycline is contraindicated during pregnancy because of its effects on the fetus and the mother. The normal risk of hepatotoxicity is increased in the mother during pregnancy (22,23). This increased risk may be the result of altered renal clearance from the hemodynamic effects, discussed earlier, becoming accentuated in pyelonephritis and resulting in higher than therapeutic levels. The chelating property of tetracycline results in tetracycline–calcium orthophosphate complexes. This poses a risk of discoloration of the teeth in the offspring of pregnant women treated with tetracycline. The period of greatest damage seems to be after the fourth month of gestation (24). This same chelating property can cause deposition in bones with a depression of bone growth. Nitrofurantoin (Macrodantin) may be safely used during the first two trimesters of pregnancy. This drug should not be used in patients with known or potentially compromised renal function, such as those with toxemia, hypertension, or diabetes. There are no special considerations for the use of this drug beyond those in nonpregnant patients (4). The quinolones, norfloxacin (Noroxin) and ciprofloxacin (Cipro), FDA class C, are nalidixic-acid derivatives that can cause central nervous system reactions, intracranial hypertension, rare blood dyscrasias, and hemolytic anemia in young children ( 25). This class of medications should be avoided in pregnancy. During pregnancy, changes in the vaginal environment occasionally allow overgrowth of normal organisms. Candida is a normal component of vaginal flora and requires no treatment unless bothersome symptoms exist. Should these infections be transmitted during birth, they are easily treated in the normal newborn. Clotrimazole (Mycelex) is safe for use during pregnancy in women with symptomatic Candida vaginitis ( 26). Fluconazole (Diflucan) is categorized as class C because animal studies at very high chronic doses resulted in poor maternal weight gain and various malformations. The likelihood of problems with single-dose therapy appears remote, but no human studies exist. Trichomonas is found in 3 to 15% of asymptomatic women at gynecology clinics and in 20 to 50% of women at sexually transmitted diseases clinics ( 27). The growth of trichomonas is stimulated by the more alkaline environment of the vagina during pregnancy ( 28). The infectious process associated with trichomonas vaginitis during pregnancy does not appear to harm the fetus. The initial therapy should be directed toward symptomatic relief, with tub baths twice daily and biweekly douching with a weak solution of vinegar and water. Clotrimazole has been shown to be effective occasionally against trichomonas when conservative therapy fails ( 26). Metronidazole (Flagyl) use in pregnancy is controversial; studies show it to be carcinogenic in rodents and mutagenic in bacteria. Metronidazole should be used in patients in whom symptoms persist despite the therapies outlined, and then only during the second half of pregnancy (28).

GASTROINTESTINAL MEDICATIONS Heartburn is a frequent complaint during pregnancy because of either esophageal reflux of gastric contents or reflux of bile through the pyloric and lower esophageal sphincters. In general, antacid preparations in the usual doses are well tolerated and safe during pregnancy. Sodium bicarbonate should be avoided because it is absorbed in greater proportion than other antacids ( 14), and, if used excessively, may alter maternal and fetal pH with effects on enzyme function, oxygen–hemoglobin dissociation, and many other sensitive metabolic processes in the fetus. Sucrulfate (Carafate), cimetidine (Tagamet), ranitidine (Zantac), and famotidine (Pepcid) are all class B medications and appear safe. Studies in animals have demonstrated no fetal harm at extremely high doses (29). Nizatidine (Axid), omeprazole (Prilosec), and cisapride (Propulsid) are C class medications because of adverse effects in animal studies, as documented in the Physicians Desk Reference. Hemorrhoids are best treated with increased dietary fiber or one of the bulk-forming fiber preparations available to prevent constipation. Anal analgesia may help, with either sitz baths or one of the nonsteroidal soothing ointments or suppositories, such as Anusol ( 30,31). The standard initial treatment for nausea and vomiting associated with pregnancy is reassurance that it is a transient problem and advice that instigating factors be avoided ( 30). For vomiting associated with disease states, it is customary to rest the gastrointestinal tract for several hours and then slowly advance the diet, beginning with clear liquids. When these modalities fail, early aggressive treatment with intravenous fluids is encouraged to avert maternal dehydration and altered fetal circulation. Many alternatives exist for the pharmacologic treatment of vomiting. There is great concern in the general public over the pharmacologic treatment of nausea in pregnancy, based primarily on the drug Bendectin. The Fertility and Maternal Health Advisory Committee of the FDA reviewed published and unpublished data on Bendectin and was unable to demonstrate a direct increase in birth defects with its use ( 32). The manufacturers, however, voluntarily removed the drug from the market because of the mounting costs of defending Bendectin's safety. Trimethobenzamide (Tigan) is an antinauseant that appears to be safe for use during pregnancy ( 33). Prochlorperazine (Compazine) and metoclopramide (Reglan), both phenothiazines, are probably safe. The phenothiazines should be regarded as second-line therapy because of the small risk for maternal hypotension associated with phenothiazines and the resultant placental insufficiency ( 14). Meclizine (Antivert), a class B medication, is an antihistamine used primarily to prevent motion sickness. Studies in rodents show teratogenicity at high doses, but human studies do not indicate any risk in humans. It may be prudent to notify patients of this theoretic risk before prescribing ( 31,34).

ANTICONVULSANTS

Seizure control during pregnancy requires diligent attention to serum concentrations of anticonvulsant medications to maintain therapeutic drug levels during the hemodynamic and metabolic changes of pregnancy. Phenytoin may be cleared at twice the rate seen in nonpregnant women. One study has shown that seizure frequency during pregnancy increases in 45%, decreases in 5%, and remains unchanged in 50% of women ( 34). The level of control during pregnancy is best predicted by the level of control during the preceding two years. No evidence exists to contraindicate the rapid intravenous use of standard drugs to control status epilepticus, although the shorter-acting preparations such as midazolam (Ativan) may be preferred to shorten the exposure time (35). Although the FDA has deemed benzodiazepines as class D medications, their use is justified by research showing that levels and duration of hypoxia and acidosis, even with a short seizure, are significant and comparable to those seen with asphyxiated newborns (36). Benzodiazepines are not advised in pregnancy except for short-term use in status epilepticus. Major malformations occur at a slightly higher rate in the offspring of patients with epilepsy; these cannot always be related to a specific medication ( 37,38). Maternal complications, including hyperemesis, vaginal bleeding, toxemia, delayed labor, and forceps delivery, are increased twofold in epileptic pregnancies ( 39,40). The cause of all these changes is unclear, but they may be attributable to many factors including the disease itself, common genetic predisposition to epilepsy and other malformations, specific drugs, and deficiency states induced by drugs or seizures. The known teratogenic potential of anticonvulsants has changed with recent evidence of associations between the use of some anticonvulsants and malformations. Trimethadione is associated strongly with fetal malformation and mental retardation in a high proportion of those exposed ( 41). Sodium valproate appears to cause a greatly increased risk for spina bifida ( 42). Prenatal testing for neural tube defects should be offered to patients exposed to this medication during pregnancy. Carbamazepine (Tegretol) has a significant risk for minor craniofacial and limb malformations and developmental delays ( 43). The fetal hydantoin syndrome includes craniofacial anomalies, limb deformities, deficient growth, and mental retardation observed in the offspring of women on phenytoin therapy. The proven incidence of this syndrome is low and has never been shown prospectively. The avoidance of seizures during pregnancy is of paramount importance to protect the developing fetus. When control of seizures is impossible without the use medications that carry a teratogenic risk, patients should be counseled on these risks, and informed consent should be obtained before using potentially teratogenic medications.

RESPIRATORY MEDICATIONS Women with asthma have a slightly higher incidence of complications and adverse outcomes of pregnancies than those without asthma. Higher infant mortality rates are noted in patients whose asthma is continually active throughout the pregnancy. The offspring of women with asthma have a higher incidence of hypoxemia at birth than controls, but there are no significant differences in the rates of malformation, disease, or birth injury ( 44,45). Both minute ventilation and oxygen consumption increase significantly during pregnancy. The major concern in pregnant women with asthma is maintaining fetal oxygenation. Probability is nearly equal that an asthmatic condition will deteriorate, improve, or remain unchanged throughout pregnancy ( 46). b-adrenergic drugs cause peripheral vasodilation and may shunt blood from the fetus as the uterine vessels constrict; however, the true significance of this effect is unknown. The Perinatal Collaborative Project ( 46) found a statistically significant increase in malformations in a group of mother–child pairs exposed to epinephrine in the first 4 months of pregnancy. It is unclear whether the severity of asthma itself or the treatments required caused these malformations. When possible, epinephrine should be avoided during pregnancy if other modalities will suffice. Isoproterenol (FDA class D) and ephedrine (FDA class C) have not been well studied in pregnancy, but no increased risk for malformation has been shown clinically. These medications should not be used in pregnancy unless the clinical situation leaves no alternative but to expose the fetus to unknown risk. Terbutaline (FDA class B) and other b 2 stimulants are given by continuous infusion to arrest premature labor through the inhibition of uterine activity. Theoretically, b stimulants administered near term could prolong labor, although this seems unlikely with the low dosages used to treat asthma. Although no controlled studies have been performed, no adverse effects from the use of terbutaline have been found in humans ( 14,47). Terbutaline should be reserved for patients in whom safer forms of therapy have failed (48).

2

Metaproterenol (FDA class C) is safe in both the aerosol and the oral form. No adverse effects in human fetuses and no increased incidence of side effects in pregnant women has been noted in 20 years of clinical use. Although animal studies have shown high doses to be harmful ( 45,49), the aerosol form requires only one tenth the oral dose and should be considered safe. The Perinatal Collaborative Project did not demonstrate any increased risk with the use of aminophylline or theophylline. The side effects of theophylline preparations remain the same in pregnant as in nonpregnant patients. To avoid neonatal theophylline toxicity, close attention must be paid to serum theophylline levels during pregnancy. Theophylline is cleared at twice the rate in pregnant women as in nonpregnant women. Theophylline levels should be maintained in the lower therapeutic range, although cases have been reported in which neonatal toxicity was associated with maternal levels of 11 to 13 mg/mL (50). Cromolyn sodium has not been studied prospectively. No fetal damage, however, has been observed over its long clinical history of use ( 51). Many combination products used in patients with asthma contain phenobarbital. There is no evidence to suggest that its use causes undue risk to the mother or the fetus. The value of phenobarbital in asthma therapy, however, has not been shown. Oral glucocorticoids are highly effective in the treatment of severe asthma. Three groups of mothers were studied retrospectively, including those using prednisone for short-course therapy, daily prednisone initiated during pregnancy, and continued daily prednisone initiated before pregnancy ( 52). The study failed to reveal any adverse effects in the offspring during the first 2 years of life. Corticosteroids should not be withheld when indicated during pregnancy, but the lower doses required with aerosol forms are preferred (53).

COLD MEDICATIONS Decongestants may be indicated for certain conditions during pregnancy if there is significant maternal discomfort. Many of these products are combination medications, and the clinician should be aware of potential adverse effects of all the components. Pseudoephedrine has been studied and can be used safely during pregnancy. The cautious use of phenylephrine appears to be safe ( 14,53), but studies are contraindicatory. Dextromethophan and guaifenesin both appear to be safe based on the major epidemiologic studies (47,54,55). Antihistamines may be needed to treat various conditions, including urticaria, angioedema, drug reactions, and allergic and vasomotor rhinitis. The well-established antihistamines, chlosphreniramine and brompeniramine, appear to be safe for use in pregnancy. Diphenhydramine (Benadryl) appears to be safe, although an unconfirmed study suggests a correlation with cleft palate ( 56). Current data suggest its safety ( 53). During the last two weeks of pregnancy, antihistamine use has been associated with an increased risk for retrolental fibroplasia in premature infants ( 57).

IMMUNIZATIONS The commonly used tetanus and diphtheria and tetanus immunoglobulin appear to be safe for use during pregnancy. Hepatitis B vaccine is a killed virus vaccine and appears to be safe for use during pregnancy, though this has not been proven in a controlled study ( 58). Live virus vaccines, such as those for smallpox, measles, mumps, varicella, and rubella, carry a small, theoretic risk of viremia with resultant fetal infection and thus are contraindicated in pregnancy according to the Centers for Disease Control and others (57,58,59,60 and 61).

ANALGESICS The analgesic and antipyretic of choice in pregnancy is acetaminophen. It appears to have no teratogenic effects when taken in the usual doses, although renal changes may occur in the offspring of heavy acetaminophen users ( 62). In the past, aspirin was the most frequently used drug during pregnancy. Salicylates readily cross the placental barrier and are more slowly eliminated by the fetus because of the immaturity of the glucuronidation and renal excretory pathways. Numerous

studies of the effect of salicylates on pregnancy outcome have failed to be definitive. The antiprostaglandin effect of these medications may inhibit uterine contraction, and it has been shown in animals and humans to increase the average length of gestation, the frequency of postmaturity, and the mean duration of spontaneous labor (63). Of theoretic concern is premature closure of the ductus arteriosus as a result of prostaglandin inhibition ( 64). Nonsteroidal anti-inflammatory drugs have similar effects and should be avoided. Earlier in pregnancy, salicylates are the second line analgesic to antipyretic behind acetaminophen. The FDA panel on over-the-counter medications concluded that aspirin was a potentially hazardous medication in pregnancy. The FDA recommended that all labels of aspirin-containing products include the warning, “Do not take this product during the last two months of pregnancy except under the advice and supervision of a physician” (65). Local anesthetics are weak bases and, as with narcotics, are subject to ion trapping in the fetal circulation ( 66,67). Weak bases can be converted to the nonionic form as a result of hyperventilation associated with pain. The nonionic form then crosses the placental blood barrier to the relatively acidotic fetal circulation, converts to its ionized form, and is trapped until cleared by fetal metabolism. Local anesthetics have been shown to be myocardial depressants with an even greater negative inotropic effect when combined with acidemia ( 68). Therefore, prolonged exposure to local anesthetics during labor, as with epidural blocks, should be avoided, especially when there are signs of fetal distress. The vascularity of the pelvic region causes a rapid rise in maternal plasma anesthetic levels during perivaginal and paracervical blocks. This direct diffusion can result in higher levels in the fetal serum than in the maternal serum ( 69,70). In a study of 17 fetuses treated with 200-mg paracervical blocks, seven had episodes of significant bradycardia ( 71). Those with bradycardia had a mean mepivacaine level of 4 mg/mL, whereas those with levels below 3 mg/mL showed no adverse effects. A similar 3 mg/mL threshold was found for lidocaine. Zador et al. ( 68) have developed a protocol for peridural anesthesia that successfully maintains umbilical vein lidocaine levels below 0.6 mg/mL. Other research has shown that the addition of epinephrine (1:400,000) to bupivicaine halved the maternal levels and decreased the fetal level by 30% ( 72). Local infiltration for various outpatient procedures appears to be safe during pregnancy. Using a 1% solution generally results in a total dosage of less than 5 mg lidocaine. Nearly complete absorption from a subcutaneous site occurs over a 4-hour period and should not exceed the threshold established ( 73). Interestingly, subcutaneous intercostal nerve blocks with 400 mg lidocaine resulted in a mean peak level of only 2.0 mg/mL ( 74). Narcotic use (therapeutic as well as recreational) during pregnancy can affect the fetus and neonate in two ways. It may cause fetal hypoxia and acidosis secondary to maternal respiratory depression and by direct fetal or neonatal depression once the narcotic has crossed the placental barrier. Narcotics remain in the fetal circulation for prolonged periods because of underdeveloped degradation pathways and ion trapping. For example, meperidine has a half-life of 18 hours in the neonate compared with 3 hours in adults ( 66). Retrospective studies of narcotic-addicted mothers indicate a higher incidence of meconium-stained amniotic fluid, anemia, low birth weight, and stillbirth ( 75,76). To minimize the effects of narcotics on the fetus or neonate, guidelines should be followed: 1. 2. 3. 4.

Avoid prolonged use of narcotics during pregnancy. Avoid acute detoxification—e.g., naloxone in suspected or known narcotics addicts—because of possible deleterious effects on the fetus ( 14). Approach deliveries in narcotics-addicted mothers as high risk with the potential for serious neonatal depression. Keep antidotes at hand. Administer intravenous medications for pain control in labor only during uterine contractions. Placental blood flow from the maternal side ceases as the uterine intramural pressure rises during contractions, thus decreasing the bolus reaching the fetus ( 77).

Both morphine sulfate and meperidine appear safe for cautious use during pregnancy. Careful titration to the desired effect must be followed to minimize the risk for respiratory depression in either the mother or the neonate ( 78). Codeine use during the first trimester is linked loosely to cleft lip and palate ( 79). Therefore, avoid the use of codeine during the first trimester or near term because of incidences of neonatal codeine withdrawal when nonaddicted mothers used codeine at the end of pregnancy (80). Nitrous oxide in a 50% oxygen–50% nitrous oxide mixture is used frequently as an analgesic in the prehospital setting and during labor. No significant differences in mean Apgar scores at 1 and 5 minutes were observed in babies of mothers receiving continuous nasal nitrous oxide with supplemental nitrous oxide during contractions (81). Nitrous oxide does not seem to impair adjustment to early life or to have ill effects when used during labor. Exposure of health care personnel to low levels of nitrous oxide has been implicated in an increased incidence of spontaneous abortion and fetal malformations in these workers ( 82). The FDA warns health professionals who may become pregnant that chronic occupational exposure to nitrous oxide may pose a risk to the fetus ( 83). No evidence to date, however, implicates the short-term intermittent use of 50:50 nitrous oxide and oxygen mixture in causing adverse effects during pregnancy.

SUBSTANCES OF ABUSE The effects of individual drugs of abuse or recreation are difficult to isolate because studies indicate that most abusers use multiple drugs. Use of alcohol, tobacco, caffeine, and cocaine has been related to retarded fetal growth and developmental delays. Alcohol is associated with the group of manifestations known together as the fetal alcohol syndrome (84). This syndrome includes growth retardation, tremulousness, hyperactivity, attention deficit, and at least two of the following facial anomalies: narrow eye width, ptosis, thin upper lip, and hypoplasia of the midfacial area. The critical period for alcohol teratogenicity appears to be near the time of conception ( 85). The typical levels of alcohol intake have not been shown to be teratogenic (86), yet abstinence should be encouraged because the more subtle behavioral findings of the alcohol syndrome may manifest themselves at lower levels of maternal use. The deleterious effects and potential sudden death associated with cocaine use have been well documented elsewhere. The vasoconstriction, sudden hypertension, decreased uterine blood flow, cardiac arrhythmias, and anorexic effects of cocaine appear to result in growth retardation and an association with abruptio placenta (87).

CARDIAC DRUGS Given its natural occurence, rapid clearance, and lack of effect on the fetal heart, adenosine (Adenocard) should be used to treat SVT in a pregnant patient. Verapamil has been used successfully but carries the risk for maternal hypotension, bradycardia, or asystole with secondary fetal effects ( 88). Electrical cardioversion is necessary when maternal hemodynamic status threatens the fetus (89). Pregnant women are at increased risk for intravascular thrombosis. Heparin is safe when it is closely monitored and does not cross the placenta. Warfarin (Coumadin) is contraindicated because of well-documented teratogenic effects ( 90).

ANTIDEPRESSANT MEDICATIONS Tricyclic antidepressant drugs and serotonin-uptake inhibitors have been evaluated by children's IQ test results and language development skills. In utero exposure to these medications does not affect IQ, language development, or behavioral development in preschool children ( 91). Previous evaluation had not demonstrated significant alterations during pregnancy ( 92,93).

NATIONAL CONTACTS In response to the need for information on medical, environmental, and occupational exposure during pregnancy, consultation services such as the Florida Teratogenic Information Service have been established. This service can be contacted at: University of Florida, 904-392-4104 University of Miami, 305-547-6549 University of South Florida, 813-974-2262 Regional Poison Control Center References 1. 2. 3. 4.

LaFauce L, Williams C, Osborne W, Moffett M: The Florida teratogen information service. Fla Med Assoc 1988;12:814–816. Marwick C: FDA ponders approaches to curbing adverse effects of drug used against cystic acne. JAMA 1988;259:3225. Moore KL, ed.: The developing human. In: Clinically oriented embryology. 2nd ed. Philadelphia, WB Saunders, 1977:133. Lewis BV: Drug therapy in pregnancy. Practitioner 1978;221:566.

5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93.

Pregnancy categories for prescription drugs. FDA Drug Bulletin; September 1979. Whipkey RR, Paris PM, Stewart RD: Drug use in pregnancy. Ann Emerg Med 1984;13:346. Harjulehto T, Aro T, Saxen L: Long term changes in medication during pregnancy. Teratology 1988;37:145. Paris P, ed.: Pain management in emergency medicine. Norwalk, CT: Appleton & Lange, 1988:420. Caldwell J, Cluff L: Adverse reactions to antimicrobial agents. JAMA 1974;230:77. Philipson A: Pharmacokinetics of ampicillin during pregnancy. J Infect Dis 1972;136:370. Bernard B, Barton L, Abate M, et al: Maternal fetal transfer of cefazolin in the first twenty weeks of pregnancy. J Infect Dis 1977;136:377. Weinstein AJ, Gibbs RS, Gallagher M: Placental transfer of clindamycin and gentamycin in term pregnancy. Am J Obstet Gynecol 1976;124:688. Good R, Johnson G: The placental transfer of kanamycin during late pregnancy. Obstet Gynecol 1976;38:60. Berkowitz RL, Coustan DR, Michizuki TK, eds.: Handbook for prescribing medications during pregnancy. Boston: Little, Brown, 1986:221–224. Weinstein AJ: Treatment of bacterial infections in pregnancy. Drugs 1979;17:56. Weinstein L: Antimicrobial agents: penicillin and cephalosporins. In: Goodman L, Gillman A, eds. The pharmacologic basis of therapeutics. 7th ed. New York: MacMillan, 1985. Fenton LJ, Light IJ: Congenital syphilis after maternal treatment with erythromycin. Obstet Gynecol 1976;47:492. Weinstein L: Antimicrobial agents: tetracyclines and chloramphenicol. In: Goodman L, Gillman A, eds. The pharmacologic basis of therapeutics. 7th ed. New York, MacMillan, 1996. Burns LE, Hoggman JE, Cass AB: Fatal circulatory collapse in premature infants receiving chloramphenicol. N Engl J Med 1959;261:13. Conway N, Birt BD: Streptomycin in pregnancy: effect on the fetal ear. Br Med J 1965;2:260. Brumfitt TW, Purswell R: Trimethoprim—sulfa methoxazole in the treatment of bacteriuria in women. J Infect Dis 1973;128:657. Kunelis CT, Peters RL, Edmondson HA: Fatty liver of pregnancy and its relationship to tetracycline therapy. Am J Med 1965;38:359. Davis JS, Kaufman RH: Tetracycline toxicity: a clinicopathologic study with special reference to liver damage and its relation to pregnancy. Am J Obstet Gynecol 1966;95:523. Weyman J: Tetracycline and teeth. Practitioner 1965;195:661. New HC: Quinolones: a new class of antimicrobial agents with wide potential uses. Med Clin North Am 1988;72:623. Haram K, Digraines A: Vulvovaginal candidiasis in pregnancy treated with chlotrimazole. Acta Obstet Gynecol Scand 1978;57:453. Rein MF, Chapel TA: Trichomonas, candidiasis and the minor venereal diseases. Clin Obstet Gynecol 1975;18:73. Fouts AC, Krauss J: Trichomonas vaginalis: reevaluation of its clinical presentation and laboratory diagnosis. J Infect Dis 1980;141:137. Sifton DW, Westley GJ, Pfohl B, eds.: Physician's desk reference. Montvale, NJ: Medical Economics Data Production Company, 1998. Landers DV, Green JR, Sweet RL: Antibiotic use during pregnancy and the postpartum period. Clin Obstet Gynecol 1983;26:401. Biggs JSG, Vesey EJ: Treatment of gastrointestinal disorders of pregnancy. Drugs 1980;19:70. Dworken HJ, ed.: Gastroenterology: pathophysiology and clinical applications. Boston: Butterworth, 1982:512–513. Indications for Bendectin narrowed. FDA Drug Bulletin. 1981;2:5. Millovich L, Van Den Berg BJ: An evaluation of teratogenicity of certain antinauseant drugs. Am J Obstet Gynecol 1976;125:244. Knight AH, Rhind EG: Epilepsy in pregnancy— a study of 153 pregnancies in 59 patients. Epilepsia 1976;16:99. Montouris GD, Fenichel GM, McLain LW: The pregnant epileptic, a review and recommendations. Arch Neurol 1979;36:601. Orringer CE, Eustace JC, Wunsch CD, et al: Natural history of lactic acidosis after grand mal seizures. N Engl J Med 1977;297:796. Shapiro S, Sloane D, Harty SC, et al: Anticonvulsants and parental epilepsy in the development of birth defects. Lancet 1976;1:272. Shapiro S, Sloane D, Harty SC, et al: Hydantoins (phenytoins)—Human teratogens? J Pediatr 1977;90:673. American Academy of Pediatrics Committee on Drugs. Anticonvulsants in pregnancy. Pediatrics 1979;63:331. Bjerkedal T, Bahna SL: The course and outcome of pregnancy in women with epilepsy. Acta Obstet Gynecol Scand 1973;52:245. Feldman GL, Weaver DD, Lourien EW: The fetal trimethadione syndrome report of an additional family and further delineation of this syndrome. Am J Dis Child 1977;131:1389. Munro J: Valproate, spina bifida, and birth defects registries. Lancet 1988;2:1404. Editorial. Jones KL, Lacro RV, Johnson KA, Adams J: Pattern of malformations in the children of women treated with carbamazepine during pregnancy. N Engl J Med 1989;320:1661. Bahna SL, Bjerkedal T: The course and outcome of pregnancy in women with bronchial asthma. Acta Allergiol (KBH) 1972;27:397. Turner ES, Greenberger PA, Patterson R: Management of the pregnant asthmatic patient. Ann Intern Med 1980;6:905. Heinonen OP, Slone D, Shapiro S: Birth defects and drugs in pregnancy. Littleton, MA: Publishing Sciences Group, 1977. Sinaiko RJ, German DF: Perspective on asthma in pregnancy. West J Med 1979;131:315. Bergman B, Hedner T: Antipartum administration of terbutaline and the incidence of hyaline membrane disease in pre-term infants. Acta Obstet Gynecol Scand 1978;58:217. Arwood LL, Dasta JF, Friedman C: Placental transfer of the theophyllin: two case reports. Pediatrics 1979;63:844–846. Dykes MHM: Evaluation of an antiasthmatic agent chromolone sodium. JAMA 1974;227:1061. Synder RD, Synder D: Corticosteroids for asthma during pregnancy. Ann Allergy 1978;41:340. Greenberger P, Patterson R: Safety of therapy for allergic symptoms during pregnancy. Ann Intern Med 1976;89:234. Aselton PA, Jick H, Milunsky A, et al: First-trimester drug use and congenital disorders. Obstet Gynecol 1985;65:451–455. Jick H, Holmes LB, Hunter JR, et al: First-trimester drug use and congenital disorders. JAMA 1981;246:343–346. Saxen I: Cleft palate and maternal diphenhydramine intake. Lancet 1974;1:407. Adverse reactions to small pox vaccination. MMWR 1978;28:265. Barry M, Bia F: Pregnancy in travel. JAMA 1989;261:728. Epidemiology—unnecessary small pox vaccination. Br Med J 1979;2:1155. Levine MM, Edsall G, Bruce–Chwatt LJ: Live virus vaccines in pregnancy: risks and recommendations. Lancet 1974:34. American Centers for Disease Control Rubella Vaccine Registry. Rubella vaccination during pregnancy—United States, 1971–1981. MMWR 1982;31:477. Schenkel B, Vorherr H: Nonprescription drugs during pregnancy: potential teratogenic and toxic effects upon embryo and fetus. J Reprod Med 1974;12:27. Lewis RB, Schulman JD: Influence of acetylsalicylic acid, an inhibitor of prostaglandin synthesis, on the duration of human gestation and labor. Lancet 1973;2:11. Goodman L, Gillman A, eds.: The pharmacologic basis of therapeutics. New York: MacMillan, 1985:678–679. Corby DJ: Aspirin and pregnancy: maternal and fetal effects. Pediatric 1978;62:930. Caldwell J, Notarianni LJ: Disposition of pethadine in childbirth. Br J Anaesth 1978;50:307. Brown WU, Bell GC, Lorie AO, et al: Newborn blood levels of lidocaine and mepivacaine in the first postnatal day following maternal epidural anesthesia. Anesthesiology 1975;42:698. Anderson KE, Gennser G, Nilson E: Influence of mepivacaine on isolated fetal hearts at normal and low Ph. Acta Physiol Scand 1970;343:34. Petrie RH, Paul WL, Miller FC, et al: Placental transfer of lidocaine following paracervical block. Am J Obstet Gynecol 1974;120:791. Staffenson JL, Shnider SM, DeLurimier AA: Transarterial diffusion of lidocaine. Anesthesiology 1970;32:459. Asling JH, Shnider SM, Margolis AJ, et al: Paracervical block anesthesia in obstetrics. Am J Obstet Gynecol 1970;107:626. Beazly JM, Taylor G, Reynolds F: Placental transfer of bupivacaine after paracervical block. Obstet Gynecol 1972;39:2. Ballard BE: Lidocaine hydrochloride absorption from a subcutaneous site. J Pharm Sci 1975;64:781. Scott DB, Jebson PJR, Braid DP, et al: Factors affecting plasma levels of lignocaine and prilocaine. Br J Anaesth 1972;44:140. Ostrea EM, Charez CJ: Perinatal problems in maternal drug addiction: a study of 830 cases. J Pediatr 1979;94:292. Stone ML, Salerno LJ, Green M, Zelson C: Narcotic addiction in pregnancy. Am J Obstet Gynecol 1971;109:716. Albright GA: Anesthesia in obstetrics. Menlo Park, CA: Addison–Wesley, 1978:140–148. Bracken MB, Holford TR: Exposure to prescribed drugs in pregnancy and association with congenital malformations. Obstet Gynecol 1981;58:336–344. Mangurten HH, Benawra R: Neonatal codeine withdrawal in infants of nonaddicted mothers. Pediatrics 1980;65:159–160. Morrison JC, Wiser WL, Rosser JI: Metabolites of meperidine related to fetal depression. Am J Obstet Gynecol 1973;115:1132. McAneny DM, Daughty AG: Self-administered nitrous oxide/oxygen analgesia in obstetrics. Anesthesia 1963;18:488. Cohen EN, Brown BW, Wu ML, et al: Occupational disease in dentistry and chronic exposure to trace anesthestic gases. J Am Dent Assoc 1980;101:21. Vessy MP: Epidemiological studies of the occupational hazards of anesthestics—a review. Anesthesia 1978;33:430. Rosett H: Clinical perspectives of the fetal alcohol syndrome. Alcoholism 1980;4:119. Ernhart CB, Sokol RJ, Martier S, et al: Alcohol teratogenicity in the humans: ADTL assessment and specificity, critical period, and threshold. Am J Obstet Gynecol 1987;156:33. Plant M, Plant M: Family alcohol problems among pregnant women: links with maternal substance use and birth abnormalities. Drug Alcohol Depend 1987;20:213–219. Acker D, Sachs B, Tracey K, Wise W: Abruptio placentae associated with cocaine use. Am J Obstet Gynecol 1983;146:220. Mason BA, Ricci–Goodman J, Koos BJ: Adenosine in the treatment of maternal paroxysmal supraventricular tachycardia. Obstet Gynecol 1992;80:478–480. Briggs GG, Freeman RK, Yaffe SJ: Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 4th ed. Baltimore: Williams & Wilkins, 1994. Hirsh J, Foster V: Guide to anticoagulant therapy, part II: oral anticoagulants. Circulation 1994;89:1469–1480. Nulman I, Rovet J, Stewart DE, et al: Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997;336:258–262. Misri S, Sivertz K: Tricyclic drugs in pregnancy and lactation: a preliminary report. Int J Psychiatr Med 1991;21:157–171. Chambers CD, Johnson KA, Dick LM, et al: Birth outcomes in pregnant women taking fluoxetine. N Engl J Med 1996;335:1010–1015.

Chapter 56.6 Medication and Breast Milk Principles and Practice of Emergency Medicine

CHAPTER 56 OBSTETRIC EMERGENCIES

6 Medication and Breast Milk Ronald K. Smith Capsule Introduction Physiology Specific Medications Antibiotics Pulmonary Drugs Cardiovascular Drugs Antineoplastic Agents Analgesic Drugs Neuroleptic and Anticonvulsant Drugs Phenothiazines and Haloperidol Miscellaneous Drugs and Environmental Pollutants

CAPSULE The evolution of the pharmacologic management of maternal illness, in concert with possible effects in the breast-fed neonate and infant, poses a serious responsibility for all practicing physicians. Much of our knowledge concerning drugs in breast milk has been limited to case reports and research studies of limited size, making unequivocal guidelines impossible. The best general recommendations that can be made are to consider all medications transferable to the infant through breast milk, to become familiar with the routes of metabolism and secretion of the drugs used, and to select the least toxic agent after considering its half-life and pattern for maternal dosing. Breast-feeding should be initiated before maternal dosing and should be withheld for a reasonable period, usually 4 hours, to minimize the infant's exposure to medications. Prudence and the risk–benefit ratio should be the guidelines when considering medication for the lactating mother.

INTRODUCTION “Primum non nocere.” Never has this adage been more appropriate than when considering the maternal–neonatal relationship and pharmacologic intervention. The warning that “all drugs cross into breast milk” is good advice to heed but provides little assistance in deciding treatment regimens. Our goal is to review the pharmacokinetics involved in maternal and neonatal systems and to establish reasonable guidelines for the emergency practitioner in prescribing medications for breast-feeding mothers. The question of which drugs are safe during breast-feeding probably had its origin in antiquity. In 1908, C.B. Reed expressed such concerns and difficulties as: The transmission of medical substances through the milk of the mother to the baby is a subject of more than usual interest and more than usual obscurity. Many cases have been reported with the object of putting the phenomenon on a real scientific basis, but owing to the prevalence of tradition and the absence of thorough and accurate methods in correcting the data, the observations are for the most part quite valueless 1,2). (

Today the concerns persist, and, with the resurgence of interest in breast-feeding, especially in the more industrialized countries, the treatment problems facing the prescribing physician are accentuated. Emergency physicians have faced a profound lack of information in this area and often have been forced to rely on anecdotal reports citing adverse reactions in small numbers of patients—sometimes in only one patient ( 3,4). In this chapter, the known data of the 1990s are brought into view.

PHYSIOLOGY Breast milk is a complex solution of water, protein, and fats in an emulsified state. Its ratio of fat and protein varies from the initiation of lactation with colostrum formation to that of mature human milk. Colostrum is high in protein content and has lesser amounts of fat and lactose in lesser volumes than mature milk ( 5). The colostrum phase persists for approximately 1 week. This is followed by transitional milk; volume and fat content increase, and protein content diminishes. The final phase of mature milk shows its contents to be 95% water, with fat increasing and ranging from 8.7 to 120.5 mg/mL and protein content decreasing but ranging from 7 to 20 mg/mL, with albumin relatively constant at 0.4 mg/mL (6). The pH of breast milk ranges from 6.35 to 7.65 but generally is more acidic than that of human plasma (2). Daily human milk production ranges from 600 to 1000 mL ( 6). The chemical characteristics of breast milk—in association with the body's plasma content and mechanisms of passive diffusion, lipid solubility, molecular weight, pH, ionization, protein binding, distribution to maternal tissues, and maternal dosage—determine the drug concentration found in human breast milk ( 2,3,5,7). Of these physiochemical factors, fat solubility is the most important and pH/pKa are prime considerations ( 3,5). Partitioning of drugs between maternal plasma and breast milk can occur readily if drugs remain ionized and poorly soluble. In the nonionized state, drugs become more lipid soluble, less protein bound, and more diffusible into breast milk. Medications and pollutants that are relatively weak bases pass into breast milk because it is more acidic than plasma, whereas weak acids with low pKs remain trapped within the maternal plasma. A milk-to-plasma ratio of drugs has been developed and researched ( 3,4,5,6 and 7). The significance of the milk-to-plasma ratio in breast milk is that variations in drug bioavailability occur because of time, constituent content, and dosage in the maternal system. In offering breast milk to the nursing infant, the mother has performed an initial semiselective screening for transmissible xenobiotics. The neonatal and infant gastrointestinal, hepatic, and renal systems and body water content additionally influence total drug availability within the body. Neonatal and infant extracellular fluid volume and total body fat content are age dependent and are reviewed in Table 56–6.1.

Table 56–6.1. Body Water and Total Body Fat Content 3

A lower relative fat content in infants results in reduced sequestration of fat-soluble drugs in adipose tissue and greater availability and potential toxicity in the brain despite the low breast milk concentration of medications. The infant gastrointestinal mucosa has a high permeability for macromolecules and delayed emptying time, with resultant absorption variation because of compartment trapping in the stomach and small intestine. After absorption from the gastrointestinal tract, limited protein binding occurs because of the low albumin content, and then biotransformation occurs in the liver. Two phases of drug metabolism have been described in the liver. They are phase 1 reactions of the oxidative reductive and hydrolysis type and phase 2 reactions of the synthetic conjugation type. Primates and humans are unique in their ability for phase 1 degradation using cytochrome p450 and its coenzyme complexes, but infants have limited activity and rate of these systems compared to those of adults. Phase 2 reactions include glucuronidation, sulfation, and glutathione conjugation; they range from almost nonexistent to 100% of adult activity ( 8).

Renal metabolism demonstrates that the neonatal glomerular function is the first to mature and reaches peak activity 3 weeks after the birth of a full-term baby, whereas tubular renal activity is delayed until 6 months of age ( 3,9). These delayed elimination mechanisms account for increased drug accumulation in neonates despite low breast milk concentrations.

SPECIFIC MEDICATIONS Only a relatively small number of medications directly inhibit lactation. For example, alcohol can block the milk ejection reflex. Bromocriptine, oral contraceptives and other hormones and corticosteroids may suppress the production of milk ( 10).

ANTIBIOTICS Among the medications used by emergency physicians, antibiotics are the largest group prescribed to lactating mothers. The penicillin medications are used readily in the treatment of common infections and represent a group of weak acids that are thought to cross poorly into breast milk. They are, however, found in low levels in early breast milk and can present a problem after absorption as macromolecules by the infant gastrointestinal system because of increased gastrointestinal permeability. Low concentrations of these medications in breast milk probably are not enough to cause therapeutic effects, except to decrease the suckling infant's oral or possibly gastrointestinal flora. It has been postulated that they cause sensitization, which could lead to allergic reactions later in life ( 11,12 and 13). Cephalosporins, including of cephalexin, cephadroxil, cephalothin, cefazolin, cefotaxime, cephaprin, cefoxatin, ceftriaxone, and moxalactam have been investigated. These medications represent weak acids with a relative degree of protein binding. Low levels of transmissibility to breast milk with some of these cephalosporins seem to increase with their long-term chronic use ( 12,14,15,16 and 17). The risk to the suckling infant is that there may be a decrease in the oral and gastrointestinal flora and sensitization to these medications with allergic phenomena. Of note, the third-generation cephalosporins such as moxalactam have significant minimal inhibitory concentration against Gram-negative organisms and may allow Gram-positive organisms to flourish and resistant organisms to develop in the neonatal systems (17). Generally, first- and second-generation cephalosporins are safe during breast-feeding, but use of some third-generation cephalosporins may warrant the cessation of breast-feeding. Three potential problems exist for the nursing infant: modification of bowel flora, direct effect on the infant, and interference with the interpretation of culture results if a fever work-up is required. The sulfonamides and nalidixic acid have been known for many years to be dangerous because of the induction of hemolytic anemia when transferred by breast milk (18,19 and 20). Sulfonamides also displace bilirubin from albumin-binding sites and result in the deposition of bilirubin in neonatal cerebral tissues, leading to kernicterus. Tetracycline passage in milk has been questioned by some authors because of calcium and magnesium chelation. Yet some tetracycline forms, such as doxycycline and minocycline, have high-lipid solubility and low affinity for calcium binding and possibly greater absorption ( 21). The theoretic risk of mottled teeth in children bodes against tetracycline use in nursing mothers ( 11). Two other low-occurrence risks have been reported with tetracycline: depression of bone growth, which is dose dependent and reversible, and pseudotumor cerebri or increased intracranial pressure. These should be considered before any use of tetracyclines ( 20). Clindamycin has been found to be a basic drug of pKa 7.45 that accumulates in breast milk. Research findings demonstrate that clindamycin is concentrated widely in human serum, making the prediction of secretion into breast milk difficult. However, the cessation of breast-feeding during clindamycin administration is recommended (22). Metronidazole, often used for Trichomonas vaginalis, has been assessed for the passage to breast milk. Current recommendations are for the interruption of breast feeding for 12 to 24 hours because of metronidazole's half-life of 9 hours and its primary elimination by the kidneys. The safety and effects in suckling infants are still unknown, but allowing a 24-hour hiatus of breast-feeding ensures greatly reduced exposure in neonates and infants ( 23). The administration of quinolone antibiotics, including ciprofloxacin, is not recommended during breast-feeding because of the potential for arthropathy and other serious toxicity in the nursing infant. The manufacturer recommends that 48 hours elapse after the last dose of ciprofloxacin before breast-feeding is resumed ( 24). Although they are contraindicated in pregnancy, there are no data regarding the use of macrolide antibiotics, including clarithromycin and azrithromycin, during breast-feeding. Acyclovir has been studied at concentrations thought to be insignificant. Chloromycetin is a potent antibiotic often reserved for the most serious illnesses. Its reputation and theoretic risk for inducing the grey-baby syndrome are well recognized, but the risk probably is limited once it is transmitted through breast milk. The greater risk arises from the idiosyncratic reaction of bone-marrow aplasia with even small doses of chloromycetin, so this antibiotic is best avoided if breast-feeding is not to be terminated (11). In the United States, lactating women some day may have to confront the resurgence of tuberculosis and its pharmacologic management. Agents such as p-aminosalicylic acid and pyrazinamide have been found, in single-agent treatment, to be well below the therapeutic levels in breast milk, and they are considered safe for nursing mothers. The combination therapy of p-aminosalicylic acid and isonicotinoylhydrazine (INH) has been found to raise the serum and breast milk concentrations of isonicotinoylhydrazine and to warrant the limitation of breast-feeding ( 25). Tropical illnesses such as malaria are rare in the United States, but they remain large-scale problems in some areas. Agents such as chloroquine, dapsone, and pyrimethamine are weak bases with plasma-protein binding. They are all transmissible into breast milk, with concentrations ranging from 4.2 to 14.3 to 45%, respectively, of maternal dose, but they are unlikely to be harmful to infants. The reported problems associated with them are hemolytic anemia from dapsone and insufficient coverage for plasmodium falciparum or plasmodium vivax, as well as the possible induction of drug-resistant strains of these parasites ( 26).

PULMONARY DRUGS The methylxanthine agent theophylline has been investigated for transmission into breast milk. Two studies have found a milk-to-serum ratio of approximately 0.7, a half-life of 4 hours, and exposure to the nursing infant of approximately 1% of the total maternal dose. The full-term infant should not find this level a problem, but premature infants, who bind less theophylline to protein, may need serum monitoring of theophylline levels, especially if clinical signs of cardiac dysrhythmia, seizure, or pronounced irritability are witnessed ( 27,28). Terbutaline has been found to have a pKa of 8.8 to 11.2, with a resultant concentration in milk higher than in maternal plasma. Of the maternal dose of terbutaline, 0.2 to 0.7% has been observed to be ingested by the nursing infant without evidence of b-adrenergic stimulation, and breast-feeding need not be interrupted ( 29,30). Information in the literature on other b-adrenergic agents, such as metoproterenol and albuterol, is limited, but, on the basis of their low systemic absorption when administered by inhalation, they should be safe and not require the termination of breast-feeding.

CARDIOVASCULAR DRUGS Digitalis is a derivative of the foxglove plant. Until 1978, there appeared to be no literature on its transmission into breast milk despite its wide use for conditions such as paroxysmal atrial tachycardia, rheumatic heart disease, and congestive heart failure. Digoxin is reported to be transmissible into breast milk at insignificant levels despite maternal doses as high as 0.75 mg/day. Breast-feeding is safe if lactating mothers take digitalis because the absorbed dose in the infant is approximately 1/100 of the daily recommended dosage therapeutically needed in children ( 31,32). Because of their use as antihypertensive and antianginal interventions, an explosion of b-blocking agents has occurred since the 1960s. The research on the effects of these medications in breast milk has extended to include propranolol, atenolol, labetolol, oxyprenolol, timolol, nadolol, and some metabolites. Propranolol and its metabolites are weak, lipophilic bases that accumulate in the breast and breast milk. This accumulation, however, appears to be only 1/100 of the recommended dosage; hence, these agents are probably safe for continued breast-feeding. Observation for hypoglycemia and bradycardia in premature neonates and full-term newborns is warranted ( 33,34). Agents such as oxyprenolol, timolol, nadolol, and metoprolol appear safe for breast-feeding, despite the interesting kinetics of nadolol and metoprolol with which breast milk preferentially shows a 3.5- to 5-fold increase without a significant effect on the suckling child ( 35,36 and 37). The use of calcium-channel blockers increased during the 1970s and 1980s. Verapamil, norverapamil, and diltiazem have been been investigated for transmissibility into breast milk, and all three agents sustain measurable levels. With levels ranging from 0.01 to 0.5% of the maternal dose and from 0.0 to 0.4% of the therapeutic dose for the infant verapamil appears to be safe. ( 38,39 and 40). The information on diltiazem is limited to case reports showing breast milk levels approaching maternal serum levels, but no sampling of infant levels has been completed. Pending additional information, breast-feeding should be withheld with use of this medication (41). There is limited knowledge concerning antiarrhythmic therapy and transmission into breast milk. Case reports show that lidocaine and mexilitine

appear in breast milk, but the levels are low and breast-feeding is safe ( 42,43). Antihypertensives are used worldwide for pre-eclampsia and toxemia of pregnancy, but the information on many of these agents is limited. Clonidine crosses readily into breast milk and achieves twofold concentration levels compared to maternal serum. Evaluation of breast-fed infants whose mothers took clonidine during breast-feeding failed to show abnormalities of neurologic function, alterations in electrolyte or blood glucose levels, or any other typical side effects of sedation or xerostomia (44). Captopril, an angiotensin II enzyme-converting antagonist, is excreted into breast milk at 1% blood levels. This should result in dosages of 0.03% of the neonate's maximum therapeutic dose but could be higher because of the reduction of renal function. In a study of 12 patients receiving Captopril, several subjects, despite proper warning, nursed their children without adverse effects ( 45). Chlorthalidone, a potent, long-acting diuretic, should be terminated for 3 days after ingestion because of maternal milk concentrations approaching serum concentrations and an extended half-life, with a resultant reduced excretion in the neonate ( 46). Nimodipine has been used to treat subarachnoid hemorrhage, with concentration detected in breast milk similar to those in plasma ( 47).

ANTINEOPLASTIC AGENTS Doxorubicin, cisplatin, cyclophosphamide, and methotrexate have been investigated for passage into breast milk. All these agents have been shown to appear in breast milk, and, because of their potential for adverse effects even at low levels, necessitate the cessation of breast-feeding ( 48,49 and 50).

ANALGESIC DRUGS Pain and its control often motivate patients to seek medical attention. The abuse liability of pain medication concerns every physician, and its potential has come to the forefront in the 20th century. Acetaminophen and aspirin represent a large group of over-the-counter, readily available pain medications that have been investigated for breast milk transmission. Acetaminophen and phenacetin are relatively weak, hydrophilic acids that can cross into maternal milk. The levels achieved by acetaminophen are significantly low and appear safe for continued breast-feeding ( 51,52). Salicylates are acidic and polar and poorly cross lipid membranes; although they appear in breast milk, they do not necessitate the cessation of nursing if taken at recommended dosages ( 51). The recognition of the antiplatelet effect of salicylates should be considered at higher doses when used by nursing mothers ( 11). Nonsteroidal anti-inflammatory drugs such as tolmetin, naproxen, ibuprofen, piroxicam, and mefenamic acid appear in breast milk. The piroxicam family achieves the highest maternal serum level per maternal dose but does not appear to be detectable in sampled infant plasma. The nonsteroidal anti-inflammatory drugs, as a group, should be safe for the continuance of nursing ( 20,53,54 and 55). Narcotic agents such as codeine, morphine, and methadone have been shown to appear in breast milk. Although they appear safe at recommended therapeutic doses, their effects in neonates at excessive doses, in concert with low liver detoxification, raise many doubts of their safety ( 11,51). Tramadol, a newer pain medication, has not been studied and is not recommended in nursing mothers.

NEUROLEPTIC AND ANTICONVULSANT DRUGS Postpartum depression and chronic psychiatric problems are increasingly recognized, and the need for medication in these nursing mothers presents a difficult dilemma. The literature on anxiolytic and psychotropic agents is limited to case studies and a few trials of small numbers. The available recommendations for neuropsychiatric agents are summarized in Table 56–6.2. In utero exposure to either tricyclic antidepressants or fluoxetine does not affect IQ, language development or behavioral development in preschool children ( 56). This is in accord with results in experimental animals subjected to high doses of fluoxetine ( 57).

Table 56–6.2. Recommendations for Neuropsychiatric Agents

PHENOTHIAZINES AND HALOPERIDOL Although it may be safe in low doses, the American Academy of Pediatrics classifies haloperidol as an agent of concern. Chlorpromazine induces drowsiness and lethargy in the newborn (62). Phenobarbital is generally not recommended, nor is doxepin ( 70). Lithium carbonate, a well-known agent used for bipolar affective disorders, is absolutely contraindicated during breast-feeding because of its reported toxic accumulation in breast milk that leads to lethargy, hypotonia, and cyanosis ( 6). Epilepsy in its various forms, from tonic–clonic to absence seizures, covers a broad spectrum of pharmacologic management options. Often the need for long-term management with multiple agents must be balanced against the desire of the mother to breast-feed. Carbamazepine, phenytoin, phenobarbital, and ethosuximide have been reviewed in the literature. Phenytoin and carbamazepine have been shown to produce maximum dosage levels of 0.4 mg/kg and 2.5 to 4 mg/kg, respectively; therefore, it appears to be safe for continued breast-feeding ( 72,73). Phenobarbital has been reported to cause sedation and the induction of liver enzymes in infants, making it unsafe during breast-feeding ( 74). Although the American Academy of Pediatrics considers valproic acid to be compatible with breast-feeding, some authors have recommended against its use during nursing because of the potential threat of fetal hepatotoxicity in children younger than 2 years (62). Ethosuximide is an agent with high bioavailability and lipid solubility, limited protein binding, an extended half-life, and moderate concentrations in breast milk. This increasing concentration compares to that of agents such as lithium and results in the sedation of breast-fed infants. Breast-feeding should be terminated if ethosuximide is used for the treatment of absence seizures ( 3).

MISCELLANEOUS DRUGS AND ENVIRONMENTAL POLLUTANTS Warfarin is an orally active anticoagulant used in cardiovascular disease and thrombophlebitis. It is widely accepted that its transmission into breast milk is too low to pose a risk to nursing infants, but current recommendations still include giving vitamin K to the neonate whose mother requires high doses of anticoagulants. Other anticoagulants, such as phenindione, are contraindicated in continued breast-feeding ( 20). Heparin, in contrast, appears to pose little risk to the breast-feeding infant because it does not appear in breast milk ( 6). Alcohol and its use in modern society pose multiple problems. Reports of fetal alcohol syndrome have stirred great concern worldwide. Research has demonstrated that ethanol can be found in breast milk. Concentrations of ethanol are found in blood and infant ingestions that approach 20% of the maternal dose (20). Pseudo-Cushing's syndrome was reported in an infant whose mother consumed at least fifty 12-ounce cans of beer each week in addition to other alcoholic beverages ( 75). It is recommended that lactating mothers limit their use of alcohol to avoid the effects of ethanol on their infants. Nicotine is transmissible to breast milk in low concentrations, and some authors have suggested possible clinical ramifications ( 4,20). To avoid the ingestion of nicotine by their infants, it is recommended that lactating mothers stop smoking. Corticosteriods, such as prednisolone and prednisone, appear in breast milk in low levels and do not appear to pose a problem, but caution is advised in nursing mothers (76,77 and 78). Estradiol and oral contraceptives also appear in breast milk but do not appear to harm the suckling child despite reports of gynecomastia ( 79).

Iodine appears to pass into breast milk in moderate levels, even through vaginal absorption from such sources as povidone–iodine suppositories ( 80). It can affect infant thyroid function and should not be used during nursing. Propylthiouracil has been reported to concentrate in breast milk at 41 to 462 mg/day, but it is unlikely to interfere with neonatal thyroid metabolism and nursing may continue ( 81). Atropine has long been recognized as crossing the plasma–milk barrier, with recorded concentrations high enough to stimulate anticholinergic effects, necessitating the termination of breast-feeding ( 11). Ergotism, reported as a common problem from use of ergot alkaloids, also necessitates its cessation. Radiopharmaceuticals such as gallium citrate and I 131, radioactive sodium, and technetium products are best avoided in lactating mothers ( 20,74). Trace elements such as fluoride, magnesium, and calcium have been detected in breast milk from mothers who have required treatment with magnesium sulfate or who live in regions in which fluoride has been added to public water. These agents appear to pose little threat to the breast-fed child ( 82,83). Over-the-counter medications represent an important class of readily available agents. In general, these multiple agents, when taken as directed by the manufacturer, should be safe in lactating women because they represent the least toxic formulations of medications at the lowest effective dosages ( 3). Some nonsedating prescription antihistamines, including cetirizine and terfenadine, are not recommended in nursing mothers. Environmental pollutants have been recognized increasingly as toxins that cause adverse biologic change. PCB, PBB, DDT, and other multiple insecticides, as well as heavy metals and hydrocarbons, pose definite problems, but their final transmission and toxicity await additional research ( 4). Table 56–6.3 summarizes agents that are either contraindicated, to be used with caution, or noncontroversial in breast-feeding mothers.

Table 56–6.3. Summary of Drug Use in Breast-Feeding Mothers

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66.

Reed CB: A study of the conditions that require the removal of the child from the breast. Surg Gynecol Obstet 1908;6:514. Nation RL, Hotham N: Drugs and breast feeding. Med J Aust 1987;146:308. Rivera–Calimlim L: The significance of drugs in breast milk. Clin Perinatol 1987;14:51. Giacoia GP, Catz CS: Drugs and pollutants in breast milk. Clin Perinatol 1979;6:181. Syversen GB, Ratkje SK: Drugs distribution within human milk phases. J Pharm Sci 1981;74:1071. Beeley L: Drugs and breast feeding. Clin Obstet Gynecol 1981;8:291. Giacoia GP, Catz CS: Drug therapy in the lactating mother. Postgrad Med 1988;83:211. Mannering GJ: Drug metabolism in the newborn. Fed Proc 1985;44:2302. Morselli PL: Clinical pharmacokinetics in neonates. Clin Pharmacokinet 1976;1:81. Kacew S: Adverse effects of drugs and chemicals in breast milk on the nursing infant. J Clin Pharmacol 1993;33:213–221. Medical Letter. Drugs in breast milk. 1976;16:25. Kafetzis DA, Siafas CA, Georgakopoulos PA, et al: Passage of cephalosporins and amoxicillin into the breast milk. Acta Paediatr Scand 1987;70:285. Rasmussen F: Mammary excretion of benzylpenicillin, erythromycin and penethamate hydro iodide. Acta Pharmacol Toxicol 1959;16:194. Yoshioka H, Cho K, Takimoto M, et al: Transfer of cefazolin into human milk. J Pediatr 1979;94:151. Dresse A, Lambotte R, DuBois M, et al: Transmammary passage of cefoxitin: additional results. J Clin Pharmacol 1983;23:438. Kafetzis DA, Brater DC, Fanourgakis JE, et al: Ceftriaxone distribution between maternal blood and fetal blood and tissues at parturition and between blood and milk postpartum. Antimicrob Agents Chemother 1983;23:870. Miller RD, Keegan KA, Thrupp LD, et al: Human breast milk concentration of moxalactam. Am J Obstet Gynecol 1984;148:348. Rasmussen F: Mammary excretion of sulphonamides. Acta Pharmacol Toxicol 1958;15:139. Belton EM, Jones RV: Hemolytilanemia due to nalidixil acid. Lancet 1965; 691. Atkinson HC, Begg EJ, Darlow BA: Drugs in human milk: clinical pharmacokinetic considerations. Clin Pharmacokinet 1988;14:217. Neavonen PJ: Interactions with the absorption of tetra-cyclines. Drugs 1976;2:45. Steen B, Rane A: Clindamycin passage into human milk. Br J Clin Pharmacol 1982;13:661. Erickson SH, Oppenheim GL, Smith GH: Metronidazole in breast milk. Obstet Gynecol 1981;57:48. Briggs GG, Freeman RK, Yaffee SJ: Drugs in pregnancy and lactation. Williams & Wilkins, 1994. Holdiness MR: Anti-tuberculosis drugs and breast feeding. Arch Intern Med 1984;144:888. Edstein MD, Veenendaal JR, Newman K, et al: Excretion in chloroquine, dapsone and pyrimethamine in human milk. Br J Pharmacol 1986;22:733. Berlin J, Cheston M: Excretion of the methylxanthines in human milk. Semin Perinatol 1981;5:389. Stec GP, Greenberger P, Rao TI, et al: Kenetics of theophylline transfer to breast milk. Clin Pharmacol Ther 1980;28:404. Boreus LO, DeChateau P, Lindberg C, et al: Terbutaline in breast milk. Br J Clin Pharmacol 1982;13:731. Lunnerholdm G, Lindstrom B: Terbutaline excretion into breast milk. Br J Clin Pharmacol 1982;13:729. Loughnan PM: Digoxin excretion in human breast milk. J Pediatr 1977;92:1019. Finley JP, Waxman MB, Wong PY, et al: Digoxin excretion in human milk. J Pediatr 1979;94:339. Bauer JH, Pape B, Zajicek J, et al: Propranolol in human plasma and breast milk. Am J Cardiol 1979;43:860. Smith MT, Livingstone I, Hooper WD, et al: Propranolol, propranolol gluconide, and naphthoxylactic acid in breast milk and plasma. Ther Drug Monit 1983;5:87. Devlin RG, Duckin KL, Fleiss PM: Nadolol in human serum and breast milk. Br J Clin Pharmacol 1981;12:393. Fidler J, Smith V, Deswiet M: Excretion of oxyprenolol and timolol in breast milk. Br J Obstet Gynecol 1983;90:961. Sandstrom B: Metoprolol excretion into breast milk. Br J Clin Pharmacol 1980;9:518. Andersen HJ: Excretion of verapamil in human milk. Eur J Clin Pharmacol 1983;25:279. Miller MR, Withers R, Bhamra R, et al: Verapamil and breast feeding. Eur J Clin Pharmacol 1986;30:125. Anderson P, Bondesson U, Mattiason I, et al: Verapamil and norverapamil in plasma and breast milk during breast feeding. Eur J Clin Pharmacol 1987;31:625. Okada M, Inove H, Nakamura Y, et al: Excretion of diltiazem in human milk. N Engl J Med 1985;312:992. Zeisler JA, Gaarder TD, DeMesquita SA: Lidocaine excretion in breast milk. Drug Intell Clin Pharm 1986;20:691. Lewis AM, Johnston A, Patel L, et al: Mexilitene in human blood and breast milk. Postgrad Med J 1981;57:546. Hartikainen–Sorrt AL, Heikkinenk JE, Koivisto M: Pharmacokinetics of clonidine during pregnancy and nursing. Obstet Gynecol 1987;6:598. Devlin RG, Fleiss PM: Captopril in human blood and breast milk. J Clin Pharmacol 1981;21: 110. Mulley BA, Parr GD, Pau WK, et al: Placental transfer of chlorthalidone and its elimination in maternal milk. Eur J Clin Pharmacol 1978;13:129. Tonks AM: Nimodipine levels in breast milk. Aust NA J Surg 1995;65:693–694. Egan PC, Costanza ME, Dodion P, et al: Doxorubicin and cisplatinin excretion into human milk. Cancer Treat Rep 1985;69:1387. Wiernik PH, Duncan JH: Cyclophosphamide in human milk. Lancet 1971;1:912. Johns DG, Rutherford LD, Leighton PC, et al: Secretion of methotrexate into human milk. Am J Obstet Gynecol 1972;112:978. Findlay JWA, DeAngelis RL, Kearney MF, et al: Analgesic drugs in breast milk and plasma. Clin Pharmacol Ther 1981;29:625. Bitzen PO, Gustafson B, Jostell KG, et al: Excretion of paracetomol in human breast milk. Eur J Clin Pharmacol 1981;20:123. Seagraves R, Waller ES, Goehrs HR: Tolmetin in breast milk. Drug Intell Clin Pharm 1985;19:55. Jamali F, Stevens DRS: Naproxen excretion in milk and its uptake by the infant. Drug Intell Clin Pharm 1983;17:910. Buchanan RA, Eaton CJ, Koeff ST, et al: The breast milk excretion of mifanamic acid. Curr Ther Res 1968;10:592. Nulman I, Rovet J, Stewart DE, et al: Neuro development of children exposed in utero to antidepressant drugs. N Engl J Med 1997;556:258. Nulman I, Koren G: The safety of fluoxetine during pregnancy and lactation. Teratology 1996;53:304. Bader TF, Newman K: Amitriptyline in human breast milk and the nursing infant's serum. Am J Psychiatry 1980;137:855. Brixen–Rasmussen L, Halgrener J, Jorgensen A: Amitriptyline and nortriptyline excretion in human breast milk. Psychopharmacology 1982;76:94. Gelenberg AJ: Amoxapine, a new antidepressant, appears in human milk. J Nerv Ment Dis 1979;167:635. Blacker KH, Weinstein BJ, Ellman GL: Mother's milk and chlorpromazine. 1962, 178. Kuller J, Katz VL, McMahon MJ, et al: Pharmocologic treatment of psychiatric disease in pregnancy and lactation: fetal and neonatal effects. Obstet Gynecol 1996;87:789. Kemp J, Ilett KF, Booth J, et al: Excretion of doxepin and N-desmethyldoxepin in human milk. Br J Clin Pharmacol 1985;20:497. Stewart RB, Karas B, Springer PK: Haloperidol excretion in human milk. Am J Psychiatry 1980;137:849. Verbeeck RK, Ross SG, McKenna EA: Excretion of trazodone in breast milk. Br J Clin Pharmacol 1986;22:367. Steiner E, Villen T, Hallberg M, et al: Amphetamine secretion in breast milk. J Clin Pharmacol 1984;27:123.

67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84.

Erkkola R, Kanto J: Diazepam and breast feeding. Lancet 1972;1:1235. Brandt R: Passage of diazepam and desmethyldiazepam into breast milk. Arzneim–Forsch (Drug Res) 1976;26:454. Summerfeld RJ, Neilsen MS: Excretion of lorazepam into breast milk. Br J Anesth 1985;57:1042. Goldberg HL, Nissim R: Psychotropic drugs in pregnancy and lactation. Int J Psychiatry Med 1994;24:129. Hardell LI, Lindstrom B, Lonnerholm G, et al: Pyridostigmine in human breast milk. Br J Clin Pharmacol 1982;14:565. Steen B, Rane A, Lonnerholm G, et al: Phenytoin excretion in human breast milk and plasma levels in nursed infants. Ther Drug Monit 1982;4:331. Froescher W, Eichelbaum M, Niesen M, et al: Carbamazepine levels in breast milk. Ther Drug Monit 1984;6:266. O'Brien TE: Excretion of drugs in human milk. Am J Hosp Pharm 1974;31:844. Binkiewicz A, Robinson MJ, Senior B: Pseudo-Cushing syndrome caused by alcohol in breast milk. J Pediatr 1978;93:965. McKenzie SA, Selley JA, Agnew JE: Secretion of prednisolone into breast milk. Arch Dis Child 1975;50:894. Katz FH, Duncan BR: Entry of prednisone into human milk. N Engl J Med 1975;293:11. Lawrence RA: Corticosteroid effect on lactation. JAMA 1991;265:2409. Nilsson S, Nygren K-G, Johansson EDB: Transfer of estradiol to human milk. Am J Obstet Gynecol 1978;132:653. Postellon DC, Aronow R: Iodine in mother's milk. JAMA 1982;247:463. Kampmann JP, Hansen JM, Johansen K, et al: Propylthiouracil in human milk. Lancet 1980;1:736. Ekstrand J, Spak CJ, Falch J, et al: Distribution of fluoride to human breast milk. Caries Res 1984;18:93. Cruikshank DP, Varner MW, Pitkin RM: Breast milk magnesium and calcium concentrations following magnesium sulfate treatment. Am J Obstet Gynecol 1982;143:685. Eriksson G, Swahn CG: Concentration of baclofen in serum and breast milk from lactating women. Scand J Clin Lab Invest 1981;41:185.

Chapter 56.7 Postpartum Infections Principles and Practice of Emergency Medicine

CHAPTER 56 OBSTETRIC EMERGENCIES

7 Postpartum Infections Mark D. Westfall Capsule Introduction Differential Diagnosis Mastitis Endometritis Prophylaxis Septic Pelvic Thrombosis Cellulitis of the Perineum and Pelvic Floor Parametritis Conclusions

CAPSULE The postpartum woman who seeks emergency department (ED) treatment for a fever or an infection is of growing concern. Even though legislation extending the length of a hospital admission for an uncomplicated vaginal delivery to 48 hours and for an uncomplicated cesarean delivery to 96 hours will become law in 1998, the popularity of home delivery, the increasing number of uninsured patients, and other factors indicate the likely potential for the emergency physician to see more patients with acute postpartum infections. The emergency physician must have an increased awareness of this and a high index of suspicion for the patient with a serious and potentially life-threatening postpartum infection. An even greater challenge for the emergency physician is the patient receiving home health care. Patients are now receiving home antibiotics and heparin and often are referred to the ED when problems develop. Therefore, the emergency specialist must be well versed in all stages of postpartum diseases and all kinds of treatment.

INTRODUCTION Prehospital Care Paramedical personnel and base station attendants treating postpartum infections must watch for signs of hypovolemia, sepsis, and shock. Initial management should include a brief but thorough physical examination with particular attention given to the abdomen, frequent review of vital signs, and aggressive fluid administration with an isotonic solution if hypotension is present. The patient should be placed on a cardiac monitor and oxygen. The flow of oxygen should be adequate to maintain a pulse oximetry reading of 100%.

DIFFERENTIAL DIAGNOSIS The differential diagnosis of the febrile postpartum or postoperative patient with fever or other evidence of infection is listed in Table 56–7.1 (1,2). After taking a thorough history and performing a physical examination that includes breast, abdomen, perineum, and pelvic examination, laboratory studies should include a complete blood count, urinalysis, and possibly chest radiography. Strong consideration should be given to performing ultrasonography to look for the retained products of conception and a pelvic mass or abscess (2,3). If the urine is positive for red blood cells and lacks significant white blood cells, an intravenous pyelogram is indicated to look for renal lithiasis and hydronephrosis. Many of the diagnoses on the list of differentials are discussed in other sections of this text. The following discussion is limited to the diagnoses unique to the postpartum patient: mastitis, endometritis, septic pelvic thrombosis, cellulitis of the perineal and pelvic floor, and parametritis. Other causes of fever are dealt with in the appropriate chapters.

Table 56–7.1. Differential Diagnosis of Acute Postpartum Fever or Other Evidence of Infection

MASTITIS Mastitis is found in 1 to 2% of postpartum women (1), and it occurs in two forms. The first is the epidemic or nosocomial form acquired from an infant whose nasopharynx has become colonized with Staphylococcus aureus. It usually occurs within days of delivery and requires the isolation of mother and infant ( 4). Infection of the deep glandular tissues and abscess formation occur in 5 to 11% of women and have been associated with milk stasis and delay in the initiation of antibiotic treatment (5). The nonepidemic or endemic form of the disease, unusual today, develops after sporadic nursing or when the infant is being weaned. The bacteria responsible for the infection include a variety of aerobic and anaerobic organisms. S. aureus is found in 50% of the patients. Group A and group B streptococci and Haemophilus are other frequently identified organisms ( 1,4). In the nonepidemic form of mastitis, the periglandular tissues become inflamed and superficial cellulitis is often noted. It develops weeks to months after delivery. Abscesses of the breast are rare in this form of the disease. The diagnosis is usually clinical and is based on symptoms of pain, fever, edema, local erythema, and purulent discharge. Examination of the breast milk often shows numerous polymorphic nucleocytes and Gram-positive cocci. Breast milk may be cultured to help identify the offending organism. The emergency physician's responsibility lies in making the diagnosis, sending laboratory specimens for culture, and initiating appropriate antibiotics. The antibiotic coverage must reflect the fact that S. aureus is a common and virulent etiologic organism for this infection. Outpatient therapy should include a b-lactamase-resistant penicillin such as dicloxacillin or a first-generation cephalosporin such as cephalexin. Parenteral therapy, such as nafcillin, may be necessary if the patient is unable to tolerate oral medication or requires hospitalization ( 1,4,5 and 6). Other common therapies include warm moist packs to the breast and breast pumping or feeding. Mothers who breast-feed should be reassured that it is safe to continue during treatment ( 5). The treatment of a breast abscess is incision and drainage and usually includes the cessation of breast-feeding. Ultrasound-guided percutaneous drainage has been shown to be effective and may reduce the disfigurement of an open procedure ( 7).

ENDOMETRITIS Endometritis is well known as the most identifiable cause of infectious morbidity in the postpartum patient. Patients who undergo cesarean section have a 20- to 30-fold greater risk of endometritis than those who have vaginal delivery ( 1,4). Studies show that 20 to 25% of patients undergoing abdominal delivery may develop endometritis (2,8,9). Risk factors are listed in Table 56–7.2 (8,9,10,11 and 12).

Table 56–7.2. Factors Related to the Development of Endometritis

Pathophysiology The pathophysiology of endometritis is thought to involve ascending cervicovaginal flora as a cause of infection. The difficult aspect of this disease is identification of the bacteriologic cause. The bacteria of the noninfected woman and the incidence of occurrence are noted in Table 56–7.3 (13). Because the common pathogens for endometritis are found within the vagina as normal flora, the prediction of a potential group of pathogens is not difficult ( 1,8,11,14,15) (Table 56–7.4). This finding also necessitates the use of a broader spectrum of antibiotics because specific bacterial identification requires culture results. Some of the more common anaerobic pathogens include peptococcus, peptostreptococcus, clostridium, and bacteroides species. Common aerobic pathogens include Neisseria gonorrhea, Escherichia coli, Klebsiella, and Gardnerella vaginalis (15,16,17,18,19 and 20).

Table 56–7.3. Microorganisms Found in the Genitourinary Tract

Table 56–7.4. Postpartum Infection Pathogens

Clinical Presentation The signs and symptoms of puerperal morbidity (endometritis), as outlined by the United States Joint Committee on Maternal Welfare, are abdominal pain, fever, and an odorous discharge. The temperature must be 100.4 F (38°C) or higher on two consecutive days within the first 10 days postpartum, exclusive of the first 24 hours. A temperature of 101.6F (38.7°C) or greater within the first 24 hours may signify a more serious and virulent infection, possibly streptococcus ( 15,16). On physical examination, uterine tenderness in association with a foul-smelling lochia and fever may be the only symptoms, and other symptoms that may be associated with endometritis include malaise, nausea, and vomiting. The laboratory evaluation of these patients must include cultures of blood, urine, and cervical secretions. The latter should include aerobic, anaerobic, gonococcal, and chlamydial studies. Treatment The current recommendations for treatment include intravenous fluids, antipyretics, and parenteral antibiotics. Clindamycin (900 mg every 8 hours) and gentamicin (1.0 to 1.5 mg/kg every 8 hours) have become the standard initial antibiotic regimen. Numerous alternative regimens have been evaluated, and they are listed in Table 56–7.5 (1,4,8,21). If no response to adequate antibiotic doses is noted in 48 to 72 hours, another source of illness should be considered, and a third antibiotic may be added to obtain additional coverage against resistant organisms such as Enterococcus (ampicillin, 2g every 4 to 6 hours or piperacillin, 3 g every 6 hours) (4,19,21,22,23 and 24). If the patient fails to improve after an additional 48 hours, strong consideration should be given to the presence of a pelvic mass or septic pelvic thrombosis, and a repeat examination and computed tomographic (CT) imaging are in order ( 1,9). One study revealed the daily cost of ampicillin–sulbactam as $47.27 compared to $98.70 for the standard triple antibiotic regimen of ampicillin, gentamicin, and clindamycin. The treatment failure rate was 17.6% and 9.5%, respectively (24).

Table 56–7.5. Antibiotic Regimens for the Treatment of Endometritis

PROPHYLAXIS Antibiotic therapy is prudent in all patients in labor who have a fever, particularly those in the high-risk categories for endometritis (premature labor, abdominal surgery during labor, premature rupture of membranes, and cesarean section). These patients should receive prophylactic parenteral antibiotics before or up to 1 hour after delivery (1,4). In addition to reducing the risk for postpartum endometritis by 50%, the use of antibiotics may allow for the selection of resistant bacteria such as Streptococcus faecalis and Enterobacter cloacae (8).

SEPTIC PELVIC THROMBOSIS Another clinical syndrome that occurs in the febrile postpartum patient is septic pelvic thrombosis. This disease may be seen during the immediate postpartum period. It is an uncommon complication of pregnancy that affects 1 of 2000 postpartum women and 1 to 2% of patients with postpartum endometritis. Although it is rare, septic pelvic thrombosis is increasing in incidence as the cesarean section rate rises ( 1,3). Mortality ranges from 4 to 10% (26). This syndrome may be difficult to diagnose and can mimick an acute abdomen. The intraoperative danger of septic pulmonary emboli is heightened by manipulation. Hence, preoperative diagnosis is most important. Computed tomography is useful (26), but ultrasonography may be diagnostic. Pathophysiology Numerous factors put pregnant and postpartum women at a greater risk for septic pelvic thrombosis. First, the pregnant woman is known to have increased hypercoagulability because of an increased level of clotting factors. Second, the pelvic veins are sensitive to estrogen and demonstrate changes that increase the chance for injury. Third, the pelvic veins in the pregnant or postpartum woman are known to have relative venous stasis that causes increased venous capacity and decreased blood flow ( 1). Once septic pelvic thrombophlebitis occurs, there can be extension into any of the local vessels, including the inferior vena cava; the right ovarian vein; clot in left ovarian vein, which extends from the uterine and internal iliac veins to the inferior vena cava; left uterine vein; and right ureter. Clinical Presentation The symptoms are fever, tachycardia out of proportion to the fever, and possibly a palpable pelvic vein on pelvic examination. The fever is often high and spiking. The patient usually does not appear ill and actually feels well between fever spikes ( 15,26). Occasionally, the patient with septic pelvic thrombosis has dyspnea, tachypnea, and pleuritic chest discomfort related to the occurrence of pulmonary embolus. In the patient with suspected postpartum endometritis, persistent fever after treatment with the appropriate antibiotics suggests the presence of a septic pelvic thrombosis. The diagnosis is made by pelvic venography and abdominal–pelvic CT scan (25). If pulmonary involvement is a consideration, blood gas analysis, chest radiography, electrocardiography, and ventilation perfusion lung imaging are in order (1). Treatment The therapy for septic pelvic thrombosis is heparin. In this disease, heparin is both diagnostic and therapeutic. The patient is given an 80 U/kg bolus and then placed on an 18 U/hour drip. The drip subsequently is adjusted by monitoring the partial thromboplastin time. The fever should decrease in 24 to 48 hours. Heparin most often is given concomitantly with antibiotics for a 7- to 10-day period. If the fever and abdominal symptoms do not improve after a 36- to 48-hour trial of heparin and antibiotic therapy, pelvic and abdominal CT imaging should be performed to look for surgical conditions such as pelvic abscess ( 22).

CELLULITIS OF THE PERINEUM AND PELVIC FLOOR Postpartum vaginal secretions can contain between 108 and 109 organisms per gram of fluid ( 1). It is remarkable that only 1% of patients who have episiotomies, vaginal lacerations, and paracervical or pudendal blocks acquire infections related to these procedures. In general, the etiologic organisms are Staphylococcus, Streptococcus, and Gram-negative organisms such as Bacteroides ( 1). The diagnosis is made if the patient complains of persistent perineal discomfort, occasional worsening of vaginal discharge, and fever. The patient is found to have erythema, edema, and occasionally a tender mass on physical examination. The treatment for local cellulitis wound consists of a penicillinase-resistant penicillin, or a first- or second-generation cephalosporin. If an abscess is identified by ultrasonography or CT, surgical drainage is the definitive treatment.

PARAMETRITIS Parametritis, also termed pelvic cellulitis, commonly is suspected if the patient does not respond to adequate antibiotic therapy in 48 to 72 hours. This diagnosis is rarely made in the ED. Repeat examination may reveal continued tenderness in the lower abdominal and pelvic regions. The patient has a persistent fever of 100°F or higher in the absence of another source of infection ( 15). Ultrasonography and CT are rarely useful, but occasionally they identify a localization of fluid that would require surgical drainage. The pathophysiology is an extension of a puerperal infection in which the bacteria enter the parametrial tissue by direct extension, by means of lymphatic spread, or across the wall of an infected vein of thrombophlebitis. The common pathogens are similar to those found in endometritis. The therapy for pelvic cellulitis includes prolonged intravenous antibiotics, repeated examinations to rule out surgical disease, and repeated cultures to look for resistant organisms. Heparin therapy may be indicated if septic pelvic thrombosis cannot be ruled out ( 22). Long-term complications of this disorder include extensive scarring throughout the affected tissue.

CONCLUSIONS All sources of infection must be considered: water, wind, wounds, and walking. Often the source may be a superficial cellulitis, such as endemic mastitis or cellulitis of the episiotomy or even Candida. The emergency physician must realize that he or she may see deep tissue and more complex infections such as epidemic mastitis, and cellulitis. Patients with these infections often require hospitalization, intravenous antibiotics, and occasionally surgical exploration or drainage. Ultrasonography is useful in the identification of retained products of conception and some pelvic abscesses. It helps in locating a breast abscess and in the placement of therapeutic percutaneous drains. Should the ultrasound evaluation be indeterminate or the patient's condition not improve after adequate antibiotics treatment, CT imaging may be helpful in evaluating a pelvic abscess or septic thrombosis. The treatment regimen reflects the severity of an infection. If the patient does not respond to appropriate antibiotic therapy or has pulmonary symptoms in the absence of pneumonia, the diagnosis of septic thrombosis should be considered. Heparin in this case is both diagnostic and therapeutic. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

Isada NB, Grossman JH: Perinatal infections. In: Obstetrics: normal and problem pregnancies. New York: Churchill Livingstone, 1986:979–1047. Sweet RL, et al: Appropriate use of antibiotics in serious obstetric and gynecologic infections. Am J Obstet Gynecol 1983;146:719. Lee CY, Madrazo BL, Parks S, Sandler M: Ultrasonic evaluation in the management of postpartum infection. Henry Ford Hosp Med J 1987;35:58. Monga M, Oshiro BT: Puerperal infections. Semin Perinatol 1993;17:426–431. Olsen CG, Gordon RE Jr: Breast disorders in nursing mothers. Am Fam Physician 1990;41:1509–1516. Hamadeh G, Dedmon C, Mozley PD: Postpartum fever. Am Fam Physician 1995;52:531–538. Karstrup S, et al: Acute puerperal breast abscess: ultrasound guided drainage. Radiology 1993;188:807–809. Faro S: Postpartum endometritis in infections in pregnancy. In: Gilstrap LC, Faro S, eds. New York: Wiley–Liss, 1990:45–54. Druelinger L: Postpartum emergencies. Emerg Med Clin North Am 1994;12:219–237. Bergstrom S, Libombo A: Low birth weight and post-partum endometritis–myometritis. Acta Obstet Gynecol Scand 1995;74:611–613. Seo K, McGregor IA, French JI: Preterm birth is associated with increased risk of maternal and neonatal infection. Obstet Gynecol 1992;79:75–80. Newton ER, Prinoda TJ, Gibbs RS: A clinical and microbiologic analysis of risk factors for puerperal endometritis. Obstet Gynecol 1990;75:402–406. Sommers HM: The indigenous microbiota of the human host. In: Youmans GP, ed. The biologic and clinical basis of infectious diseases. 3rd ed. Philadelphia: WB Saunders, 1985:76–78. Faro S: Postpartum endometritis. In: Gilstrap LC, Faro S, eds. Infections in pregnancy. New York: Wiley–Liss, 1990:1–5.

15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26.

Pritchard JA, MacDonald PC, Gant NF: Williams obstetrics. 17th ed. Norwalk: Appleton–Century–Crofts, 1985:719–726. Calhoun BC, Brost B: Emergency management of sudden puerperal fever. Obstet Gynecol Clin North Am 1995;22:357–367. Watts DH, Krohn MA, Hillier SL, Eschenbach DA: Bacterial vaginosis as a risk factor for post-cesarean endometritis. Obstet Gynecol 1990;75:52–58. Berenson AB, Hammill HA, Martens MG, Faro S: Bacteriologic findings of post-cesarean endometritis in adolescents. Obstet Gynecol 1990;75:627–629. Gunning JE: A comparison of piperacillin and clindamycin plus gentamycin in women with pelvic infections. Surg Gynecol Obstet 1986;163:1. Gibbs RS: Postpartum infection. In: Charles D, ed. Current therapy in obstetrics. Philadelphia: BC Decker, 1988:184–189. Landers DV, Green JR, Sweet RL: Antibiotic use during pregnancy and the postpartum period. Clin Obstet Gynecol 1983;26:391. Yonekura ML: The treatment of endomyometritis. J Reprod Med 1988;33:579. Sanford JP, Gilbert DN, Sande MA: The Sanford guide to antimicrobial therapy: 1996. Vienna, VA: Antimicrobial Therapy, 1996:59–61. Resnik E, Harger JH, Kuller JA: Early postpartum endometritis: randomized comparison of ampicillin/sulbactam vs. ampicillin, gentamicin and clindamycin. J Reprod Med 1994;39:467–472. Keogh J, MacDonald D, Kelehan P: Septic pelvic thrombophlebitis: an unusual treatable postpartum complication. Aust N Z J Obstet Gynecol 1993;33:204–207. Brown CE, Dunn DH, Harrell R, et al: Computed tomography for evaluation of puerperal infections. Surg Gynecol Obstet 1991;172:285–289.

Chapter 57.1 Pelvic Pain in Women:Evaluation Principles and Practice of Emergency Medicine

CHAPTER 57 GYNECOLOGIC EMERGENCIES

1 Pelvic Pain in Women:Evaluation Stephen J. Wheeler Capsule Introduction Anatomy and Pathophysiology Etiology of Pain and Referred Pain Prehospital Management Causes of Pelvic Pain in Pregnancy Endometriosis Laboratory and Other Procedures Pregnancy Testing Ultrasonography Culdocentesis

CAPSULE Pelvic pain has multiple causes and a complex pathophysiology. The cause of amenorrhea is assumed to be pregnancy until proven otherwise, and ectopic pregnancy must be ruled out in all pregnant patients. Ruptured hemorrhagic ovarian cysts and tuboovarian abcesses are other life-threatening conditions. Current pregnancy tests are sensitive, reliable, and extremely useful in the emergency department (ED). The most serious diagnosis must be assumed to be the cause of the pain until it is ruled out. If the patient is unstable, she should be stabilized and transported to the operating room as soon as possible. Certain stable patients may be discharged with adequate follow-up.

INTRODUCTION The woman who seeks treatment in the ED for pelvic pain can present the emergency physician with a diagnostic dilemma. A diagnosis often can be made in the ED, but occasionally additional investigations, such as laparoscopy, are required. The cause of the pain may be benign or potentially lethal (e.g., ectopic pregnancy). A detailed gynecologic history helps to elucidate the exact cause. This needs to be supplemented with laboratory testing as a sexual history and the possibility of pregnancy are unreliable. In an analysis of more than 2000 patients who underwent laparoscopy for pelvic pain (after gastrointestinal and urinary causes were eliminated), the most frequent causes were salpingitis, infection, and adhesions (23%), ectopic pregnancy (19%), and endometriosis (25%). In almost 20%, no diagnostic findings were discovered with laparoscopy (1).

ANATOMY AND PATHOPHYSIOLOGY The female pelvis contains several organ systems. In the nongravid patient, the entire reproductive system is housed within the pelvis, and any part of it may be the source of pelvic pain. It contains parts of the gastrointestinal and urinary systems, which also may be a source of pelvic pain. Finally, the organs in the pelvis may not be the cause of the pain, but the pelvis may be the site of referred pain. The vagina lies inferoposterior to the pubic ramus. It is lined with a stratified squamous epithelium, which renders it relatively resistant to infection. The inferior vagina and perineal region are innervated by the somatic nervous system by way of the pudendal nerves (roots S2, S3, and S4), which provide well-localized sensation. The superior vagina is innervated by the autonomic nervous system and is less sensitive to pain than the inferior vagina. Pain from the inferior vagina is specific, whereas pain from the superior vagina is poorly localized and may be referred. The uterus is described as a pear-shaped hollow organ composed of the cervix and the body. Its vaginal surface is lined with a stratified squamous epithelium, which changes to a simple columnar epithelium in the endocervical canal (squamocolumnar junction). The columnar epithelium is susceptible to irritation and more vulnerable to infection. The body of the nongravid uterus overlies the bladder in most women and is palpable on bimanual examination, however, in some women it lies posteriorly (retroverted uterus) and cannot be palpated. A retroverted uterus has the rare potential to become problematic in a pregnant woman because it can become trapped in the pelvis as it enlarges, resulting in infarction and subsequent pain. The innervation of the uterus is limited chiefly to the endocervical canal. The nerves derive from the pelvic autonomic system by way of the superior, middle, and inferior hypogastric plexuses. The nerve fibers are mainly sympathetic from the T10 to L2 nerve roots. Pain, therefore, is registered as diffuse lower abdominal pain. The uterus is suspended and held by five pairs of ligaments. The major ligaments are the broad ligaments that support the uterus and are covered by a fold of peritoneum. Within the broad ligaments travel blood vessels, nerves, and the round ligament. Stretching of these ligaments can occur during pregnancy and may cause pain. On each side of the fundus are the fallopian tubes. They are 9 to 11 cm long and open into the peritoneal cavity. The tubes consist of three parts: the infundibulum, the isthmus, and the ampulla. The ampulla is the most common site for ectopic pregnancies in the fallopian tube. Its nerve supply is parasympathetic, mainly vagal, and sympathetic nerve roots T10 to L2. There are a few fibers from the sensory somatic nerves, roots T10 to L2, that can provide specific point tenderness and are helpful in localizing pain. Figure 57–1.1 depicts the anatomy of the pelvis.

Figure 57–1.1. Female pelvis, in median section. (Reprinted with permission from Clemente CD. Gray's Anatomy of the Human Body. 30th ed. Philadelphia: Lea & Febiger, 1985.)

ETIOLOGY OF PAIN AND REFERRED PAIN In women of reproductive age, pelvic pain usually originates in the reproductive system but may originate from the urinary or gastrointestinal system. A complete history, thorough physical examination, and routine laboratory tests help to differentiate these diagnoses. In some patients, an inflamed appendix can hang down into the pelvis and lie alongside an ovary or a fallopian tube. In such cases, it can be mistaken for pelvic inflammatory disease, a tuboovarian abscess, or even an ectopic

pregnancy in patients with a positive pregnancy test. Whether the pain is thought to originate from the reproductive system or from another source, it must be thoroughly characterized. Where is the pain located? Pain originating from an organ often is localized not to that organ but to the skin area supplied by the spinal nerve at the spinal level of the autonomic nerve ( 2). The pain may be diffuse because of the innervation of the visceral peritoneum. Frequently, the pain is not only felt in the pelvis but referred to the perineum, lower abdomen, back, or thighs (3). Table 57–1.1 lists the usual sites of referred pain and the organs most likely to be the causes of the pain.

Table 57–1.1. Localization of Referred Pain

If the pain originates from an area or an organ that has autonomic innervation, the pain is poorly localized and diffuse ( 2). The stretching of the capsule of an organ, the distension of a hollow viscus, and the stretching of a ligament are all transmitted by way of the autonomic system and, hence, register as diffuse pain. Various processes result in this type of stress; a hemorrhagic cyst, tuboovarian abscesses, and round ligament stretching in pregnancy are some examples. Adhesions from pelvic inflammatory disease or other processes also result in a diffuse pelvic pain. Localized pain often is caused by parietal peritoneal irritation, either an infectious (pus) or irritative (blood) process; however, a large amount of pus or blood in the peritoneal cavity causes more generalized pain. Table 57–1.2 lists the diffuse and localized causes of acute pelvic pain. Nervous pain can originate in the genitofemoral nerve and manifest as pelvic pain with pain in the labia majora and thigh ( 4).

Table 57–1.2. Causes of Acute Pelvic Pain

Just as important as the location of the pain is the temporal relationship of the pain. A monthly cyclic pain suggests several diagnoses, but the timing of the pain can help differentiate them. A midcycle pain may indicate mittelschmerz, pain with menses may be primary or secondary dysmenorrhea, and pain before menses may be premenstrual tension syndrome. Table 57–1.3 lists all the causes of cyclic pelvic pain. Sudden onset of pelvic pain may be an ominous sign because it may suggest sudden vascular insufficiency or an acute hemorrhage into a capsule. A slow, gradual onset of pain may suggest an infectious or irritative process, but it may progress rapidly. Visceral distension is usually a slow process, but again, the rate of distension may vary widely and could occur rapidly in a hemorrhagic event. Patients with bilateral tubal ligation may also present with acute pain. Pregnancy must be ruled out, and although less likely, pelvic inflammatory disease is surprisingly common (12%) (5).

Table 57–1.3. Causes of Cyclic Pelvic Pain

Occasionally, patients appear in the ED with exacerbation of chronic pelvic pain. Often an extensive work-up has already been done ( 6). An acute process may overlie a chronic problem ( 6,7 and 8). Table 57–1.4 and Table 57–1.5 show the clinical conditions that cause chronic pelvic pain.

Table 57–1.4. Clinical Classification of Chronic Pelvic Pain

Table 57–1.5. Differential Diagnosis of Pelvic Pain

PREHOSPITAL MANAGEMENT All prehospital personnel should consider the patient as a whole and should consider the circumstances in which she is found. If there are other injuries, e.g., from trauma, the management will be different than that for isolated pelvic pain. The basic procedures should be performed in all patients, and an evaluation should be made of vital signs and mental status. The possibility of an ectopic pregnancy must be considered in all patients of childbearing age because rupture, hemorrhage, and shock can occur, usually between 4 to 8 weeks (9,10 and 11). If the patient appears unstable, intravenous lines should be started and fluid given for cardiovascular support. She should be monitored. In the apparently stable patient, monitoring is still required, but she may be brought to the ED for evaluation less urgently.

CAUSES OF PELVIC PAIN IN PREGNANCY Ectopic Pregnancy A full discussion of ectopic pregnancy is presented in Chapter 56–2 but because of its importance, a few words are indicated here. Intrauterine Pregnancy Any irregular vaginal bleeding should be considered a complication of pregnancy until proven otherwise. Vaginal bleeding in the first half of pregnancy is often a sign of a threatened abortion. In intrauterine pregnancy, unlike ectopic pregnancy, bleeding usually precedes the pain, and the pain is often crampy and refers to the back. Pelvic examination reveals a closed cervix with no tissue loss, and the uterus may be enlarged and tender. Ectopic pregnancy must be ruled out through ultrasound. Treatment consists of bed rest, oral fluids, and observation, but 50% of these patients go on to abort. If they are not bleeding profusely and do not show signs of hypovolemia, with no indication of ectopic pregnancy and a normal ultrasound they may be discharged, with explicit instructions to return if any of the following occur: increased bleeding, passage of tissue, or the signs of hypovolemia. Close follow-up of these patients is essential. Inevitable abortion occurs when the bleeding is accompanied by the rupture of the membranes and the internal os begins to dilate. The pain is crampy and may be severe, with possible radiation into the back. Gynecologic consultation is required with possible dilation and curettage (D&C). An incomplete abortion occurs when the products of conception have passed partially from the uterine cavity. They may be protruding through the external os or found in the vagina. Bleeding and pain persist until the entire conceptus has passed and the abortion is complete. Gynecologic consultation is required to ensure the passage of all the products of conception. A D&C usually will be required to accomplish this and to halt bleeding. A patient with completed abortion may occasionally present in the ED. The patient usually has had pain and bleeding, which may have subsided by the time she is seen, accompanied by the passage of a large clot or tissue. Physical examination reveals a closed cervix and a uterus of normal size. These patients should have blood drawn for a quantitative bhCG and for type and screening to determine Rh status. If the patient knows that her Rh type is negative, Rhogan should be given. All these patients should be seen by a gynecologist in 48 hours for additional evaluation and repeat quantitative serum bhCG levels. Adenexal Torsion and Ovarian Cysts For adenexal torsion to occur, there must be an abnormality of the adenexa, usually a cystic enlargement of the ovary. Most of these are benign, but 5 to 15% are malignant. Paraovarian cysts are much less common than ovarian cysts but are also capable of torsion ( 12). Tubal enlargement secondary to a hydrosalpinx or pyosalpinx predisposes to torsion of the tubes. Previous gynecologic surgery, especially sterilization, also can predispose to tubal torsion. Functional and pathologic cysts may rupture, causing pain by sudden intracapsular distension or leaking onto the peritoneum, causing irritation. An acute rupture of a corpus luteal cyst usually is accompanied by the sudden onset of pain and may occur in pregnant and nonpregnant women. In the pregnant patient, it may be clinically indistinguishable from ectopic pregnancy. Ultrasonography may not even be able to sort them out because a cyst may measure 3 to 4 cm and lie alongside a fallopian tube. If a hemoperitonium is suspected, however, the treatment is the same (i.e., emergency laparotomy to control bleeding and shock). Rupture may occur in the persistent corpus luteal cyst in a nonpregnant patient. In such cases, the pregnancy test result is negative, and ultrasonography usually provides the diagnosis. If the diagnosis is clear and the patient is stable, the patient may be admitted for close observation on the gynecology ward. The consultant, however, must be fully aware of her condition and prepared for emergency intervention.

ENDOMETRIOSIS Endometriosis can be a source of acute or chronic pelvic pain. It is caused by the growth of endometrial tissue outside the uterus, and the pain is cyclic because of the changes in the menstrual cycle. The cause of this ectopic growth is not understood. It may be that endometrial embryonic tissue has developed outside the uterus, or that tissue may have arrived after development by hematogenous spread or retrograde flow from the fallopian tubes ( 13). The most common sites for extrauterine tissue are the ovaries, posterior cul-de-sac, and uterosacral ligaments. Advanced disease may involve the fallopian tubes, round ligaments, bladder, and intestines. When the patient menstruates, the ectopic endometrial tissue sloughs and bleeds, accounting for the cyclic nature of the symptoms. The pain is deep and constant, and it may be bilateral. Depending on the extent of the disease, the patient may have dyspareunia, rectal tenesmus, dysuria, and hematuria. Infertility is common in patients with endometriosis (14). Physical examination findings vary according to the extent and location of the disease. The pelvic area is usually tender on bimanual exam, but masses are usually not palpated except in advanced disease. Laparoscopy is the diagnostic procedure used to make the definitive diagnosis. Fibroids A fibroid is a uterine leiomyoma, a benign tumor of the uterine myometrium. Its growth is stimulated by elevated estrogen levels. The usual symptoms of a fibroid tumor are dysmenorrhea, altered menstrual bleeding, and pain. Such tumors cause menorrhagia but usually do not alter the menstrual cycle. A fibroid may be asymptomatic but becomes symptomatic as it enlarges, stretching and compressing the surrounding tissues and causing a constant, dull pain. If it becomes large enough, it can compress structures such as nerve roots, ureters, and other organs. The symptoms vary according to the structure affected, i.e., neuropathies, urinary frequency, or constipation. Occasionally a fibroid becomes pedunculated, which allows it to rotate on its stalk and compromise its vascular supply, causing a sudden

onset of ischemic pain. Pelvic Inflammatory Disease Pelvic inflammatory disease (PID) is a term used to cover multiple pathologic processes. Generally, it indicates an acute salpingitis, but infections of the endometrium, parametrium, fallopian tubes, ovaries, or pelvic peritoneum also are labeled PID. Chronic pelvic pain from an infectious process is called chronic PID. It is now thought that PID is a polymicrobial process, with lower genital tract infections a prerequisite that predisposes the upper tract to infection. Chlamydia have been seen increasingly as a major cause of PID ( 15). A break in the normal cervical barrier leads to the spread of exogenous pathogenic microbes and endogenous flora into the upper reproductive tract ( 16). There is no typical patient with PID, although some patients may be mislabeled as having PID the moment they enter the ED. Only 16% of patients with a laparoscopy-confirmed PID diagnosis had classical symptoms of abdominal pain and tenderness, cervical motion tenderness, adenexal tenderness, and purulent vaginal discharge ( 17). Table 57–1.6 lists the criteria for making the clinical diagnosis of PID. These criteria are based on a review of presenting signs and symptoms in patients who had laparoscopy-diagnosed PID. A pregnancy test must be performed and ectopic pregnancy ruled out in all patients. (See also Chapter 63–1.)

Table 57–1.6. Criteria for Making Diagnosis of Pelvic Inflammatory Disease

Tuboovarian Abscesses A tuboovarian abscess is a complication of salpingitis caused by the trapping of purulent material in an occluded fallopian tube. It may occur when pus drains from the distal end of the tube into the peritoneum and is walled off, causing secondary abscess formation. Rupture is an acute surgical emergency, and the mortality rate is greater than 50% if there is no surgical treatment. Complete abdominal hysterectomy and bilateral salpingoopherectomy may be necessary to prevent death. Pelvic pain may be a symptom of an unruptured abscess. On examination, adenexal masses may be palpable and tender. ( Table 57–1.7 lists the clinical signs and symptoms of tuboovarian abscesses.) An abscess may extend itself to involve the ovary and may be difficult to differentiate from a cyst on ultrasonography. Rarely, an appendiceal abscess that has formed in the pelvis may be mistaken for a tubal abscess, and septic venous thrombosis may manifest itself similarly.

Table 57–1.7. Characteristics of Tuboovarian Abscesses

Patients with possible unruptured tuboovarian abscesses should be admitted ( Table 57–1.8), started on broad-spectrum intravenous antibiotics, and observed carefully. If there is no response within 72 hours, they will require surgical drainage. Patients with abscesses larger than 8 cm may require surgery sooner because antibiotics are ineffectual and these abscesses have a high risk of rupturing. Bilateral unruptured abscesses require surgical drainage more often because they are more resistant to antibiotic therapy and, hence, they rupture more frequently. Complications of tuboovarian abscesses are infertility (even if only one tube is involved) and chronic pelvic pain.

Table 57–1.8. Indications for Hospitalization in PID

Mittelschmerz Pain from an ovulating graafian follicle is called mittelschmerz pain. It occurs in the middle of the menstrual cycle and appears as localized unilateral peritoneal irritation without systemic signs. The symptoms usually last a few hours and may last up to 2 days, but they do not progress. Pregnancy test results are always negative. Primary Dysmenorrhea

Primary dysmenorrhea is a clinical condition involving regular pain with menstruation, but it has no physiologic basis. Its onset is soon after menarche with the beginning of regular ovulatory cycles. The pain is usually progressive in intensity and diminishes only after the first pregnancy. There is often a family history of this condition. Secondary dysmenorrhea has an identifiable cause and may occur at any time in the reproductive years. Often it is accompanied by infertility, and the symptoms are related to the underlying cause—which could be any of the conditions previously discussed, as well as endometriosis, adenomyosis, fibroids, polyps, intrauterine devices, infection or inflammation, adhesions, and ovarian cysts. Primary dysmenorrhea is usually a menstrual cramp or an ache that may radiate to the back or thighs. Associated symptoms are headache, fatigue, nausea, vomiting, diarrhea, dizziness, and sometimes fainting. The pathophysiology is thought to be prostaglandin mediated and is enhanced by progesterone in the luteal phase of the menstrual cycle. The treatment for moderate to severe dysmenorrhea is nonsteroidal anti-inflammatory medications and may include birth control pills. Supportive therapy is useful and includes bed rest, moist heat to the lower abdomen, and psychologic support. The treatment for secondary dysmenorrhea is based on correction of the underlying cause and symptomatic treatment of the pain. Prepubertal Pelvic Pain Pelvic pain in the prepubertal patient is rarely caused by a disease in the reproductive tract. Other causes must be considered. Chief among these should be the possibility of child abuse (Chapter 129–4). Often a nonspecific complaint such as lower abdominal or pelvic pain is the sign of an abused child. Look for inconsistencies in the history and physical examination. The genitals and perineum should be examined directly and careful notes taken. Ask the child if anyone has been touching, fondling, or kissing her genitals. Remember that the person who is abusing the child is usually well known to the child and may be a family member. If any suspicion of child abuse is present, the child should be taken into protective custody. Always consider other possibilities for pelvic pain, including nonreproductive tract factors, especially urinary tract infections. Table 57–1.9 lists the causes of prepubertal pelvic pain.

Table 57–1.9. Causes of Prepubertal Pelvic Pain

Postmenopausal Pelvic Pain The causes of postmenopausal pelvic pain are similar to the causes of pelvic pain during reproductive life, with some exceptions. Complications of pregnancy are not included in the differential diagnosis, but if you have any concerns regarding a possible pregnancy, a pregnancy test must be performed. Atrophic vaginitis secondary to estrogen deficiency is a common source of pelvic pain, but this should be a diagnosis of exclusion. A pelvic examination may reveal other potential causes, and, in the elderly, the possibility of a neoplastic process must be considered. If the results of the pelvic examination are abnormal, the patient should have urgent gynecologic follow up. Table 57–1.10 lists postmenopausal causes of pelvic pain and bleeding. The treatment of atrophic vaginitis consists of topical estrogen creams or suppositories and good hygiene. Vaginal infections should be ruled out and appropriate antibiotic treatment started if indicated.

Table 57–1.10. Causes of Postmenopausal Pelvic Pain and Bleeding

LABORATORY AND OTHER PROCEDURES All patients evaluated for pelvic pain require a full physical examination. Routine laboratory tests should include a complete blood count with a differential diagnosis to look for signs of infection or blood loss. A type and screen should be sent for Rh typing and blood should be drawn for pregnancy and quantitative testing if ectopic pregnancy is considered ( 14,15 and 16). Routine chemistry may be helpful in patients who are dehydrated, septic, or have an underlying medical disorder. Urine should be collected in all patients. If the patient is unable to urinate or is bleeding vaginally, she should be catheterized. The urine should be sent for routine and microscopic examination. Smears of the vaginal secretions are occasionally helpful. In Trichomonas infections, the motile trichomonads can be seen on normal saline slides in 50 to 63% of patients. On another slide, 10% potassium hydroxide should be added. In Gardnerella infections, a fishy odor is released; and in Candida infections, the hyphae and buds of the yeast are seen after the epithelial cells are dissolved. The saline slide should be examined for clue cells, which are vaginal epithelial cells coated with bacteria in Gardnerella infections.

PREGNANCY TESTING Pregnancy tests can be performed on either urine or serum. The urine qualitative tests are reliable and can detect HCG levels as low as 25 IU/I. This allows detection of pregnancy before the first period has been missed ( 18,19 and 20). This allows the ED to test all women of child-bearing age quickly, reliably, and cheaply. Remember that these tests do not differentiate between ectopic and intrauterine pregnancies.

ULTRASONOGRAPHY Pelvic ultrasonography is useful in the emergency setting in three major groups of patients with pelvic pain; the nongravid woman with severe pelvic pain; the first-trimester patient with pain, bleeding, or both; and the third-trimester patient with bleeding. The first two will be discussed here.

Ultrasonography is no longer needed to confirm pregnancy in a patient in the emergency setting, but is helpful in establishing the presence of a gestational sac and nongravid anatomic derangements. In the nongravid patient, there are several conditions in which it may be extremely helpful to use ultrasonography. Early manifestations of PID are usually normal sonographically, or patients may have nonspecific signs such as haziness that are extremely difficult to detect. The later complications of PID, tuboovarian abcesses, and hydrosalpinx or pyosalpinx are easier to detect by ultrasonography. Tuboovarian abcesses may be identified in various stages of organization. Their appearance is variable, but usually a cystic adenexal mass with thick walls, internal separations, and debris is seen. A hydrosalpinx or a pyosalpinx is specifically suspected when a beaded, tubular, fluid-filled adenexal structure is seen. Ultrasonography is highly sensitive for certain abnormalities of the female reproductive system, such as ovarian cysts, ovarian neoplasms, endometriosis, and uterine leiomyomas. The specificity of identification can vary among them and from patient to patient, but in the ED, a presumptive diagnosis can be made to rule out the possibility of a life-threatening disorder. Ultrasonography has its greatest use in the ED for the pregnant patient in her first trimester, but there are certain limitations to its use. It is a fast and fairly reliable method of determining the site of pregnancy. The classic ultrasonographic findings of an ectopic pregnancy are an ectopic gestational sac, an enlarged nongravid uterus, and free fluid in the cul-de-sac ( 21). An ectopic gestational sac is a rare finding, however, and the other findings are nonspecific. Therefore, the criteria for determining the presence of an ectopic pregnancy are based on the assumption that the coexistence of an intrauterine pregnancy and an ectopic pregnancy is extremely rare (1 in 10,000 to 30,000 pregnancies) ( 22). If an intrauterine pregnancy can be established, the risk of an ectopic pregnancy is greatly diminished. An intrauterine pregnancy is suggested by the presence of a double gestational ring within the uterus. This double ring is thought to represent the two layers of decidua (vera and capsularis) separated by the uterine cavity, and it can be observed as early as 4 weeks after fertilization. In as many as 20% of ectopic pregnancies, decidua casts may form within the uterus. These casts are usually homogeneous and can be distinguished from gestational sacs, but in certain instances their appearance can mimic that of an intrauterine pregnancy. Ultrasonography may be useful in patients with a possible blighted ovum. As mentioned previously, 50% of patients who have vaginal bleeding in the first trimester have spontaneous abortions. Ultrasonography helps to identify patients who are about to abort or who have retained gestational products. The appearance of a fetal demise may vary but is usually distinctively different from that of a viable pregnancy. The retained tissue may undergo hydropic degeneration. Two essential characteristics are used to distinguish a nonviable from a viable pregnancy. A gestational sac of 3 cm should have an identifiable fetal pole. If none is present, the pregnancy is nonviable. If a fetal pole is identified, with a crown-rump length of 25 mm, there will be signs of fetal movement and cardiac motion representing a viable pregnancy. If there is no motion, it is a nonviable pregnancy. Occasionally, a gestational sac has a crown-rump length of less than 25 mm. In such cases, fetal motion may not be present and fetal viability may not be ascertainable. If one suspects fetal nonviability, the patient should have a follow-up study in 7 to 10 days. If there has been no change in the size of the fetus during this period, or if the gestational sac has shrunk, the fetus is nonviable. If these criteria are followed, no false diagnosis of a nonviable pregnancy will be made. Other nonviable pregnancies can be diagnosed by ultrasonography. A blighted ovum has the typical appearance of an intrauterine gestation sac greater than 3 cm in diameter but does not have an identifiable fetal pole. Trophoblastic disease may simulate a blighted ovum, but it usually appears as an echogenic mass within the uterine cavity. In a missed or incomplete abortion, the retained tissue may undergo hydropic degeneration and simulate trophoblastic disease. Ultrasonography can be a useful tool in the ED. It can provide much useful information quickly; however, the information it provides is nonspecific, and the conclusions made from it must be considered as part of the patient's overall condition. It is not to be used as an ultimate decision maker but as a tool to help in diagnosis and disposition. The increased use of probes with sensitive ultrasound allow better resolution and earlier diagnosis ( 23,24) (e.g., ectopic at 3 to 4 weeks), which can make possible the use of nonsurgical therapies (e.g., methotrexate).

CULDOCENTESIS Culdocentesis can be performed quickly and safely in the ED ( Fig. 57–1.2). It involves the introduction of a needle through the vaginal wall into the pouch of Douglas, the most dependent portion of the peritoneal space. Fluid can then be aspirated and analyzed. The technique has been used primarily to detect ruptured ectopic pregnancies in stable patients, but it is indicated whenever peritoneal fluid is needed to help in making the diagnosis. Conditions in which culdocentesis may be of value are ruptured or leaking ectopic pregnancies, ruptured or leaking corpus luteal cysts, PID, other intra-abdominal infections, and blunt abdominal or pelvic trauma in patients in whom diagnostic peritoneal lavage is contraindicated because of previous abdominal surgery. The complications of this procedure are few, and it is reportedly as safe as peripheral intravenous cannulation. The most common complication is the rupture of an unsuspected tuboovarian abscess. Others include perforations of a pelvic kidney, the bowel, or the uterine wall. Most complications can be prevented by careful bimanual examination before the procedure. Perforation of the bowel and uterine walls seldom results in problems. Contraindications to culdocentesis are pelvic masses detected on bimanual examinations, a nonmobile retroverted uterus, coagulopathies, and prepubertal patients. Usually ultrasonography precedes culdocentesis and can reduce the need for this procedure. Interpretation of aspirated fluid is shown in Table 57–1.11.

Figure 57–1.2. Culdocentesis. (Reprinted with permission from Wilson JR, Beecham CT, Carrington ER. Obstetrics and gynecology. 9th ed. St. Louis: CV Mosby, 1991.)

Table 57–1.11. Interpretation of Culdocentesis Fluid

References 1. Kontoravdis A, Chryssikopoulos A, Hassiakos D, et al: The diagnostic value of laparoscopy in 2365 patients with acute and chronic pelvic pain. Int J Gynaecol Obstet 1996;52:243–248.

2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

Basu HK: Major common problems: pelvic pain. Br J Hosp Med 1981;26:150. Kamm MA: Chronic pelvic pain in women—gastroenterologic, gynecologic or psychological. Int J Colorectal Dis 1997;12:57–62. Perry CP: Laparoscopic treatment of genitofemoral neuralgia. J Am Assoc Gynecol Laparosc 1997;4:231–234. Abbuhl SB, Muskin EB, Shofer RS: Pelvic inflammatory disease in patients with bilateral tubal ligation. Am J Emerg Med 1997;15:271–274. Eschenbach DA, Wolner-Hanssen P, Hawes SE, et al: Acute PID: associations of clinical and laboratory findings with laparoscopic findings. Obstet Gynecol 1997;89:184–192. Gaul JN: Evaluation of chronic pelvic pain. Minn Med 1988; 71. Beard RW, Reginald PW, Wadsworth J: Clinical features of women with chronic lower abdominal pain and pelvic congestion. Br J Obstet Gynaecol 1988;95:153. Brenner PF, Roy S, Mishell DR Jr: Ectopic pregnancy: a study of 300 consecutive cases. JAMA 1980;243:673. Pittaway DE: bhCG dynamics in ectopic pregnancy. Clin Obstet Gynecol 1987;30:129. Gretz EG, Quagliarello J: Declining serum concentrations of the b-subunit of human chorionic gonadotrophin and ruptured ectopic pregnancy. Am J Obstet Gynecol 1987;156:940. Alpern MB, Sandler MA, Madrazo BL: Sonographic features of paraovarian cysts and their complications. Am J Roentgenol 1984;143:157. Gerbie AB, Merill JA: Pathology of endometriosis. Clin Obstet Gynecol 1988; 31. Muse K: Clinical manifestations and classification of endometriosis. Clin Obstet Gynecol 1988; 31. Scholes D, Stergachis A, Heidrich FE, et al: Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med 1996;334:1362. Chapin DS: Pelvic inflammatory disease. Medical Times, August 1987. Cunanan RG Jr, Courey NG, Lippes J: Laparoscopic findings in patients with pelvic pain. Am J Obstet Gynecol 1983;146:589. Emancipator K, Cadoff EM, Burke MD: Analytical versus clinical sensitivity and specificity in pregnancy testing. Am J Obstet Gynecol 1988; 158:613. Norman RJ, Buck RH, Rom L, Joubert SM: Blood or urine measurement of human chorionic gonadotropin for detection of ectopic pregnancy? a comparative study of quantitative and qualitative methods in both fluids. Obstet Gynecol 1988;71:315. Bandi ZL, Schoen I, DeLara M: Enzyme linked immunosorbent urine pregnancy tests. Am J Clin Pathol 1987;87:236. Nyberg DA, Laing FC, Jeffery RB: Sonographic detection of subtle pelvic fluid collections. Am J Roentgenol 1984;143:261. Chinn DH, Callen PW: Ultrasound of the acutely ill obstetrics and gynecology patient. Radiol Clin North Am 1983;21:585. Marn CS, Bree RL: Advances in pelvic ultrasound: endovaginal scanning for ectopic gestation and graded compression sonography for appendicitis. Ann Emerg Med 1989;18:1304. Arbel-De Rowe Y, Tepper R, Rosen DJ, et al: The contribution of pelvic ultrasonography to the diagnostic process in pediatric and adolescent gynecology. J Pediatr Adolesc Gynecol 1997;10:3–12.

chapter 57.2 Vaginal Infections Principles and Practice of Emergency Medicine

CHAPTER 57 GYNECOLOGIC EMERGENCIES

2 Vaginal Infections Christopher K. Wuerker and Joseph C. Howton Capsule Infectious Causes of Vaginitis Noninfectious Causes of Vaginitis Medicolegal Pearls

CAPSULE Vaginitis is a common emergency department (ED) complaint. In 90% of patients, it is caused by Candida albicans, Gardnerella vaginalis (bacterial vaginosis), or Trichomonas vaginalis. Vaginal discharges with pH >4.5 can be treated with metronidazole. The thick white discharge of candidiasis, along with any vulvocutaneous involvement, is treated with an imidazole cream. Recurrent infection usually is caused by reinfection by sexual partners or by an underlying disease. Wet preparation of vaginal secretions, revealing large amounts of white cells, requires investigation for cervicitis and pelvic inflammatory disease (PID). Vulvovaginal abscess usually is caused by a polymicrobial infection and the obstruction of Bartholin's gland. It is treated with incision and drainage and the placement of a drain. Table 57–2.1 describes the characteristics of common vaginitides.

Table 57–2.1. Characteristics of Common Vaginitides

INFECTIOUS CAUSES OF VAGINITIS Bacterial Bacterial vaginosis (also called G. vaginitis) is a shift in the normal vaginal flora from lactobacilli toward anaerobes, including Gardnerella, Bacteroides, and Mobiluncus. G. vaginalis is probably a normal occupant because it is found in as many as 70% of healthy, asymptomatic women ( 1). Although by definition Gardnerella is found in all cases of bacterial vaginosis, the clinical syndrome probably requires coinfection with other organisms, disrupting the normal vaginal flora (1). Among the signs of bacterial vaginosis is increased gray or yellow, foul or fishy-smelling vaginal discharge. Itch and vulvar irritation are minimal. The characteristic discharge and odor are noted on examination even though the cervix and vaginal mucosa appear normal. pH testing of the discharge reveals a relative alkaline environment caused by the lack of lactobacilli. To make a diagnosis using the method devised by Amsel et al requires three of these four criteria: characteristic discharge, positive sniff test, pH >4.5, and clue cells on wet mount (2). Clue cells are stippled epithelial cells seen on a wet-mount preparation of vaginal secretions. The stippling or granular bodies of clue cells are thought to be caused by adherent Gardnerella and other organisms attached to the external cell wall. Although they were once thought pathognomonic, clue cells may be seen in normal secretions. The sniff test (amine test) refers to the release of a fishy odor when 10% or 20% KOH is added to vaginal secretions; in most patients, however, the odor is detected during the pelvic examination. The treatment of choice is metronidazole either as a 2 g dose repeated once in 48 hours or as 500 mg twice daily for 7 days ( 3). Intravaginal metranidazole gel can be used as well. In pregnant or metronidazole-sensitive patients, 300 mg clindamycin three times a day or 500 mg ampicillin four times daily for 7 days is a less effective alternative. If there is a relapse, evaluate the patient for underlying disease, use of a broad-spectrum antibiotics, coinfection with C. albicans, and possible inoculation of Gardnerella by an asymptomatic male partner. Fungal Candida vulvovaginitis (monilia) is a fungal infection most commonly caused by Candida albicans. Candida is a ubiquitous organism; vaginitis is caused by an overgrowth of the yeast in an altered host environment from antibiotics, diabetes, or immunoincompetence (acquired immune deficiency syndrome, cancer, chemotherapy, corticosteroids, and pregnancy). The infection causes an itchy, thick, white vaginal discharge. Vulvar involvement results in burning irritation, external dysuria, and dyspareunia. On examination, the vaginal mucosa is erythematous, and adherent white fungal plaques and occasional fissures appear in addition to the characteristic discharge. Vulvar–cutaneous candidiasis appears as geographic erythema with satellite lesions. Although classically hyphae are seen on a KOH wet preparation of a vaginal secretion (one to two drops 10%–20% KOH), the diagnosis should be based on clinical findings because KOH preparations are falsely negative in up to 50% of patients ( 4,5). The treatment of choice is topical application of one of the imidazole creams (clotrimazole, miconazole, butoconazole, or terconazole). Current dosage options for clotrimazole are 100 mg vaginally for 7 days, 200 mg for 3 days, and 500 mg once. Creams can be applied externally to treat vulvar involvement. Less effective alternatives include nystatin or boric acid capsules. Recurrent infections are common and frustrating, especially in patients with diabetes or impaired cell-mediated immunity. Treatment strategies include prolonged treatment for two to three weeks, treatment of sex partners (check for balanitis), and chronic suppressive treatment using an imidazole daily or for the 5 days before menses. Oral ketoconazole has been effective for suppressive treatment ( 6). Using fluconazole in a single dose (150 mg), side effects tend to be mild and cure rates are high in uncomplicated disease ( 6A). Attempts at eradicating Candida from the gastrointestinal tract using oral nystatin have not proven effective. Protozoan TRICHOMONAS VAGINALIS Trichomonas vaginalis is a sexually transmitted protozoan that infects the vagina and lower urinary tract. There is a gray or yellow–green discharge (classically frothy but commonly not), and odor is minimal. Pruritus is usually severe and is associated with vulvar irritation and dysuria. Trichomonas, however, may be asymptomatic in

up to 50% of patients (7). On examination, the characteristic discharge is noted, along with mild vaginal erythema. A brightly erythematous “strawberry lesion” of the cervix is pathognomonic but rare. The pH of vaginal secretions may be normal (10 on arrival. After 4 hours of therapy, parameters are pH >7.35, H CO3 >20, normal physical findings, and the ability to consume fluids ( 16). Those who are moderately or severely ill require admission to an intermediate care or an intensive care unit. Most patients with DKA have a serious underlying illness that precipitated the ketoacidosis. If there is any suspicion of infection, the patient should receive broad-spectrum antibiotics for the most likely sources. Table 64–1.7 summarizes the treatment of DKA.

PITFALLS AND MEDICOLEGAL PEARLS Diabetic ketoacidosis is always an emergency. Failure to recognize the condition or its severity is the leading cause of death from it. Fluid deficits are large, and replacement must be vigorous. Electrolyte shifts are massive during illness and treatment. Failure to anticipate the drop in potassium can be deadly. Patients with DKA frequently have an underlying serious illness. Pregnant women with diabetes are especially prone to DKA even with minimal physiologic stress. Because DKA is particularly harmful to the fetus, it must be treated vigorously. Patients with severe DKA often have reached the limits of their respiratory compensation; anything that hinders ventilation can cause a fatal downward spiral. Always look out for infection and sepsis in patients with DKA. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

Katz MA: Hyperglycemia-induced hyponatremia calculation of expected serum sodium depression. N Engl J Med 1973;289:843. Fisher JN: Diabetic ketoacidosis: low dose insulin therapy by various routes. N Engl J Med 1977;297:238. Vinicor F, Lehrner LM, Karn RC, et al: Hyperamylasemia in diabetic ketoacidosis: sources and significance. Ann Intern Med 1979;91:200. Slovis CM, Mork VG, Slovis RJ, Bain RP: Diabetic ketoacidosis and infection: leukocyte count and differential as early predictors of serious infection. Am J Emerg Med 1987;5:1–5. Ouellet LM, Brook MP: Emphysematous pyelonephritis: an emergency indication for the plain abdominal radiograph. Ann Emerg Med 1988;17(7)722–724. Simon BL: Pseudomyocardial infarction and hyperkalemia: a case report and subject review. J Emerg Med 1988;6:511–515. Kitabchi AE, Wall BM: Diabetic ketoacidosis. Med Clin North Am 1995;79:9–37. Hillman K: Fluid resuscitation in diabetic emergencies—reappraisal. Intensive Care Med 1987;13:4. Adrogue HJ, Barrero J, Eknoyan G: Salutary effects of modest fluid replacement in the treatment of adults with diabetic ketoacidosis: use in patients without extreme volume deficit. JAMA 1989;262:2108–2113. Butkiewicz EK, Leibson CL, O'Brien PC, Palumbo PJ, Rizza RA: Insulin therapy for diabetic ketoacidosis: bolus insulin injection versus continuous insulin infusion. Diabetes Care 1995;18:1187–1190. Moller DE, Flier JS: Mechanisms of disease: insulin resistance—mechanisms, syndromes, and implications. N Engl J Med 1991;325:938. Morris LR, Murphy MB, Kitabchi AE: Bicarbonate therapy in severe diabetic ketoacidosis. Ann Intern Med 1986;105:836–840. Okuda Y, Adrogue HJ, Field JB, Nohara H, Yamashita K: Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endocrinol Metab 1996;81:314–320. Wilson HK: Phosphate therapy in diabetic ketoacidosis. Arch Intern Med 1982;142:517. Fisher JN, Kitabchi AE: A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. Baillieres Clin Endocrinol Metab 1983;57:177–180. Bonadio WA, Gutzeit MF, Losek JD, Smith DS: Outpatient management of diabetic ketoacidosis. Am J Dis Child 1988;142:448–450.

Suggested Readings Brouhard BH: Fluid and electrolyte therapy. Clin Pediatr (Phila) 1997;36(7):401–402. Genuth SM: Diabetic ketoacidosis and hyperglycemic hyperosmolar coma. Curr Ther Endocrinol Metab 1997;6:438–447. Rosenbloom AL, Hanas R: Diabetic ketoacidosis (DKA): treatment guidelines. Clin Pediatr 1996;35(5):261–266. Umpierrez GE, Khajavi M, Kitabchi AE: Review: diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic syndrome. Am J Med Sci 1996;311:225–233.

Chapter 64.2 Hypoglycemia Principles and Practice of Emergency Medicine

CHAPTER 64 DIABETES AND COMPLICATIONS

2 Hypoglycemia R. Carter Clements Capsule Introduction Pathophysiology and Anatomy Prehospital Assessment and Stabilization Clinical Presentation and Examination Differential Diagnosis Initial Stabilization Laboratory Findings Management and Indications for Admission Pitfalls Medicolegal Pearls

CAPSULE Hypoglycemia occurs when a mismatch of endogenous glucose need with exogenous and endogenous glucose availability derails the metabolic engine of normal glucose homeostasis. There are many causes, and it is the duty of the emergency physician both to establish the cause of the episode and to treat the resultant sympathetic and cerebral dysfunction. In practice, the sequence of these events may be reversed. The population with diabetes is at greatest risk for the development of hypoglycemia. The occurrence of this disorder without obvious cause should be of grave concern to the emergency physician. Several treatment modalities are available to prehospital and definitive care providers; intravenous D50W, 25 to 50 g, is the most commonly used in the acute setting.

INTRODUCTION As the care of patients with diabetes becomes more sophisticated, we should see a decrease in the incidence of hypoglycemia. The current emphasis on aggressive, tight control of diabetes, however, may result in an increase in the number of hypoglycemia-related visits in the short term ( 1). For the present, it is a common, severe, and potentially lethal abnormal state about which we must have intimate knowledge and understanding. In the regulation of serum glucose, insulin is the major endocrine agent in the induction of hypoglycemia. Glucagon and epinephrine are its major antagonists. Excess of insulin is the most common cause of hypoglycemia. Its most likely source is exogenous, and its most frequent causes are iatrogenic and therapeutic complications. Symptoms are classic or nonclassic. Classic hypoglycemia shows adrenergic symptoms and signs, which are followed by progressive neurologic dysfunction that ends in coma and death if untreated. Nonclassic symptoms, including focal neurologic lesions, are myriad. Diagnosis must be swift to minimize the occurence of complications, permanent neurologic damage, and death. Focus is placed on identifying the cause of the episode; it is mandatory to determine this before discharge. Therapy must be rapid. Immediate intravenous glucose and thereafter maintenance glucose infusion, if needed, must be administered. Difficult-to-control patients may require high-percentage dextrose solution infusion or adjunctive glucagon, cortisol, or diazoxide. If hypoglycemia cannot be controlled with therapy or if the cause cannot be stated with accuracy and assurance, hospital admission is necessary. Because of the complex nature of this diagnosis, the potential to err is high. It is incumbent on the emergency physician to take a measured, organized, conservative approach to diagnosis and management of hypoglycemia in all its manifestations if therapeutic and medicolegal misadventures are to be avoided. Hypoglycemia is a problem commonly seen in the emergency department (ED). Potter et al. (2) have reported their ED experience with adult patients with hypoglycemia in a large urban population. They found that excessive insulin administration was the most likely cause (98%) in their population. At least 9% of their patients with diabetes had hypoglycemic episodes requiring emergency treatment, and 64% of these required admission ( 2). Another study looked at the patients with severe hypoglycemia seeking care at an inner-city urban ED over a 1-year period and found that 73% of incidences were secondary to either a missed meal (52%) in patients with diabetes or to alcohol (21%) consumption ( 3). Fischer et al. ( 4) reported episodes of hypoglycemia among hospital patients and found that 45% had diabetes and that 90% of their episodes were secondary to excessive insulin. Renal disease alone was found to be the single predisposing factor in 28% of admitted patients. Hypoglycemia as a complication of the treatment of hyperkalemia was seen in 9% of these patients. The authors ( 4) reported an in-hospital mortality rate of 27%, although none of the patient deaths were directly the result of hypoglycemia. Malouf and Brust ( 5) reported a 1-year experience with symptomatic hypoglycemia in an inner city ED. Diabetes, sepsis, or alcoholism caused 90% of hypoglycemia in 125 patients. For all episodes, stupor or coma was seen in 52%, affective derangement or confusion in 30%, seizures in 7%, anxiety in 8%, and hemiparesis in 2%. Fourteen patients died, but only one died of hypoglycemia ( 5). A universal standard definition is elusive, but a serum glucose level less than or equal to 50 mg/dL (less than or equal to 2.75 mOsm/L) with appropriate symptoms that resolve when serum glucose levels return to normal is powerfully suggestive ( 6). It should be kept in mind that some patients may have normal serum glucose levels of less than 50 mg/dL, without symptoms of hypoglycemia. Such as finding is more common in the pediatric and female populations ( 7,8). Hypoglycemia's array of symptoms arises from excessive adrenergic activity and progressive central nervous system (CNS) dysfunction in the presence of depressed serum glucose levels. Depending on the rapidity of the onset of hypoglycemia, the expression of these symptoms may be variable ( 8A). Ultimately, however, if no treatment is forthcoming, the patient enters an altered state of consciousness ( 9). It is no surprise that the care of these patients frequently falls to the emergency practitioner. The symptoms of hypoglycemia frequently resolve before the patient is evaluated by a physician because of the characteristically rapid response to treatment with D 50W either in the field by prehospital care providers or in the ED by nursing staff. This may cause the physician to underestimate the severity of the event. This entity has a complex pathophysiology with numerous causes. The emergency physician must not only treat the metabolic derangement but must avidly seek and correct the underlying cause. The diagnosis should read “hypoglycemia secondary to .” If the “blank” is not known with certainty, the patient should be admitted to establish the definitive cause. The most frequent culprits are exogenous insulin, sufonylureas, and ethyl alcohol, with insulin by far the leader. Frequently, hypoglycemia is a complication of a previous treatment, but because the symptoms are acute and severe, the patient is most likely to be treated in the ED when it occurs. Many patients with hypoglycemia can be evaluated rapidly and released after counseling and education about changes in therapy or lifestyle. This assumes that they are at their baseline level of function and that the cause is clear. It is incumbent on the emergency physician to convey information about the hypoglycemic episode to the patient's primary care provider to prevent recurrence and to limit the potential for sickness and possible death to the patient.

PATHOPHYSIOLOGY AND ANATOMY Euglycemia is the ultimate goal of the complex system of neurohormonal and organ interactions involved in glucose homeostasis in the human body. This homeostasis is absolutely necessary to preserve normal brain metabolism and function. Essentially, the metabolism of the CNS is driven by the oxidation of approximately 150 g/ay of glucose that must be immediately available from the circulation. Mild to moderate hypoglycemia can cause abnormal cognitive function even in the absence of other symptoms in healthy men (10). Cryer and Gerich (1) reported that brain glucose uptake is directly proportional to the arterial glucose concentration. The brain's reserves of glucose are minimal, at best sufficient for only a few minutes of continued normal activity. Auer ( 11) has suggested that hypoglycemic brain damage may begin rapidly after hypoglycemic coma has become clinically manifest. Hypoglycemia is, therefore, an abnormal condition that presents an immediate threat to life. In the euglycemic state, the body's demand for glucose is balanced by the ingestion of glucose or the endogenous production of glucose. The time elapsed since the last meal determines which of these mechanisms is dominant. The latter mechanism achieves primacy in the postabsorptive state, which is at least 5 to 6 hours after the last meal. An overnight fast of 8 to 14 hours definitely places the patient in the postabsorptive group. The internal mechanisms of glucose production are hepatic glycogen breakdown (glycogenolysis) and de novo glucose synthesis (gluconeogenesis) using lactate, pyruvate, glycerol, and alanine. The immediate clinically important site of these activities is the liver, although in starvation (2- to 3-day fast), the kidneys are capable of gluconeogenesis and muscles regularly produce glucose for their own consumption by glycogenolysis and release lactate in the process of anaerobic catabolism. Glycogen stores are sufficient only for the first day of

starvation in the average person. After that, gluconeogenesis provides the lion's share of endogenous glucose supply ( 9). The coordination of these activities is endocrine and neurohormonal. Insulin is the major hormone in the control of serum glucose. It has a hypoglycemic effect and inhibits glycogenolysis and gluconeogenesis. The hyperglycemia-inducing arm of this euglycemia feedback loop is populated by several humeral factors, including glucagon, epinephrine, growth hormone, and cortisol. These factors, considered as a group, are referred to as the “counterregulatory hormones” of glucose metabolism (12). That is, they act to return serum blood glucose levels to normal levels from hypoglycemic levels. Glucagon is the most powerful, epinephrine is the next in potency, and the rest are of minor importance for the normal subject. Insulin is produced in the pancreatic b-islet cells, glucagon is produced in the pancreatic a-islet cells, growth hormone is produced in the pancreatic b-islet cells, epinephrine is produced in the adrenal medulla, and cortisol is produced from the hypophyseal pituitary axis. Hypoglycemia results when the excessive use or the inadequate production of glucose causes a decline in the serum level, resulting in end-organ deprivation of this primary energy metabolism precursor. The terminal event in the natural history of this process is neuroglycopenia, as initially described by Marks et al. ( 13), with progressive failure of central neural metabolism and function causing coma, neuronal death, and ultimately the death of the patient if treatment is unavailable.

PREHOSPITAL ASSESSMENT AND STABILIZATION In patients who have already experienced episodes of hypoglycemia and have received instruction from home care providers for managing diabetes, hypoglycemic episodes frequently are recognized and treated early. If that fails, 911 calls for emergency medical service (EMS) are necessary. Severe episodes of hypoglycemia are defined as those that require a hospital visit or the intervention of another person. Prehospital care providers are skilled in the diagnosis and symptomatic treatment of hypoglycemia because this diagnosis is universally addressed in the EMS treatment protocols of altered level of consciousness. Once diagnosed, patients with mild cases are treated with oral sugar-containing fluids and intravenous fluids as needed. The patient with hypoglycemia, however, may have nonclassic symptoms beyond the diagnostic ability of prehospital personnel. The administration of intravenous glucose or intramuscular glucagon will increase serum glucose levels in patients who are otherwise systemically intact. Unless the patient has sustained prolonged neurologic insult, the effect of glucose is rapid. The effect of glucagon is much less dramatic; it takes 10 to 20 minutes to be clinically apparent. The patient who so recently had hypoglycemia may now be in a postictal state because of hypoglycemic seizures, may have suffered significant trauma during the episode, or may have persistent neurologic or cardiovascular signs and symptoms caused by the episode. All these factors can limit efforts at field stabilization.

CLINICAL PRESENTATION AND EXAMINATION Hypoglycemia may exhibit classic or nonclassic constellations of symptoms. The classic ones include sympathomimetic and then neuroglycopenic symptoms. The adrenergic or sympathomimetic symptoms include (but are not limited to) pallor, palpitations, tachycardia with or without hypertension, tremor, diaphoresis, anxiety, and affective hyperactivity. The intensity of the counterregulatory response and adrenergic symptoms is proportional to the depth of the fall in serum glucose level more than to the rate of fall or to the absolute decrease in serum glucose ( 1). Counterregulation begins at higher glucose levels than do symptoms. Cardiac ischemia (14) and arrhythmias from hypoglycemia have been reported. In rapidly evolving hypoglycemia, the adrenergic phase may be transient as symptoms of cerebral dysfunction quickly become dominant. If neuroglycopenia evolves, the patient may have any of the myriad signs or symptoms. The patient may complain of weakness, headache, or decreased visual acuity or blindness. Confusion or coma with muscle laxity is common, but the patient may exhibit altered cognitive function while awake ( 10), visual hallucinations ( 15), hemiplegia (strangely, the right side is affected more often than the left) ( 16,17), aphasia, tetany, seizures, or flaccid coma. Cardiac or respiratory arrest is not unknown. If the patient has had a seizure from hypoglycemia, he or she may have shoulder dislocation(s) or other orthopedic trauma ( 18,19). Such dislocations, when present, are often posterior. Their occurrence should be a clue to grand mal seizures from any cause. These findings are summarized in Table 64–2.1.

Table 64–2.1. Symptoms and Signs of Hypoglycemia

The physical examination usually shows a decreased level of consciousness with or without excessive adrenergic outflow. There may be signs of the long-term complications of diabetes, and, if not, they should be sought. There also may be evidence of liver failure, renal disease, endocrinopathies, neoplastic disease, or psychiatric disease. Examination of the fundus to look for retinopathy and papilledema is mandatory. Tachycardia should be seen but may be abolished by severe neuroglycopenia or b blockade. Hypertension is variably present. Diaphoresis is common and may be the only adrenergic symptom in the patient with hypoglycemia on a nonselective b-blocking agent. Facial flushing and urticaria have been reported. Evidence of liver failure is ominous because hypoglycemia occurs if there is more than an 80% loss of hepatic function.

DIFFERENTIAL DIAGNOSIS The initial differential diagnosis for the patient with hypoglycemia is most often that of altered level of consciousness. It should be confirmed by the demonstration of decreased serum glucose, with adrenergic excess or neurologic dysfunction, and by the resolution of normal function after the restoration of physiologic serum glucose levels following a suitable interval (Whipple's triad) ( 20). Once the diagnosis of hypoglycemia has been firmly established, the emergency physician must determine whether the episode was reactive (postprandial) or fasting (postabsorptive). The differential diagnosis of hypoglycemia is summarized in Table 64–2.2.

Table 64–2.2. Differential Diagnosis of Hypoglycemia

Postprandial or reactive hypoglycemia may have an alimentary cause because it is seen in patients who have undergone the types of surgery that alter the normal anatomy of the upper gastrointestinal system, among them pyloroplasty, partial or complete gastrectomy, and gastrojejunostomy. In this condition, the rapid absorption of ingested glucose causes an increased release of insulin, which is followed in 2 to 3 hours by hypoglycemia. Patients with prediabetic syndromes may have glucose intolerance with initial hyperglycemia and subsequent postprandial hypoglycemia. Other causes of postprandial hypoglycemia are rare. They include galactosemia, hereditary fructose intolerance, and inborn enzymatic deficiencies, and they become apparent during childhood ( 21). Despite the fact that most patients would prefer a diagnosis of functional postprandial–reactive hypoglycemia, this diagnosis is uncommon in the adult population. Most often, signs and symptoms cannot be demonstrated consistently to coincide with depressed glucose levels after mixed meals. In actuality, the physical complaints are due to neurotic illness for the vast majority of patients in this group ( 7). Hypoglycemia after fasting is designated as postabsorptive and is potentially more ominous because it implies relative or absolute failure of counterregulatory mechanisms. In the fasting state, the patient's glucose homeostasis is under primary control by counterregulatory hormones, which should be protective against the development of hypoglycemia. Fasting hypoglycemia is caused by an excess of circulating insulin relative to available serum glucose. Exogenous therapeutic insulin excess is the most common cause of fasting hypoglycemia. Other causes of fasting hypoglycemia include excessive pancreatic b-cell insulin production, extrapancreatic tumors, organ failure, drugs that cause excessive insulin secretion or failure of counterregulation, counterregulatory hormone deficiencies, and several systemic diseases. Excessive pancreatic b-cell insulin production may be seen in b-cell islet tumors and hyperplasia and in drugs that cause an increased secretion of endogenous insulin, such as the sulfonylurea oral hypoglycemic drugs. Extrapancreatic tumors can produce insulinlike factors that may produce hypoglycemia despite normal serum insulin levels. Hepatic and renal failure have been associated with decreased serum glucose with or without frank hypoglycemia. In liver disease, this may be caused by glycogen depletion or deficient gluconeogenesis either alone or in combination. The kidneys and the liver are the primary sites of insulin elimination. Thus, for the patient with renal failure and diabetes, insulin requirements decrease as the disease progresses. In addition, the kidneys are gluconeogenic during prolonged fasting. These factors, together with the chronically malnourished state of most patients with renal failure, contribute to hypoglycemia. It should be noted that compared with normal controls, patients with diabetic and nondiabetic renal failure are at increased risk for profound hypoglycemia during the acute management of hyperkalemia ( 22). Patients with congestive heart failure or cardiogenic shock may have hypoglycemia, perhaps caused by liver dysfunction induced by passive congestion or hypoperfusion. Infarction or ablation of the adrenals or pituitary may result in hypoglycemia secondary to counterregulatory hormone deficit. Similarly, hypothyroidism may cause hypoglycemia. Multiple drugs are known to cause hypoglycemia either by increasing serum insulin or by inhibiting counterregulation. Insulin and the sulfonylureas produce hypoglycemia in overdosage and may even do so in therapeutic doses. Both agents may be taken in overdosage when the patient is attempting suicide or seeking admission because of covertly induced (factitious) hypoglycemia ( 23). Ethanol is a well-known cause of hypoglycemia because of the inhibition of gluconeogenesis in glycogen-deficient persons. Repeatedly, salicylate-induced hypoglycemia has been reported to be associated with overdosage, especially in the pediatric population (7). Acetaminophen-induced hypoglycemia is caused by liver necrosis, seen in overdosage. Numerous other drugs implicated in hypoglycemia ( 24,25,26 and 27) are listed in Table 64–2.3.

Table 64–2.3. Hypoglycemia-Inducing Drugs

Seltzer reviewed 1418 cases of hypoglycemia secondary to drugs. Sulfonylureas caused 63% of the cases, with alcohol, propranolol, and aspirin causing another 19%. Pentamidine, disopyramide, ritodrine, and quinine caused 7% more ( 24). Recently hypoglycemia has resulted from the inadvertent dispensing of sulfonylurea agents to patients without diabetes. This pharmacy error was caused by the similarity of proprietary names and drug appearance ( 28). Deficiencies of glucagon, epinephrine, cortisol, and growth hormone can cause failure of counterregulation with subsequent episodes of hypoglycemia. These deficits may be congenital or acquired. Congenital deficiencies are obvious early in life. Acquired disease is associated with disease or trauma of the liver, pancreas, adrenals, and pituitary. Of particular note to the emergency physician are patients with long-standing insulin-dependent diabetes and patients on long-term steroid treatment. Those with long-term diabetes have acquired deficiency in the secretion of glucagon and epinephrine ( 9). These patients are prone to hypoglycemia, which is likely to be severe if nonselective b-adrenergic blockers are prescribed. If patients on long-term steroids suddenly discontinue their medication, they may have hypoglycemia as a symptom of Addisonian crisis. For them, parenteral steroids with glucocorticoid and mineralocorticoid activity constitute mandatory, life-saving emergency therapy. Systemic disorders, such as sepsis and shock, may cause hypoglycemia, primarily from liver failure. This is especially true for patients with preexisting liver disease. Autoimmune diseases, such as systemic lupus erythematosus and Grave disease, and lymphoreticular neoplasms, such as Hodgkin disease, can cause the generation of autoantibodies to insulin or insulin receptors that may have agonist rather than antagonist activity ( 29,30). The differential diagnosis of pediatric hypoglycemia deserves special mention. In addition to the causes discussed already, the emergency physician must add the following when confronted with the hypoglycemic child: neonatal hypoglycemia, hypoglycemic ketosis, prolonged starvation, child abuse, and multiple inborn errors of metabolism (31). Essentially, all children born in the ED should be considered at risk for neonatal hypoglycemia and should be screened rapidly. Blood glucose levels less than 40 mg/dL should be treated as indicated with intravenous D50W in a dose of 1 to 2 mL/kg, repeated as needed. Responses to therapy should be documented by heel stick and oral glucose supplementation administered. Starvation or drug-induced hypoglycemia in children should raise a high suspicion of child abuse or pediatric psychiatric disease in the previously healthy child or adolescent ( 32).

INITIAL STABILIZATION On arrival in the ED, the adult patient should undergo rapid history and physical assessment, with the usual emphasis on airway, breathing, and circulation (the ABCs). History attained from prehospital care providers or family can be diagnostic and valuable. The history should focus on precipitating, predictive, or exacerbating factors in the genesis of hypoglycemia. The length of time since the last meal, the presence of diabetes, prior episodes of hypoglycemia, and drug therapy (especially with insulin and sulfonylureas) must be documented. Potential clues to the etiology of hypoglycemia include concurrent liver, renal, endocrine, or neoplastic disease, recent prescriptions, signs of depression, alcohol or stimulant abuse, and other diseases that cause the patient to be chronically malnourished (see Table 64–2.2). An intravenous line should be established rapidly and blood specimens obtained for initial serum glucose evaluation and other studies that may be indicated if the cause of the hypoglycemic episode is not immediately obvious. Blood should be tested with a reagent strip at the bedside to speed the diagnosis. The older “dextro-sticks” are less accurate and provide lower readings. If the patient is conscious, the history can be taken at this time and the patient treated with oral glucose solution. If not, 25 to 50 g of 50% glucose in water solution should be administered by intravenous push, and the patient should be placed on supplemental oxygen and a cardiac monitor. Thiamine, 100 mg intramuscularly, should be given concomitantly. If immediate intravenous access is not possible, the patient should be

treated with 1 to 2 mg of intramuscular glucagon. This may be repeated once in 10 to 20 minutes, although the usefulness of higher doses is suspect. Intravenous administration of 5% or 10% dextrose in water in volumes of at least 2 to 3 mL/minute should be administered after bolus therapy has been given. If mental status permits, the patient should be given oral glucose supplementation in addition, preferably as a mixed snack or meal, to ensure against recurrence. Patients who do not respond to this therapy must be evaluated for other causes of the altered level of consciousness. The patient should undergo a repeat examination to document any response to initial therapy and to be evaluated for nonpharmacologic causes of the episode, as previously discussed, if the cause is unknown. Blood samples for posttreatment serum glucose analysis should be taken. Other laboratory and diagnostic studies should be ordered as necessary.

LABORATORY FINDINGS If therapy is successful, the patient will have a serum blood glucose level of 50 mg/dL or below on the initial specimen and will show a serum glucose rise of at least 100 to 200 mg/dL on posttreatment analysis. Blood should not be allowed to stand for a protracted period before separation because elevated leukocyte counts from hematologic malignancy or reactive leukocytosis may accelerate glucolysis in vitro, causing artifactual hypoglycemia ( 23). Hypoglycemia has been reported in a patient with leukemia (AML) who did not have leukocytosis ( 33). Additional glucose testing should be performed if there is a severe reaction to document the failure of the recurrence of hypoglycemia. The patient should undergo serum electrolyte analysis. If the patient is in a hyperinsulinemic state, the administration of high doses of intravenous glucose may cause electrolyte abnormalities, in particular hypokalemia. Although rarely necessary in the ED, serum obtained at the time of initial examination may be analyzed for levels of insulin, proinsulin, C-peptide, and antibodies to insulin or its receptor as indicated by the clinical findings and course. In exogenous insulin excess or endogenous insulin excess, insulin levels are elevated from sulfonylureas or pancreatic b-cell islet tumors. Proinsulin levels are elevated only when endogenous insulin secretion is elevated. Alternately, C-peptide levels indirectly measure proinsulin levels because C-peptide is liberated during the proteolytic conversion of proinsulin to insulin. Antibodies to insulin occur in autoimmune diseases and when heterologous insulins, such as those derived from pork or beef or (to a much lesser extent) homologous insulins, have been administered. Insulin receptor antibodies are seen only in autoimmune diseases. The levels of these various compounds should be measured in patients in whom the cause of hypoglycemia is not evident. Specific patterns of measured levels may be diagnostic or suggestiv e. Such testing is beyond the scope of ED care. Qualitative blood and urine toxicologic testing can be conducted to determine drug-induced hypoglycemia. Cerebrospinal fluid glucose concentration is depressed after an episode of hypoglycemia, and recovery may take several hours. This can be an important diagnostic modality in the patient who does not respond well to therapy and in whom no other cause of CNS dysfunction is found (34).

MANAGEMENT AND INDICATIONS FOR ADMISSION After initial stabilization has been achieved, the patient should be monitored for recurring hypoglycemia. The duration of this period of observation is arbitrary, but it should be at least 2–4 hours while the patient is receiving treatment. An intravenous glucose solution of 5% or 10% may be administered during this observation, and the trend of serum glucose should be followed at regular intervals by either fingerstick or laboratory measurement. Patients should be fed a full meal as soon as their mental status allows it. Patients requiring 10% dextrose infusion during emergency therapy should be admitted for additional treatment and observation. Patients whose hypoglycemia is caused by “regular” insulin excess, nutritional deficit, or alcohol can be amenable to ED stabilization and subsequent discharge. However, episodes of hypoglycemia caused by “intermediate” or “long-acting” insulins and first-generation (tolbutamide, chlorpropamide, tolazamide, and acetohexamide) or to second-generation (glyburide, glipizide, and gliclazide) sulfonylurea oral hypoglycemic agents are at risk for prolonged hypoglycemia secondary to the extended half-life of these agents. It is improvident to discharge them. Seltzer ( 24) recommends that all patients with severe drug-induced hypoglycemia be treated with intravenous 10% glucose for at least a day until sustained hyperglycemia can be documented. Additional episodes of hypoglycemia should be treated with increased concentrations of intravenous glucose (up to 20% dextrose), and consideration should be given to the addition of glucagon, cortisol, or diazoxide to the treatment regimen. The drug treatments for hypoglycemia are given in Table 64–2.4. Failure to stabilize the serum glucose by an initial emergency bolus and maintenance therapy, hypoglycemia requiring an escalating intensity of treatment, or an episode of unexplained hypoglycemia warrants medical admission for observation, treatment, and additional diagnostic workup, as indicated. If the planned disposition is discharge, the patient should be watched for at least 1 to 2 hours after supplemental glucose is discontinued and the continuation of euglycemia is quantitatively documented. Athletes who present to the ED with hypoglycemia should be treated in a similar fashion with observation and retesting after glucose ( 24A).

Table 64–2.4. Drugs Used in the Treatment of Hypoglycemia

PITFALLS Failure to determine the cause of a hypoglycemic episode is a serious concern for the emergency physician. These patients must be admitted because no guarantee can be given that hypoglycemia will not recur. This situation is fraught with potential morbidity and mortality for the patient and extreme medicolegal risk for the physician. Inadequate treatment or an insufficient period of observation can cause the recurrence of hypoglycemia and carry the same attendant risks. Somogyi reaction is defined as morning hyperglycemia caused by nocturnal hypoglycemia, related to excessive doses of intermediate or long-acting insulin. This effect is controlled through counterregulatory mechanisms. The treatment of this complication of diabetes is reduction, not increase, of the insulin dose. Thus, good communication between the emergency practitioner and the primary care provider is imperative. The ED physician often sees and treats the hypoglycemic event itself, but the primary care provider may be aware only of elevated fasting glucose levels if the patient is a poor historian and the emergency physician is not assiduous in reporting. The increasing use of human recombinant insulin has several potential negative effects. Human-source insulin is less likely than animal-source insulin to cause the patient to recognize impending hypoglycemia because it causes fewer adrenergic symptoms ( 35). The potential for more frequent severe reactions is obvious, especially in patients on tight glycemic control protocols. Additionally, human-source insulin is less immunogenic than animal-source insulin, and this may make the diagnosis of factitious hypoglycemia more difficult. One should not rely on the historical evidence of abnormal glucose levels from a 5-hour oral glucose tolerance test to diagnose hypoglycemia (7). The test has poor specificity and may show as many as 50% of patients to be hypoglycemic, although hypoglycemia is seldom demonstrated after the physiologic mixed-nutrient meal testing of serum glucose. Patients with hypoglycemia from hyperinsulinism caused by pancreatic or other tumors frequently respond well to ED treatment and may have stable blood glucose levels on short-term observation. They may need as much as 72 hours of enforced in-hospital fasting to manifest another bout of hypoglycemia ( 39). Despite the patient's apparent stability, he must be admitted if there is no known diagnosis that clarifies the cause of the hypoglycemic episode. At the least, these patients must receive extremely urgent follow-up care. Frequently, 50% glucose solution is administered by the peripheral vein, but this risks subcutaneous infiltration with tissue necrosis because of the osmotic load of the solution. The potential for local venous thrombosis and vein sclerosis is high.

MEDICOLEGAL PEARLS Hypoglycemia at the extremes of the age range may result from child abuse or elder abuse, and this should always be kept in mind when the differential diagnosis in the pediatric and geriatric populations is considered. Notification of child or adult protective services is mandatory and legally protective to the patient and physician if circumstances are suspicious. The patient with hypoglycemia often has chronic disease. They may become depressed, and the hypoglycemic episode may be the result of a suicide attempt by drug overdose. The physician should be sensitive to the subtle signs of depression, especially if the patient with hypoglycemia does not have diabetes or does have a history of psychiatric disease, and the physician should not be afraid to act to prevent the possibility of another attempt. Failure to diagnose suicidal intent may incur physician liability. This is also true for the patient with factitious hypoglycemia. Any patient with an altered sensorium as a result of a motor vehicle accident should undergo serum glucose determination ( 37,38 and 39). Many states require that episodes of loss of consciousness be reported to public health agencies, who route the information to the Department of Motor Vehicles. Failure to diagnose hypoglycemia in this event is a medical and legal disservice to the patient. Failure to report the episode undermines public health and safety and makes the emergency physician liable in the event of additional traffic mishaps involving the patient. This liability may include wrongful death of the patient or the patient's victim. The use of any hypertonic glucose solution to treat presumed hypoglycemia in the presence of cerebral ischemic or acute anoxic injury may result in the exacerbation of a poor neurologic outcome. The physician who blindly treats these patients without point-of-care testing does so at his own risk ( 40,41). The decision to treat must be individualized based on clinical and historical fact. It is especially important to document the instructions given to the patient concerning changes in therapeutic regimen and lifestyle and the required follow-up. If possible, contact the patient's physician and document that contact. References 1. 2. 3. 4. 5. 6. 7. 8.

Cryer PE, Gerich JE: Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus. N Engl J Med 1985;313:232. Potter J, Clarke P, Gale EA, et al: Insulin-induced hypoglycaemia in an accident and emergency department: the tip of an iceberg? Br Med J 1982;285:1180. Feher MD, Grout P, Kennedy A, et al: Hypoglycaemia in an inner-city accident and emergency department: a 12-month survey. Arch Emerg Med 1989;6:183. Fischer KF, Lees JA, Newman JH: Hypoglycemia in hospitalized patients: causes and outcomes. N Engl J Med 1986;315:1245. Malouf R, Brust JC: Hypoglycemia: causes, neurological manifestations, and outcome. Ann Neurol 1985;17. Field JB: Hypoglycemia: definition, clinical presentations, classification, and laboratory tests. Endocrinol Metab Clin North Am 1989;18:27. Nelson RL: Hypoglycemia: fact or fiction? Mayo Clin Proc 1985;60:844. Bolli GB, Fanelli CG: Unawareness of hypoglycemia. N Engl J Med 1995;333:1711.

8A. Service FJ: Hypoglycemia. Endocrinol Metab Clin North Am 1997;26:937–955. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

Campbell PJ, Gerich JE: Mechanisms for prevention, development, and reversal of hypoglycemia. Adv Intern Med 1988;33:205. Stevens AB, McKane WR, Bell PM, et al: Psychomotor performance and counterregulatory responses during mild hypoglycemia in healthy volunteers. Diabetes Care 1989;12:12. Auer RN: Progress review: hypoglycemic brain damage. Stroke 1986;17:699. Gerich JE, Campbell PJ: Overview of counterregulation and its abnormalities in diabetes mellitus and other conditions. Diabetes Metab Rev 1988;4:93. Marks V, Marrack D, Rose FC: Hyperinsulinism in the pathogenesis of neuroglycopenic syndromes. Proc R Soc Med 1961;54:747. Pladziewicz DS, Nesto RW: Hypoglycemia-induced silent myocardial ischemia. Am J Cardiol 1989;63:1531. Nakanishi T: Visual hallucination without the disturbance of consciousness in hypoglycaemic attack: report of an unusual case—consideration on psychic symptoms related to hypoglycaemia. Igaku Kenkyu 1988;58:421. Foster JW, Hart RG: Hypoglycemic hemiplegia: two cases and a clinical review. Stroke 1987;18:944. Lala VR, Vedanarayana VV, Ganesh S, et al: Hypoglycemic hemiplegia in an adolescent with insulin-dependent diabetes mellitus: a case report and a review of the literature. J Emerg Med 1989;7:233. Hepburn DA, Steel JM, Frier BM: Hypoglycemic convulsions cause serious musculoskeletal injuries in patients with IDDM. Diabetes Care 1989;12:32. Litchfield JC, Subhedar VY, Beevers DG, Patel HT: Bilateral dislocation of the shoulders due to nocturnal hypoglycaemia. Postgrad Med J 1988;64:450. Whipple AO: The surgical therapy of hyperinsulinism. J Int Chir 1938;3:237. Betteridge DJ. Reactive hypoglycaemia. Br Med J 1987;295:286. Williams PS, Davenport A, Bone JM: Hypoglycaemia following treatment of hyperkalaemia with insulin and dextrose. Postgrad Med J 1988;64:30. Horwitz DL: Factitious and artifactual hypoglycemia. Endocrinol Metab Clin North Am 1989;18:203. Seltzer HS: Drug-induced hypoglycemia: a review of 1418 cases. Endocrinol Metab Clin North Am 1989;18:163.

24A. Holtzhausen LM, Noakes TD: Collapsed ultraendurance athlete: proposed mechanisms and an approach to management. Clin J Sport Med 1997;7:292–301. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40.

Bailey CJ, Flatt PR, Marks V: Drugs inducing hypoglycemia. Pharmacol Ther 1989;42:361. Schattner A, Rimon E, Green L, et al: Hypoglycemia induced by co-trimoxazole in AIDS. Br Med J 1988;297:742. Aron DC: Endocrine complications of the acquired immunodeficiency syndrome. Arch Intern Med 1989;149:330. Huminer D, Dux S, Rosenfeld JB, Pitlik SD: Inadvertent sulfonylurea-induced hypoglycemia: a dangerous, but preventable condition. Arch Intern Med 1989;149:1890. Moller DE, Ratner RE, Borenstein DG, Taylor SI: Autoantibodies to the insulin receptor as a cause of autoimmune hypoglycemia in systemic lupus erythematosus. Am J Med 1988;84:334. Walters EG, Tavare JM, Denton RM, Walters G: Hypoglycaemia due to an insulin-receptor antibody in Hodgkin's disease. Lancet 1987;1:241. Haymond MW: Hypoglycemia in infants and children. Endocrinol Metab Clin North Am 1989;18:211. Dershewitz R, Vestal B, Maclaren NK, Cornblath M: Transient hepatomegaly and hypoglycemia: a consequence of malicious insulin administration. Am J Dis Child 1976;130:998. Al Hilali MM, Majer RV, Penney O: Hypoglycaemia in acute myelomonoblastic leukaemia: report of two cases and review of published work. Br Med J 1984;289:1443. Kaplinsky N, Frankl O: The significance of the cerebrospinal fluid examination in the management of chlorpropamide-induced hypoglycemia. Diabetes Care 1980;3:248. Heine RJ, van der Heyden EA, van der Veen EA: Responses to human and porcine insulin in healthy subjects. Lancet 1989;2:946. Service FJ, Dale AJ, Elveback LR, Jiang NS: Insulinoma: clinical and diagnostic features of 60 consecutive cases. Mayo Clin Proc 1976;51:417. Ratner RE, Whitehouse FW: Motor vehicles, hypoglycemia, and diabetic drivers. Diabetes Care 1989;12:217. Stevens AB, Roberts M, McKane R, et al: Motor vehicle driving among diabetics taking insulin and nondiabetics. Br Med J 1989;299:591. Tortella BJ, Lavery RF, ReKant M: Utility of routine admission serum chemistry panels in adult trauma patients. Acad Emerg Med 1995;2:190–194. Nee PA, Scane AC, Lavelle PH, et al: Hypothermic myxedema coma erroneously diagnosed as myocardial infarction because of increased creatine kinase MB. Clin Chem 1987;33(6):1083–1084. 41. Browning RG, Olson DW, Stueven HA, et al: 50% dextrose: antidote or toxin? Ann Emerg Med 1990;19:683–687.

Chapter 64.3 Nonketotic Hypertonicity in Diabetes Mellitus Principles and Practice of Emergency Medicine

CHAPTER 64 DIABETES AND COMPLICATIONS

3 Nonketotic Hypertonicity in Diabetes Mellitus Kristi Koenig, Eric Stirling and Joseph C. Howton Capsule Pathophysiology Prehospital Care Clinical Presentation Differential Diagnosis Initial Stabilization Laboratory Procedures Management and Admission Criteria Pitfalls Medicolegal Pearls

CAPSULE A syndrome of severe hyperglycemia, alteration of consciousness, hyperosmolality, and cellular dehydration without severe ketoacidosis, usually occurring in elderly, noninsulin-dependent patients with diabetes, was formerly known as nonketotic hyperosmolar coma. In recent years, this term has come to be recognized as a misnomer: True coma is present in less than 10% of patients with this condition. Alternative terms that have been used include hyperosmolar nonketotic uncontrolled diabetes, the diabetic hyperosmolar state, or nonketotic hypertonicity (NKH). This syndrome is characterized by dehydration, hyperglycemia, and increased effective osmolarity in the absence of significant ketoacidosis. Of special note is evidence correlating the serum sodium concentration to the level of obtundation ( 1). Although uncommon, NKH has a high mortality rate. Rapid emergency department (ED) recognition, aggressive but closely monitored fluid and insulin therapy, and a thorough search for precipitating causes substantially decrease morbidity and mortality rates.

PATHOPHYSIOLOGY A thorough comprehension of the underlying pathophysiology in nonketotic hypertonicity (NKH) is essential to guide therapy. Under normal circumstances, there is an increase in insulin release by the b-cells in the pancreas after a meal so that glucose can be used by the tissues. In the presence of b-cell deficiency, the resultant insulin release is inadequate to maintain normal glucose levels. The b-cells are presumably working maximally, even in the fasting state. When there is insufficient insulin secretion after a meal or when insulin resistance develops, hyperglycemia results. Along with the relative insulin deficiency, elevated levels of the counter/regulatory hormones glucagon, cortisol, and catecholamines are present. This causes decreased peripheral glucose use and increased hepatic glucose production. Hyperglycemia, resulting in an osmotic diuresis, ensues. Dehydration eventually leads to a decrease in glomerular filtration rate and an increase in stress, which causes an increase in counterregulatory hormone production. Spiraling hyperglycemia and worsening dehydration result. The exact mechanism by which serum glucose levels are allowed to continue to rise without the production of ketones is poorly understood, and multiple theories have been proposed ( 2,3 and 4). Some experiments suggest that dehydration and hyperosmolarity limit lipolysis and ketogenesis (5,6). It may be that sufficient insulin is present from endogenous or exogenous sources to prevent excessive lipolysis and the resultant production of ketoacids, but not to prevent hyperglycemia. Thus, ketoacidosis does not develop. If dehydration leading to extracellular fluid depletion occurs, however, NKH may develop. The key concept is that severe dehydration at the cellular level results from these metabolic abnormalities, and this dehydration is responsible for the clinical presentation.

PREHOSPITAL CARE Prehospital care workers should realize that, although most patients with NKH are elderly, patients of any age, including infants, have been described. Approximately one third of patients are known to have noninsulin-dependent diabetes and to be taking oral hypoglycemic agents. A history of recent illness is common. It is important to suspect and treat recipitating causes, which include infection, myocardial infarction, cerebrovascular accident, and hypothermia. Prominent symptoms include alteration of consciousness, weakness, polyuria, vomiting, and abdominal pain. Prehospital personnel should consider treatment with 25 g of 50% dextrose in water and 2 mg intravenous (IV) naloxone for all patients with altered levels of consciousness. Supportive care, including cardiac monitoring, frequent assessment of vital signs, and appropriate fluids for dehydration should be instituted. Rapid transport is essential. There is controversy over the use of IV dextrose in patients with altered levels of consciousness who may have increased intracranial pressure, or in those whose glucose levels are already significantly elevated. The current accepted viewpoint is that the glucose load given has a minor effect on brain edema compared to the major effect created by uncorrected hypoglycemia. The glucose load given to a patient who already has marked hyperglycemia does not cause additional deterioration because the percentage added is small.

CLINICAL PRESENTATION The most common patient with NKH is elderly, female, older than 60, has noninsulin-dependent diabetes, and has a history of progressive debility over a few days or weeks. It must be remembered that NKH may be the first manifestation of diabetes, or it may be a complication of insulin-dependent diabetes when the patient has taken enough insulin to prevent ketosis but not hyperglycemia ( 7). It may develop in younger patients, especially those who are obese and have borderline diabetes with severe intercurrent illness. The most common precipitating factors are Gram-negative pneumonia, uremia with vomiting, and acute viral syndromes ( 8). Other bacterial infections, pancreatitis, discontinuation of oral hypoglycemic agents, silent myocardial infarction, cerebrovascular accidents, or trauma may also trigger NKH. In the hospital, causes include vigorous diuretic use, steroids, hyperalimentation, and propranolol use. The mechanism of action of diuretics is thought to be volume depletion, hypokalemia, and insulin suppression. Propranolol blocks insulin release and masks the autonomic responses to hypoglycemia. Clinically, patients have dehydration, fever, obtundation, and either polyuria or oliguria. One third have hypotension. Various neurologic symptoms, including seizures, focal deficits, full-stroke syndromes that resolve with therapy, and global dysfunction occur. In one study, 12 of 33 patients later shown to have NKH were diagnosed with “probable acute stroke” (8). Toxidromes secondary to poisoning or overdose may predominate. Cardiac or respiratory failure may be either a cause or an effect.

DIFFERENTIAL DIAGNOSIS Several metabolic disorders can mimic NKH. The most common is diabetic ketoacidosis. Hypoglycemic coma has a more rapid onset and is without dehydration. Uremia may have a similar onset and alteration of consciousness, but dehydration is not present. Sepsis with lactic acidosis also may yield hyperglycemia, and it may be difficult to identify the primary cause. Alcoholic ketoacidosis rarely produces the degree of obtundation and dehydration seen with NKH. Structural coma also may present with hyperglycemia and dehydration, but to a much lesser degree than NKH. The onset of myxedema coma is similar, but physical signs and the absence of significant hyperglycemia serve to differentiate. Severe hypernatremia may mimic all the findings of NKH, with only the serum glucose to differentiate ( Table 64–3.1).

Table 64–3.1. Differential Diagnosis of Nonketotic Hyperosmolar Coma

INITIAL STABILIZATION Therapy must be started immediately, even as the diagnosis is being considered. Once the patient is stabilized, therapy can proceed more slowly. This prevents the condition of the patient with little reserve from worsening while allowing gradual correction of the metabolic abnormalities. It is helpful to keep a time flow sheet to record vital signs, laboratory data, all therapy, and changes in physical and mental status. If the patient is hypotensive, isotonic saline should be infused to restore extracellular volume. One to two liters are required in the first 2 hours. The IV should then be switched to 0.45% normal saline to prevent excessive extracellular volume repletion. This may be used initially if hypotension is absent. It should be noted that controversy persists over the ideal choice of fluid when considering normal saline versus half-normal saline, so that reviewing the fluid resuscitation choice of the admitting physician may be helpful. Total water deficits average 100 mL/kg of body weight, and one-half should be given over the next 24 hours, with either 5% dextrose in water or 5% dextrose in 0.45% saline depending on volume status and serum sodium. Ventilatory status and airway are the first priorities and should be managed by clinical assessment and pulse oximetry. Oxygen and cardiac monitoring should be instituted, and dysrhythmias should be managed according to standard advanced cardiac life support (ACLS) protocols. Much of the cardiac irritability seen in NKH resolves with fluid and insulin therapy. Insulin therapy is of less importance than fluids. Many patients with NKH are sensitive to small doses, and no more than 10 IV units should be given initially. After this, a continuous infusion of 0.1 U/kg per hour, or hourly IV or intramuscular (IM) 5- to 10-unit boluses can be administered. Hourly measurement of serum glucose should be performed. The rare instances of cerebral edema during NKH treatment have all occurred when the serum glucose fell below 250 mg/dL. Therefore, glucose should be added to fluid replacement as the serum level approaches 250 mg/dL.

LABORATORY PROCEDURES Initial laboratory measurements should include serum glucose, electrolytes, blood urea nitrogen, creatinine, magnesium, and phosphorus. Serum ketones, arterial blood gases, complete blood counts, and urinalysis complete the basic workup. If deemed clinically necessary, creatine phosphokinase, thyroid studies, toxicology screens, serum amylase, liver function studies, blood cultures, and specific blood levels of medications should be drawn. Osmolality can be calculated using the formula (Na + K) ( 2) + (serum glucose)/18 + BUN/2.8. In NKH, the osmolality is usually more than 350 (normal, 280 to 300). Measured serum osmolality is not necessary unless an osmolar gap is suspected (e.g., in methanol poisoning). The serum glucose is often more than 1000 mg/100 mL and may reach 2000 mg/100 mL. Potassium is variable, but total body potassium is decreased. Bicarbonate levels are normal unless the patient has concomitant metabolic acidosis or chronic hyperventilation. The anion gap is normal in uncomplicated NKH. Leukocyte counts may be elevated without demonstrable infection, and the leukocyte count may be normal despite sepsis. The serum sodium is now thought to be a useful index of cerebral cellular hydration and to be useful in identifying patients at risk for coma or neurologic abnormalities. It must first be corrected for the serum glucose with the formula that states that serum sodium will fall 1.6 mEq/L for each 100 mg/100 mL increment above normal of the serum glucose ( 9). For example, the expected serum sodium for a serum glucose of 1100 mg/100 mL would be 140 (normal serum Na) – (1100 – (100 × 1.6)) = 124 mEq/L. If the corrected serum sodium is more than 140 mEq/L, more free-water depletion than predicted is present. More aggressive replacement of water is then indicated. The patient with focal neurologic syndromes should undergo computed axial tomography even though resolution may occur with NKH treatment. Oxygen administration and cardiac monitoring have already been discussed.

MANAGEMENT AND ADMISSION CRITERIA Although the mortality rate from NKH has dropped from approximately 40%, which was the rate 20 years ago, it remains at approximately 10%. Because of the high mortality rate and need for continuous monitoring, an intensive care unit setting is preferred for the management of NKH. Although patients may have severe hypertonicity, fluid replacement is essential to restore blood pressure and urine output and to prevent cardiovascular collapse and death. Careful intake and output records are mandatory. Central venous pressure monitoring should be considered in elderly or hemodynamically unstable patients and those with underlying cardiac disease. Fluid replacement should result in a maximum of 2 mEq/L per hour drop in the serum sodium level. Rebound cerebral edema and seizures may result if this is exceeded. Glucose should be added to the IV solution when the serum level drops below 300 mg/100 mL. Potassium should be added when the level drops below 5 mEq/L and urine output is ensured. If potassium phosphate is used, it must be remembered that the formula is K 2PO4, and the potassium is twice that in KCl. Insulin in the amount of 0.1 U/kg body weight per hour, or hourly 5- to 10-unit boluses IM or IV, provides a smooth decrease in the serum glucose level. To avert hypoglycemia, however, continuous IV infusion is preferred. Seizures are especially problematic in the patient with NKH. The differentiation between over vigorous therapy and underlying causes must be made rapidly. Hypoxia, meningitis, or structural lesions, drugs causing seizures, or an underlying seizure disorder must be distinguished. Phenytoin (Dilantin) is relatively contraindicated because of its inhibition of insulin secretion and its predilection to worsen existing metabolic abnormalities. Diazepam and phenobarbital are preferred for seizure control. It is tempting simply to “correct the numbers” in NKH. The underlying pathophysiology and precipitating factors are the determinants of survival and must be addressed. Communication with the family is critical, both to learn the patient's history and to convey the severity of the patient's condition.

PITFALLS Look for unsuspected sepsis, meningitis, myocardial infarction, or overdose in the patient with NKH who remains obtunded or refractory to timely fluid and insulin therapy. There is a fine line between the necessarily aggressive volume replacement and fluid overload in the elderly patient. Invasive monitoring often is needed. Persistent oliguria mandates a workup for acute tubular necrosis. Hypokalemia, hypophosphatemia, or hypomagnesemia may delay recovery and increase respiratory failure and cardiac dysrhythmias. Appropriate supplementation avoids these pitfalls. The serum glucose level may fall rapidly with therapy. If the level is not checked hourly, hypoglycemia may occur accompanied by seizures or continued coma.

MEDICOLEGAL PEARLS Beware of iatrogenic precipitants of NKH—hyperalimentation, steroids, diuretics, and b blockers. Beware of nursing home or family neglect—deprivation of fluids, noncompliance with oral hypoglycemic agents, bedsores with sepsis, and so on. Beware of poisonings in the elderly patient with diabetes; they can precipitate NKH or obscure the diagnosis. References 1. 2. 3. 4. 5. 6. 7. 8.

Daugirdas JT, Kronfol NO, Tzamaloukas AH, et al: Hyperosmolar coma: cellular dehydration and the serum sodium concentration. Ann Intern Med 1989;110:855–857. Kitabchi AE, Murphy MB: Diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma. Med Clin North Am 1988;72:1545. Malone JK, Meacham JE, Ryan PJ, et al: The hyperglycemic hyperosmolar syndrome. Indiana Med 1988;81:766–768. Butts DE: Fluid and electrolyte disorders associated with diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic coma. Nurs Clin North Am 1987;22:827. Gerich J, Penhos JC, Gutman RA, Recant L: Effect of dehydration and hyperosmolarity on glucose, free fatty acid and ketone body metabolism in the rat. Diabetes 1973;22:264–271. Gerich J, et al: Clinical and metabolic characteristics of hyperosmolar nonketotic coma. Diabetes 1971;20:228. Geheb MA: Clinical approach to the hyperosmolar patient. Crit Care Clin 1987;3:797. Arieff AI, Carroll HJ: Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of therapy in 37 cases. Medicine 1972;51:73. 9. Katz MA: Hyperglycemia-induced hyponatremia—calculation of expected serum sodium depression. N Engl J Med 1973;289:843–844.

Suggested Readings Genuth SM: Diabetic ketoacidosis and hyperglycemic hyperosmolar coma. Curr Ther Endocrinol Metab 1997;6:438–447. Gowrishankar M, Cheema–Dhadli S, Halperin ML: Advances in diabetic ketoacidosis and hyperosmolar syndrome pathogenesis and management. Br J Hosp Med 1995;54:2–3, 95–99. Lorber D: Nonketotic hypertonicity in diabetes mellitus. Med Clin North Am 1995;79:39–52. Umpierrez GE, Khajavi M, Kitabchi AE: Review: diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic syndrome. Am J Med Sci 1996;311:225–233. Wachtel TJ: The diabetic hyperosmolar state. Clin Geriatr Med 1990;6:797–806.

Chapter 64.4 Lactic Acidosis Principles and Practice of Emergency Medicine

CHAPTER 64 DIABETES AND COMPLICATIONS

4 Lactic Acidosis Douglas M. Salyards and Joseph C. Howton Capsule Lactate Metabolism Definition of Lactic Acidosis Diagnosis of Lactic Acidosis Classification and Clinical Presentation of Lactic Acidosis Type A Lactic Acidosis Type B Lactic Acidosis Treatment of Lactic Acidosis Prognostic Value of Lactic Acid Levels Medicolegal Pearls

CAPSULE Lactic acidosis is the most common form of metabolic acidosis and the form most commonly encountered by the emergency physician. Two broad categories of lactic acidosis exist: type A is associated with tissue hypoxia, and type B is associated with other disease conditions.

LACTATE METABOLISM Lactate is a metabolic byproduct of glycolysis and is in equilibrium with pyruvate in the following reaction: Pyruvate + NADH + H ® Lactate + NAD This reaction is catalyzed by lactate dehydrogenase (LDH) and requires nicotinamide adenine dinucleotide (NADH) and hydrogen ion (H). Three main factors determine the level of lactate. First, lactate cannot be used in any other intracellular reaction and is, therefore, dependent on the ultimate fate of pyruvate (1). Pyruvate is used as a substrate for glucose in gluconeogenesis and is oxidized in mitochondria to C O2 and H2O. Second, NADH is reoxidized to NAD along the electron transport chain. This process is halted during anoxia—hence, the effect on the redox state and resultant buildup of lactate and acidosis during shock and tissue hypoxia. Third, the lactate concentration is affected by intracellular pH and its effects on lactate transport, enzymatic reactions, and the lactate–pyruvate ratio. A decrease in pH causes a resultant decrease in the uptake of lactate by the liver, and when pH falls below 7.0, the liver may begin to produce lactate (2). Lowering the pH, however, generally causes decreased lactate production, whereas raising it causes elevated lactate production. Lactate is used primarily by the liver and kidneys, although under some circumstances skeletal and even cardiac muscle is capable of extracting some lactate from the circulation ( 3). The liver normally clears up to 50% of the lactate produced through the process of gluconeogenesis ( 3). The kidney normally clears approximately 30% of lactate, also through gluconeogenesis rather than by clearance. The ability of the liver to clear lactate during pathologic states such as seizure and shock, however, is not clearly defined. Studies of hemorrhagic shock induced in dogs with low flow states to the liver have shown variable rates of clearance of lactate by the liver, from markedly reduced to normal (3). In addition, it has been shown that in low flow states, the liver actually may produce lactate, contributing to the acidosis ( 3). It is thought that lactic acidosis can be caused by increased production from tissues other than the liver, by decreased uptake in the liver, and, when blood flow and oxygenation to the liver are reduced, by increased production by the liver. All these contributions are variable and depend on the underlying cause ( 3). The kidney reabsorbs lactate up to concentrations of 6 to 10 mM to provide the necessary substrate for the production of bicarbonate and reversal of the acidosis ( 4). This is why rebound alkalosis can occur with bicarbonate administration after underlying factors are corrected.

DEFINITION OF LACTIC ACIDOSIS Lactic acidosis is an ion gap metabolic acidosis associated with an elevated blood lactate concentration usually of 0.5 to 5 mEq/L. The general consensus is that a lactate concentration of 4 mEq/L or greater, with a significant lowering of pH, is evidence of lactic acidosis ( 1). No firm criteria for pH has been agreed on. The pH may even be normal if underlying alkalosis is present ( 1A).

DIAGNOSIS OF LACTIC ACIDOSIS The diagnosis of lactic acidosis is usually not difficult and can initially be suspected on the basis of clinical conditions. The presence of anion gap metabolic acidosis associated with a clinical disorder in which lactic acidosis is known to occur, most often in a patient with compromised cardiovascular function, provides a high degree of certainty for the diagnosis of lactic acidosis ( 5). Other causes of anion gap metabolic acidosis must, of course, be excluded, and this is usually possible with a rapid determination of the blood lactate level ( Fig. 64–4.1).

Figure 64–4.1. Initial workup of lactic acidosis.

CLASSIFICATION AND CLINICAL PRESENTATION OF LACTIC ACIDOSIS Lactic acidosis is classified into two broad categories. Type A lactic acidosis is associated with tissue hypoxia, and type B is associated with all other disease states (Table 64–4.1) (6).

Table 64–4.1. Classification of Lactic Acidosis

TYPE A LACTIC ACIDOSIS Associated with tissue hypoxia, type A lactic acidosis is the most common type seen in the emergency department (ED). Any condition causing shock can lead to this condition, which may include hemorrhage, sepsis, myocardial infarction with cardiogenic shock, poisoning, and pulmonary embolism. It is important to remember that there may be decreased tissue perfusion without an initial measurable drop in blood pressure and that hypoxemia may not be present. Lactate is accumulated because tissue hypoxia causes the increased production of lactic acid and hydrogen ion, and this may be exacerbated by a decreased blood flow to the liver, causing reduced clearance or even the production of lactate by the liver. Clinically, the patient may have nausea, vomiting, and agitation, and these may develop into stupor and frank coma if the shock is severe. The acidosis causes compensatory hyperventilation in a patient who is not obtunded, perhaps the most common feature. Hypoxia without shock, as seen in pulmonary edema, status asthmaticus, severe exacerbation of chronic obstructive pulmonary disease, and asphyxiation, also may cause type A lactic acidosis. The hypoxia is usually severe and acute and most often is associated with an inability to compensate for the respiratory insult.

TYPE B LACTIC ACIDOSIS Type B lactic acidosis occurs with an elevated blood lactate level and no evidence of tissue hypoxia or shock. Many of these disorders are uncommon and initially may go undiagnosed. This type may appear slowly or abruptly with no apparent cause. The pH may be lowered, normal, or even elevated. Type B lactic acidosis is divided into subtypes associated with systemic disorders, drugs, toxins, and hormones; and enzyme defects. Patients with noninsulin-dependent diabetes mellitus often have a mildly elevated lactate level, a condition attributed to a defect in pyruvate oxidation. During ketoacidosis, blood lactate levels may be elevated several times, which contributes to metabolic acidosis. This elevation is probably caused by inhibitory effect of ketones on hepatic lactate uptake. Lactic acidosis is common in grand mal seizures, probably because of the overproduction of lactate. This condition is self-limited and requires no treatment. When the seizure ends, lactate serves as a substrate for the production of bicarbonate, and the acidosis is corrected. Although lactic acid levels often are increased in primary hepatic disease, frank lactic acidosis is rare, perhaps because of large functional reserves for hepatic uptake of lactate by the liver. Lactic acidosis can occur when additional stresses are placed on the liver, particularly by ethanol consumption or hypoglycemia ( 3). Occasionally, lactic acidosis has been associated with malignancies, particularly acute lymphocytic leukemia and solid tumors ( 3). Other disease states in which lactic acidosis has been reported include thiamine deficiency, metabolic acidosis ( 7), acute and chronic renal insufficiency, and Reye syndrome. No clear causal relationships have been defined. In type B lactic acidosis resulting from drugs, hormones, and toxins, alcohol is the most common cause. The increase in lactate levels associated with ethanol is caused by decreased clearance by the liver rather than by increased production of lactate ( 8). This is seldom severe, and the lactate level rarely exceeds 3 mM ( 8). Lactic acidosis can occur with ethanol consumption when other factors, such as liver disease, seizures, hypoglycemia, or diabetes mellitus, are present. Lactic acidosis in the alcoholic is easily reversible by the administration of glucose ( 9). Drugs associated with lactic acidosis include the oral hypoglycemic phenformin (which has been withdrawn from the market), salicylates, fructose, sorbitol, catecholamines, and methanol. Type B lactic acidosis associated with enzyme defects are listed in Table 64–4.1. Lactic acidosis has been associated with hypoglycemia, usually in association with enzyme defects in gluconeogenesis or glycogenolysis, primarily in children, or in adults with underlying hepatic or renal disease or alcoholism ( 1,3). When hypoglycemia and lactic acidosis occur together, the acidosis may not be reversible until the hypoglycemia is corrected, and often glucose may be all that is needed ( 3).

TREATMENT OF LACTIC ACIDOSIS The existence of lactic acidosis implies a serious underlying disease state. There is uniform agreement that the primary aspect of treatment in lactic acidosis consists of identification and treatment of the underlying cause ( Fig. 64–4.2). In the most common form, type A, associated with shock, this implies the restoration of blood pressure, cardiac output, and tissue perfusion. Volume replacement is achieved with fluids, plasma, or whole blood as necessary. Ventilation and oxygenation must be ensured. In this scenario, vasopressors are to be avoided because they may increase tissue hypoxia. In type B lactic acidosis, the underlying causes must be addressed but are usually much more difficult to determine.

Figure 64–4.2. Treatment of lactic acidosis.

Controversy surrounds the use of sodium bicarbonate in the treatment of lactic acidosis, although it has long been a mainstay of therapy. Severe lactic acidosis has numerous adverse effects, including depression of myocardial contractility and cardiac output, increased occurrence of ventricular arrhythmias, and impairment of response to catecholamines. Theoretically, treatment with sodium bicarbonate should be beneficial because it lessens the adverse hemodynamic effects of acidosis and restores the myocardial responsiveness to catecholamines. Early, aggressive use of bicarbonate may produce adverse effects, such as volume overload and congestive failure from the high sodium load, a left shift of the oxyhemoglobin dissociation curve and reduced tissue oxygenation, rebound alkalosis secondary to the

conversion of lactate to bicarbonate, and electrolyte disturbances. The use of bicarbonate in initial cardiopulmonary resuscitation has been curtailed. Several open trials have demonstrated no benefit from intravenous sodium bicarbonate administration in patients with lactic acidosis or diabetic ketoacidosis, and its routine use in cardiopulmonary resuscitation was abandoned many years ago. The weight of current evidence is against the use of intravenous sodium bicarbonate in the treatment of acquired forms of lactic acidosis. Occasionally, vasodilating drugs such as nitroprusside have been used successfully in the treatment of lactic acidosis ( 3). Theoretically, the reduction in afterload might increase cardiac output, tissue perfusion, and tissue oxygenation. These agents must be used carefully because uncontrolled vasodilation may lead to worsening hypoxia and acidosis. Hemodialysis and occasionally peritoneal dialysis have been used in the treatment of lactic acidosis because they may be successful in treating volume overload and hyperlactatemia.

PROGNOSTIC VALUE OF LACTIC ACID LEVELS Controversy surrounds the use of lactic acid levels to predict the outcome of certain clinical states. Because of its relationship to tissue perfusion, some studies show that the lactate level has prognostic significance for the outcome ( 3,10,11). This occurs primarily in disease states associated with low tissue perfusion, such as septic, cardiogenic, and hemorrhagic shock and pulmonary embolism. Other studies have both supported and refuted these findings. Underlying clinical states, including liver disease and nutritional state, could account for these differences. Perez et al. ( 10) noted that mortality rates increased from 18% to 73% in patients with lactate levels above 4.4 mEq/L. Weil and Afifi ( 11) found that only 11% of patients with a lactate level greater than 4 mEq/L survived circulatory shock. Others have noted that rapid clearance of lactate during therapy has more prognostic significance than peak lactate concentration ( 12,13). During rewarming of patients with hypothermia, washout may occur and cause increased lactate levels even though the patient's condition is actually improving ( 14).

MEDICOLEGAL PEARLS In lactic acidosis, the pH may be normal or even elevated if underlying alkalosis is present. The most common early sign of lactic acidosis may be compensatory hyperventilation. Severe hypoxia causing tissue hypoxia may produce lactic acidosis without shock. To date, no therapy specifically designed to lower arterial blood lactate levels has reduced mortality rates significantly. Prompt recognition and treatment of the underlying causes of lactic acidosis remain the cornerstone of treatment. During rewarming of a patient with hypothermia, washout may occur, causing the lactate level to increase even though the patient is improving clinically. References 1. Relman AS: Lactic acidosis: acid-base and potassium homeostasis. New York: Churchill Livingstone 1978:65–100. 1A. Ishihara K, Szerlip HM: Anion gap acidosis. Semin Nephrol 1998;18:83–97. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

Lloyd MH, Iles RA, Simpson BR, et al: The effect of stimulated metabolic acidosis on intracellular pH and lactate metabolism in the isolated perfused rat liver. Clin Sci Mol Med 1973;45:543. Kreisberg RA: Lactate homeostasis and lactic acidosis. Ann Intern Med 1980;92:227. Yudkin J, Cohen RD, Slack B: The haemodynamic effects of metabolic acidosis in the rat. Clin Sci Mol Med 1976;50:177. Waters WC, Hall J, Swartz WB: Spontaneous lactic acidosis. Am J Med 1963;35:781. Cohen RD, Woods HF: Clinical and biochemical aspects of lactic acidosis. Boston: Blackwell Scientific, 1976. Oliva PB: Lactic acidosis. Am J Med 1970;48:209. Kreisberg RA, Owen WC, Soegal AM: Ethanol-induced hyperlactatemia: inhibition of lactate utilization. J Clin Invest 1971;50:166. Miller PD, Heinig RE, Waterhouse C: Treatment of alcoholic acidosis. Arch Intern Med 1978;138:67. Perez DI, Scott HM, Duff J, et al: The significance of lactic acidemia in the shock syndrome. Ann NY Acad Sci 1965;119:1133. Weil MH, Afifi AA: Experimental and clinical studies of lactate and pyruvate as indicators of the severity of acute circulatory failure (shock). Circulation 1970;41:989. Vincent JL, Dufaye P, Berre J, et al: Serial lactate determination during circulatory shock. Crit Care Med 1983;11:449. Falk JL, Rackow EC, Leavy J, et al: Delayed lactate clearance in patients surviving circulatory shock. Acute Care 1985;11:212. Reuler JB: Hypothermia: pathophysiology, clinical settings, and clinical management. Ann Intern Med 1978;89:519.

Suggested Readings Bakker J, Gris P, Coffernils M, et al: Serial blood lactate levels can predict the development of multiple organ failure following septic shock.

Am J Surg 1996;171:221–226.

Cooper DJ: Hemodynamic effects of sodium bicarbonate (letter, comment): Intens Care Med 1994;20:306–307. Cooper DJ, Walley KR, Wiggs BR, Russell JA: Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis: a prospective, controlled clinical study (see comments). Ann Intern Med 1990;112:492–498. Kellum JA, Kramer DJ, Pinsky MR: Strong ion gap: a methodology for exploring unexplained anions. J Crit Care 1995;10:51–55. Kreisberg RA: Lactate homeostasis and lactic acidosis. Ann Intern Med 1980;92:227. Murphy FT, Manown TJ, Knutson SW, Eliasson AH: Epinephrine-induced lactic acidosis in the setting of status asthmaticus. South Med J 1995;88:577–579. Mizock J: Controversies in lactic acidosis. JAMA 1987;258:497. Sing RF, Branas CA, Sing RF: Bicarbonate therapy in the treatment of lactic acidosis: medicine or toxin? J Am Osteopath Assoc 1995;95:52–57. Stacpoole PW: Lactic acidosis. Endocrinol Metab Clin North Am 1993;22:221–245.

CHAPTER 65 ADRENAL INSUFFICIENCY AND ADRENAL CRISIS Principles and Practice of Emergency Medicine

CHAPTER 65 ADRENAL INSUFFICIENCY AND ADRENAL CRISIS David Baldwin, Jr. Capsule Pathophysiology Prehospital Assessment Clinical Presentation Abnormal Laboratory Results Differential Diagnosis Initial Management Follow-Up Management Pitfalls and Medicolegal Pearls

CAPSULE Although relatively uncommon, decompensated adrenal insufficiency is an important diagnostic consideration in a variety of acute medical conditions. Decompensation typically is provoked by a superimposed acute medical or surgical process that may overshadow underlying cortisol deficiency. Clues for this diagnosis are often nonspecific, yet the prompt institution of parenteral corticosteroid therapy is essential to stabilize these patients successfully. Acute adrenal insufficiency has a range of causes and occurs in patients of any age, from neonates to the elderly ( 1). Beware of adrenal crisis if there is severe infection (particularly meningococcal) or trauma.

PATHOPHYSIOLOGY The adrenals are highly vascular glands that secrete the glucocorticoid cortisol and the mineralocorticoid aldosterone. Cortisol is critical for the maintenance of arterial vascular tone and blood pressure and helpful in the maintenance of metabolic functions. Cortisol secretion is regulated strictly by the pulsatile secretion of hypothalamic corticotrophin-releasing factor (CRF), which triggers the release of pituitary adrenocorticotrophic hormone (ACTH). The latter directly stimulates the cortisol-producing cells of the adrenal. The operational integrity of these cells is critically dependent on the presence of ACTH. In its absence, these cells atrophy and lie dormant. During periods of stress, CRF, ACTH, and cortisol secretion are increased many times their basal rates. Aldosterone has two important roles in the regulation of renal tubular function. The first is its stimulation of the retention of salt and water. The second is its stimulation of the secretion of potassium by the distal nephron. Aldosterone secretion is not regulated by the pituitary but by potassium ion concentration and by the renin-angiotensin system. A decrease in renal blood flow triggers release of the enzyme renin, which catalyzes the conversion of hepatic angiotensinogen to angiotensin I. Angiotensin-converting enzyme (ACE) converts this to the potent vasoconstrictor angiotensin II, which raises systemic blood pressure and directly stimulates the release of aldosterone from the adrenals. Thus, salt and water are retained, blood pressure is raised, and renin release decreases as renal perfusion is improved.

PREHOSPITAL ASSESSMENT Most patients with adrenal crisis have a history of chronic adrenal insufficiency or exogenous glucocorticoid treatment. They should wear an emergency bracelet that identifies their need for exogenous steroids in times of stress. Such bracelets should be sought during the initial prehospital assessment. These patients and their families should have available, and be taught to administer, 100 mg of cortisone acetate intramuscularly (IM) or 4 mg dexamethasone IM at the first sign of severe stress, such as an infection or an accident.

CLINICAL PRESENTATION Patients may have adrenal crisis at any age. The typical infant with severe salt-wasting congenital adrenal hyperplasia exhibits vomiting, weight loss, and dehydration between 2 and 4 weeks of life. Hyponatremia, hyperkalemia, hypoglycemia, and acidosis are usually present and should immediately suggest this diagnosis. Ambiguous genitalia or precocious virilization are important clues ( 2). The clues to diagnosis in adults may be more subtle. Patients with chronic adrenal insufficiency have weight loss, weakness, anorexia, orthostasis, and abdominal pain. Acute stress may provoke adrenal crisis with vomiting, fever, shock, confusion, or coma. The most common stress factor is acute infection, which must be sought diligently in all such patients. Trauma, the acute surgical abdomen, and myocardial infarction are other common examples. Alternatively, an acute medical illness may cause acute adrenal destruction and add adrenal crisis to the patient's underlying condition. The classic example of this is the Friderichsen–Waterhouse syndrome of overwhelming sepsis, often caused by meningococcus. Another example recognized with greater frequency is acute adrenal hemorrhage associated with anticoagulants or seen after surgery in patients with hypotension ( 3). Hyperpigmentation, especially of knuckles and palmar creases, is an important clinical clue to chronic primary adrenal insufficiency, but it is missing in patients with adrenal insufficiency related to pituitary failure with ACTH deficiency. The most common example of ACTH deficiency, or secondary adrenal insufficiency, is seen in patients chronically treated with exogenous corticosteroids, such as prednisone. Recovery of the pituitary–adrenal response to stress may take as long as 1 year after high-dose chronic steroid therapy.

ABNORMAL LABORATORY RESULTS In primary adrenal insufficiency, the following abnormal laboratory values and conditions are seen: hyponatremia (80%) (if 95%) of this technique. With the patient's mouth open to the fullest extent, a 25-gauge long needle punctures the mucosa at a point higher than and slightly lateral to the conventional inferior alveolar nerve block. The needle is inserted distolateral to the maxillary second molar at the height of the mesiolingual cusp of the second molar. It is directed toward the intertragic notch of the external ear. The needle is advanced slowly while the barrel of the syringe is maintained slightly above the contralateral mandibular canine and first bicuspid. The neck of the condyle is contacted gently at a depth of approximately 25 mm. The needle is withdrawn slightly, and aspiration is performed. Then 1.5 to 1.8 mL of anesthetic solution slowly is injected. If contact with the condylar neck is not achieved at a penetration depth of 27 mm, the needle position should be reassessed. Medial deflection of the needle is the most common cause of failure to contact the neck of the condyle.

Figure 115.11. Gow–Gates inferior alveolar nerve block. A. Area anesthetized. B. Proper position of the needle and syringe. C. Insertion of the needle is higher than the conventional inferior alveolar nerve block; needle advancement is distolateral toward the neck of the condyle.

Inferior Alveolar Nerve Block “Akinosi” Technique The Akinosi inferior alveolar nerve block ( 8) is reserved for situations in which limited mandibular opening precludes conventional approaches. A 25-gauge, 3.6-cm needle is recommended for successful anesthesia. The buccal tissues are retracted laterally by the index finger or thumb, and the maxillary trough is visualized. The needle puncture site is located medial to the ramus of the mandible directly adjacent to the maxillary tuberosity at the height of the mucogingival junction of the maxillary molars. The syringe slowly is directed posteriorly as the barrel of the syringe is held parallel to the facial surface of the maxillary teeth. The needle penetrates to a depth of 25 mm. In contrast to the conventional inferior alveolar nerve block, no contact with bone is obtained. The tip of the needle lies medial to the mandibular foramen close to the branches of the mandibular nerve. Aspiration is performed, and if it is negative, 1.5 mL of anesthetic solution is deposited. Lingual Nerve Block The lingual nerve lies anterior and slightly medial to the inferior alveolar nerve ( Fig. 115.12). Because of the proximity of the two nerves, the lingual nerve block usually is performed concurrently with the inferior alveolar nerve block. It provides analgesia to the anterior two thirds of the tongue, the floor of the mouth, and the lingual mucosa and mucoperiosteum of the mandible. To perform the lingual nerve block, the anesthetist locates the same landmarks that are required for the inferior alveolar nerve block. The needle penetrates approximately 1 cm or is slowly withdrawn 4 to 6 mm from the lingual periosteum of the mandibular sulcus after the inferior alveolar nerve block. Aspiration is performed, and 0.5 mL of anesthetic solution is deposited. The nerve may be blocked by submucosal infiltration 5 mm below and 5 mm behind the third molar region.

Figure 115.12. Lingual nerve block. A. Area anesthetized. B. Proper position of the needle and syringe. C. Insertion of the needle is similar to inferior nerve block, but penetration is 5 mm less.

Buccal Nerve Block The buccal nerve provides sensory innervation to the soft tissues lateral to the mandibular molars and frequently is not anesthetized by the inferior alveolar nerve block (Fig. 115.13). To access the buccal nerve, a 25- or a 27-gauge short needle is inserted distolateral to the mandibular third molar and slightly medial to the external oblique ridge, where the buccal nerve passes over the anterior border of the ramus. With the bevel of the needle directed toward bone, the needle is slowly advanced while the barrel of the syringe is maintained parallel to the occlusal plane. A few drops of anesthetic are deposited. When the needle penetrates approximately 3 mm, the periosteum gently is contacted. The needle is slightly withdrawn, the solution is aspirated, and 0.5 mL of anesthetic is deposited slowly.

Figure 115.13. Buccal nerve block. A. Area anesthetized. B. Proper position of the needle and syringe. C. Insertion of the needle is distolateral to mandibular third molar and slightly medial to the external oblique ridge.

Mental Nerve Block The mental nerve exits from the mental foramen generally apical and slightly anterior to the second bicuspid root. It innervates the lower lip and mucous membrane of the anterior mucolabial fold ( Fig. 115.14). With the mouth nearly closed, the nerve is anesthetized easily at this location by retracting the cheek laterally and penetrating the mucosa of the mandibular vestibule between the roots of the bicuspid teeth. The needle, with the bevel toward bone, is inserted from a lateral superior direction until gentle contact with the periosteum occurs near the apex of the second bicuspid root. The needle is slightly withdrawn, and 0.5 to 1 mL of solution is slowly deposited. The exact location of the mental foramen can be determined in advance if panoramic radiographs are available for review.

Figure 115.14. Mental nerve block. A. Area anesthetized. B. Proper position of the needle and syringe. C. Needle penetrates the mucosa of the mandibular vestibule between the biscuspid teeth.

ADVERSE EFFECTS Local anesthetics are safe drugs with a wide therapeutic index, yet complications may arise despite careful attention to proper technique. For the most part, untoward reactions are the direct consequence of the pharmacologic properties of the agent, the presence of a vasoconstrictor or other additive, rapid systemic absorption, concomitant drug therapy, and vasovagal response, with psychogenic reactions the most common. Other adverse experiences include idiosyncratic reactions, diminished patient tolerance, immediate blanching of the facial skin, deviation of the eye and transient blurring or loss of vision, facial nerve palsy, hematoma formation (Fig. 115.15), and hypersensitivity reactions such as angioedema, urticaria, dermatitis, or anaphylaxis ( 1A,9,10,11 and 12). Usually hypersensitivity is attributed to methylparaben, a bacteriostatic and fungistatic preservative included in multiple-dose vials. Tissue sloughing, myositis, parasthesia, and postinjection pain may occur if excessive amounts of local anesthetic solution are deposited or if the needle damages a nerve during the injection. Recurrent herpes simplex is a common postanesthetic lesion.

Figure 115.15. An adverse reaction to intraoral local anesthesia. A. Facial appearance. B. Hematoma formation as a result of needle penetration of the inferior alveolar vascular bundle.

Serious adverse reactions, generally systemic in nature, result directly from the amount and rate of drug dose ( Table 115.2) and drug absorption relative to drug elimination. Rapid absorption caused by a too-rapid injection, inadvertent intravascular injection, or injection into a highly vascular area are common causes. Other causes include altered detoxification, administration of too large an amount of local anesthetic, injection of the wrong concentration, injection without a vasoconstrictor, and failure to correct for the patient's physical status. Different local anesthetics that are equally potent may differ markedly in their toxicity. The signs and symptoms of toxicity predominate in the central nervous and cardiovascular systems.

Table 115.2. Relative Toxicities of Intraoral Local Anesthetics

Local anesthetics readily cross the blood–brain barrier. At low plasma levels, there is no central nervous system effect. At toxic levels, however, the drug depresses the central inhibitory centers. This depression is characterized by lightheadedness, yawning, apprehension, excitement, talkativeness, slurred speech, disorientation, dizziness, blurred vision, muscle twitching, convulsions, and unconsciousness. The excitatory manifestations, which may be brief or not apparent at all, are followed by depression of the facilitatory centers manifested by lethargy, dyspnea, apnea, bradycardia, peripheral vasodilation, hypotension, shock, coma, respiratory arrest, and cardiac arrest. Sympathomimetic vasoconstrictors, along with the release of endogenous catecholamines, may elicit adverse effects in some patients. In healthy persons, the effect is usually transitory because the total dose of epinephrine is small. Mild side effects include heart palpitations, throbbing headache, tenseness, and tremor. In patients with chronic cardiovascular disease, severe reactions may cause cardiac arrhythmias, chest pain, or cardiac arrest ( 13). Because of these effects, vasoconstrictors should be used with caution in patients with hyperthyroidism, pheochromocytoma, cardiovascular disease, and recent myocardial infarction. In addition, long-acting anesthetics, such as etidocaine and bupivacaine, have more cardiac depressant properties than lidocaine. Deaths have been documented after caudal anesthesia using long-acting anesthestics. Hypersensitivity reactions to local intraoral anesthesia are rare. When they occur, urticaria and difficulty in breathing are the first clinical manifestations. If the symptoms progress to anaphylaxis, immediate action is required. Epinephrine (0.5 mL of a 1:1000 solution) delivered into the floor of the mouth or subcutaneously, followed by oxygen, Benadryl, intravenous access, and hydrocortisone, is indicated. It is prudent for the clinician to realize that sulfites, which are added to local anesthetics containing vasoconstrictor, can precipitate bronchospasm in patients with asthma. Therefore, local anesthetics containing vasoconstrictor should be used with caution in patients with extrinsic asthma.

FAILURE OF INTRAORAL LOCAL ANESTHESIA

Failure to achieve optimal local anesthesia usually results from an insufficient knowledge of anatomy, individual anatomic variation, faulty technique, variations caused by age, patient fear, and occasionally ineffective solution. To minimize anesthesia failure, the patient should be calmed and reassured. The anatomy of the region should be mentally pictured and the technique to be performed well understood. The final step, accurate delivery of the drug, is required to ensure success. Even with the best-planned effort, local anesthesia may fail. Inadequate anesthesia occurs most often in association with the inferior alveolar nerve block. Some reasons for incomplete anesthesia are failure to consider that the mandibular foramen in children is relatively lower than it is in adults; the patient may close his or her mouth during the injection, which can misdirect the needle or allow the solution to diffuse away from final target site; supplemental innervation from the mylohyoid, lingual, buccal, or upper cervical nerves; the presence of aberrant branches from the inferior alveolar owing to a bifid mandibular foramen ( 14), and (5) low tissue pH associated with inflammation (abscessed tooth), which prevents profound anesthesia ( 15). In the latter instance, nerve block anesthesia delivered sufficiently proximal to the inflamed tissue may help.

DRUG INTERACTIONS Adverse drug interactions are rare at the doses typically used for dental procedures. Awareness of drug interactions, however, helps to prevent unwanted systemic reactions to local anesthetics or vasoconstrictors. To prevent untoward drug interactions, the following interactions are provided. Local anesthetics can potentiate the sedative and cardiorespiratory depressant effects of central nervous system depressant drugs; thus, reduced doses are recommended. Sulfonamides are inhibited by metabolites of ester-type anesthetics; therefore, procaine, chloroprocaine, or tetracaine should not be used when a sulfonamide is being taken by a patient. Metals react adversely with local anesthetics, resulting in the release of metallic ions and severe local irritation. Disinfecting agents containing heavy metals should not be used to disinfect the skin or mucous membranes. A mild hypertensive response may result from the use of local anesthetics with a vasoconstrictor in patients taking monoamine oxidase inhibitors, tricyclic antidepressants, and phenothiazines. Concurrent use of propranolol may enhance the b-adrenergic, cardiostimulatory effects of epinephrine. A patient who has consumed barbiturates, smokes cigarettes, or is taking b blockers or an H2 histamine antagonist may have prolonged plasma levels of local anesthetic drug resulting from reduced metabolism, but the effect is probably not clinically significant.

MEDICOLEGAL PEARLS A stepwise approach to local intraoral anesthesia should include a thorough medical evaluation, proper drug selection, and correct patient positioning. The anesthetist should be careful to allay the fears of the patient, obtain informed consent before the procedure, and use a topical anesthetic if feasible and available. Minimal drug dose and concentration necessary to accomplish the objective, along with a vasoconstrictor, should be used. The oral anesthetist should always aspirate before the injection, inject slowly, and closely monitor the patient. He or she should be cognizant of the overall dose of drug and vasoconstrictor, realizing that no local anesthetic ever exerts a single action and its systemic effect varies with the choice of drug, vascularity of the region, presence of a vasoconstrictor, and the patient's physical condition. Reduced dosages for children and for elderly and debilitated patients are recommended. The amount, concentration, and route of delivery of the local anesthetic, as well as the patient's response and disposition, should be documented in the medical record. Life support equipment, monitoring devices, and antidotes should always be available.

NATIONAL CONTACTS The emergency physician should obtain the appropriate supplies and instruments to perform intraoral local anesthesia. The following companies have been listed merely to help locate the required items: Astra Pharmaceutical Products, Inc., 50 Otis Street, Westborough, MA 01581; (508) 366–1100. Peerless International, Inc., 438 Depot Street, South Easton, MA 02375, 1-800-527-2025. References 1. Milam SB, Giovannitti JA. Local anesthetics in dental practice. Dent Clin North Am 1984;28:493–508. 1A. Danbland M, Muller R, Lipp M: The incidence of complications associated with local anaesthesia in dentistry. Anesth Prog 1977;44:132–141. 2. 3. 4. 5. 6.

Sisk AL. Comparison of etidocaine and lidocaine for control of intra- and post-operative bleeding and pain. J Oral Maxillofac Surg 1986;44:16–20. Jastak JT, Yagiela JA. Vasoconstrictors and local anesthesia: a review and rationale for use. JADA 1983;107:623–630. Shannon IL, Isbell GM. Adrenocortical response in patients receiving intraoral injections. Oral Surg 1963;116:1145–1149. Clutter J. Epinephrine and hemodynamic changes in man. J Clin Invest 1980;66:94–101. Minasian A, Yagiela JA. The use of amide local anesthetics in patients susceptible to malignant hyperthermia. Oral Surg Oral Med Oral Pathol 1988;60:405–415.

6A. Koren G, Pastuszak A, Ito S: Drugs in pregnancy. N Engl J Med 1998;338:1128–1137. 6B. Saso M, Isen D, Nenninger S, et al: Mandibular nerve block. J Can Dent Assoc 1997;63:805–808. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

Gow–Gates GAE. Mandibular conduction anesthesia: a new technique using extraoral landmarks. Oral Surg 1973;36:321–330. Akinosi JO. A new approach to the mandibular nerve block. Br J Oral Surg 1977;15:83–87. Cooper JC. Deviation of eye and transient blurring of vision after mandibular nerve anesthesia: report of a case. J Oral Surg 1962;20:151–152. Kronman JH, Giunta JL. Reflex vasoconstriction following dental injections. Oral Surg Oral Med Oral Pathol 1987;63:542–544. Traeger KA. Hematoma following inferior alveolar injection: a possible cause for anesthetic failure. Anesth Prog 1979;26:122–123. Nique TA, Bennett CR. Inadvertent brain-stem anesthesia following extraoral trigeminal V2–V3 blocks. Oral Surg 1981;51:468–470. Lilienthal B. Cardiovascular responses to intraosseous injections containing vasoconstrictors. Oral Surg 1976;42:552–558. Langlais RP, Broadhus R, Glass BJ. Bifid mandibular canals in panoramic radiographs. JADA 1985;110:923–927. Kaufman E, Weinstein P, Milgrom P. Difficulties in achieving local anesthesia. JADA 1984;108:205–207. Maxwell GM. The cardiovascular effects of Octapressin. Arch Int Pharmacodyn Ther 1965;158:17–23.

Suggested Readings Allen GD. Dental anesthesia and analgesia (local and general). 3rd ed. Baltimore: Williams & Wilkins, 1984:48–177. Kretzchmar JL, Peters JE: Nerve blocks for regional anaesthesia of the face. Am Fam Physician 1997;55:1701–1704. Lipp M, Daublander M, Fuder H: Local anaesthesia in dentistry. New York: Quintessance Publishing, Co., 1993. Malamed SF. Handbook of local anesthesia. 4th ed. St. Louis: CV Mosby, 1996. Roberts DH, Sowray JH. Local analgesia in dentistry. Bristol, UK: Wright Publishing, 1987:1–160.

Chapter 116.1 Odontogenic Pain: Toothache and Pain of Dental Origin Principles and Practice of Emergency Medicine

CHAPTER 116 TOOTHACHE AND PAIN OF DENTAL ORIGIN

1 Odontogenic Pain: Toothache and Pain of Dental Origin Bruce R. Rothwell Capsule Type of Pain Pathophysiology and Anatomy Clinical Presentation and Examination Differential Diagnosis Procedures Initial Stabilization and Management Pain Relief National Contacts

“For there was never yet philosopher that could bear the toothache patiently” William Shakespeare

CAPSULE Pain of dental origin is one of the more common predicaments confronting patients and emergency care providers alike. Despite significant advances in preventive and restorative dental care, toothaches and more advanced dental problems continue to necessitate urgent treatment for many. Although most persons seek attention from dentists when pain originates in the oral region, many obtain care through emergency medical care facilities. In addition to the relatively straightforward diagnosis and short-term management of the uncomplicated toothache, orofacial pain may indicate more serious underlying maladies. A differential diagnosis of other varieties of orofacial pain syndromes must be considered in the workup of odontogenic pain ( 1A,1B). Most simple toothaches without infection or involvement of other oral structures can be managed by elementary measures to alleviate pain until more definitive dental care can be obtained. Hospitals or other emergency care facilities with dental support can arrange to provide timely dental diagnosis and treatment even for relatively complex situations. Health care providers performing triage operations in the emergency department (ED) may have to separate patients requiring immediate care from those for whom a delay in extensive treatment will not pose a problem. Odontogenic pain may be referred to regions distant from the site of the affliction and may mimic a number of other conditions, including sinusitis, neuralgia, and arthritis. In addition, in many patients, pain appearing to emanate from the sinuses, the temporomandibular point, or other facial structures may in fact be of dental origin. Thus, appropriate history, examination, and diagnosis are essential for proper management. Despite significant reductions in the prevalence of dental diseases in the United States, pain of dental origin continues to be one reason many patients contact emergency treatment facilities. With the changing frequency of dental disease, there has been a shift in the demographics of those most likely affected ( 1). Dental problems are now more common in lower socioeconomic groups and among those less likely to receive regular dental care. These people are also more likely to seek only episodic medical care and to go to emergency facilities for acute dental problems.

TYPE OF PAIN Dental pain may follow carious destruction of dental tissues, involvement of pulpal tissue resulting in periapical abscesses, or periodontal infections. Most of these conditions are lumped into the “toothache” category. Other less dentally oriented ailments can result in orofacial pain. These include dentoalveolar trauma, bacterial and viral infections of soft tissues, neuralgias of facial nerves, sinusitis, and temporomandibular disorders. Sometimes dental pain can result directly or indirectly from dental treatment. Recently placed dental restorations can cause mild to severe discomfort, and older fillings can deteriorate to a state in which teeth become painful. Teeth with large fillings can lose structural integrity after repeated masticatory stress and become cracked, with or without displacement of the broken fragment, and often with pain on biting. Toothaches often are baffling. Teeth are visceral structures with sensory capabilities similar to those of other visceral organs. Dental pulps are individual, separate organs with discrete connections to the neural system. Pain of dental origin can occur acutely with little or no forewarning, or it can be a chronic condition with either increasing severity or diminishing tolerance on the part of the sufferer. Truly acute problems are less common and can result from fractured teeth, pulp exposures, or infectious processes that impact vital structures. More commonly, there is some portent of an affliction with mild or intermittent discomfort that, when ignored, later develops into more intense distress. Although the result may seem similar, there is often a considerable difference in the extent and progress of the underlying disease process. Management of odontogenic pain can vary from definitive treatment to simple pain relief. Depending on the nature of the symptoms and the availability of dental services, a treatment decision can be formulated concerning the extent of management. With uncomplicated toothaches, pain relief with analgesics, local anesthetics, or dental blocks allows a patient to seek more definitive dental therapy later. If there is an infection, particularly one involving vital structures of fascial spaces, more definitive treatment and appropriate antibiotics are necessary.

PATHOPHYSIOLOGY AND ANATOMY Oral Anatomy and Terminology Teeth and the immediately adjacent supporting soft tissues and bone are most likely to be the affected structures in painful processes. Teeth are comprised of enamel, dentin, and cementum, and they contain neural and vascular elements in the pulpal tissue. Teeth are embedded in the alveolar bone, attached and supported by periodontal soft tissues. Connection between root surfaces and bone is effected through periodontal ligament fibers. The five exposed surfaces of the teeth are referred to as buccal or facial (lateral), mesial (anterior), distal, lingual, or palatal (medial), and occlusal (the top biting surface) ( Fig. 116–1.1).

Figure 116–1.1. Tooth anatomy, sagittal section.

There are generally 20 teeth in the deciduous dentition and up to 32 adult teeth, although third molars (wisdom teeth) are often missing because of previous extraction or lack of eruption. The deciduous teeth erupt between the ages of 6 months and 2½ years, and the permanent teeth begin to erupt at approximately age 6. The oral cavity can be divided into four parts and is referred to by quadrant designations such as upper right (UR) or lower left (LL). The permanent dentition is

designated by a 1-to-32 numbering system, beginning with number 1 in the maxillary right posterior (third molar) and moving sequentially in a clockwise direction to the maxillary left (no. 16), mandibular left (no. 17), and back to mandibular right posterior (no. 32) ( Fig. 116–1.2).

Figure 116–1.2. Normal adult dentition with full complement of 32 teeth.

Dental Caries Caries continue to be one of the most common afflictions of the oral cavity. Dental caries is caused by bacteria, which produce substances that destroy mineralized tooth structures and can ultimately result in infections of pulpal tissues. It is often an asymptomatic process because enamel is not innervated, and involvement of the dentin may be only mildly and intermittently painful. The development of dental caries is a lengthy course, commonly extending over months or years. This chronic process can become acutely painful when the decay involves extensive amounts of dentin or invades the pulpal tissue. Although caries can occur insidiously, it is more likely to be a result of long-term dental neglect. Most cases of dental pain involve extensive carious destruction of several teeth. Caries often undermines existing dental restorations, with resultant fracture of the teeth or displacement of the filling material. Carious exposure of dental pulp can lead to intense toothaches and eventually to bacterial infection of pulp and periapical tissues. Inflammatory Conditions Many conditions that can result in orofacial pain may appear to originate in the dental structures. Most are infectious or inflammatory conditions involving the periodontal structures. Gingivitis is inflammation of the gingival tissues immediately adjacent to the teeth, and periodontitis is the extension of that inflammation to the periodontium and alveolar supporting bone. These are often painless processes and are not usually confused with odontogenic pain, but some acute varieties (e.g., necrotizing ulcerative gingivitis) produce symptoms not unlike simple tooth pain. In patients with dental neglect, caries, periodontal disease, and other conditions exist concurrently, and it may be difficult to sort out the primary cause of the acute complaints. Extension of the process of caries or exposure of pulpal tissues by other means produces inflammation of the neurovascular tissues of the dental pulp. Pulpitis can be confined to the tooth or extend to affect the periapical tissues at the end of the root. Most of what is referred to as “dental abscess” is a result of pulpitis or other periapical abnormality. These conditions are covered in more detail in other chapters. The Uncomplicated Toothache One of the early decisions that must be made in managing a patient with pain of apparent dental origin is the assessment of the level of involvement and the extent of the process. Clearly, most “toothaches” are not serious problems, but extension of infections to fascial spaces of the head and neck or dentoalveolar trauma are situations that require expeditious management ( 2,2A). Pain originating from the teeth, usually as a result of caries, without involvement of other structures or systemic reaction, may be classed as an uncomplicated toothache and managed accordingly. These uncomplicated situations are not accompanied by fever, swelling, lymphadenopathy, or other signs of infection. In addition, traumatic avulsion of teeth and fractures are not noted in the history. Usually, the cause is readily apparent and is limited to the dental structures. Usually caries is the underlying process, with the concomitant production of varying degrees of pulpal inflammation (pulpitis). Reversible pulpitis produces dental pain of short duration as a reaction to specific stimuli such as cold, heat, or percussion. Irreversible pulpitis produces pain by specific provocation or no exact cause, and the painful episode often extends well beyond the inciting event. Irreversible pulpitis often awakens people from sleep or may keep them from sleeping. It is not uncommon for a person with a toothache to come to an ED in the early morning hours after unsuccessful attempts to sleep. Dental pain also may result from previously placed dental restorations that have become defective. This process usually involves a slowly developing, slowly increasing progression of pain on chewing hot, cold, or sweet foods. It may be something as overt as a large filling that has fallen out or a crown or bridge that has become dislodged. Defective restorations that are not dealt with expeditiously often develop caries around the leaking or open margins of the restorations. Long-standing fillings that have fallen out frequently are associated with grossly carious teeth. Recently placed dental restorations may become acutely painful. Most restorative materials are dental pulp irritants, good thermal conductors, or both. It is relatively common for people to have increased hot or cold sensitivity after the placement of amalgams or gold alloy crowns, and many dentists advise patients of this possibility. Generally, this tenderness is relatively minor and usually resolves over a few weeks. More prolonged or intense pain could indicate irreversible pulpal distress. Trauma often causes dental pain, either immediately after the injury or as a delayed phenomenon. Generally, the history of an injury is clear, but it may not be readily apparent to the practitioner, particularly if time has elapsed. Even patients with no clear history of trauma to the dentition can have dental pain from injuries to the teeth. Posterior teeth with preexisting restorations are particularly prone to the “cracked tooth syndrome,” in which repeated occlusal forces cause a cusp to fracture incompletely from the body of the tooth. Continuing occlusal forces produce pain in the tooth on chewing or percussion. This condition is particularly difficult to diagnose because there is often no clinical or radiographic evidence of the incomplete fracture. Patients may experience several weeks of discomfort before the fragment is dislodged from the remainder of the tooth. Paradoxically, the associated pain is diminished by then.

CLINICAL PRESENTATION AND EXAMINATION History A pertinent medical history should be obtained from patients with dental complaints, particularly regarding allergies, current medications, medical problems, and difficulties with dental treatment. Information about the chief symptom should include a description of the nature, severity, and character of the pain. The location of the painful area and factors (hot, cold, percussion) that elicit distress should be determined, along with the duration of pain after removal of the stimulus. Any recent dental care, particularly in the same region as the current symptoms, should be considered in the evaluation. Physical Examination For even apparently routine toothaches, the standard vital signs of pulse, blood pressure, and temperature should be obtained. Although most dental phenomena are localized, infectious processes may produce fever, and patients with more complicated oral abnormalities may have diminished water intake and resultant fluid imbalances. Before the intraoral examination, particular extraoral and facial structures should be examined and palpated. Because most oral structures are drained by lymph node chains in the neck, the sublingual, submental, anterior cervical, and preauricular lymphatics should be palpated to distinguish inflammatory enlargement or soreness. In addition, facial structures should be inspected for localized swelling, and both sides should be compared for alterations in symmetry. Percussion and palpation can

be carried out over the maxillary and frontal sinuses to help rule out involvement of these structures. Because pain related to tooth pain is often referred to the preauricular region, the temporomandibular joint (TMJ) and surrounding structures should be palpated for associated manifestations to aid in the differentiation of the source. Even toothaches with pain radiating to the TMJ generally do not produce pain on palpation directly over the joint region. After the extraoral examination, intraoral structures can be examined by visual inspection, palpation, and percussion methods. Soft tissues usually are examined before the periodontium and teeth, with particular regard for swellings, erythema, and alterations in normal anatomy. The oral mucosa consists of three general types: the masticatory mucosa covering the hard palate and gingiva, the lining mucosa of the lips and cheeks, and the specialized mucosa covering the dorsum of the tongue (3). All normal tissues are various shades of pink, from the coral pink of the gingiva to the more vermilion hue of the lining mucosa. Intense erythema of the mucosa indicates local or underlying inflammation. Inflammation of the periodontium, particularly the gingiva immediately adjacent to the teeth, is readily apparent with moderate to intense erythema. If available, periodontal probes can be used to scrutinize the gingival sulcus. After the mucosal and periodontal examination, the dentition can be examined visually and percussion, palpation, and other tests can be performed. Teeth should be examined for obvious carious lesions, fractures, defective restorations, or cracks. If the pain can be localized to a specific quadrant, closer attention can be paid to those teeth, and percussion of each tooth can elicit the offending site. The blunt end of a small instrument, such as a dental mirror, can be used to tap on the occlusal (biting) surface of each tooth. Approximately 80% of teeth with painful pulpitis will react positively to percussion ( 4). If an intraoral, high-intensity fiber-optic light source is available, teeth can be transilluminated to check for cracks and interproximal carious lesions. In many patients, the application of heat or cold to teeth can elicit temperature-dependent symptoms. Cold applied to individual teeth using small chips of ice or cotton rolls sprayed with ethyl chloride is a relatively simple diagnostic aid for many forms of pulpitis. Although some toothaches are relieved by cold, most are aggravated by the direct application of ice, allowing localization of the problem. Dentists often use an electric pulp tester to determine the vitality of individual teeth, but this instrument may not be available to the physician in the ED. Teeth with inflamed periapical regions are often tender on biting. It is possible for traumatic occlusion to be the underlying cause of odontogenic pain when a tooth in premature contact produces acute or chronic damage to the adjacent periapical tissues and the resultant pain. Thus, an examination of the occlusion often elicits at least the region of involvement. Radiographs Radiographs are valuable diagnostic tools to determine the cause of odontogenic pain. Although it is possible for pain to emanate from a tooth without demonstrable changes on radiography, more commonly the underlying cause is apparent. Intraoral periapical films are the best method to image each tooth and its surrounding periodontium. If these are unavailable in the ED, extraoral films can be used instead, but have much less resolution as to teeth. Panoramic radiographs depict a broad overview of the jaws, dentition, and TMJs, and they are a good screening tool. If no dental radiographs are accessible, traditional plane films of the jaws, such as right and left lateral jaw surveys, can be used to evaluate gross problems.

DIFFERENTIAL DIAGNOSIS When pain is thought to originate in the dentition, other sources must be considered in the differential diagnosis ( Table 116–1.1) regarding structures in and out of the oral cavity. The enigmatic behavior and variable nature of dental pain make a precise diagnosis difficult. As Bell characterizes the analysis of dental pain, “The extreme variability of toothache is such that a good rule for any examiner is to consider all pains about the mouth and face to be of dental origin until proved otherwise” (5).

Table 116–1.1. Differential Diagnosis—Dental Disorders

There are, however, some common characteristics of all dental pain. The discomfort is described most frequently as a dull, aching, often throbbing sensation with paroxysms of lancinating pain. Because pain arising from the dental pulp is localized poorly, it is frequently difficult to discern which arch is involved, let alone which tooth. There is considerable variation in the relationship between the stimulus and the severity of pain, both between groups and in the same person. As indicated previously, percussion, biting, and thermal factors often provoke responses, but the initiation can be spontaneous. Involvement of the periodontal structures is likely to manifest pain that is readily localized. Thus, pulpal conditions that have extended to the periapical tissues are delineated more easily, which makes the diagnosis of early pulpal inflammation difficult. In formulating a differential diagnosis for suspected odontogenic pain, an inventory of dental conditions is reasonably prudent as a first step. Pulpitis, either reversible or irreversible, is by far the most common underlying cause of pain emanating from the dentition, and pulpal involvement that has spread to the surrounding periapical tissues is next in probability. Cracked teeth or defective restorations are less common and generally less painful, and they may be the result of recurrent caries. Teeth that are in premature contact may become tender, and recent dental care that has caused either pulpitis or occlusal trauma often causes localized tooth pain. Less common conditions, such as acute necrotizing ulcerative gingivitis, periodontal abscess, or acute trauma, are unlikely to be confused with other dental conditions. Nondental situations (Table 116–1.2) can produce pain that may appears to be of dental origin. Although they are less common than odontogenic ailments in causing facial and perioral pain, they must be considered if the cause is not apparent. Teeth can become tender from pharyngeal or nasal inflammation, and maxillary sinusitis often causes teeth in an entire quadrant to be tender on percussion or biting.

Table 116–1.2. Nondental Origins of Facial Pain

Temporomandibular disorders and myofascial pain dysfunction syndromes often mimic tooth pain, particularly when the masseter or temporalis muscles are involved. Additionally, toothache pain can be referred to the ear or the preauricular region on the same side. There are several reports of cardiac pain referred to the jaws,

particularly the mandible, that may mimic dental pain ( 6,7). Conditions such as trigeminal neuralgia and other types of neuritis often produce facial pain that closely mimics tooth pain. Less common antecedents for toothache-like pain include local malignancies, Herpes zoster exacerbations, elongated styloid process (Eagle syndrome) (8), and distant malignancies such as leukemias and lymphomas (9). Several unrelated ailments can cause pain of this sort.

PROCEDURES Simple diagnostic maneuvers can be used to define the diagnosis of pain arising in the dentition. As previously indicated, the dental examination ( Table 116–1.3) begins with the history, vital signs, and evaluation of extraoral structures. After assessing any facial swelling, lymphadenopathy, or TMJ involvement, the attention can move to the intraoral structures, including soft tissues and teeth. Any swelling, erythema, purulent exudate, or alteration in the mucosa or the gingiva should be noted, and the gingival sulcus area can be investigated with periodontal probes for pocketing. Gross caries or fractured teeth generally are apparent on visual examination, but other conditions may be more subtle. If the patient can localize the pain to a particular area, percussion of the teeth in that quandrant will help to clarify the specific site. If available, transillumination can be used to scrutinize teeth for caries or cracks. The application of ice or ethyl chloride helps to determine teeth with pulpitis. Occlusal prematurities may be distinguished by palpation of individual teeth during biting.

Table 116–1.3. Dental Examination

Radiographs are extremely helpful in the analysis of coronal caries and periapical involvement. Carious destruction is visualized as a radiolucency in the relatively opaque enamel and dentin. Periapical involvement may not produce any apparent changes in the surrounding bone in early stages, but later it exhibits discrete or diffuse radiolucencies of alveolar bone. Intraoral dental films (periapical, bite-wing) render the greatest detail of dental structures but may not be available to hospital EDs. Extraoral films such as panoramic or lateral jaw films are readily available but do not provide the fine detail necessary for accurate diagnosis of subtle problems.

INITIAL STABILIZATION AND MANAGEMENT Toothache In providing treatment for dental pain, it is important to determine the extent of involvement and whether other orofacial structures are involved. For the purposes of this section, it is assumed that the main goal will be the relief of pain in the uncomplicated toothache ( Table 116–1.4). Because other situations produce pain that may simulate tooth pain, it is important to establish that the problem in question is indeed a simple toothache ( Table 116–1.5). Odontogenic pain is usually sharp or dull, with throbbing intensity localized to the jaws. There is often an obvious dental problem (caries, lost restoration) but usually no facial swelling, lymphadenopathy, or fever. Similarly, the intraoral inspection does not reveal any soft-tissue masses or purulent exudates. Involved teeth are likely to be sensitive to percussion and thermal (particularly cold) tests. Radiographs, if available, do not demonstrate any large radiolucent periapical lesions.

Table 116–1.4. Diagnosis and Management of Simple Toothache

Table 116–1.5. Simple Toothaches

PAIN RELIEF Local Anesthetics Although it has no effect on the underlying dental causes, the immediate management goal in these situations is relief of pain. It is not reasonable to expect a patient at an emergency medical facility to receive definitive treatment of dental problems, even if a dentist is available. Attention, therefore, is directed to short-term pain management. Probably the safest and most effective way to provide pain relief for an isolated dental problem is to provide a local anesthetic nerve block. With anesthetics of longer duration, patients can receive 4 to 12 hours of pain relief in a segment of the dentoalveolar process. The newer extended-duration local anesthetics, such as

bupivacaine and etidocaine, are particularly useful in affording overnight pain relief for patients until they can be treated by a dentist the next day. Oral Analgesics Oral analgesics are a mainstay for pain relief in dentistry either in place of or as a complement to local anesthesia. Tooth-related pain can be categorized as mild, moderate, or severe, and distinct analgesics or combinations are prescribed for pain relief. Orofacial pain appears to respond differently to oral analgesics because of the underlying cause. Acute pain of surgical or traumatic origin responds well to nonsteroidal anti-inflammatory drugs (NSAIDS), particularly when a loading dose is available. Ketorolac (toradol, 60 mg intramuscularly) can be administered in the ED, and response can be evaluated within 30 minutes. Toothaches of longer duration, however, may not be well relieved by NSAIDS and often require more potent narcotic analgesics, such as codeine, demerol, or oxycodone preparations. Tooth pain originates either in the dentin or from the inflammation of pulpal tissues ( 10). Typically, dental pain can be managed at the peripheral inflammatory source, the site of pain perception in the central nervous system, or both. Combinations of narcotics that act centrally to obtund the perception of pain and prostaglandin-inhibiting analgesics to manage the peripheral inflammatory pain are generally effective. For mild pain, simple oral analgesics, such as aspirin 600 mg, or one of the NSAIDS, such as ibuprofen 200 to 400 mg, are effective for adults. For those in whom an NSAID or aspirin is inappropriate, acetominophen 600 to 1000 mg is a reasonable alternative. Management of moderate dental pain generally requires combination drugs for effective analgesia. NSAIDS such as ibuprofen 600 to 800 mg are effective, particularly with a loading dose and regular administration. Gastrointestinal side effects are frequently limiting factors. Combinations of codeine and either aspirin or acetaminophen have a long-term track record of effectiveness in the management of dental pain. These combinations allow pain to be attacked centrally and peripherally with smaller doses of each component, but they encompass some of the undesirable side effects of narcotics. In addition to codeine, oxycodone provides equally effective pain relief in combination with either aspirin or acetaminophen. For both types of pain, extremely effective pain relief can be obtained with local anesthetic blocks using longer-duration drugs such as bupivacaine or etidocaine followed by oral pain medication. Because of the side effects and the potential for abuse, stronger opioid narcotics should be used with care ( 11). Drugs administered orally, such as methadone 10 mg or hydromorphone 2 mg, are effective for the short-term management of severe pain. In a small number of patients, truly severe pain and anxiety unrelieved by oral medications may require the administration of parenteral narcotics such as meperidine or morphine ( Table 116–1.6).

Table 116–1.6. Analgesic Choices for Dental Pain

Antibiotics in Tooth Infections Patients who have infections should receive antibiotics. Swelling, lymphadenopathy, fever, and similar signs often indicate an infectious process that has spread beyond the confines of the tooth. Penicillin remains the first-choice antibiotic the minimum adult dose is 500 mg four times a day for 7 to 10 days. Erythromycin or the newer use of Zithromax for 5 days is the typical alternative for patients allergic to penicillin. First-generation cephalosporins may be another alternative in selected patients. Antibiotics directed specifically at coagulase-positive Staphylococcus are not useful in most dental infections. Penicillin and similar antibiotics are helpful in relieving the pain associated with early periapical pathosis without other signs of infection. Locally Applied Salves and Gels Aside from the pharmacologic methods to deal with simple dental problems, there are effective local temporary treatments for the relief of pain. Eugenol in one form or another has been used for centuries to relieve toothaches. Eugenol is the essential ingredient in oil of cloves, and many over-the-counter toothache remedies have similar constituents that can be applied topically. Patients should be cautioned never to apply aspirin to oral tissues because it is extremely caustic to mucosa and gingiva (12). Local anesthetics such as benzocaine 20% or lidocaine 2 to 5% are available as gels or patches ( 12A) that can be applied topically to oral tissues. They are not particularly helpful in tooth-related pain, but they may provide temporary amelioration of mucosal irritation and some deeper relief. Carious lesions or defective or missing fillings can be temporarily restored, and exposed dentin can be covered with various sedative filling materials. Zinc oxide–eugenol preparations provide antiseptic qualities along with adequate sealing and thermal insulation ( 13). Loose debris can be removed with gentle irrigation or cotton swabs and the opening dried. The filling material is then mixed and condensed into the cavity with a small instrument ( 14) (Fig. 116–1.3). In many patients, fractured cusps or large missing fillings cannot be restored simply because of a lack of retention for the temporary filling material.

Figure 116–1.3. Placement of temporary filling material with condenser ( A) and carver (B). (Reproduced with permission from Klokkevold P. Common dental emergencies. Emerg Med Clin North Am 1989; 7:29–63.)

Depending on the extent of involvement of dental services with the emergency medical facility, it may be more prudent to consult a dentist early in the diagnosis and treatment phases. If dentists are less directly available to the ED, a triage mechanism should be developed regarding situations in which dental consultation is absolutely necessary. A dentist or an oral and maxillofacial surgeon should be involved in dentoalveolar trauma and avulsed teeth, orofacial or through-and-through lacerations, facial swellings from odontogenic infections, and other moderate to severe oral infections. Many simple dental problems and uncomplicated toothaches can be managed adequately in the short term by the ED until the patient can be seen by a dentist for definitive care. In remote areas a dentist may leave temporary filling material in the ED.

NATIONAL CONTACTS

If the emergency medical facility does not have a dental department or regular dental consultants, local and national sources can provide information and referral. On a regional level, the state or local dental society will be able to supply information regarding emergency dental care programs, referral mechanisms, and dentists trained in hospital dentistry or oral and maxillofacial surgery. American Association of Hospital Dentists; 211 East Chicago Avenue; Chicago, IL 60611; 312-440-2661. American Dental Association; 211 East Chicago Avenue; Chicago, IL 60611; 800-621-8099. American Association of Oral and Maxillofacial Surgeons; 9700 West Bryn Mawr Avenue; Rosemount, IL 60018. References 1. Miller AJ, Brunelle JA, Carlos JP, et al. Oral Health of United States Adults, US Dept. of Health and Human Services, August 1987. 1A. Kaplan AS: History and examination of the oro-facial pain patient. Dent Clin North Am 1997;41:367–383. 1B. Gremillion RA, Reams MT: Comprehensive oro-facial pain analysis. Gen Dent 1997;45:237–241. 2. Rothwell BR: Odontogenic infections. Emerg Med Clin 1985;3:161. 2A. Walsh LJ: Serious complications of endodontic infections. Aust J Dent J 1997;42:156–159. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Sicher H, DuBrul EL: Oral anatomy. 5th ed. St. Louis: CV Mosby, 1970. Dickey DM: Evaluation of pain of dento-alveolar origin. Dent Clin North Am 1973;17:391. Bell WD: Orofacial pains. 4th ed. Chicago: Year Book Publishers, 1989. Graham LL, Schinbeckler GA: Orofacial pain of cardiac origin. J Am Dent Assoc 1982;104:47. Batchelder BJ, Krutchkoff DJ, Amara J: Mandibular pain as the initial and sole clinical manifestation of coronary insufficiency. J Am Dent Assoc 1987;115:710. Eagle WW: Symptomatic elongated styloid process. Arch Otolaryngol 1949;49:490. Kant KS: Pain referred to teeth as sole discomfort in undiagnosed mediastinal lymphoma: report of case. J Am Dent Assoc 1989;118:587. Hargreaves KM, Troullos ES, Dionne RA: Pharmacologic rationale for the treatment of acute pain. Dent Clin North Am 1987;31:675. Terezhalmy GT, Bowen LL, Rye LA: Pharmacotherapeutics in urgent dental care. Dent Clin North Am 1986;30:399. Maron FS: Mucosal burn resulting from chewable aspirin: report of a case. J Am Dent Assoc 1989;119:279.

12A. Hersh EV, Houpt MI, Cooper SA, et al: Analgesic efficacy and safety of an intra-oral lidocaine patch. J Am Dent Assoc 1996;127:1626–1634. 13. Accepted dental therapeutics. 40th ed. Chicago: American Dental Association, 1984. 14. Klokkevold P: Common dental emergencies. Dent Clin North Am 1989;7:29.

Suggested Readings Turturro MA, Paris PM: Acute pain management. Resident Staff Physician 1996;42:12. Wright JM, Price SC, Watson WA: NSAID use and efficacy in the emergency department: single doses of oral ibuprofen versus intramuscular ketorolac. Ann Pharmacother 1994;28:309.

Chapter 116.2 Tooth Avulsions and Fractures Principles and Practice of Emergency Medicine

CHAPTER 116 TOOTHACHE AND PAIN OF DENTAL ORIGIN

2 Tooth Avulsions and Fractures Jeffrey B. Dembo Introduction Tooth Trauma Predisposing Factors Pathophysiology and Anatomy Clinical Presentation and Examination The Avulsed Tooth Initial Stabilization and Definitive Treatment Sequelae Medicolegal Pearls National Contacts

INTRODUCTION It is important to understand the treatment of dentoalveolar injuries because of the frequency with which they occur and the complications that may result. If not promptly recognized and treated, these injuries in children may interfere with tooth eruption, facial development, and occlusion. In adults, they can result in loss of esthetics, loss of function, collapse of the dental arch through tooth migration, and potential chronic infection. Emergency physicians may find themselves having to evaluate and treat these conditions, particularly in remote areas where dental care may not be immediately accessible.

TOOTH TRAUMA Tooth fractures and avulsions are examples of dentoalveolar trauma, that is, trauma involving the dentition and supporting the hard- and soft-tissue structures. Dentoalveolar trauma occurs frequently, and it may be isolated or associated with other injuries. The injury may affect teeth alone, but it may involve soft tissue as well. Children are more likely than adults to suffer dentoalveolar trauma. By age 14, it is possible that 30% of children will have sustained injuries to the primary dentition and 22% to the permanent dentition ( 1). Boys appear to be twice as prone to dentoalveolar trauma as girls. The highest incidence of trauma occurs from ages 8 through 10. The effects of tooth trauma can be life-long and may require rapid attention ( 1A). An inhaled tooth will rarely occur during trauma and require endoscopic or bronchoscopic removal ( 1B).

PREDISPOSING FACTORS Age Dentoalveolar trauma is rare in children younger 1 year, but injuries do occur (e.g., a fall from a table). A significant cause of injury in the infant can be child abuse (see Medicolegal Pearls at the end of this chapter). At 1 to 3 years, once the child begins walking and running, the incidence of injury increases because of the child's adventuresome activity combined with lack of coordination. In school-age children, playground and bicycle injuries are most common. During the teen years, sports injuries are frequent causes. In adulthood, sports injuries, motor vehicle accidents, industrial and farming accidents, altercations, and spouse abuse are potential causes of trauma. Sports Activities Hockey, football, soccer, and basketball are frequent causes of dentoalveolar injury, most often because of contact with someone else's fist or elbow. Horseback riding may be a significant source of dentoalveolar injury, too. Medical History A higher frequency of dental injuries has been noted among patients with mental retardation and cerebral palsy ( 2). Substance abuse may increase the likelihood of dentoalveolar injury. Dental Anatomy Protruding maxillary incisors or an inability to close the lips at rest may increase the chance for injury.

PATHOPHYSIOLOGY AND ANATOMY Trauma to dentoalveolar structures can be direct (tooth-object contact) or indirect (force transmitted by blow to soft tissue of lip, gingiva, and so on). The nature of the trauma influences the resultant injury. Injuries may be classified as subluxation, displacement (partial or total), or fracture. Subluxation refers to abnormal loosening of the tooth without evidence of displacement from the socket. Displacement may be partial or total. In partial displacement, the tooth position has been altered traumatically, resulting in intrusion, extrusion, and anteroposterior or lateral movement (Fig. 116–2.1). In total displacement (avulsion), the tooth has been dislodged totally from the bony socket.

Figure 116–2.1. A. Partial displacement with intrusion. B. Partial displacement with extrusion. C. Partial displacement laterally.

Fracture may involve only the tooth substance or tooth and alveolar bone. In tooth fracture, the tooth substance has been injured, resulting in the fracture of enamel, dentin, cementum, or pulp in the crown or root (Fig. 116–2.2). In dentoalveolar fracture, single or multiple teeth and the supporting alveolar bone are injured and are mobile as a unit.

Figure 116–2.2. A. Crown fracture through enamel only. B. Crown fracture through enamel and dentin. C. Crown fracture through enamel and dentin with pulp exposure.

Displacement is the most common type of injury in children. Children's teeth have short crowns and are vertical, and the alveolar bone is elastic and has a thin cortex. Thus, tooth integrity is usually spared because the supporting structures absorb much of the impact. In contrast, the adult dentition is characterized by large tooth crowns and dense supporting bone, making tooth fractures more likely.

CLINICAL PRESENTATION AND EXAMINATION A careful history is important for accurate diagnosis of dentoalveolar injuries and for ensuring the best treatment. The following questions must be addressed: 1. How did the injury occur? The traumatic event can offer clues to the nature and types of injuries sustained. For example, one should consider the energy of impact, the direction of force, and the resiliency and shape of the object. 2. When did the injury occur? The time elapsed between injury and treatment can be one of the most significant factors in the prognosis of the injured area, especially in the case of avulsed teeth. 3. Where did the injury occur? Antibiotic or tetanus prophylaxis may be indicated if a dirty wound is suspected. 4. What treatment has already been provided? Previous treatment records or a verbal report from witnesses can be helpful in treatment planning. For example, how was the tooth stored if there was an avulsion? 5. What is the patient's dental history, including dental injuries? Is the fractured incisor a new injury or an old one? Was the tooth previously treated by root canal? 6. What are the patient's subjective symptoms? Has there been spontaneous pain from any teeth? Is there any sensitivity to touch or to extremes of temperature? The clinical examination must be systematic, and specific attention should be paid to the following areas: 1. The ability to open the mouth fully, assessing for damage to the jaws or temporomandibular joint. Does the mouth open fully without deviation? A temporomandibular joint injury causes deviation toward the affected side. 2. Dental occlusion. Can the teeth be brought together in the usual manner, or does the patient state that the “bite is off”? Do all teeth appear to occlude evenly, or does one area occlude prematurely? 3. Presence of fractured, displaced, or loosened teeth. 4. Change in tooth coloration. Pulpal congestion or necrosis from injury can cause color changes (e.g., pink or grey-blue hue visible through the dentin and enamel). 5. General dental condition of the patient. Is a tooth loosened from trauma or from preexisting periodontal disease? 6. Presence of soft-tissue trauma. Lacerations or ecchymosis of the gingiva or mucosa can provide clues to the presence and location of dentoalveolar injuries. Hemorrhage in the gingival crevice of the tooth may indicate subluxation ( Fig. 116–2.3). Care should be taken to examine soft tissues thoroughly (e.g., in a lip laceration) because foreign bodies and tooth fragments may be embedded and remain undetected.

Figure 116–2.3. Hemorrhage in the gingival crevice is a common finding with subluxated and displaced teeth.

7. Missing teeth or prostheses. If a partial denture or an avulsed tooth cannot be located, be suspicious that the object may have been swallowed or aspirated. Radiographic Evaluation in Dental Trauma Radiographs useful for an accurate diagnosis include a panoramic film (panorex), periapical radiographs of the dentition, and soft-tissue films to rule out foreign bodies. Unless the beam of radiation passes directly through a line of cleavage, a tooth fracture may remain undetected; hence, radiographs taken from several directions are useful ( Fig. 116–2.4). A tooth fracture typically appears as a radiolucent line extending to the edge of the tooth but not beyond. Subluxation or displacement appears as a widening or an irregularity of the periodontal ligament space around the root.

Figure 116–2.4. A. Radiographic beam directed parallel to fracture demonstrates fracture clearly. B. Radiographic beam not parallel to fracture can make diagnosis more difficult. C. Although different radiographically, both incisors have sustained similar fractures.

A digital examination is a vital part of the evaluation. A finger or instrument (e.g., tongue blade) can be used to place pressure on a tooth to determine whether it is mobile. Only a gentle motion should be used to prevent the iatrogenic displacement of a loosened tooth. If mobility is present, note whether a single tooth or a group of teeth exhibits movement. If several teeth are mobile, it may indicate an alveolar fracture. Remember that deciduous teeth near the time of exfoliation normally exhibit mobility because of root resorption. A finger or instrument should be used to tap gently on the occlusal edge of the teeth. Sensitivity to percussion indicates damage to the periodontal ligament, supporting a diagnosis of subluxation. On the basis of the clinical and radiographic findings, the injury can be assigned to one of three categories: subluxation, displacement, or fracture.

THE AVULSED TOOTH Perhaps the most common dental trauma emergency handled by emergency department (ED) personnel is the avulsed tooth. This is a true emergency because the success of reimplantation of traumatically avulsed teeth is related directly to the length of time the tooth remains out of the socket before replacement and how it is handled during that time. When reimplanted teeth have been outside the alveolus longer than 2 hours, 95% ultimately show signs of root resorption; only 10% show resorption if reimplanted within 30 minutes ( 3). Dessication of the periodontal membrane is thought to be the major explanation for this time-dependent phenomenon, although continued exposure of the root to mechanical trauma and foreign substances plays a role ( 4). Storage of the tooth during the extraoral period is crucial. Teeth can be stored successfully in saliva for approximately 2 hours. Keeping a tooth under the tongue or in the buccal vestibule is one method for storage before replantation. The length of storage time is limited by the hypotonicity and high bacterial count of saliva. Milk taken directly from the refrigerator can be an excellent medium for storage ( 5,6). A high percentage of viable cells in the periodontal membrane are seen even after 6 hours of storage in milk. A third choice of storage medium is isotonic saline. Tap water should be used only as a last resort because it is not isotonic. This emergency measure may be handled by telephone, usually by a parent or a teacher calling to ask about an avulsed tooth. For all tooth and tooth-related injuries, prompt referral to a general dentist, pediatric dentist, or oral and maxillofacial surgeon means that the patient will receive early definitive care, which will improve the prognosis.

INITIAL STABILIZATION AND DEFINITIVE TREATMENT Subluxated Teeth Subluxated teeth usually require no immediate stabilization, but additional trauma to the tooth must be prevented ( Table 116–2.1). This includes the avoidance of additional forceful facial contact. Diet should be limited to liquids or extremely soft solids. Referral to a dentist is recommended for more definitive care and follow-up. The dentist may grind the occlusal surface of the opposing tooth to prevent contact and will perform periodic pulp vitality tests over the next 8 to 12 weeks to determine whether root canal therapy is indicated for pulpal necrosis.

Table 116–2.1. Treatment Summary

Displaced Teeth PARTIAL DISPLACEMENT Primary Tooth If the tooth has been intruded or displaced posteriorly, or if it appears radiographically to be in proximity to an unerupted permanent tooth, the displaced tooth should be extracted carefully. Fewer abnormalities develop in the permanent teeth when this treatment is performed. An extruded tooth also should be extracted, as should a tooth that is expected to exfoliate within the next 6 months. In a tooth that is about to exfoliate, generally less than half its root structure remains because of resorption. If the deciduous tooth is not in proximity to the underlying permanent tooth (e.g., anterior or lateral displacement, minimal intrusion), it can be allowed to re-erupt. Good oral hygiene should be stressed, and a soft diet should be maintained for 1 to 2 weeks. Usually, spontaneous repositioning occurs within 6 months ( 7). In some patients, orthodontic appliances may be needed to move the tooth into correct position. Permanent Tooth All permanent teeth that have been displaced should undergo definitive treatment by a dentist. If there is no gross mobility of the displaced tooth, no immediate stabilization is necessary. This existing stability may be from consolidation of a blood clot in the alveolus or from wedging of the tooth against the alveolar wall, locking it in position. If mobility is evident, temporary stabilization may be achieved by digitally repositioning the tooth. The purpose of splinting is to stabilize the injured tooth and to prevent additional damage to the pulp and periodontal ligament. Other methods of temporary stabilization include moist gauze or cotton rolls placed in the labial vestibule against the teeth or tying a figure-of-eight suture around the occlusal aspect of the affected tooth and the adjacent tooth ( Fig. 116–2.5). Ensure that this suture is placed as close to the occlusal edge as possible; placing it too close to the gingiva causes extrusion of the tooth. Aluminum foil or foil from a dental film packet can be crimped around the tooth surfaces to provide temporary stabilization. A periodontal dressing, if available, is an excellent means of stabilizing teeth and is easy to apply (e.g., COE-pak, Coe laboratories, Chicago, IL). Equal lengths of two pastes are mixed on a paper pad, and the material is adapted around the teeth and tissues, which have been cleaned and dried. The paste hardens in a short time and provides the temporary stability needed. Usually, if there is permanent tooth displacement, the dentist more definitively splints the affected tooth. Frequently, this is accomplished with a tooth-colored composite resin applied to the enamel surface of the affected and the adjacent teeth (Fig. 116–2.6). The enamel is prepared to accept this resin by application of an acid to “etch” the surface, aiding in retention of the resin. Splinting also may be accomplished with orthodontic appliances and wire, or by application of a metal arch bar with circumdental wiring of the bar (see Fig. 116–2.7).

Figure 116–2.5. A and B. This anteriorly displaced central incisor was repositioned manually and stabilized with a figure-of-eight stainless steel wire.

Figure 116–2.6. A typical resin splint used by the dentist for stabilization.

Figure 116–2.7. A. Dentoalveolar fracture with accompanying soft-tissue injuries. B. Repositioned alveolar segment with arch bar stabilization.

TOTAL DISPLACEMENT (AVULSION) Primary Tooth Reimplantation is not indicated because an avulsed deciduous tooth has a poor chance of survival if reimplanted ( 8). Referral to a dentist is necessary to determine whether a space maintainer is required to prevent the dental arch from collapsing before the permanent tooth erupts. If space is lost, permanent teeth could erupt ectopically or show a delayed eruption pattern. Permanent Tooth Immediate action is required whether the patient is seen in the dental office or the ED or consultation is handled by telephone. A few simple steps can ensure the best chance for long-term retention of the tooth. If the avulsion is discussed by telephone, the practitioner can give the instructions to the patient or to the person accompanying him or her so that prompt reimplantation can be accomplished. The practitioner should: 1. Ascertain the history of the trauma and the time elapsed since the avulsive injury. 2. Determine the extent of associated injuries; if there has been contact with soil or other contaminants, consider tetanus prophylaxis. 3. Inspect the tooth for fractures and for an evaluation of root development. (Handle the tooth only by the crown if possible.) An incompletely formed root (open apex) may yield a better prognosis even if the tooth has been avulsed for a longer than ideal time ( 9). The alveolus should be examined for signs of fractures or damage to adjacent teeth. 4. Clean the tooth. Care should be taken to avoid mechanical trauma to the root surface during handling. Do not rub or scrape the root surface because this denudes the remaining periodontal membrane. Simple rinsing with water (without drying) usually removes any foreign debris. 5. Advise on tooth storage. One of the following will suffice until reimplantation can be performed: tongue or buccal vestibule of patient; tongue or buccal vestibule of parent or another person; container of milk; container of normal saline. 6. Reimplantation of the tooth should be accomplished as quickly (within 30 minutes) and atraumatically as possible. If there is a blood clot in the socket preventing the tooth from seating, suction or curettage will dislodge the clot to allow for reimplantation. The tooth should be reimplanted by digital pressure alone. Local anesthesia can be administered as necessary. 7. Treat soft-tissue injuries. 8. Antibiotics (preferably penicillin) should be prescribed. Achieve temporary stabilization until referral to a dentist for definitive splinting and endodontic (root canal) treatment if required. Several factors may contraindicate reimplantation of an avulsed tooth. A nonfunctional tooth or one contained within an overcrowded dental arch probably should not be reimplanted. Frank periodontal disease or severe caries contraindicates reimplantation. It is undesirable to reimplant a tooth if there is a fracture of the middle or cervical third of the crown or if a fractured alveolar socket cannot support the tooth ( 10). After reimplantation, referral to a dentist is necessary for stabilization of the tooth. Acid-etch resin bonding is used frequently and is kept in place for 1 week. This short stabilization allows the resumption of normal physiologic movement of the periodontal ligament, which has been shown to minimize the chance of root resorption. Root canal therapy often is instituted several days to 1 week after reimplantation. Once the splint is removed, some tooth mobility persists, and a soft diet is maintained for several weeks. Despite adequate stabilization and follow-up, a tooth that was not reimplanted promptly has a 75 to 96% chance of undergoing external root resorption ( Fig. 116–2.8).

Figure 116–2.8. External root resorption after replantation of an avulsed tooth.

Fractured Teeth In general, fractured teeth require urgent treatment ( 10A,10B). Prompt referral to a dentist ensures that definitive therapy will be instituted with as little delay as possible. The most frequent forms of dental therapy involve endodontics or repair with acid-etch resin techniques. Fractured deciduous teeth are treated in the same manner as permanent teeth. Several distinct types of injuries may occur and are described below. CORONAL (CROWN) FRACTURES The fracture line may extend through enamel alone or through enamel and dentin. Hemorrhage from the tooth or a small pink–red dot or line within the fractured area indicates that a pulp exposure has occurred. Hemorrhage can be controlled easily by using gentle pressure on the site with sterile cotton soaked in local anesthetic combined with a vascoconstrictor. Pain may be controlled by infiltration or by appropriate nerve blocks. Avoid injecting anesthetic directly into the pulp tissue. If a small (several-millimeter) pulp exposure is noted, the vitality of the tooth may be preserved if a dentist can apply a pulp “cap” of calcium hydroxide within several hours. If a large exposure is seen, endodontic therapy should be performed as soon as possible, including the removal of all or part of the pulp contents. Although a brief delay does not adversely affect the final treatment, remember that the patient is likely to have persistent pain and sensitivity until the exposure is treated. If it is left untreated for more than 24 to 48 hours, there is a significant chance for infection to develop. Infection may develop without pulp exposure because dentin contains microtubules that can channel bacteria to the pulp chamber. A fractured tooth fragment that is mobile but is retained within the socket may have residual gingival attachment to the tooth surface. If there is danger that a patient will aspirate a loose fragment, the fragment should be removed gently with a hemostat, and care should be taken to sever the remaining attachment without tearing tissue. Otherwise, temporary stabilization of the fragment without removal is desirable. Definitive dental treatment for the tooth structure may involve merely smoothing rough edges, or it may require full restoration with a tooth-colored composite material or a crown. ROOT FRACTURES Generally, the closer the root fracture is to the apex of the tooth, the better the prognosis for healing through repair or bony union. The location of the fracture can be assessed through radiographs and by clinically observing the mobility characteristics of the tooth. If the root fracture is within the middle third or apical third (nearest the root tip), the tooth should be repositioned immediately using finger pressure and firm stabilization. The dentist places a splint to immobilize the affected tooth for 1 to 3 months, and there is a good chance for healing to occur ( Fig. 116–2.9). If the fracture is within the coronal third (near the junction of the crown and root), the crown portion should be removed if definitive endodontic therapy will not begin within a short time. A small, tightly folded gauze square can be placed over the retained root for protection and hemostasis. The dentist determines the final treatment (i.e., restoration or extraction) based on the location of the fracture and the restorability of the tooth.

Figure 116–2.9. A and B. A fracture of the apical third of the root has a good prognosis for healing if properly immobilized.

DENTOALVEOLAR FRACTURES If a tooth and its alveolar segment are mobile, gentle repositioning of the segment is indicated. Loose bony pieces not attached to periosteum should be removed. If any attachment remains, the bone should be conserved and not disturbed. Indiscriminate removal of bone can make future restoration of function and cosmetic appearance in the area difficult. The fractured segment can be stabilized by any of the methods described previously, or it can be immobilized by placement of a metal arch bar similar to the type used in the treatment of jaw fractures ( Fig. 116–2.9).

SEQUELAE Adverse sequelae of dentoalveolar trauma can compromise esthetics, function, and development of the dentofacial structures. These may include loss of tooth vitality, ankylosis (tooth fusing to bone), external or internal root resorption, infection, discoloration, loss of space in the dental arch with tooth migration, malformation of permanent teeth, premature loss of teeth, and compromised mastication and speech. Emotional distress can be common, especially when the injury involves the anterior teeth, and it is readily apparent when the patient smiles or talks.

MEDICOLEGAL PEARLS It is estimated that half the children subject to child abuse sustain facial or oral injuries ( 11,11A). The dentoalveolar injuries described previously may be manifestations of child abuse (11B). Suspicion should be aroused when a child under 3 years has dentoalveolar injuries that are poorly explained by parents or when there is a delay of hours or days in seeking treatment. Additional examination may be needed and may disclose generalized bruising, broken bones, and other evidence of abuse.

NATIONAL CONTACTS State and local dental societies are the best resources for information and referral. (See Chapter 116–1 for additional contacts.)

References 1. Andreasen JO, Ravn JJ: Epidemiology of traumatic dental injuries to primary and permanent teeth in a Danish population sample. Int J Oral Surg 1972;1:235. 1A. Fried I, Erikson P. Anterior tooth trauma in the primary dentition: incidence, classification, treatment methods, and sequelae: a review of the literature. ASDC J Dent Child 1995;62:256–261. 1B. Nathan B, McKeever J: Removing inhaled teeth. Ann Emerg Med 1997;30:552–555. 2. 3. 4. 5. 6. 7. 8.

Andreasen JO: Traumatic injuries of the teeth. Philadelphia: WB Saunders, 1981:30. Andreasen JO, Hjorting–Hansen E: Replantation of teeth: I radiographic and clinical study of 110 human teeth reimplanted after accidental loss. Acta Odontol Scand 1966;24:263. Soder PO, Otteskog P, Andreasen JO, et al: Effect of drying on viability of periodontal membrane. Scand J Dent Res 1977;85:164. Blomlof L, Andersson L, Lindskog S, et al: Storage of experimentally avulsed teeth in milk prior to replantation. J Dent Res 1983;62:912. Courts FJ, Mueller WA, Tabeling HJ: Milk as an interim storage medium for avulsed teeth. Pediatr Dent 1983;5:183. Schreiber CK: The effect of trauma on the anterior deciduous teeth. Br Dent J 1959;106:340. Needleman HL: Total tooth displacement and reimplantation. In: Hargreaves JA, Craig JW, Needleman HL, eds. The management of traumatized anterior teeth of children. New York: Churchill Livingstone, 1981:98. 9. Needleman HL: Total tooth displacement and reimplantation. In: Hargreaves JA, Craig JW, Needleman HL, eds. The management of traumatized anterior teeth of children. New York: Churchill Livingstone, 1981:103. 10. Olson RAJ: Dentition and alveolar process injuries. In: Alling CC, Osbon DB, eds. Maxillofacial trauma. Philadelphia: Lea & Febiger, 1988: 390. 10A. Bader JD, Martin JA, Shugars DA: Preliminary estimates of the incidence and consequences of tooth fracture. J Am Dent Assoc 1995;126:1650–1654. 10B. Nelson LP, Shusterman S: Emergency management of oral trauma in children. Curr Opin Pediatr 1997;9:242–245. 11. Becker DB, Needleman HL, Kotelchuck M: Child abuse and dentistry: orofacial trauma and its recognition by dentists. J Am Dent Assoc 1978;97:24. 11A. Jessee SA: Orofacial manifestations of child abuse and neglect. Am Fam Physician 1995;52:1829–1834. 11B. Welburg RR, Murphy JM: The dental practitioner's role in protecting children from abuse: the orofacial signs of child abuse. Br Dent J 1998;184:61–65.

Chapter 116.1 Gingival Hemorrhage Principles and Practice of Emergency Medicine

CHAPTER 117 GINGIVA

1 Gingival Hemorrhage James T. Amsterdam Capsule Pathophysiology Prehospital Assessment and Stabilization Clinical Presentation Differential Diagnosis and Procedures Management and Indications for Admission Pitfalls Medicolegal Pearls

CAPSULE Oral hemorrhage may develop spontaneously from the gingiva or, more commonly, it may be a result of dental treatment, especially the surgical extraction of teeth. A systematic approach to oral hemorrhage identifies the cause in most cases and aids in overall management.

PATHOPHYSIOLOGY Gingival bleeding originates from capillaries within the gingiva. Postextraction bleeding usually results from oozing of blood from the alveolar bone, but it may originate from capillary bleeding from the traumatized gingiva around the socket or from an arteriole ( 1). Major vessel bleeding is not a problem. Therefore, this kind of bleeding usually responds to local measures such as direct pressure, suture ligation, or hemostatic agents. Dental trauma, periodontal surgery (even scaling or curettage), and especially tooth extraction may reveal the first manifestation of an unrecognized coagulopathy (e.g., factor IX deficiency, platelet dysfunction) ( 2).

PREHOSPITAL ASSESSMENT AND STABILIZATION Patients requiring prehospital care for gingival hemorrhage are likely to have significant bleeding. Attention first should be directed to the airway. If the patient is unable to control the airway because of massive bleeding, intubation is required. The prehospital care provider should exercise extreme infection control precautions (gloves, goggles, mask) because much blood is likely to splatter. Once adequate ventilation has been established, the circulatory status should be evaluated. If the patient has inadequate perfusion, a large bore line should be established and volume replacement initiated with crystalloid. At the same time, local measures should be initiated to control bleeding (i.e., direct pressure to the bleeding site). Fortunately, most patients with gingival hemorrhage are not in extremis. Transporting the patient in comfort and with a gauze to bite on is all that is usually required.

CLINICAL PRESENTATION The history from a patient with bleeding gingiva should include any recent dental scaling, curettage, or prophylaxis, dental extraction, and trauma. Like the prehospital care provider, the emergency physician should wear gloves and a mask, at the minimum, when examining patients; eye protection is recommended strongly. Patients with gingival bleeding are prone to coughing and gagging. There should be adequate lighting, good suction, and a large supply of gauze. Begin the examination by having the patient rinse with saline, and expectorate any clots and debris. Dry the mouth with suction and gauze and evaluate the bleeding, which may be localized to an extraction or surgical site or may diffusely involve all the gingiva.

DIFFERENTIAL DIAGNOSIS AND PROCEDURES Postextraction Bleeding Patients commonly bleed from dental extraction (3). This bleeding may be secondary to local trauma or excessive intraoral negative pressure (spitting, smoking, use of straws). A medication history is useful. Patients may have taken many aspirin tablets, alone or in combination with a narcotic, for pain before or immediately after the extraction. The effects of even one aspirin may linger for a week or more ( 2). Patients may be taking anticoagulants, or other medications affecting clotting components. Occasionally, hemophilia can present with postextraction bleeding. If there are clots in the oral cavity, they should be removed with suction and gauze. The patient should be encouraged to do no additional spitting and to bite down on gauze for 20 minutes. If the bleeding has not stopped, the area of the socket should be infiltrated with 1% to 2% lidocaine combined with 1:100,000 epinephrine ( 4). The resultant anesthesia allows the patient to bite harder, and the local vasoconstrictor helps to stop bleeding. Gauze pressure is then reapplied for 20 minutes. If the patient is still bleeding after 20 minutes, place a small piece of absorbable knitted fabric (Surgicel) or gelatin foam (Gelfoam) in the socket and secure it with a 3-0 or 4-0 black silk suture. Continued oozing despite these procedures warrants a coagulation profile (CBC, platelet count, PT/PTT) because many coagulapathies first occur after dental extraction. Postextraction bleeding may be the result of poor surgical technique. Multiple extractions without a surgical flap or bony recontouring may be prone to bleeding. Such areas may need additional sutures or complete alveoloplasty by the oral and maxillofacial surgeon ( 5) (Fig. 117–1.1 and Fig. 117–1.2).

Figure 117–1.1. Interradicular alveoloplasty. A. Narrow-beaked rongeur removes septa without raising a flap or destroying the labial plate. B. Weakened labial plate is collapsed to palatal plate by thumb pressure. The gingiva is then sutured. (Reproduced with permission from Kruger GO. Complicated exodontics. In: Kruger GO, Textbook of oral and maxillofacial surgery. 6th Ed. St. Louis, CV Mosby, 1984, p. 68.)

Figure 117–1.2. Single tooth alveoloplasty. A. Isolated tooth with high alveolar bone (pre-extraction). B. After tooth removal, wedge-shaped portions of gingiva are removed from the socket. C. Bony reduction with rongeur. D. Smoothing with bone file. E. Final suturing. (Reproduced with permission from Kruger GO. Compkicated exodontics. In: Kruger GO, ed. Textbook of oral and maxillofacial surgery. 6th Ed. St. Louis: CV Mosby, 1984, p. 115.)

Bleeding After Periodontal Surgery Patients frequently bleed after periodontal surgery. Periodontal therapy may include deep scaling and curettage of the tissues or surgery involving gingival flaps and grafts. The tissue at the surgical site usually is covered with a dressing called a periodontal pack (e.g., Coe–Pak). This surgical dressing is extremely critical to the healing of the wound (6). Therefore, if it is dislodged, the periodontist should be notified at once. If there is bleeding around the pack, care should be taken not to disturb or remove the pack. This type of hemorrhage usually responds to peroxide rinses and local pressure. Sustained vigorous hemorrhage should be evaluated in a manner similar to that used for postextraction bleeding. Blood Dyscrasias Periodontal disorders have been described in association with blood dyscrasias, such as leukemia, cyclic neutropenia, thrombocytopenia, pancytopenia, and other coagulopathies, including all the factor deficiencies, which might not be apparent until the system is stressed, e.g., from postextraction or periodontal surgery ( 7). Acute leukemia, particularly the acute granulocytic form, causes massive infiltration of leukemic cells into the gingival tissues. The hyperplastic gingivitis thus produced may be so marked as to almost cover the teeth. The gingiva is edematous and bluish-red. Varying degrees of gingival inflammation have been described, and the tissue is subject to bleeding either spontaneously or from trauma ( Fig. 117–1.3).

Figure 117–1.3. Periodontal manifestations of acute leukemia.

Thrombocytopenia purpura initially may be evident by gingival bleeding, intramucosal hemorrhages, and prolonged bleeding from trauma. Thrombocytopenia from various causes, including alcoholism and quinidine sensitivity, may be accompanied by gingival bleeding.

MANAGEMENT AND INDICATIONS FOR ADMISSION Most gingival hemorrhage or postextraction bleeding responds to the local measures described previously. If the patient has suffered massive hemorrhage, admission may be warranted. Grade 1 hemorrhage usually requires no replacement; grade 2 hemorrhage requires 1 to 2 L crystalloid infusion and may not require admission, depending on the age of the patient. Higher degrees of hemorrhage indicate that the patient has sustained shock and requires admission ( 8). If blood dyscrasias are identified, the patient may require admission, depending on the condition that has been identified, the patient's response to treatment, or both.

PITFALLS The patient should not be discharged until the emergency physician is satisfied that the hemorrhage has stopped. The patient should be cautioned about creating negative intraoral pressure and should avoid aspirin, aspirin-containing compounds, and similar agents.

MEDICOLEGAL PEARLS All patients with gingival or postextraction bleeding do not require a coagulation profile. Patients who do not respond to local measures, however, may have an underlying blood dyscrasia, and this should be pursued. Patients who require a hemostatic pack, especially Surgicel, should be cautioned that an acute alveolar osteitis (dry socket) is likely to develop. These patients should be warned that, if they experience extreme pain and a bad taste in 2 to 3 days, a dry socket is the likely diagnosis. The patient should either contact the dentist immediately or return to the emergency department for treatment. References 1. 2. 3. 4. 5. 6. 7. 8.

Alling D, Alling R: Hemorrhage and shock. In: Kruger GO, ed. Textbook of oral and maxillofacial surgery. 6th ed. St. Louis: CV Mosby, 1984. Lynch MA: Bleeding and clotting disorders. In: Lynch MA, Brightman V, Greenberg M, eds. Burket's oral medicine. 9th ed. Philadelphia, JB Lippincott, 1994. Reynolds DC: Special considerations in exodontics. In: Kruger GO, ed. Textbook of oral and maxillofacial surgery. 6th ed. St. Louis: CV Mosby, 1984. Amsterdam J, Hendler B, Rose L. Emergency dental procedures. In: Roberts J, Hedges J, eds. Clinical procedures in emergency medicine. Philadelphia, WB Saunders, 1997. Kruger GO: Complicated exodontics. In: Kruger GO, ed. Textbook of oral and maxillofacial surgery. 6th ed. St. Louis: CV Mosby, 1984. Corn H: Mucogingival surgery and associated problems. In: Goldman H, Cohen DW, eds. Periodontal therapy. 5th ed. St. Louis: CV Mosby, 1973. Greenberg MS: Hematologic disease. In: Lynch MA, Brightman V, Greenberg M, eds. Burket's oral medicine. 8th ed. Philadelphia, J.B. Lippincott Co., 1984. Textbook of advanced trauma life support. Chicago: American College of Surgeons, Committee on Trauma, 1998.

Chapter 117.2 Gingival and Periodontal Abscesses Principles and Practice of Emergency Medicine

CHAPTER 117 GINGIVA

2 Gingival and Periodontal Abscesses James T. Amsterdam Capsule Pathophysiology Clinical Presentation Differential Diagnosis Procedures Medicolegal Pearls

CAPSULE Periodontal and gingival problems are usually chronic and insidious. Many patients are unaware that they have gum inflammation (gingivitis). Minor problems such as bleeding during toothbrushing, however, may cause alarm and motivate the patient to seek care in the emergency department (ED). Other conditions such as an acute periodontal abscess are painful and may be a more likely cause for seeking immediate attention.

PATHOPHYSIOLOGY Normal Periodontium The normal periodontium can be divided into two major components, the gingival unit and the attachment apparatus (1). Gingival Unit The gingival unit is composed of the soft tissues investing the teeth and the alveolar bone. The gingiva is covered by stratified squamous keratinized epithelium. It extends from the free gingival margin to the mucogingival junction. Apical to the mucogingival junction is the alveolar mucosa which is covered by nonkeratinized, stratified squamous epithelium and is continuous with the mucosa of the lip and cheek. In healthy persons, the gingiva is attached tightly to the tooth and has a stippled appearance similar to that of an orange peel ( 2). From a level that is coronal to the margin of the alveolar bone to the level of the cementoenamel junction, connective tissue fibers from the gingiva insert into the cementum and cover the root of the tooth. Coronal to the epithelial attachment is a space bounded on one side by enamel and on the other by a continuation of the gingival epithelium. This space, called the gingival sulcus, is the cuff that is formed around the necks of the teeth by the gingival tissues. The gingiva lining this space is not attached to the tooth and is, therefore, called free gingiva. The gingiva apical to the base of the gingival sulcus is called attached gingiva. In the healthy periodontium, the gingival sulcus is rarely more than 2 to 3 mm deep. Attachment Apparatus The attachment apparatus is the group of structures that attach the teeth to the jaws. It consists of the cementum covering the root, the alveolar bone surrounding the root, and the periodontal ligament. The periodontal ligament is composed of collagen fibers that insert on one end in the alveolar bone and on the other end in the cementum, thus serving as a double periosteum. The union of the tooth to the alveolar bone is not a calcific union but a fibrous attachment. The anatomy of the attachment apparatus is illustrated in Figure 117–2.1.

Figure 117–2.1. Histologic relationships of marginal gingiva. (Reprinted with permission from Loe H, Listgarten M, Periodontium. In: Goldman H, Cohen D, eds. Periodontal therapy. 5th ed. St. Louis, CV Mosby, 1973).

Periodontal abscesses can result directly from periodontal disease or mechanical problems. Gingivitis is an inflammation of the gingiva in response to an irritant such as dental bacterial, plaque, or other factors (e.g., hormonal changes from puberty or menopause, diabetes, other immune deficiencies) ( 3). Once the alveolar bone is involved (periodontitis), there is a breakdown of the attachment apparatus. Alveolar bone is destroyed, and the gingival sulcus develops into a periodontal pocket of several millimeters in depth compared to the 2- to 3-mm depth of a healthy sulcus. This pocket becomes a reservoir for plaque and other debris. If it becomes obstructed, a true abscess develops. Stretching of these tissues causes pain. A similar mechanical obstruction can occur in a relatively healthy gingival sulcus from something as simple as a popcorn kernel and also may result in an abscess. Because these abscesses result from entrapped dental bacterial plaque, numerous dental microorganisms are involved ( 3). In addition, many anaerobic organisms are present. These organisms appear to be susceptible to penicillin, cephalosporins tetracyclines, and erythromycin. Moreover, the anaerobic organisms seem susceptible to the tetracyclines.

CLINICAL PRESENTATION Patients with gingival abscess have localized swelling of the gingiva adjacent to the area involved. There may or may not be some spontaneous drainage in the area of the gingival margin or an area of pointing and maximum fluctuance. On palpation with the gloved finger or tongue blade, the area is usually tender. There should be no spontaneous pulsations or thrills over the swelling. The patient may be febrile. The gingival abscess may be the focus of more extensive infection of the head and neck, but this should be obvious on initial examination.

DIFFERENTIAL DIAGNOSIS Periodontal Abscess

The periodontal abscess is a swelling of the gingiva secondary to the entrapment of plaque and debris in a pocket. Occasionally, an arteriovenous malformation can be mistaken for an abscess. Abscesses of this nature usually respond to local curettage, warm saline irrigation, and antibiotics (phenoxymethyl penicillin 250 mg four times a day, tetracycline 250 mg four times a day, doxycycline 100 mg twice a day, or erythromycin or a 5-day course of Zithromax). Because local curettage in the ED may be difficult, sometimes conservative incision and drainage are indicated (See “ Procedures”). The periodontal abscess may be secondary to a mechanical obstruction, such as a popcorn kernel or a piece of food. This problem ultimately will have to be treated with local curettage to remove the offending agent ( 3). Parulis Occasionally, a periodontal abscess is the direct result of an infection at the apex of a tooth from a necrotic pulp. A periapical abscess may erode through the cortical plate of the alveolar bone, extend subperiosteally, and give the impression of a periodontal abscess (parulis). Although the treatment is the same as that for the periodontal abscess, ultimately the tooth itself will have to be treated with endodontics (root canal) or extracted ( 3). Combined Periodontal–Endodontic Lesion A complicated type of periodontal abscess, similar to the parulis, has a focus of infection from the mechanical properties of a periodontal pocket and the periapical infection associated with a necrotic pulp. Until both conditions are managed, recurrent bone destruction and periodontal involvement continue. Referral to a general dentist or endodontist (root canal specialist) is important to manage this complex entity ( 4). Acute Necrotizing Ulcerative Gingivitis An acute destructive disease of the periodontium, acute necrotizing ulcerative gingivitis (ANUG) is found most often in adolescents and young adults, especially those under stress (5). It is the only periodontal lesion in which bacteria invade non-necrotic tissue. Other signs and symptoms include fever, malaise, and localized lymphadenopathy (5A). Rarely are resistant organisms involved, but if abscess development occurs, beware of resistant staphyloccia or streptococci (see Chapter 62-1). A rapidly developing mediastinitis is a potentially fatal complication ( 6A). It begins most often as painful, edematous interdental papillae (tissue between the teeth). The affected areas ulcerate and a grayish pseudomembrane forms, leaving a tender bleeding surface when removed ( Fig. 117–2.2.). Necrosis of the interdental papillae follows, and the interdental tissue appears “punched out.” The patient complains of foul breath and a metallic taste in the mouth.

Figure 117–2.2. Acute necrotizing ulcerative gingivitis involving (A) maxillary and (B) mandibular anterior gingiva.

The oral bacteria involved in this process consist of large numbers of fusobacteria and spirochetes. Other fusospirochetal disease (such as Vincent angina, extension of ANUG to the fauces and tonsils, cancorum oris, and pulmonary abscesses) are characterized as necrotizing ulcerative processes. In addition to bacteria, immunologic factors have been reported to contribute to the pathogenesis of ANUG. Other factors that contribute to the development of ANUG include fatigue, emotional stress, and smoking (2). Usually, ANUG occurs in large numbers of people living together in close quarters, such as in the trenches during World War I (hence the name trench mouth), college dormitories, and military barracks. This has fostered the belief that ANUG is a communicable disease; however, to date no evidence exists to support this theory (6). Patients come to the ED complaining of painful gums, bad breath, and a metallic taste in the mouth. Frequently, periodontal abscesses may be associated with the condition because underlying periodontal disease is a predisposing factor and recurrent ANUG distorts gingival morphology, making the periodontium more susceptible to pocket formation. Saline rinses and the administration of either penicillin, tetracycline, or doxycycline bring the patient dramatic relief. Follow-up with a general dentist or periodontist is important because ANUG leaves behind bony destruction that makes the patient more susceptible to periodontal infection. Minor to major periodontal therapy may be required to restore a healthy architecture to the periodontium; the patient then can perform adequate home care to remove plaque and prevent additional disease. The need for referral should be well documented in the chart.

PROCEDURES Incision and drainage may be required in the treatment of a periodontal abscess. A stab incision toward the bone is all that is usually required to drain a periodontal abscess (7). A small amount of spreading can be performed with a mosquito hemostat, and there may or may not be room for a drain (Penrose or iodoform), depending on the size of the abscess ( Fig. 117–2.3). The patient rinses with intraoral warm saline, which continue drainage. Follow-up with a dentist should occur in 1 to 2 days.

Figure 117–2.3. Incision and drainage of a periodontal abscess. (A) Abscess. (B) Incision. (C and D) Blunt dissection and drainage. (Reprinted with permission from Amsterdam J, Hendler B, Rose L. Emergency dental procedures. In: Roberts J, Hedges J, eds. Clinical procedures in emergency medicine. 1st ed. Philadelphia: WB Saunders, 1997.)

Hospital Admission Admission is warranted for a periodontal abscess if the lesion is the focus of a more serious infection of the head and neck. Occasionally, a patient with ANUG may be dehydrated and require intravenous fluids and parenteral antibiotics. Before draining a periodontal abscess, care should be taken to determine whether the patient requires systemic bacterial endocarditis prophylaxis ( 8).

MEDICOLEGAL PEARLS Systemic bacterial endocarditis prophylaxis should be undertaken carefully in patients who require it. Especially in ANUG, referral to a general dentist or a periodontist is important for additional treatment. The patient should understand the importance of this, and it should be documented in the chart. The patient also should be aware of the signs and symptoms of spread of infection to the head and neck and return to the ED if they feel worse. References 1. 2. 3. 4. 5.

Linde J: Textbook of clinical periodontology. Chapter 1. Copenhagen: Munksgaard, 1983. Loe H, Listgarten M: Anatomy and histology, part I. In: Goldman HM, Cohen DW, eds. Perio-dontal therapy. 6th ed. St. Louis: CV Mosby, 1980. Weisgold A: Dental medicine. . In: Kaye D, Rose LF, eds. Fundamentals of internal medicine. 1st ed. St. Louis: CV Mosby, 1983. Amsterdam M: Periodontal prosthesis: twenty-five years in retrospect. Alpha Omegan 1974; December. Barnes GP, Bowles WF, Carter HG. Acute necrotizing ulcerative gingivitis: a survey of 218 cases. J Periodontol 1973;44:35.

5A. Wilson S, Smith GA, Preisch J, et al: Non-traumatic dental emergencies in a pediatric emergency department. Clin Pediatr 1997;36:333–337. 6. Schluger S. Necrotizing ulcerative gingivitis in the army: incidence, communicability, and treatment. J Am Dent Assoc 1949;38:174. 6A. Haraden BM, Zwemer FL, Jr.: Descending necrotizing mediastinitis. Complication of a simple dental infection. Ann Emerg Med 1997;29:683–686. 7. Amsterdam J, Hendler B, Rose L. Emergency dental procedures. In: Roberts J, Hedges J, eds. Clinical procedures in emergency medicine. Philadelphia: WB Saunders, 1997. 8. Klokkevold P. Common dental emergencies. Dent Clin North Am 1989;7:29.

CHAPTER 118 TRIAGE Principles and Practice of Emergency Medicine

CHAPTER 118 TRIAGE Stephanie von Ammon Cavanaugh and William S. Gilmer Early Triage Assessment and Management Structuring the Physician's Assessment

A psychiatric emergency is a disturbance of affect, behavior, or thought that is judged by the patient, medical staff, family, or friends to require prompt intervention because the patient is: (a) potentially or actively suicidal or homicidal; (b) displaying acute or alarming psychiatric symptoms (e.g., psychotic symptoms); or (c) experiencing acute subjective psychologic distress. Usually, patients who require emergent care are severely depressed, suicidal, psychotic, or violent, or in a state of panic. The cause of these psychiatric disorders may be an identifiable organic factor, a psychiatric disturbance, or both. Identifying organic factors (Chapter 120) is a critical emergency department function. Emergently, the patient must be prevented from hurting himself or herself and others, and from leaving the hospital (eloping). An adequate evaluation must be performed, including a psychiatric and medical history from the patient and, because many patients are unable to give an accurate history, from family and friends. If a family member does not accompany the patient, a collateral history should be obtained over the phone. A mental status examination, a physical examination, and appropriate laboratory tests should be performed. Finally, a provisional diagnosis is formulated, and a treatment plan and/or disposition plan outlined, often in conjunction with a psychiatrist. Emergency physicians need shared conferences with their psychiatric consultants to increase agreement particularly as to patient's harm to self or others and need for hospitalization ( 1).

EARLY TRIAGE ASSESSMENT AND MANAGEMENT Before a more thorough evaluation by the emergency physician, observation by triage personnel is important when a patient with disturbance of affect, behavior, or thought presents to the emergency department (ED). First, the patient's level of consciousness should be assessed. An impaired level of consciousness alerts emergency personnel to the emergent need for more attentive medical and neurologic evaluation. The patient should be observed for signs of psychosis. Is the patient conversing with nonexistent others? Does he or she appear extremely suspicious or paranoid? Are the patient's verbalizations entirely out of touch with reality? Such a patient is psychotic and should be attended to more quickly. Signs of agitation on initial presentation should be noted. This behavior, if ignored or handled inappropriately, may escalate and pose a serious threat to the patient and others in the ED. The patient with a profound depressive stance, characterized by slumped and dejected posturing, sad faces, and downcast gaze, may be suicidal. Asking about suicidal ideation is an immediate priority. After general triage questioning (e.g., chief complaints, medications and drugs, suicidality), the patient's vital signs should be recorded and the patient should be assisted into a hospital gown. Always ask a psychiatric patient, “May I take your vital signs?” and, “May I help you into your hospital gown?” because some paranoid patients may interpret such action as a physical threat. A hospital gown not only facilitates the physical examination but also protects the patient and others in the ED from harm by concealed weapons. In addition, it may discourage a patient from abruptly leaving before full assessment and disposition or assist in the detection of a patient who elopes from the ED. Separating the patient from his or her belongings also protects the patient and personnel from concealed weapons and elopement. If a patient adamantly refuses to change into a hospital gown or to be separated from his or her belongings, triage personnel should suspect that the patient may be carrying illicit substances or concealed weapons or suffering from a mental disorder with paranoid features. In emergent cases presenting with severe disorganization, disorientation, or suspected overdose, it may be necessary to search personal belongings without the patient's permission to obtain identifying information, telephone numbers of family members and friends for collateral history, clues to ingested substances, and concealed weapons. Security Concerns Place the patient in a room where he or she can be readily observed and heard by hospital personnel. Ideally, the room should be physically separate from other medical evaluation areas to allow privacy and minimize overstimulation of the agitated patient. A potentially violent or suicidal patient must never be placed in an evaluation room with access to medical instruments or other injurious objects. In addition, one-to-one supervision must be provided for such patients and for patients who are confused or agitated. If a separate room is available for psychiatric emergencies on an ongoing basis, it should be painted pale pink, the color suggested as most calming to the agitated patient ( 2). Children present unique requirements and a pediatrician usually must be involved early, particularly in cases of suicidal children or adolescents ( 3). Security personnel should be alerted to the possibility of violent behavior and asked to report to the emergency area. They should be given specific instructions regarding their role with the patient, and depending on local policy, advised to leave weapons before assisting with the potentially violent patient. When a patient's behavior threatens to pose immediate harm to himself or herself and others, placement in physical restraints is required. Triage personnel trained in applying restraints should instruct security and other personnel without experience in assisting in the restraining process. Emergent use of psychotropic medication (e.g., chemical restraints) ordered by the emergency physician may be needed (usually haloperidol, lorazepam, or both). Medical monitoring, including pulse oximetry, is then needed for such patients, which provides advantages in the psychotic patient ( 4). Triage personnel should ask people accompanying the patient to the ED to wait until they have spoken to the evaluating emergency physician. In many cases, family and friends can provide comfort for the patient while waiting for evaluation and disposition. They also may deter the more disturbed patient from eloping from the ED or from disturbing other patients, provide collateral history, and support the physician in his or her treatment plan or disposition. The presence of family and friends, however, should not replace the role of security in monitoring the potentially suicidal or violent patient. In some cases, those accompanying the patient may cause him or her to be more agitated or psychotic. When this occurs, family and friends should be asked to wait in an area separate from the patient.

STRUCTURING THE PHYSICIAN'S ASSESSMENT A Safe Environment for the Interview Observations about the patient, triage information, and collateral history help to establish whether or not it is safe for the physician to interview the patient alone in a room with the door closed. Patients who are confused, paranoid, psychotic, agitated, or angry, or who have a history of violence, may be of risk to the physician. In addition, some patients evoke a gut feeling in the physician of fear or uneasiness. Such intuition is valuable in suggesting that the physician may not be safe with the patient. If the physician does not feel safe, then a safe environment for the interview must be provided. In addition to protecting the physician from danger, a safe environment is reassuring for the disorganized or potentially violent patient. The physician may wish to leave the door open, keep a safe distance from the patient, or have a security guard or other staff member present during the interview. In some cases, after a brief evaluation, psychotropic medication is administered to decrease agitation, and the interview is continued when the patient is calmer. Finally, physical restraints may be required before the interview can be conducted safely. With all patients, it makes good sense to ask, “Is it all right if we sit down and talk?” “Are you comfortable in this room?” and “Would it be all right if I closed the door?” The physician should always sit by the door and have a clear means of escape. If the physician miscalculates and the patient threatens or attempts harm, then the physician should stay out of the patient's reach. Because the violent patient is frightened by his or her loss of control, the physician should reassure the patient that he or she is safe and will not be harmed or allowed to harm others. The physician should immediately get help. To ensure quick access, each ED should have a prearranged system for requesting security and other personnel to assist in dealing with a violent patient. Five additional people are needed to restrain the patient, one for each limb and one to apply the restraints. Often a show of force calms the patient, who then can be brought under control verbally and have restraints applied without use of physical force. Collateral History A collateral history is vital to the assessment of the psychiatric patient in the ED. Interviewing family and friends before interviewing the patient can help focus the

interview, particularly with the more disturbed patient. It is important, however, to remember that history from those accompanying the patient may be biased and should be evaluated for accuracy like all other data. Although the initial assessment should be conducted with the patient alone, conducting the interview with trusted family members or friends may facilitate the interview with the paranoid, confused, psychotic, or noncommunicative patient. A joint interview also can elucidate family or interpersonal problems and supports. Valuable information from family and friends includes onset and progression of symptoms, recent stress, past personal and family psychiatric and medical history, drug abuse, medications, and the reasons why the patient was brought to the ED. If no one accompanies the patient to the ED and history is unclear in the patient with a psychiatric emergency, every attempt should be made to obtain a collateral history from family or friends over the phone. Physicians, therapists, and facilities who have previously treated the patient may also provide valuable information. The Patient Interview The emergency physician who develops a positive relationship with a psychiatric patient is more likely to obtain accurate data and compliance with disposition and treatment. Being willing to listen and understand the patient's experience accurately (empathy) assists in this process. In the busy ED environment, listening attentively for a few minutes to the reason why the patient came to the ED, without interrupting or structuring the interview, helps the patient feel understood. Also, such unstructured time allows the physician to observe the patient's mood, behavior, patterns of speech, and disorganized or psychotic thinking that may not be evident in a structured interview. Although many patients readily answer questions from the psychiatric history and mental status examination in an organized fashion, some patients require other approaches. The patient who is overly detailed, circumstantial, tangential, disorganized, or psychotic often requires a structured interview, first focusing on the history of the present illness. Such patients need to be brought back to the question asked in a tactful, emphathic manner until it is satisfactorily answered, with statements or questions such as; “I realize that what you were discussing is important to you, but I was wondering if we could return to what I was asking you?” “Excuse me for interrupting you, but . .” or, “Have you noticed that it is difficult for you to stay on the topic?” Specific questions often yield more data than open-ended questions with such patients. Sometimes the patient has such severe psychopathology that a history and complete mental status examination are difficult to obtain. In such cases, a collateral history is essential. A severely disturbed patient should never be left alone while the examiner is obtaining a collateral history. Severely depressed patients may also present a challenge to the psychiatric interviewer. They may have a long latency time before answering questions, and answer in single sentences without elaboration or make little effort to answer questions. Gentle persistence and repetition of unanswered questions is helpful in interviewing such patients. “I know you are feeling very depressed (hopeless, discouraged, etc.), but it is important that I understand what you've been going through.” Understanding and following the patient's affective state or feelings is important during the psychiatric interview. The patient's feelings should be clarified. “Tell me what you were (are) feeling.” What was the experience like for you?” “Were (are) you depressed (anxious, angry, confused, etc.)?” Following the patient's affect during the interview yields valuable data about emotionally charged areas for the patient. Some patients become overwhelmed by their feelings and are unable to convey this experience to the examiner. Providing support, providing structure, or later returning to the emotionally charged subject are useful techniques: “I know this is terribly painful for you.” “Let me ask you some specific questions so that it's easier for you to tell me about this.” “Maybe we can return to this later.” With the anxious, psychotic, or cognitively impaired patient, overwhelming affect may be evidenced by increased disorganization. Specifically clarifying the affect at such a point is helpful. “Was what you were just talking about upsetting you?” “Tell me how you felt.” Many psychotic patients, however, are unable to elucidate the affect, and disorganization is the only clue to the emotionally charged area. In addition to understanding feelings, it is essential to follow other leads in the psychiatric interview. Vague statements should be clarified. If a patient stops talking suddenly, ask what happened. If connections in a patient's thinking are not clear, the examiner might state, “I'm not sure that I understand the connection between e.g., the police and . . . . Would you explain that, please?” If a statement seems peculiar, attempt to understand the meaning. If a patient appears preoccupied or hallucinating, ask him or her what is going on. Rather than challenge the patient's psychotic thinking, attempt to understand his or her distorted perception of reality. This is accomplished by listening with as few comments as possible, except those that clarify the patient's hallucinations or delusions. However, some patients who are delusional and hallucinating may need to be reassured that they are safe (e.g., “The FBI cannot hurt you here.” “There is no poison gas coming through the window.”). Interpreting reality to the patient should be differentiated from arguing with his or her psychotic view of the world, which only increases agitation. During the interview, the examiner must set firm limits on inappropriate behavior (e.g., “It is better not to wander around because it disturbs other patients.”). Seductive behavior is dealt with by putting physical distance between the interviewer and the patient, setting limits on the behavior, and having a “chaperone” present. The latter is increasingly important due to the possibility of false allegations against physicians. There are situations in which allowing certain behaviors facilitates the psychiatric interview. For example, a nonpsychotic but agitated patient may be better able to tolerate the interview while pacing the room. If a patient has difficulty communicating in English, translation into the primary language is essential for the psychiatric evaluation. Medical personnel are preferred for translation. If they are unavailable, the evaluator should assess the reliability of the family member or friend assisting in translation. The examiner should always asks the translator to translate questions and responses verbatim. The specifics of the psychiatric history are outlined in Table 118.1 The screening mental status examination should include assessment of the following: (a) general appearance, level of consciousness, relationship to the interviewer, activity level, unusual movements and body position; (b) mood and affect; (c) thought process, including amount, rate of productivity, continuity, and coherence; (d) thought content including delusions, suicidal and homicidal ideation; (e) perceptual disturbances, specifically hallucinations; and (f) intellectual functioning.

Table 118.1. Psychiatric History

The Physical Examination and Other Diagnostic Tests RULE OUT ORGANIC CAUSES Organic factors that could cause or contribute to psychiatric symptoms must be ruled out. Lack of identification or proper treatment of an organic brain syndrome, particularly delirium, can result in treatment errors that may not be reversible. A physical examination (including a focused neurologic examination) and appropriate laboratory evaluation should be performed. As with other procedures, the psychiatric patient should always be asked, “May I examine you?” “May I draw your blood?” An organic cause for psychiatric symptoms should be considered until proven otherwise in patients who are older, are posttrauma have a medical illness, are postpartum, are taking prescribed medications known to cause behavioral symptoms, have a history of drug or alcohol abuse, or have no previous psychiatric history. A person with a receptive or fluent aphasia, particularly acute, may be confused with one whose communication is hampered by psychotic thinking. A patient who shows inattention; clouding of consciousness; or deficits in orientation, memory, and intellectual functioning has in most cases a delirium, dementia, or amnestic disorder. Patients who for any reason (e.g., psychosis, agitation, depression, mania) are unable to complete the portion of the mental status examination that tests intellectual functioning warrant careful “organic”1 evaluation. Patients with chronic psychosis may integrate their pain into a delusion. For

example, one patient with a perforated appendix felt this was due to smoke in his abdomen. 1 “Organic” is defined as owing to a medical condition (including head trauma) or a substance (alcohol or drug intoxication or withdrawal, medication side effect, vitamin deficiency, or toxin).

References 1. Gabrick L, Levitt MA, Bassett M, et al: Agreement between emergency department physicians and psychiatrists regarding admission decisions. Acad Emerg Med 1996;3:1027–1030. 2. Schauss AG: Tranquilizing effect of color reduces aggressive behavior and potential violence. Orthomolecular Psychiatry 1979;8:218. 3. Press BR, Khan SA: Management of the suicidal child or adolescent in the emergency department. Curr Opin Pediatr 1997;4:237–241. 4. Battaglia J, Moss S, Rush S, et al: Haloperidol, lorazepam, or both for psychotic agitation. Am J Emerg Med 1997;15:335–341.

Suggested Readings American Psychiatric Association's psychiatric glossary. Washington, DC: American Psychiatric Press, 1994. Bassuk EL, Birk AW: The concept of emergency care. In: Bassuk EG, Birk AW, eds. Emergency psychiatry, concepts, methods, and practices. New York: Plenum Press, 1984. Bassuk EL, Skodol AW: The first few minutes: identifying and managing life-threatening emergencies. In: Bassuk EG, Birk AW, eds. Emergency psychiatry, concepts, methods, and practices. New York: Plenum Press, 1984. Breslow RF, Klinger BR, Erickson BJ: Acute intoxication and substance abuse among patients presenting to a psychiatry emergency service. Gen Hosp Psych 1996;18:183–191. Cavenar JO, Jr, Cavenar MG, Hillard JR, et al: Basic concepts of emergency care. In: Walker JI, ed. Psychiatric emergencies, intervention and resolution. Philadelphia: J B Lippincott, 1983. Folstein MF, Folstein S, McHugh, PR: The minimental status examination. J Psychiatr Res 1975;12:180. Glossary of technical terms. In: Diagnostic and statistical manual of mental disorders. 3rd ed, revised. Washington, DC, American Psychiatric Press, 1994. Kaplan HI, Sadock BJ: Typical signs and symptoms of psychiatric illness. In Kaplan HI, Sadock BJ, eds. Comprehensive textbook of psychology. Baltimore: Williams and Wilkins, 1996. Leigh H: Mental status examinations: systemic observation of the patient. In: Leigh H, ed. Psychiatry in the practice of medicine. Menlow Park, CA: Addison-Wesley, 1983. Leigh H, Feinstein AR, Reiser MF: Systemic approach to comprehensive care: the patient evaluation grid. In: Leigh H, ed. Psychiatry in the practice of medicine. Menlow Park: Addison-Wesley, 1983. MacKinnon RA, Michels R, eds: The psychiatric interview in clinical practice. Philadelphia: W.B. Saunders, 1971. Michels R, Marzuk PM: Progress in psychiatry. N Engl J Med 1993;329:552–556. Scheiber SC: Psychiatric interview, psychiatric history and mental status examination. In: Talbott JA, Hales RE, Udofsky SC, eds. Textbook of psychiatry. Washington, DC: American Psychiatric Press, 1988. Shader RI, Greenblatt DJ: Drug therapy: use of benzodiazepines in anxiety disorders. N Engl J Med 1993;328:1398–1406.

CHAPTER 119 TIPS FOR INITIAL EVALUATION OF THE NEUROPSYCHIATRIC PATIENT Principles and Practice of Emergency Medicine

CHAPTER 119 TIPS FOR INITIAL EVALUATION OF THE NEUROPSYCHIATRIC PATIENT Craig A. Taylor and Barbara C. Good Capsule Mental Status Change Behavioral Changes Summary

CAPSULE The neuropsychiatric patient presents unique evaluation and diagnostic challenges to the emergency department (ED) physician. The particular psychiatric disorder this patient manifests—one of behavior, mood, or cognition, or a psychosis—may exist along with, and in some cases as a result of, an underlying neurologic problem. The goals of the ED physician evaluating the neuropsychiatric patient are: (a) to stabilize or calm the agitated or aggressive patient to protect him or her as well as those nearby; (b) to establish a presumptive diagnosis or determine the cause in a broad context (i.e., determine whether the disorder is most likely medical, neurologic, or psychiatric); and (c) on the basis of the underlying condition, to determine whether the patient should be discharged with outpatient follow-upor assigned to an inpatient medical, neurologic, or psychiatric unit. Differential Diagnosis Differential diagnosis in neuropsychiatry is a complex process. Data collected should be oriented toward organic disease; the clinical examination should include an expanded mental status examination in which cognitive functions and common organic behavior signs are evaluated ( Table 119.1) (1).

Table 119.1. Plan of Action for Diagnosing a Patient with Neuropsychiatric Symptoms

Dysfunction can result from a variety of central nervous system (CNS) disorders including infectious disease, vascular disorders, tumors, trauma, hydrocephalus, degenerative disorders, and demyelinating diseases, or from medical disease such as sepsis, toxin exposure, metabolic disease, immune disorders, and the indirect effects of cancer (Table 119.2).

Table 119.2. Neurologic Disorders that can Produce Neuropsychiatric Disturbances ( 1)

Neuropsychiatric symptoms can manifest as disturbances in cognition, behavioral changes, alterations in personality, or mood disturbances (e.g., mania, depression, anxiety, poor affective regulation; disturbances in thought processes and content). What makes these patients difficult to diagnose and evaluate is the concomitant expression of neurologic, medical, and neuropsychiatric symptoms. Most neuropsychiatric patients can be placed in one of two major categories: (a) the individual who presents with neuropsychiatric symptoms but no prior history of a CNS disturbance (2); or (b) the individual who presents to the ED with a neuropsychiatric disturbance evidenced by behavioral change and who has a known CNS deficit. In the latter case, the ED physician must focus on the variety of presentations of the different medical and neurologic disorders ( Table 119.3).

Table 119.3. Neurobehavioral Symptoms Associated with Specific Areas of Brain Dysfunction ( 11)

As with general psychiatric emergencies, the neuropsychiatric patient with underlying CNS disturbance presents to the ED because some change in behavior has occurred that requires immediate control or treatment. Management and treatment will depend on a history including information from family and friends, and on

thorough physical, neurologic, and mental status examinations ( Table 119.4) (3). A consideration of the neuropsychiatric perspective is useful and can help to differentiate the diagnosis. In particular, remember that (a) brain dysfunction affects the patient's ability to give an accurate history; (b) brain dysfunction can modify the expression of mental symptoms and behavior; and (c) psychiatric history and mental status data can be regarded as potentially localizing findings ( 4). It is also important to be familiar with specific neurobehavioral symptoms that reflect underlying abnormalities of brain function ( Table 119.3).

Table 119.4. Medical History of the Neuropsychiatric Patient: Key Questions to Ask

Medications the patient has in his or her possession may give the ED physician clues about the source of the problem brought to the ED and the name of the prescribing physician, who perhaps could be contacted for additional information ( 5). Physical and Neurologic Examination A complete physical and neurologic examination helps to differentiate medical and neurologic conditions that may be contributing to the neurobehavioral presentation. Particular attention to the patient's appearance and behavior can be revealing and often can substitute for part of the formalexamination when the patient is uncooperative (4). Vital signs can be informative; e.g., an elevated blood pressure would increase the suspicion of occult stroke as a cause of neurobehavioral symptoms (4). Although the neurologic examination is a key part of the neuropsychiatric evaluation and can reveal ongoing neurologic disturbance, it is importantto remember that this examination can be of limited sensitivity and value in discerning a neurologic basis of a neurobehavioral disturbance and can benormal in the face of gross brain disease (4). The neurologic examination should include the cranial nerves, which can help elucidate the differentialdiagnosis. Abnormalities of olfaction (cranial nerve I) occur in a variety of neurologic disorders such as closed head injury (with and without loss of consciousness) and meningiomas. Anosmia and hyposmia can be associated with changes in sexual behavior, food preference, and appetite, and when these are associated with orbitofrontal damage, patients may show disinhibition, impulsivity, and inappropriate social behavior ( 6). Right facial asymmetry (cranial nerve VII) can be associated with aphasias. Mental Status Examination Mental status may be overlooked in patients admitted to the ED. In one study, among 298 patients entering the ED whose chief complaint was psychiatric, there was failure to document mental status at triage in 56% of cases ( 7). Among patients in whom medical disease should have been identified, 80% were deemed “medically clear.” The mental status examination is critical to the neuropsychiatric evaluation, and it should be structured and sufficiently detailed to (a) serve asa baseline for future comparisons; (b) inform about underlying neurologic disturbances ( Table 119.5); and (c) allow for the detection of confusional states. In addition to observations of appearance, motor behavior, affect, mood, verbal output, thought structure and content, and perceptions that areobserved and elicited during the interview, the mental status examination should focus specifically on assessing level of arousal, attention, concentration, language function, memory, constructions, abstractions, insight, judgment, and praxis. Although this chapter does not fully discuss the variouscognitive screens that exist, several have proved to be reliable and are easily administered (8).

Table 119.5. Clinical Implications of Selected Cognitive Deficits ( 12)

In addition, the patient should be evaluated for depression, anxiety, mania, and thought disorders. These problems may be unrelated to a neurologicdisorder, or they may be due to a progressive or stable neurologic disorder. The presence of these symptoms in an otherwise neurologically stable or nonacute patient requires psychiatric intervention. The presence of alcohol or illicit drug use should also be investigated in any patient who presentswith acute mental status or behavioral changes. Diagnosis and Disposition Neuropsychiatric symptoms can be difficult to diagnose under any circumstances. When such symptoms occur in a person who is CNS compromised becauseof brain injury or deficit, diagnosis can be particularly problematic. Neurologic disorder can present with a wide array of neurobehavioral disturbances ( Table 119.6). At bottom, aberrant behavior in these patients may be theresult of several different processes, each of which may require a separatetreatment ( 9).

Table 119.6. Neuropsychiatric Symptoms Associated with Selected Central Nervous System Disorders

The physician must ascertain whether symptoms are acute, subacute, or chronic, as this may help differentiate those symptoms that (a) are related to a state phenomenon, such as worsening of a neurologic or medical condition, which can result in a new onset of neuropsychiatric conditions; or (b) are the expression of some behavioral symptoms that result from another underlying neuropsychiatric condition. As an example of the former, depression in a person with traumatic brain injury or developmental disabilities may manifest as aggression. Neuropsychiatric symptoms that have a chronic nature but occur as an exacerbation are frequently associated with psychosocial stressors and often relate more to an adjustment disorder than to any change in medical/neurologic status or substantial psychiatric disorder warranting additional evaluation or pharmacologic intervention. While it is not necessarily the place of the ED physician to determine the etiology behind a particular neuropsychiatric presentation, it is important to ascertain the nature and extent of the symptoms so that appropriate disposition from the ED can be undertaken, and it is in this context that the physician must determine the relative acuity and the medical, neurologic, or psychiatric etiology of the disturbance so that appropriate disposition can be determined. Certain conditions of a psychiatric nature, including destructiveness, disorganization such as that seen in acute intoxication or schizophrenia, depression, disorientation due to severe organic mental disturbances, and conditions requiring detoxification will require psychiatric inpatient hospitalization, whether or not the patient has an underlying CNS disturbance. But it is incumbent on the ED physician to avoid the notion that all psychiatric presentation requires psychiatric admission. In dealing with persons with a known brain injury, it is extremely important to ascertain whether there is an exacerbation of the underlying neurologic condition or a medical condition that is manifesting as neuropsychiatric symptomatology. To the extent that neuropsychiatric symptoms are associated with an underlying neurologic and/or medical change, only stabilization of those conditions will result in stabilization and improvement in neuropsychiatric symptoms. In those cases in which the neurologic condition is stable and static over time, and no other medical conditions exist, and medications are not felt to be responsible for the symptom presentation, the physician should ask whether a full neuropsychiatric evaluation and treatment strategy would be necessary. The acuity of the symptoms and their relatedness to psychosocial factorswill determine whether an individual needs to be hospitalized or can be discharged back to their living arrangement with appropriate follow-up. Patients who exhibit conditions that appear to be psychosocially mediated, i.e., who have behavioral or mood disturbances that arise as a consequence of environmental stressors, can often be discharged from the ED to the home setting and followed up by counselors and/or psychiatrists and by arranging necessary support with a strategic plan, in case symptoms become more acute. When symptoms are thought to reflect a primary disorder that arises out of brain dysfunction, such as a major depression, manic episode, or psychosis, and they interfere significantly with the ability of the patient to function, inpatient evaluation and treatment are required, predominantly to safeguard the patient and those involved in their care. There are few cases, as noted subsequently, in which immediate ED intervention is necessary, the obvious one being the acutely aggressive or agitated patient (Table 119.7).

Table 119.7. Steps to Take in the Control of the Aggressive or Violent Neuropsychiatric Patient

MENTAL STATUS CHANGE Persons with brain injury or neurologic disorders can present with a variety of cognitive changes, both acute and chronic. Patients with a known neurologic condition who present with an acute change in mental status, including changes in level of arousal, confusion, disorientation, or a disorganized thought process, require a workup for an acute medical condition and/or an exacerbation of the underlying neurologic disturbance. For example, a patient with known epilepsy who presents with acute change in mental status, either peri-ictal or postictal, should probably be sent for an EEG. In a patient with a history of multi-infarct dementias who experiences an acute change in mental status, there may be ongoing cerebrovascular involvement. In the latter instance, a CT scan will be helpful in determining new onset strokes. In general, in patients with ongoing, active neurologic disease or degenerative disorders, the new onset of mental status changes frequently reflects a worsening of the neurologic illness. As always, any acute mental status changes need to be tied to possible medication effect or medication changes or to illicit drug or alcohol use. And as with any patient, a full medical workup is necessary to rule out any medical contribution to the mental status change. In patients who have a known history of cognitive disturbance secondary to a neurologic process, establish whether the current mental status is chronic and stable. This can be done by obtaining a history from friends or relatives accompanying the patient. Many brain injury disorders, e.g., traumatic brain injury, stroke, and status postoperative procedures such as removal of a tumor or repair of an aneurysm, present with static cognitive changes. The essential task for the ED physician is to ascertain the extent, nature, and course of the cognitive changes. If such changes are considered acute and not chronic and form the basis of the ED presentation, the physician must determine whether this is attributable to an exacerbation of a neurologic disorder or of an associated medical disorder, in which case evaluation by a neurologic or medical team is necessary. If the mental status changes appear to be related to the evolution of the CNS disease or arise de novo in an individual with static CNS disease, then that individual needs to be evaluated psychiatrically and/or neuropsychiatrically and appropriate interventions undertaken. Depending on the acuity of the symptoms and their impact on the person's ability to care for themselves or be safe in their environment, the physician must decide whether the patient can be treated and evaluated more effectively as an impatient or as an outpatient.

BEHAVIORAL CHANGES Behavioral changes are often presented in the most urgent and difficult ED situations. The agitated or aggressive patient can be difficult to manage in the ED setting, posing a threat not only to themselves but also to those providing care and evaluation. Behavioral changes can be acute or chronic; when they are chronic, they are prone to acute exacerbation and may reflect underlying processes such as mania, depression, or mental status changes including disorganization of thought or psychotic processes, or they may be responses to environmental stressors. In the agitated or aggressive patient, safety must be the primary consideration. Often the agitated patient is unable to provide a history; input from accompanying friends or relatives or from previous medical records can be invaluable. Again, the fundamental rules for ascertaining onset of the behavioral change, relative acuity, and associative factors in an individual with a neurologic disorder should be followed. Psychotropic medication may be required to calm the aggressive or agitated patient ( Table 119.8) (10).

Table 119.8. Psychotropics That Can Be Used to Calm the Aggressive or Agitated Patient ( 10)

SUMMARY In the patient with brain damage, trauma, or illness who presents with a psychiatric problem, the differential diagnosis is sorted out by obtaining a careful history; performing meticulous physical, mental, and neurologic examinations; and applying a thorough knowledge of the range of neuropsychiatric symptoms associated with various CNS disorders. References 1. Strub RL, Wise MG: Differential diagnosis in neuropsychiatry. In: Yudofsky SC, Hales RE, eds. Textbook of neuropsychiatry. Washington, DC: American Psychiatric Press, 1992. 2. Popkin MK: Syndromes of brain dysfunction presenting with cognitive impairment or behavioral disturbance: delirium, dementia, and mental disorders due to a general medical conditions. In: Winokur G, Clayton PJ, eds. The medical basis of psychiatry. 2d ed. Philadelphia: WB Saunders, 1994:17–37. 3. Cain HD: Flint's emergency treatment and management. Philadelphia: WB Saunders, 1985:615–627. 4. Mueller J, Fogel BS: Neuropsychiatric examination. In: Fogel BS, Schiffer RB, Rao SM, eds. Neuropsychiatry. Baltimore: Williams & Wilkins, 1996. 5. Huff S: Altered levels of consciousness. In: Shaw SM, Kelly KM, eds. Emergency neurology: principles and practice. New York: Cambridge University Press, 1998. 6. Sano M, Marder K, Dooneief G: Basal ganglia diseases. In: Fogel BS, Schiffer RB, Rao SM, eds. Neuropsychiatry. Baltimore: Williams & Wilkins, 1996:805–825. 7. Tintinalli JE, Peacock FW, Wright MA: Emergency medical evaluation of psychiatric patients. Ann Emerg Med 1994;12:859–862. 8. Folstein MF, Foltstein SE, McHugh PR: MiniMental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189. 9. Sovner R: Behavioral and affective disturbances in persons with mental retardation—a neuropsychiatric perspective: preface. Semin Clin Neuropsychiatry 1996;1:90–93. 10. Hyman SE: The violent patient. In: Hyman SE, Tesar GE, eds. Manual of psychiatric emergencies. 3d ed. Boston: sLittle, Brown 1994:28–37. 11. Lezak MD: Neuropsychological assessment. 3d ed. New York: Oxford University Press, 1995. 12. Strub RI, Black FW: The mental status examination in neurology. 3d ed. Philadelphia: Davis, 1993. 13. Cummings JL, Diaz C, Levy M, et al: Neuropsychiatric symptoms in neurodegenerative diseases: frequency and significance. Semin Clin Neuropsychiatry 1996;1:241–247. 14. Roberts GW, Leigh PN, Weinberger DR: Neuropsychiatric disorders. London: M Wolfe, 1993. 15. Taylor C, Price TP: Neuropsychiatric assessment. In: Silver JM, Yudofsky SC, Hales RE, eds. Neuropsychiatry of traumatic brain injury. Washington, DC: APA Press, 1994:81–132. 16. Neppe VM, Tucker GJ: Neuropsychiatric aspects of seizure disorders. In: Yudofsky SC, Hales RE, eds. APA textbook of neuropsychiatry. Washington, DC: APA Press, 1992. 17. Starkstein SE, Robinson RG: Neuropsychiatric aspects of cerebral vascular disorders. In: Yudofsky SC, Hales RE, eds. APA textbook of neuropsychiatry. Washington, DC: APA Press, 1992. 18. Price TP, Goetz KL, Lovell MR: Neuropsychiatric aspects of brain tumors. In: Yudofsky SC, Hales RE, eds. APA textbook of neuropsychiatry. Washington, DC: APA Press, 1992. 19. Markowitz JC, Perry SW: Effects of immunodeficiency virus on the central nervous system. In: Yudofsky SC, Hales RE, eds. APA textbook of neuropsychiatry. Washington, DC: APA Press, 1992. 20. Filley CM: Neurobehavioral aspects of cerebral white matter disorders. In: Fogel BS, Schiffer RB, Rao SM, eds. Neuropsychiatry. Baltimore: Williams & Wilkins, 1996;913–933.

CHAPTER 120 EMERGENCY DEPARTMENT PSYCHIATRIC EMERGENCIES Principles and Practice of Emergency Medicine

CHAPTER 120 EMERGENCY DEPARTMENT PSYCHIATRIC EMERGENCIES Stephanie von Ammon Cavanaugh and William S. Gilmer Capsule Mental Disorders due to a Medical Condition or Substance Psychosis Suicidal Patients: Emergency Assessment Violence Acute Psychologic Distress Somatic Complaints without Demonstrable Organic Disease Psychotropic Medication

CAPSULE The most common psychiatric problems seen in patients who present to the emergency department (ED) include: (a) mental disorders secondary to a medical condition (including head trauma) or substance (alcohol or drug intoxication or withdrawal, side effect of medication, vitamin deficiency, or toxin), (b) psychosis (c) suicidal ideation or attempt, (d) potential or actual violent behavior, (e) acute subjective psychologic distress such as depressed or anxious mood, (f) somatic complaints without demonstrable physical illness which are linked to psychologic factors. This chapter reviews the differential diagnosis and treatment of these common psychiatric emergencies. Table 120.1 and Table 120.2 outline the mental status features of common mental disorders secondary to a medical condition or substance as well as common primary psychiatric disorders. Table 120.3 presents the definition and assessment of the features of the mental status examination.

Table 120.1. Mental Status Features in Common Organic Brain Syndromes (1,2)

Table 120.2. Mental Status Features of Common Psychiatric Syndromes

Table 120.3. Mental Status Examination

MENTAL DISORDERS DUE TO A MEDICAL CONDITION OR SUBSTANCE Diagnostically, it is essential to distinguish patients with a mental disorder ( 1) secondary to a medical condition (including head trauma), a substance (alcohol or substance withdrawal, medication side effect, vitamin deficiency, or toxin), or both from those with a primary psychiatric disorder. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) (1994) has dropped the terms “organic brain syndrome” and “organic mental disorders” because many primary psychiatric disorders have structural or functional brain abnormalities (i.e., alterations in neurotransmitters in mood disorders and structural brain abnormalities in schizophrenia). This terminology has been replaced by mental disorders due to a medical condition or substance in which there is “evidence from the history, physical examination, or laboratory findings” that the disturbance is the direct physiologic consequence of a medical condition (including head trauma) or substance (alcohol or drug intoxication or withdrawal, side effect of medication, vitamin deficiency, or toxin). In this chapter “organic” will mean due to a medical disorder or substance ( 1), but this in no way negates the presence of biochemical or structural brain abnormalities in primary psychiatric disorders. Failure to identify and treat a mental disorder due to a medical condition or substance, particularly a delirium, may be life threatening, cause increased morbidity (i.e., brain damage), and result in harmful, inappropriate, or inadequate treatment and medical/legal exposure. Patients who are more likely to have an “organic” cause for psychiatric symptoms are those: (a) without a previous psychiatric history, (b) over age 45, (c) taking medications with central nervous system (CNS) effects, (d) abusing drugs or alcohol, (e) with concurrent medical illness, or (f) have sustained trauma. A good history, including a collateral history, vital signs, a physical examination, a focused neurologic examination, and appropriate screening laboratory and radiographic tests assist in identifying the “organic”1 causes of psychiatric syndromes.

Memory deficits are present in delirium, dementia, and amnestic syndrome. Delirium is an acute disorder with a fluctuating course in which there is evidence of disturbance in consciousness; reduced ability to focus, sustain, or shift awareness; memory impairment; incoherent speech, delusions, and visual hallucinations (1; Table 120.1). Memory deficits and deterioration of higher intellectual functions (poor abstraction, aphasia, apraxia, agnosia) are present in dementia without disturbances in consciousness. Memory difficulties and confabulation without dysattention, clouding of consciousness, or deterioration of intellectual functioning are characteristic of the amnestic disorder (1). “Organic”1 mood disorder, “organic” anxiety disorder, “organic” psychotic disorder, “organic” catatonic disorder, and “organic” personality changes can mimic primary psychiatric disorders. Patients with these disorders have no disturbance in consciousness, little memory impairment, and minimal difficulties with higher intellectual functioning. In psychotic disorder (2) due to a medical condition or substance, the most prominent features are delusions and hallucinations; those with a catatonic disorder (3) secondary to a medical condition or substance present with a catatonic picture. Those with a mood disorder (4) secondary to a medical condition or substance have a depressed, expansive, or euphoric mood; and those with an anxiety disorder (5) have attacks or obsessions and compulsions, signs and symptoms of a prominent anxiety, panic attacks, or obsessions or compulsions. Those with personality changes secondary to a medical condition or substance have changes in personality ( 3).

PSYCHOSIS Psychotic patients are out of touch with reality. They display one or more of the following: (a) inappropriate or bizarre appearance or behavior; (b) inappropriate, bizarre, flat, euphoric, or depressed affect; (c) illogical thinking manifested by abnormalities in the form of speech (i.e., poverty of speech, pressured speech, flight of ideas, loosening of associations, incoherence, and paraphasias); (d) delusions and/or (e) hallucinations. Psychotic patients are brought to the ED by family, friends, or those in the community because the patient's behavior is alarming to those around them. These patients may present themselves to the ED because they are frightened or perplexed, or because at some level they realize their psychotic symptoms warrant medical evaluation and treatment. Chronically mentally ill patients who are psychotic may also attempt to use the ED as an outpatient clinic to receive referrals, prescription refills, or medication dosage changes. The differential diagnosis of psychosis includes psychotic mental disorders secondary to a medical condition or substance, mania with psychotic features, depression with psychotic features, schizophrenia, schizophreniform disorder, schizo-affective disorder, brief psychotic disorder, and delusional disorder. Psychotic “organic” 1 mental disorders include delirium, dementia with superimposed hallucinations or delusions, “organic” psychotic disorder, “organic” catatonic disorder, and psychotic “organic” mood disorders. Refer to the preceding section for characteristics of mental disorders due to a medical condition or substance. After ruling out a medical disorder or substance causing the psychotic process, primary psychiatric disorders may be considered. A patient with a major depressive episode (4) may develop psychotic symptoms. In a psychotic depression, the signs and symptoms of a major depressive episode usually precede the psychotic symptoms. These symptoms include at least five of the following for a 2-week period: depressed mood, marked diminished interest or pleasure in activities, significant weight gain or loss, decreased or increased appetite, insomnia or hypersomnia, fatigue or loss of energy, diminished ability to think or concentrate or indecisiveness, psychomotor agitation or retardation, feelings of worthlessness or inappropriate guilt, or suicidal ideation or attempt. Delusions or hallucinations are consistent with depressive themes of guilt, punishment, persecution, disease, death, or nihilism. The patient may have a personal or family history of depressive and/or manic episodes (Table 120.2). The average age of onset of a depressive illness is the mid-20s, but the onset may be at any age. A patient with a manic episode (4) often develops psychotic symptoms. The signs and symptoms of a manic episode include elevated, expansive, or irritable mood; inflated self-esteem, grandiosity, decreased need for sleep, pressure of speech, flight of ideas, subjective experience of racing thoughts, distractibility, increased goal-directed activity, unrestrained buying sprees, sexual indiscretion, or foolish business investments. The symptoms may precede the psychotic symptoms or occur simultaneously. Delusions or hallucinations associated with a manic episode are consistent with themes of inflated power, worth, knowledge, identity, or special relationship to a famous person or deity. Paranoid delusions, although less common, also may be present ( Table 120.2). The patient may have a previous personal and/or family history of depressive and/or manic episodes. The onset of bipolar disorder is usually in the 20s, is rare after 45, but can occur at any age. With a mixed episode patients meet criteria for both a depressive and manic episode. Between depressive, manic, or mixed episodes, patients with a major mood disorder usually return to their previous level of functioning. With schizophrenia (3), psychotic symptoms rather than a mood disorder are primary. The patient has at least a 1-month history of the active phase of the disorder, characterized by two or more of the following: (a) delusions that are most commonly bizarre or fragmented, including thought broadcasting, thought insertion, thought withdrawal, and delusions of being controlled; (b) hallucinations that often include two voices commenting on the patient's thoughts and behavior; (c) disorganized speech (e.g., incoherence, derailment, or looseness of associations); (d) grossly disorganized behavior or catatonia (e.g., motoric immobility, waxy flexibility, negativism, posturing, echolalia, and echopraxia.); (e) negative symptoms, e.g., affective flattening, alogia (poverty of speech and content), and alvolition (difficulty in initiating goal-directed behavior). Continuous symptoms of the disorder must persist for 6 months and include the prodromal phase or residual phase in addition to the active phase. During the prodromal or residual phases, only negative symptoms may persist or two of the symptoms mentioned in the active phase, which may be present in an attenuated form, such as odd beliefs or unusual perceptual experiences. The patient usually exhibits significant impairment in social and occupational functioning. Patients with schizophrenia never return to their previous level of functioning between more active psychotic episodes. The onset of schizophrenia is usually in adolescence or young adulthood and almost never after the age of 45. It is important to note that hallucinogens, psychostimulants, and chronic alcoholic hallucinosis can cause a schizophreniform-like picture. Catatonia is commonly caused by “organic” factors. Patients with a schizo-affective disorder (3) have an uninterrupted period in which they meet criteria for a mood disorder but also meet criteria for schizophrenia, with at least a 2-week period during which the patient has hallucinations or delusions without mood symptoms. A brief psychotic disorder (2) usually follows a stressful event, has an abrupt onset, and shows rapid shifts from one affect to another or overwhelming confusion. The psychotic symptoms are rarely as bizarre as in schizophrenia. The episode lasts a few days to a few weeks and never more than a month. After the psychotic episode, the person can be expected to return to his or her previous level of functioning. In a delusional disorder ( 2), circumscribed nonbizarre delusions occur with themes of erotomania, grandiosity, persecution, jealousy, love, or disordered bodily function, but no bizarre, peculiar, or odd affect, speech, or behavior. In psychotic mood disorders, schizophrenia, schizo-affective disorder, schizophreniform disorder, delusional disorder, and brief psychotic disorders, there is no clouding of consciousness, disorientation, or memory deficits as seen in delirium and dementia. Significant impairments in attention and concentration caused by a disordered affective state, psychotic thinking, hallucinations, or delusions are often present, however, and make assessments of intellectual functioning difficult to impossible. Delirium and psychotic dementia classically present with vivid visual hallucinations, whereas the nonorganic psychotic disorders present primarily with auditory hallucinations. Psychotic patients may harm themselves or others or elope. As a result, the psychotic patient should be closely observed until evaluation by the emergency physician. Triage management, a safe environment for the interview and evaluation, and structuring the interview with a psychotic patient are discussed in Chapter 118 and Chapter 119. Chapter 121 discusses the use of restraints with the psychotic patient, and the use of psychotropic medication is discussed later in this chapter. If a psychotic disorder secondary to a medical condition or substance is suspected, the use of psychotropic drugs should be carefully evaluated because level of consciousness may be an important indicator of deteriorating physical condition and is altered by psychotropic medication. Actively psychotic patients, except in rare instances, require hospitalization. Commitment and hospitalization are reviewed in Chapter 121.

SUICIDAL PATIENTS: EMERGENCY ASSESSMENT2 Patients with suicidal ideation, who have attempted suicide, or with other self-inflicted harm commonly present to the ED. Patients with various psychiatric problems may be suicidal, but not express these thoughts without being asked. However, the strongest predictor of suicide is pre-existent psychiatric illness ( 5). Suicide risk should be assessed in all patients who present to the ED with psychiatric problems, regardless of whether the clinical situation seems to warrant it. The patient should be asked about present and past suicidal ideation and attempts, and attempted and completed suicides by family members. Men commit suicide three times as often as women, whereas women attempt suicide two to three times as often as men (6,7 and 8). For men, the suicide rate increases up to the seventh decade, then declines; for women, the suicide rate peaks between ages 55 and 65 ( 9,10). Whites and American Indians are at higher risk than blacks ( 6,10). People who live alone, feel no one cares, are without friends, and have limited social supports are at greatest risk for suicide ( 6,9,11). Those who are single, widowed, separated, divorced, married without children, married with children over 18, and married with children under 18 are in descending order for risk of suicide ( 6,9,11). A past history of attempted suicide increases the risk (9,11). Less than ten percent of those who attempt suicide go on to kill themselves ( 11A). The risk of suicide is higher for those who have a family history of completed or attempted suicide and serious or terminal illness increases the risk ( 11). Sense of hopelessness and inability to see into the future are highly correlated with future suicide ( 12,13). Suicidal ideation with paranoid ideation or hallucinations commanding the patient to harm himself or herself also increases the risk of suicide. Depression with severe agitation or panic disorder increases suicide risk ( 11). Certain stresses are statistically associated with increased suicide risk: recent loss within 6 months, severe financial difficulties, job loss, severe family stress, childbirth, recent surgery, chronic severe illness, and

intractable pain ( 4,8,11). It is crucial to note that a patient without any of these risk factors can be acutely suicidal. In 1968, Solomon (14) outlined a simple but useful framework: Thoughts (common), Means (how a person would do it), Action (e.g., buying a gun or rope, checking out a bridge), Attempt (once an attempt is made, a person is more likely to try again). This framework is simply used in the ED. Any action steps (e.g., finding the means) increases risk. In the United States firearms are most commonly associated with death through suicide (60%), followed by poisoning (in women) and hanging (in men) ( 14A). Seventy percent of patients who commit suicide have a major depressive disorder, mixed bipolar disorder, panic disorder, schizophrenia, psychotic organic mental disorder, alcoholism, drug abuse, or a borderline character disorder ( 10,13,15). In the ED, these diagnostic categories are also likely to present with suicidal ideation, a suicide attempt, or self-inflicted injuries. Patients with depressed mood regardless of diagnosis often have suicidal ideation. The following depressed patients are at significant risk for suicide: those who are hopeless, agitated, or psychotic; those with previous attempts; those with recent loss of a loved one; those with a plan and the means to carry it out; and those with a suicide in the family. Patients who are manic can sometimes also display depressed features (mixed bipolar disorder) with suicidal ideation, which can be missed if not specifically asked for. Psychotic patients of all diagnostic categories discussed in the preceding section can be at risk for self-harm and should be asked about suicidal ideation. Psychotic patients may be driven to harm themselves because of delusions and hallucinations. Paranoid delusions can drive a patient to self-harm. “I took an overdose (or attempted to jump out the window) because I was so frightened and wanted to get away from the people who were trying to harm me.” Delusions of guilt or worthlessness may drive a patient to a suicide attempt. “I am such a horrible person, I must die.” Or, “I don't want my children to know me.” Patients with command hallucinations that suggest self-harm are at risk. “The voice commanded me to take the overdose (or jump in front of the train).” Or, “God told me to stab myself so I could join him in heaven.” Psychotic thinking can at times inadvertently result in self-harm. “I poured gasoline on myself and lit it to purify my thoughts.” Finally, psychotic persons may be of harm to themselves because of poor judgment or inability to assess the environment accurately. A schizophrenic may walk without a coat or shoes in subzero weather in a dangerous neighborhood, or a delirious patient may pull out an endotracheal tube. Patients with severe personality disorder may develop a pattern of suicide attempts to deal with anger, interpersonal rejection, loss of self-esteem, or anxiety. In addition, some severely personality disordered patients superficially cut themselves to relieve anxiety or to “feel real” without suicidal intent. These patients are not at severe risk but may miscalculate and seriously harm or kill themselves. Patients with a severe personality disorder may sometimes become so disordered that suicide attempts become bizarre and potentially lethal. Inquiry into the nature of past self-destructive attempts helps to identify this group. Another group of patients with less severe or no character pathology may become suicidal or make a suicide attempt under severe environmental stress. Most commonly seen are suicide attempts that occur after a disagreement or rejection by a parent, spouse, or significant other. Such suicidal ideation or attempt is usually a cry for help, or a way to punish or get the attention of the significant other. On the other hand, adolescents who lose self-esteem and also experience the rupture of a valued relationship may impulsively make a lethal attempt. Alcohol or drug abuse alone or combined with depression, psychosis, character pathology, or environmental stress greatly increases the risk of suicide. Drugs and alcohol alter mood, weaken defenses, impair judgment, and may result in marked increase of the dysphoric mood and suicidal ideation. For example, the mildly depressed man with passive suicidal ideation, marital stress, and job difficulties may become severely depressed and make a lethal suicide attempt under the influence of alcohol. Patients with a mental disorder secondary to intoxication or withdrawal from alcohol or drugs also may harm themselves. Finally, patients with alcohol or drug abuse may miscalculate drug intake and inadvertently overdose. Patients who are actively suicidal can be extremely creative in carrying out a suicide attempt in the ED or during transfer to a medical, surgical or psychiatric facility. For this reason, the patient must be separated from medical equipment or belongings that could be used for self-injury. In addition, one-to-one supervision (not by a family member) for the patient is mandatory in the ED and during transfer to a medical, surgical, or psychiatric facility. If a patient requires leather restraints because of active attempts at self-harm, one-to-one supervision also is required. Full leather restrains should never be used in lieu of one-to-one supervision. Evaluation of suicidal intent is a complex process. A suicidal patient should never be sent home without evaluation by a psychiatrist or mental health professional. A patient who has made a suicide attempt should be given emergency medical or surgical care. If medically unstable, the patient should be transferred to a medical or surgical unit with one-to-one supervision (not by a family member) until a psychiatric consultant decides that the supervision is no longer necessary. If medically stable, the patient should be admitted to a psychiatric unit. A patient who has made a suicide “gesture,” e.g., an overdose of three acetaminophen tablets, is still at risk because the severity of the suicide attempt does not necessarily correspond with the severity of the patient's future risk for suicide. A patient who has made a suicide attempt may tell the emergency physician that he or she is no longer suicidal. Patients may feel fine in the protected environment of the ED, only to deteriorate when they return to their home environment. Also, acutely suicidal patients may lie so that they may return home to complete the suicide. The emergency physician should never make a contract with a patient not to commit suicide and then discharge the patient home because the emergency physician does not have an ongoing relationship with the patient. The emergency physician should be suspicious of the patient who “accidentally” overdoses. Patients with an “accidental” overdose should never be sent home when medically stable until they can be assessed for suicidality, and every attempt has been made to corroborate the patient's story with a collateral history. Table 120.4 and Table 120.5 illustrate some of the heightened risk factors.

Table 120.4. Suicide Risk Factors

Table 120.5. Estimated Suicide Rates for U.S. Population Subgroups (per 100,000 per year)

VIOLENCE Patients who are psychotic, paranoid, manic, under the influence of drugs or alcohol, character-disordered with poor impulse control, or who have a mental disorder secondary to a medical disorder or substance may harm others ( 16). Occasionally, a suicidal patient may attempt to kill others, usually family members, before his or her own suicide. Consequently, all suicidal patients should be asked about homicidal ideation. Harm directed toward others is of two types: First, patients may have

thoughts of harming a specific person within their environment, usually a family member or a person with whom they perceive they have a significant or special relationship. Second, patients may be violent to anyone in their environment as the result of agitation, poor impulse control, or psychotic disorganization. The best predictor of danger, whether specifically or more generally directed, is a history of violent behavior ( 16). In psychiatric patients, harm directed at a specific person is often the result of paranoid delusions or command hallucinations. Paranoid patients may have thoughts of inflicting harm on a specific individual in the environment to protect themselves. “My mother is heading the conspiracy. I must stop her.” Paranoid patients may also harm loved ones to protect them from supposed harm. For example, a woman with a postpartum psychosis killed her baby so that he could be protected by God and not harmed by the Devil, whom she felt was threatening the baby's safety. A command hallucination may tell a patient to harm a specific person. “God told me to kill my husband because he is evil.” ED personnel must also be alert to patients who may escalate to more generally directed violence in the ED. An extremely agitated, disorganized, psychotic patient may become assaultive, at times with minimal warning. Manic patients who are extremely irritable and hyperactive may become combative if they feel that ED personnel are interfering with their activities. Paranoid patients may fear that ED personnel will harm them and become violent to protect themselves. Command hallucinations may direct patients to harm those in the ED. Patients with mental disorders due to a medical illness or substance may become agitated and combative because they are unable to process the environment accurately as a result of memory deficits, inability to abstract, poor impulse control, delusions, and hallucinations. Those with alcohol and drug intoxication or withdrawal may become violent for similar reasons. Patients with personality disorders and poor impulse control may become violent when angry, hurt, anxious, stressed, criticized, or prevented from doing what they wish. Patients with poor impulse control are even more dangerous when under the influence of drugs or alcohol. Chapter 118 discusses the importance of putting all psychiatric patients in a hospital gown and separating them from their belongings to prevent access to weapons, and providing a safe environment for those assessing the potentially violent patient. The severely agitated psychiatric patient without a mental disorder due to a medical condition or substance often can be prevented from becoming violent by decreasing agitation with psychotropic medication. Patients who threaten to escalate to violence must be physically restrained, as discussed in Chapter 121. Patients who are of harm to others must be hospitalized. Duty to protect the specific person to whom violent intent is directed is also discussed in Chapter 121.

ACUTE PSYCHOLOGIC DISTRESS Patients may present to the ED because of severe psychologic distress associated with depression, mania, anxiety, panic, or overwhelming environmental stressors. Depressive moods can be associated with a major depressive disorder; a mixed bipolar disorder; dysthymia; an adjustment disorder with depressed mood; a relationship, academic, occupational, or phase of life problem; or bereavement. The criteria for a major depressive disorder are defined earlier in this chapter. Patients with less severe depressive disorders may come to the ED with depressed affect. Patients with a dysthymic disorder (4) have had a depressed mood almost every day for at least 2 years with at least two of the following: poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low-self-esteem, poor concentration or difficulty in making decisions, and/or feelings of hopelessness. Various stresses or losses in the environment can result in a depressed mood, which brings the patient to the ED. A patient with an adjustment disorder with depressed mood (17) has had an identifiable stress within 3 months and demonstrates impairment in occupation, social, or interpersonal functioning with symptoms of depressed mood, tearfulness, and/or hopelessness in excess of a normal and expectable reaction to stressors. A patient may present with a relationship, academic, occupational, or phase of life problem (18), with a depressed mood, which is understandable or expectable in response to a stressor in the environment ( 17). Patients with bereavement (18) present with sadness or depressed mood, diminished ability to think and concentrate, indecisiveness, fatigue, poor appetite, and/or insomnia. Guilt, if present, deals with things not done by the survivor. Thoughts of death are confined to feelings that the patient would be better off dead or wishes that he or she had died with the loved one. Preoccupation with worthlessness, marked psychomotor retardation, prolonged or marked functional impairment, or hallucinatory experiences other than hearing the voice of or transiently seeing the image of the decreased person, usually suggests that the bereavement is complicated by a major depressive disorder ( 18). The emergent use of psychotropic medication with depressed patients is discussed later in this chapter. Patients with a major depressive episode and suicidal ideation, severe agitation, and/or psychotic symptoms must be hospitalized; those with no suicidal ideation or mild psychotic symptoms, mild treatable agitation, an excellent support system, and referral to a psychiatrist within a short period of time often may be sent home. Usually, the emergency physician is best served by an on-site psychiatric or social service consultation. Patients with a dysthymic disorder are rarely hospitalized unless they are suicidal, and because they may respond to antidepressants, should be referred to a psychiatrist for evaluation. Patients with an adjustment disorder; a relationship, academic, occupational, or phase of life problem; or bereavement often improve after a discussion of their difficulties. Referral to a mental health facility is appropriate. Patients who are suicidal in response to stress or loss should be hospitalized. Manic patients, described earlier in this chapter, may initially experience euphoria. As the manic episode becomes more severe, however, the patient may experience a markedly unpleasant irritability, drivenness, or hyperactivity that causes him or her to seek help in the ED. Psychotropic medication may be acutely helpful to take the edge off the unpleasant feeling in the ED. Hospitalization is usually necessary. Patients with a mixed bipolar disorder may have signs and symptoms of both a major depressive disorder and a manic episode and require hospitalization. Patients with an anxiety or panic disorder often visit the ED because of overwhelming anxiety and panic ( Table 120.2). Patients with a panic disorder (5) have discrete episodes of panic that, for the most part, come “out of the blue.” The patient has four of the following symptoms: (a) palpitations, pounding heart, or accelerated heart rate; (b) sweating; (c) trembling or shaking; (d) sensations of shortness of breath or smothering; (e) feeling of choking; (f) chest pain or discomfort; (g) nausea or abdominal distress; (h) feeling dizzy, unsteady, lightheaded, or faint; (i) derealization (feelings of unreality) or depersonalization (being detached from oneself); (j) fear of losing control or going crazy; (k) fear of dying; (l) paresthesias (numbness or tingling sensations); or (f) chills or hot flushes. Patients with a panic attack should be treated with psychotropic medication as discussed later in this chapter. Patients with a panic attack need reassurance that the episode will subside and that the disorder is highly treatable with psychotropic medication ( 19). Patients should be given a referral to a psychiatrist before discharge from the ED. A patient with an anxiety disorder visits the ED when the anxiety has become unbearable. An anxiety disorder (18) is defined as anxiety or worry with three of the following six symptoms for 6 months: (a) restlessness or feeling keyed up or on edge, (b) being easily fatigued, (c) difficulty concentrating or mind going blank, (d) irritability, (e) muscle tension, or (f) sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep). It is important to differentiate an anxiety disorder from agitated depression, in which the patient experiences internal anxiety or agitation with a full-blown depressive disorder. Patients with an anxiety disorder should be treated with psychotropic medications, as described in the subsequent chapter. Patients whose anxiety or panic continues to be intolerable may need hospitalization. An adjustment disorder with anxious mood (16) is a reaction to an identifiable stressor with impairment in occupational, social, or interpersonal functioning with symptoms of anxiety, worrying, and/or jitteriness in excess of a normal or expectable reaction to the stressor. Patients with a relationship, academic, occupational, or phase-of-life problem may experience understandable anxiety. Patients with one of these problems or with an adjustment disorder often respond with reduced anxiety after discussing their problems with the emergency physician. Referral to a mental health facility is appropriate. A patient who has been acutely stressed by an intensely traumatic event such as rape, spousal abuse, traumatic or violent injury, death of a loved one, or a serious threat to his or her life or integrity may present to the ED with intense psychologic distress. Some patients and families who have experienced a severe trauma respond to empathy, reassurance, support, structure, and an outpatient referral. Patients who are so traumatized that they continue to be uncontrollably upset, unable to communicate, unable to provide for basic functions for themselves, and have no support system that can manage their emotional state may need hospitalization for a day or two until psychologic reintegration begins to occur. A medical or surgical unit, particularly if the patient has physical injuries, is a supportive environment for such a patient. A psychiatric consultation on a medical/surgical unit is usually preferable to psychiatric hospitalization for the severely traumatized patient.

SOMATIC COMPLAINTS WITHOUT DEMONSTRABLE ORGANIC DISEASE The emergency physician must always keep in mind that physical complaints that do not appear to have a demonstrable organic disease may represent undiagnosed physical illness. In addition, patients with somatic complaints as a result of a psychiatric illness can develop coexistent physical illnesses. Patients with panic disorder and anxiety disorder often present to the ED with complaints suggesting physical illness from overwhelming autonomic arousal. Patients with panic and anxiety disorders are frightened by these symptoms. Reassurance that the symptoms are real but not indicative of physical illness and that the disorder

is highly treatable with psychotropic medication is comforting to these patients ( 19). Depressed patients, particularly the elderly, can present with somatic complaints with the signs and symptoms of a depressive illness. It is important to remember that many medical conditions and substances can cause depressive illness and that physical complaints plus a depressive illness may be the result of physical disease. Disposition should allow for work-up of possible “organic” causes of depression and also provide appropriate psychiatric treatment. Patients with acute or chronic psychosocial stresses commonly present to the ED with physical complaints. There is often a psychophysiologic basis for these complaints, as with tension headache or gastrointestinal disturbance. Other patients may falsely perceive or amplify familiar or normal sensations. These patients often are unaware of the relationship between the stress and the physical symptoms. When physical symptoms appear to be related to stress, discussion of this possible link with the patient, symptomatic treatment such as ibuprofen for headache or antacids for gastrointestinal distress, and reassurance that no serious physiologic disorder exists are useful interventions. Follow-up with the primary care physician and, if the stress is severe or long-term, also with a mental health professional should be suggested. It is important to note that patients who have been sexually or physically abused may present with vague somatic complaints. The management of these problems is discussed elsewhere in this textbook. Somatoform disorders include somatization disorder, hypochondriasis, psychogenic pain disorder, and conversion disorder. The somatic symptoms of these disorders are “real” to these patients, and the psychologic origin of the somatic complaint is out of the patient's awareness. The symptoms are not feigned by the patient, but unconsciously produced. The evaluation and ED treatment of this group of interesting and difficult disorders is discussed in Chapter 62. Somatization disorder (20), which has also been called Briquet's syndrome or hysteria, is a disease with somatic complaints in multiple systems for which no pathophysiologic mechanism can be found for the symptoms. The patient, however, has taken medication, seen a physician, or altered his or her lifestyle as a result of the symptoms. The onset of this disorder is prior to age 30, but usually begins earlier in adolescence or young adulthood. The patient's female family members are more likely to have somatization disorder, and male relatives are more likely to have sociopathy. Drug abuse and depression also are common in relatives. To meet criteria for this disorder, the patient must have the following symptoms: (a) four pain symptoms: a history of pain related to at least four different sites or functions (e.g., head, abdomen, back, joints, extremities, chest, rectum, during menstruation, during sexual intercourse, or during urination); (b) two gastrointestinal symptoms: a history of at least two gastrointestinal symptoms other than pain (e.g., nausea, bloating, vomiting other than during pregnancy, diarrhea, or intolerance of several different foods); (c) one sexual symptom: a history of at least one sexual or reproductive symptom other than pain (e.g., sexual indifference, erectile or ejaculatory dysfunction, irregular menses, excessive menstrual bleeding, vomiting throughout pregnancy); (d) one pseudoneurologic symptom: a history of at least one symptom or deficit suggesting a neurologic condition not limited to pain (conversion symptoms such as impaired coordination or balance, paralysis or localized weakness, difficulty swallowing or lump in throat, aphonia, urinary retention, hallucinations, loss of touch or pain sensation, double vision, blindness, deafness, seizures; dissociative symptoms such as amnesia; or loss of consciousness other than fainting). The patient usually has a history of seeing multiple physicians during the course of the illness. Because collateral history and old medical records often are unavailable, it may be difficult to make a definitive diagnosis in the ED. The somatic symptoms of somatization disorder are stable over time and respond poorly to psychiatric treatment. Intervention is directed toward preventing the patient from having unnecessary procedures and surgery and inappropriately using health care services. A referral should be made to a primary care physician or psychiatrist who can help prevent this inappropriate use of health care services. These patients may also have alcohol and drug abuse, depressive and anxiety symptoms, conversion disorder, and suicidal ideation and attempts. When patients present with these psychiatric symptoms, a psychiatric referral should be made. Patients with an undifferentiated somatoform disorder (21) may not have enough symptoms to meet full criteria for a somatization disorder but have one or more unexplained physical symptoms. Often these patients have seen multiple physicians, and again, a referral to a primary care physician tolerant to unexplained physical complaints should be made. A referral to a psychiatrist should also be made if comorbid psychiatric symptoms exist. Hypochondriasis (20) is another disorder that presents with somatic complaints and is difficult to treat. The patient is preoccupied for more than 6 months with the fear of having or the idea that one has a serious illness based on the person's misinterpretation of bodily symptoms unsupported by physical evaluation. Despite reassurance that there is no medical illness, the patient continues to have the fear or belief that he or she is ill. The onset of the illness may occur any time from young adulthood to the 50s and is chronic. Hypochondriasis must be differentiated from a depressive disorder with somatic complaints and a psychotic disorder with somatic delusions. Whereas the patient with somatization disorder is usually interpersonally pleasant, although time-consuming, the patient with hypochondriasis can be demanding and unpleasant. These patients resist a referral to a psychiatrist because they view themselves as physically ill. As with somatization disorder, these patients frequently have seen many physicians. The relationship often ends when the physician becomes exasperated with the patient's angry, demanding stance and the patient becomes dissatisfied with the physician's care. These patients should be referred to a tolerant and understanding primary care physician or psychiatrist who is able to maintain an ongoing relationship with them by listening to their complaints, doing minimal diagnostic tests, and seeing the patient in frequent but controlled visits. With such treatment, inappropriate use of health care services is controlled, and some patients' somatic complaints may be improved. Patients with somatoform pain disorder (14) are another group who have had multiple workups, have seen many physicians, and may be unpleasant in their ED demands for pain medication and admission to the hospital. These patients either have no organic cause for their pain, or if there is an underlying organic pathology, the complaint of pain or social or occupational impairment is in gross excess of the organic pathology. These patients, who resist referral to a psychiatrist, are best referred to a primary care physician or, if available, a pain center with a multidisciplinary team. Conversion disorder (20) is a rare and highly treatable psychiatric illness. The symptoms are in the voluntary or sensory nervous system and mimic neurologic disease or other medical condition. The neurologic examination or workup is not consistent with neurologic disease. Symptoms are acute in onset and related to a psychosocial stressor. Because symptom production is unconscious, the patient usually is unaware of the relationship between the conversion symptoms and the stressor. Hemianesthesia, hemiparesis, and “hysterical” blindness, deafness, aphonia, seizures, movement disorders, and difficulties in walking are common presentations. Neurologic workup and prompt psychiatric evaluation and treatment are essential with this disorder. Conversionlike symptoms are common with undiagnosed neurologic disease such as multiple sclerosis. In addition, a “true” conversion disorder can become chronic without psychiatric treatment when conversion symptoms become a means of chronically coping with stress. Patients with malingering (18) are seen commonly in the ED. These patients feign physical illness for narcotics, shelter, and financial compensation, and to evade criminal prosecution. The environmental goals become obvious with careful questioning by the examiner. Ascertaining what malingering patients want is essential to preventing inappropriate use of the ED. For example, homeless patients who feign illness to obtain a hospital bed are best given referrals for an emergency shelter. Overly solicitous treatment, however, encourages use of the ED on a routine basis for this problem. Patients who feign illness for drugs should never be given the drugs they desire but rather should be referred to a drug rehabilitation program. Inquiry into recent job loss, job-related injuries, lawsuits, or consultation with a lawyer can uncover the patient who feigns illness for financial compensation. The patient's history and lack of positive physical findings should be documented on the ED record. Patients who malinger and, after evaluation, do not receive what they want from the ED personnel, may become angry and threaten a malpractice suit or physical harm. The patient should be asked firmly to leave the ED and, if necessary, should be escorted by security personnel. The patient's behavior and the emergency physician's intervention should be documented on the chart. Factitious disorder (21) is a rare psychiatric disorder in which the patient feigns illness because of a psychologic need to assume the patient role. This is the sole reason for feigning illness, whereas in malingering, there is an obvious recognizable environmental goal (e.g., shelter, monetary compensation, or avoidance of jail). Although patients with factitious disorder may secondarily demand narcotics, the compulsive need to feign illness and adopt the patient role is the primary psychologic motivation. Patients with this disorder subject themselves to extreme risk in producing these symptoms, such as by ingesting massive amounts of anticoagulants, injecting bones with feces, or instrumenting the urethra or anus to produce hematuria or rectal bleeding. These patients happily undergo invasive, dangerous, or painful medical procedures. As a result of their creative symptom production and subsequent medical care, these patients have self-inflicted or iatrogenically produced physical pathology. Many of these patients have worked in hospitals; have encyclopedic familiarity with medical jargon; and demonstrate pseudologia fantastica in which they elaborately spin falsehoods about occupations, family background, and illness in a fascinating, engaging, and often grandiose manner. In the extreme form of this disorder (Munchhausen syndrome), the patient spends all of his or her time going from city to city and hospital to hospital. Often EDs in the area have seen a patient with similar symptoms. Patients with factitious disorders may have a number of aliases. Once they are admitted to the hospital, they usually have an extensive, expensive workup, are demanding and noncompliant, and when confronted with a negative workup or discovered in voluntary symptom production, sign out against medical advice. Seasoned ED personnel are often suspicious of the elaborate, inconsistent, fantastic history, dramatic presentation, and questionable identification, insurance cards, and places of residence. The ED physician who suspects factitious disorder is frequently successful in preventing such a patient from being admitted to the hospital. Unfortunately, these are clever patients who often voluntarily produce symptoms for which admission to the hospital is mandatory. When these patients must be admitted, “rule out factitious disorder” should be written on the ED record to alert the ward physician.

Somatic delusions may be present in psychotic disorders. Psychotically depressed patients have the signs and symptoms of depression with delusions that they are physically ill, defective, or disordered. Patients who have an acute schizophrenic episode often have bizarre somatic delusions. Medicated schizophrenic patients, however, may present with less bizarre delusions. For example, a schizophrenic who felt that thoughts pressed on her eye presented to the emergency room with severe eye pain. On careful questioning, the delusion behind the pain became obvious. Patients with a delusional disorder, somatic type, often present with no symptoms other than a delusion of physical disease, defect, or disorder. The ED physician usually quickly recognizes a somatic delusion. The difficulty arises when a psychotic misperception of actual physical phenomena is thought to be purely a somatic delusion. The example of the schizophrenic in Chapter 118 with acute appendicitis who presents with “snakes in his abdomen” illustrates this.

PSYCHOTROPIC MEDICATION Agitation and Psychotic Disorganization Benzodiazepines and neuroleptics are used either separately or together to control agitation and psychotic disorganization in the ED. Lorazepam and haloperidol are used most commonly because of their efficacy and safety. Lorazepam has a half-life of 10 to 20 hours and few active metabolites. Lorazepam does not require oxidation for metabolic degradation (a process slowed by age, commonly used medications, and liver dysfunction) but only glucuronide conjugation (processes minimally effected by the factors that affect oxidation). Lorazepam decreases anxiety and agitation; it is useful for withdrawal from alcohol, barbiturates, and benzodiazepines. It may cause paradoxic excitement, particularly in patients with brain damage. The most serious side effect is respiratory depression when given to those with respiratory disease with hypercapnia, in combination with other sedatives, in large amounts, or by rapid intravenous push. Oral, intramuscular, or intravenous lorazepam 0.5 to 2 mg depending on the severity of the agitation is useful. Onset is almost immediately by intravenous push. If the patient is not adequately sedated the previous or lower doses can be repeated in 30 minutes or more depending on the route of administration. Lorazepam does not control psychotic symptoms and, if there are no contraindications, should be combined with haloperidol if the patient is agitated and psychotic. Haloperidol has minimal effects on the cardiovascular system, causes minimal orthostatic hypotension (except when given intravenous push), and has few anticholinergic side effects. Although haloperidol has been reported to lower the seizure threshold, it rarely does so except when the seizures are uncontrolled. Finally, haloperidol may cause extrapyramidal side effects (dystonia, pseudoparkinsonian symptoms, and akathisia), which can be controlled by benztropine mesylate (1 to 2 mg intramuscularly), or diphenhydramine HCl (50 mg intravenously). The recommendation is haloperidol 0.5 to 1 mg for mild agitation and psychosis, 2 to 5 mg for moderate, and 5 to 10 mg for severe. The original or a lower dose can be administered in 30 to 45 minutes. Haloperidol is rarely given in more than a 2-mg bolus at one time, but may be repeated every 30 minutes until the patient is sedated. When haloperidol is given orally, elixir, rather than tablets, is suggested to prevent “cheeking” of pills and for more rapid absorption. If lorazepam and haloperidol are used together, the dosages of each are approximated half of that for each drug alone, but each can be adjusted up or down depending on the patient's agitation and psychosis. Neuroleptics other than haloperidol are also used in the ED. Haloperidol and lithium have been reported rarely to cause irreversible brain damage in sensitive individuals. As a result, the more potent phenothiazines—fluphenazine, trifluoperazine, and the slightly more sedating perphenazine—are often used with lithium. These neuroleptics have a side effect profile similar to that of haloperidol. Less potent phenothiazine neuroleptics such as thioridazine, chlorpromazine, and mesoridazine cause fewer extrapyramidal reactions and are useful in patients with a previous history of severe extrapyramidal side effects and Parkinson's disease. (Potency of drug equivalent to 100 mg of chlorpromazine: thioridazine 100 mg, mesoridazine 50 mg, fluphenazine 1.5 to 3 mg, trifluperazine 3 to 5 mg, perphenazine 10 mg, molindone 6 to 10 mg, haloperidol 2 to 5 mg.) These less potent neuroleptics, however, have more sedative, anticholinergic, and hypotensive side effects than the more potent neuroleptics. Resperidone, 0.5 to 1.5 mg, which can only be given orally and causes some orthostatic hypotension, is another alternative in this group of patients. Clozapine, olanzapine, and sertindole, the newer atypical antipsychotics are rarely used in the ED; although they also cause less extrapyramidal side effects, they can only be given orally and are less reliable in the early treatment of psychotic symptoms. Molindone does not lower the seizure threshold but cannot be given intramuscularly. Fluphenazine, which lowers the seizure threshold only slightly, can be given intramuscularly. These latter two neuroleptics are preferred for patients with uncontrolled seizures. Those with a history of neuroleptic malignant syndrome should be given benzodiazepines to avoid the risk of the syndrome recurring. The risk: benefit ratio of using lorazepam and haloperidol to control agitation and psychotic symptoms in patients suspected of having an “organic” mental disorder, particularly delirium, should be evaluated. Sensorium is a sensitive indicator of deteriorating physical condition. Consequently, psychotropic medications should be avoided in conditions in which the level of consciousness is diagnostically critical. The goal of medicating the agitated and/or psychotic patient is adequate control of the symptoms so that assessment and disposition can be achieved. If a patient is transferred to a psychiatric facility, it is important to medicate the patient to ensure safe transfer, but not so that symptoms are obscured for evaluation by the receiving facility. In some state or county facilities, the patient may be inadvertently discharged if symptoms are obscured, only to reappear several hours later in the ED. If, in the emergency physician's judgment, the patient requires an amount of medication that obscures symptomatology, the clinical picture before medication should be documented, as should the reasons for the medication. In addition, active treatment with mood stabilizers or antidepressants should not be initiated by the emergency physician before transfer. Such medications may interfere with the treatment strategy of the receiving facility. Anxiety, Panic, Agitated Depression, and Mania Patients with hypomania and mania, who are not psychotic, are often given lorazepam, a neuroleptic, or both for control of the agitation, irritability, and hyperactive behavior. Clonazepam 1 to 2 mg, which is very sedating, can be substituted for lorazepam for hypomania and mania; it is n-acetylated but not oxidated, and can only be given orally. Patients with panic attacks, severe anxiety, or agitated depression should be treated with lorazepam 0.5 to 1 mg orally, intramuscularly, or intravenously or alprazolam 0.25 to 0.5 mg orally every half hour until the overwhelming affect subsides. A patient who has panic, anxiety, or an agitated depression that responds to benzodiazepines and is discharged from the ED should be given a 2- or 3-day supply of benzodiazepines for symptom control until the follow-up appointment. Remember that patients with such disorders have higher incidence of suicide attempts. Medications for Patients Discharged from the ED Patients who are discharged from the ED should never be given more than a few days' supply of psychotropic medications. Those who require psychotropic medication should have ongoing outpatient psychiatric care, and the need for medication will encourage the patient to obtain or continue this care. In addition, patients should never be given enough medication for an overdose that could cause significant medical morbidity and mortality. As a rule, a few days of benzodiazepines are indicated for those with panic, anxiety, or agitated depression who might withdraw without them. Additionally, a few days of neuroleptics may be indicated for those with chronic psychotic illness. Antidepressants, lithium, carbamazepine, or valproic acid should never be started in the ED because of the danger of overdose and the difficulty of monitoring side effects. Patients presently on psychotropic medications may come to the ED for refills when the medication runs out. The emergency physician may refuse to dispense these medications unless he or she is able to contact the mental health provider and confirm the present use of the medication requested. The ED is not an outpatient psychiatric clinic, and repeated availability of psychotropic drugs in the ED encourages its use for this purpose and discourages appropriate outpatient mental health care. 1

“Organic” is defined as due to a medical condition (including head trauma) or a substance (alcohol or drug withdrawal or intoxication, medication side effect, vitamin deficiency, or toxin).

2

George R. Schwartz contributed to this section.

References 1. 2. 3. 4. 5.

Delirium, dementia, and amnestic and other cognitive-disorders. In: Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994;123–163. Schizophrenia and other psychotic disorders. In: Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994;273–315. Mental disorder due to a general medical condition. In: Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994;165–174. Mood disorders. In: Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994;317–391. Anxiety disorders. In: Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994;393–444.

5A. Asnis GM, Friedman TA, Sanderson WC, et al: Suicidal behaviors in adult psychiatric patients. Am J Psych 1993;150:108–112. 6. 7. 8. 9. 10.

Hyman SE, ed: The suicidal patient. In: Manual of psychiatric emergencies. Boston: Little, Brown, 1984. Tomb DA: Psychiatry for the house officer. 2nd ed. Baltimore: Williams & Wilkins, 1984. Weisman MM: The epidemiology of suicide attempts. Arch Gen Psychiatry 1974;30:737. Hillard JR: Emergency management of the suicidal patient. In: Walker JI, ed. Psychiatric emergencies: intervention and resolution. Philadelphia: JB Lippincott, 1983. Shader RI: Assessment of suicide risk. In: Shader RI, ed. Manual of Psychiatric Therapeutics. Boston: Little, Brown, 1975.

11. Roy A. Risk factors for suicide in psychiatric patients. Arch Gen Psychiatry 1982;39:1089. 11A. Hirschfeld RM, Russell JM: Assessment and treatment of suicide patients. N Engl J Med 1997;337:910–915. 12. Beck AT: Hopelessness and eventual suicide: a 10-year prospective study of patients hospitalized with suicidal ideation. Am J Psychiatry 1985;142:559. 13. Fawcett JA: Clinical assessment of suicidal risk. Postgrad Med 1974;55:85. 14. Solomon P: The burden of responsibility in suicide and homicide. JAMA 1968;199:99. 14A. Moscicki ER. Gender differences in completed and attempted suicides. Ann Epidemiol 1994;4:152–158. 15. 16. 17. 18. 19. 20. 21.

Pokorny AD: Predictions of suicide in psychiatric patients. Arch Gen Psychiatry 1983;40:249. Monahan J, ed: The clinical prediction of violence. Washington, DC: Government Printing Office (National Institute of Mental Health), 1981. Adjustment disorders. In: Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994;623–627. Other conditions that may be a focus of attention. In: Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994;675–686. Pollard CA, Lewis LM. Managing panic attacks in emergency patients. J Emerg Med 1989;7:547. Somatoform disorders. In: Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994;445–469. Factitious disorder. In: Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994;471–475.

Suggested Readings Alavarez A: The savage god—a study of suicide. New York: Random House, 1972. Barber ME, Marsuk PM, Leon AC, et al: Aborted suicide attempts: a new classification of suicidal behavior. Am J Psychiatry 1998;155:385–389. Barraclough B, Bunch J, Nerlson B, et al: A hundred cases of suicide: clinical aspects. Br J Psychiatry 1974;125:355. Battaglia J, Moss S, Rush J, et al: Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective double blind, emergency department study. Am J Emerg Med 1997;15:335–340. Cross C, Hirschfeld R: Epidemiology of disorders in adulthood: suicide. In: Klerman G, Appelbaum P, Roth L, et al. Psychiatry 3. Philadelphia: JB Lippincott, 1988;20:1–15. Davidson P, Koziol-McLain J, Harrison L, et al: Intoxicated ED patients: a 5 year follow-up of morbidity and mortality. Ann Emerg Med 1997;30:593–597. Faberow E: The cry for help. New York: McGraw Hill, 1965. Fedden B: Suicide. London: London Press, 1938. Ferrada-Noli M, Asberg M, Ormstad K, et al: Suicidal behavior after severe trauma. J Trauma Stress 1998;11:103–112. Havens LL: Recognition of suicidal risks through the psychologic examination. N Engl J Med. 1967;276:4, 210. Isometsa MD, Henriksson MM, Aro HM, et al: Suicide in major depression. Am J Psych 1994;151:530–536. Lepine JP: Suicide attempts in patients with panic disorders. Arch Gen Psych 1993;50:144–149. Maris W: Pathways to suicide. Baltimore: Johns Hopkins University Press, 1981. Meyerson L, Wennogle L, Abel M, et al: Human brain receptor: alterations in suicide victims. Pharmacol Biochem Behav 1982;17:159. Murphy G: The physician's responsibility for suicide. I. An error of commission. Ann Intern Med 1975;82:301. Nietzsche F: The philosophy of nietzsche. From “on voluntary death” in “thus spake zarathustra.” New York: Modern Library, 1954. Pallikkathayil L, Morgan S: Emergency department nurses encounters with suicide attempters: a qualitiative investigation. Scholarly Inquiry for Nursing Practice: An International Journal. 1988;2:237–253. Pokorny AD: Prediction of suicide in psychotic patients: report on a prospective study. Arch Gen Psychiatry 1983;40:249. Schneidman E: Definition of suicide. A Wiley-Interscience publication. New York: Wiley and Sons, 1985. Schneidman E: Essays in self destruction. New York: Science House, 1969. Schneidman E: A psychologic theory of suicide. Psychiatric Ann 1976;6:51. Schneidman E, Faberow E: Los Angeles suicide prevention. Am J Public Health 1963;55:1. Schwartz GR: Loss of physicians by suicide. N Engl J Med 1967;276:1443. Simcic KJ: Treatment of suicidal patients. N Engl J Med 1998;338:262–268. Steppacher C, Mausner JS: Suicide in male and female physicians. JAMA 1974;228:3.

CHAPTER 121 PSYCHIATRIC MEDICAL LEGAL CONSIDERATIONS: CODES, RESTRAINTS, COMMITMENTS, TRANSFERS, AND COBRA REGULATIONS Principles and Practice of Emergency Medicine

CHAPTER 121 PSYCHIATRIC MEDICAL LEGAL CONSIDERATIONS: CODES, RESTRAINTS, COMMITMENTS, TRANSFERS, AND COBRA REGULATIONS Stephanie von Ammon Cavanaugh and William S. Gilmer Mental Health Code Restraints Commitment Elopement Confidentiality and duty to Protect Right to Refuse Treatment Disposition Special Problems

MENTAL HEALTH CODE Each state has a slightly different mental health code for restraints, commitment, informed consent for psychotropic medication, the right to refuse treatment, confidentiality, and the duty to protect. Emergency department (ED) physicians should be familiar with their mental health code and its interpretation in their state and hospital.

RESTRAINTS Restraints are used when ED personnel assess a patient as potentially violent or demonstrating violent behavior. State mental health codes dictate that a patient may not be restrained before he or she begins to threaten or show violent behavior. Ideally, a patient should be restrained when he or she begins to threaten violence or show “imminent signs of impending violence” and before violent behavior occurs. Liberal interpretation of “threatening or violent behavior” may be needed to ensure protection of the patient and others in the ED. The mental health code states that restraints should never be used when less restrictive methods, such as one-to-one supervision, will suffice. Psychotropic medication (chemical restraints) should be used before physical restraints in the hyperactive, agitated, nonviolent patient. In many cases, however, the agitation and disorganization are so severe that the emergency physician believes that the safety of the patient and others in the ED is best served by first restraining and then medicating the patient. Once a decision is made to restrain a potentially violent patient, at least five additional personnel are needed, one for each limb and one to apply the restraints. A strong or larger patient may require more personnel for the application of restraints. The goal is to have enough people to prevent both patient and staff members from being harmed. Often an adequate show of force calms the patient, and he or she can be brought under control verbally while the restraints are applied without need for force. In restraining a patient, as in cardiopulmonary resuscitation, one person should be in charge. This person should be familiar with the restraining process and tell those assisting exactly what to do. Security guards should be instructed to remove all weapons and to stay out of the patient's vision until the restraining team is assembled. When the restraining team is ready, the team leader should move calmly, quickly, and with authority. This attitude is reassuring to the restraining team, who may be anxious or frightened, and to the patient, who is out of control. The person in charge should tell the patient in a calm voice: “You are out of control and need to be put in restraints for your protection and ours. No one will harm you.” The patient may attempt to negotiate or threaten at this point to stop the restraining process. Nonetheless, the team must continue with the restraining process unless the physician-in-charge decides otherwise. The restraints should be secured to the solid portions of the cart or bed, not the side rails. The restraints should be tight enough to prevent escape, but not so tight as to compromise circulation or respiration. Continued monitoring is essential because numerous deaths have been reported from restraints, usually with respiratory impairment. After all four limbs are secured, pulses should be checked. Some violent patients may also need a chest restraint. It is important to remember that restrained patients can still bite. The restraining team should not leave the patient until the team leader is sure that the patient is securely and safely restrained. An ED policy mandating that restraining personnel not leave the patient until the team leader tells them to do so is advised. Triage personnel or a physician may initiate the restraining process, but the emergency physician should write an order for restraints. Both the person initiating the restraints and the physician writing the restraining order must document the reason on the chart. Although hospital guidelines vary for observing a patient in restraints in the ED, the standard of practice for a psychiatric unit is recommended both clinically and medicolegally for the ED. A patient who is restrained in the ED should never be left alone. A flow sheet documenting observation is recommended. Pulses and restraints should be checked regularly to ensure that the patient's blood flow to hands and feet is unrestricted and restraints are secure. Each state's mental health code mandates how frequently restraint orders must be rewritten. The patient in four-point leather restraints should never have an arm or leg restraint removed. Such removal can result in harm to the patient or others. If the patient cannot be taken completely out of leather restraints safely, all four restraints should remain in place. If for any reason the patient must have one arm removed from the restraints, they require one-to-one supervision until returned to all four leather restraints. Water with a straw and a urinal or a bedpan can be given to a patient in full leather restraints. Feeding of a patient in a 24-hour holding area can be accomplished easily by putting up the head of the bed or cart and feeding the patient. Personnel should be instructed that patients in leather restraints may use any persuasive argument or threat to be released, but should not release them until they are no longer potentially dangerous. An ED policy requiring a physician's order to release a patient from full leather restraints is advised.

COMMITMENT Involuntary A patient may be involuntarily committed to the hospital for psychiatric treatment when he or she, because of a mental illness or defect, is imminently dangerous to himself or herself or others or is incapable of self-care. Mental health codes vary slightly from state to state, and the emergency physician should be familiar with the mental health code of his or her state. In most states, “mental illness or defect” is not usually defined by the mental health code. Harm to oneself or others is uniformly defined as “harmful threats or acts.” The time period for “imminent harm” to self or others varies from state to state, but is typically 24 to 48 hours. A patient who is “unable to care for himself or herself” is unable to provide for basic needs such as food, water, and shelter, or demonstrates such poor judgment that he or she puts himself or herself at extreme risk. Examples include refusal to eat or drink for a protracted period of time, catatonic stupor, disorganization so great that the patient is unable to provide for basic needs, or behavior such as wandering in subzero weather without adequate clothing in a dangerous neighborhood. It is best to err on the side of safety in uncertain or borderline situations. In addition, psychiatric evaluation during the 3 to 5 days of the patient's detention before the commitment hearing allows a more certain evaluation of danger to self or others. If the patient is not considered dangerous, he or she can be released before the commitment hearing. For example, a schizophrenic patient may have a documented history of attempting to kill his mother during a previous similar episode. The patient may evade any questions pertaining to thoughts of harming his mother and refuse hospitalization. In this instance, the emergency physician is safer in committing the patient for more thorough evaluation because the risk for harm to the mother is potentially high if the patient is released. To commit a patient, the family, the hospital administrator, or the emergency nurse may petition the court for involuntary commitment. Every attempt should be made to have the family be the petitioner. Any licensed physician or, in many states, “qualified examiner” (i.e., licensed clinical psychologist) may fill out the first certificate. The examiner should write legibly and carefully document the reasons for commitment without medical jargon. For example, “The patient took 20 acetaminophen tablets in an attempt to end his life and is of harm to himself.” Or, “The patient threatened to kill his wife and is of harm to others.” Or, “The patient was found in her own excrement, playing with a doll, and had not eaten for a week. She is unable to care for herself.” The second certificate must be filled out by a psychiatrist, who may still be in training, but must be licensed in the state. In some states, a “qualified examiner” may fill out the second certificate or a second physician. Voluntary A patient may voluntarily commit himself or herself to a hospital for psychiatric treatment by signing a voluntary commitment form. Voluntary commitment is always preferable to involuntary commitment because a court hearing is not necessary. Once a patient has signed a voluntary commitment, he or she is commited to the hospital for at least 5 days, unless the treating physician feels that he or she can be released. When a patient wishes to leave the hospital, he or she signs a 5-day

notice and may be released from the hospital no later than 5 days afterward. During this period, if the treating physician feels that continued hospitalization is necessary and the patient meets criteria for involuntary commitment, proceedings for the latter may be initiated. Patients who are not committable but need psychiatric hospitalization may be required to sign a voluntary commitment to be considered for admission to many psychiatric facilities. Other psychiatric facilities (usually open units) may allow a patient to sign an informal admission, which permits the patient to leave the treating facility at any time. Patients who are not committable, but require psychiatric hospitalization and refuse admission, must sign out of the ED against medical advice (AMA). The need for psychiatric hospitalization should be carefully explained to the family with the patient present, and this documented on the chart. If the family is not present, members should be called and the patient asked to wait until their arrival. Family members who feel that the patient needs psychiatric hospitalization are often successful in persuading the recalcitrant patient to sign a voluntary commitment and enter the hospital. Providing the patient with appropriate psychotropic medication and time with the family often assists in this process. If the patient still insists on leaving, other options should be presented to the patient and family and documented on the ED record. These options include inpatient hospitalization in the near future, an immediate outpatient referral, or both. A noncommittable patient who needs hospitalization requires careful supervision at home. Often a psychotic patient is amenable to psychiatric hospitalization after 24 to 36 hours of appropriate psychotropic medication. Regardless of whether the patient seeks hospitalization at a later time, the importance of immediate outpatient care should be emphasized. Before the patient leaves the ED, an AMA (Against Medical Advice) form should be prepared and the patient asked to sign it. If the patient refuses, this should be documented on the record.

ELOPEMENT Waiting in a busy ED can be particularly stressful for a patient with a psychiatric disturbance. Because such patients may need psychiatric referral (which usually takes time), this process should be initiated promptly after triage even while other tests are in progress. Careful supervision and prompt evaluation, treatment, and disposition can help prevent the emotionally disturbed patient from eloping from the ED. Putting the patient in a hospital gown also deters the patient from leaving the emergency area and makes identification easier if elopement does occur. If a patient who has been evaluated elopes from the ED, the action taken depends on the patient's mental state. If the patient was committable, commitment papers should be initiated. Hospital security, the police, and the family should be informed, and every effort made to return the patient to the ED. These efforts should be recorded on the chart. If the patient was not committable but required psychiatric care, this AMA departure should be documented on the chart. Family members should be notified of the AMA departure. If the patient was not in need of psychiatric care, no additional action is necessary. A significant problem occurs when a patient who has not been evaluated elopes from the ED. If there is any concern that the patient may be of harm to self or others or that they may be incapable of self-care, hospital security and the police must be called and every attempt made to return the patient to the ED. If possible, the family must be notified. Collateral history often helps to establish the seriousness of the patient's mental disorder. In some EDs, a patient who elopes is assumed to be committable until after psychiatric evaluation has taken place, and elopement is handled accordingly. In conclusion, the best way to handle elopement is to prevent it. Good triage information, careful supervision, prompt evaluation, and a hospital gown are the best deterrents.

CONFIDENTIALITY AND DUTY TO PROTECT Doctor–patient communication is confidential and permission to telephone family or friends for a collateral history requires consent from the patient. If the patient is suicidal, homicidal, or unable to communicate for any reason, the emergency nature of the situation allows this privilege to be set aside. The reason for this breach of confidentiality must be documented on the chart. The discussion of clinical information obtained from the patient with family and friends again requires permission from the patient. Confidentiality may be disregarded in only one instance: when a patient makes a specific threat against a specific individual. In this case, the physician has the duty to protect this individual. Because most mentally ill patients who make such threats are hospitalized, this constitutes adequate protection. In addition, this warning may be communicated to the potential victim by the emergency physician or later by the subsequent treating psychiatrist. Because information is often lost in transfer to psychiatric facilities and patients are prematurely discharged, the emergency physician must assess the seriousness of the threat. If the evaluating physician feels that the threat is serious, the individual to whom the threats are directed should be warned by telephone or letter and this documented in the chart. Similarly, if a patient elopes from the ED and has made specific threats against a specific individual, that individual must be warned. A controversy exists about whether suicidal thoughts and actions should be communicated to family or friends without the patient's permission. Most suicidal patients readily grant such permission and are often hospitalized, so that family knowledge of suicidality is not required for safety of the patient. In some instances, patients have suicidal ideation but are not actively suicidal, and are sent home with family supervision and outpatient care. If such a patient refuses to allow the physician to discuss their suicidal thoughts with the family, hospitalization is necessary.

RIGHT TO REFUSE TREATMENT A mentally ill patient has the right to refuse diagnostic tests and treatments, even if involuntarily committed and awaiting transfer to a psychiatric facility. If a psychiatric patient refuses medical treatment as a result of a mental disorder, this treatment may be provided against the patient's wishes if significant morbidity or mortality would occur without it. For example, a hypoglycemic, schizophrenic patient who feels that intravenous glucose will poison his system and kill him may have glucose administered to him. Likewise, a delirious patient who refuses life-saving treatment may be treated. The need for emergency medical treatment should be carefully documented on the chart. Additional documentation by another physician or medical personnel supporting the need for emergency treatment provides further legal protection for the treating physician. If a psychiatric patient is imminently dangerous to self or others and refuses psychotropic medications, the physician may initiate treatment on an emergency basis. Before emergency treatment is begun, commitment should be initiated and the emergency need for such treatment documented. Again, documentation by other medical personnel of the emergency need for psychotropic medication provides further support for the emergent treatment. Some states, as part of the mental health code, require chart documentation of verbal or written communication with the patient regarding the action and side effects of all psychotropic drugs administered. If the patient is unable to understand this information because of their mental state, this also needs should be recorded on the chart.

DISPOSITION The disposition of a patient who presents with an emotional disturbance depends on the patient's psychiatric disorder, coexistent medical illness, insurance, social supports, and community resources. Disposition includes hospitalization, 24-hour hold, or outpatient referral. Hospitalization The first decision that the emergency physician must make is whether or not the patient needs hospitalization. Patients who are of harm to themselves or others or unable to care for themselves because of a mental disorder are routinely hospitalized. Most psychotic patients are hospitalized. Exceptions include chronically psychotic patients who have a stable living environment, no change in psychiatric symptomatology, stable appropriate outpatient care, and optimal treatment with psychotropic drugs with which they are compliant. Patients with a severe depressive disorder, agitated depression, or mania are most always hospitalized. Patients who have a severe anxiety disorder or panic disorder are often hospitalized, if the anxiety or panic cannot be adequately controlled by anxiolytics in the emergency room. Patients with a disturbance of affect, cognition, or behavior secondary to an “organic” 1 mental disorder should be hospitalized on a medical or psychiatric floor depending on the patient's medical status and treatment needs (e.g., delirium; dementia with agitation or deterioration of cognitive functioning; an amnestic disorder that is acute, untreated, or of unknown cause; an acute “organic” psychotic disorder; severe “organic” anxiety or mood disorders; and unmanageable “organic” personality change). The second decision of the emergency physician is where to hospitalize the patient. The patient with an acute medical or surgical problem and a psychiatric disturbance either as a result of the medical problem or coexistent with it should be hospitalized in an appropriate medical or surgical unit. Although medical or surgical units may be reluctant to accept medically or surgically ill patients with a psychiatric disturbance, most patients can be psychiatrically maintained during medical or surgical treatment with psychotropic medication, restraints, close supervision, and psychiatric consultation. There is significant risk in hospitalizing a medically or surgically unstable patient in a psychiatric unit without the appropriate resources to manage the patient's physical problem competently. A patient with a possible “organic” cause for the mental disturbance or a coexistent medical problem that requires treatment should be hospitalized where competent medical diagnostic and treatment facilities are available. For example, the elderly patient, the patient with significant but stable medical problems, and the patient with an initial

or atypical episode of a psychotic or mood disorder are best hospitalized on a psychiatric unit in a general hospital. Transfer of Psychiatric Patients The Emergency Medical Treatment and Active Labor Act of 1986 (EMTALA) and the Consolidated Omnibus Budget Reconciliation Act of 1986 (COBRA), as amended by the Omnibus Budget Reconciliation Act of 1989 (OBRA) were passed by Congress to protect the uninsured and underinsured from being unsafely transferred or being refused emergency medical treatment and apply to all EDs and hospitals that receive Medicare funds. Any hospital that has reason to believe that a patient has been transferred in violation of EMTALA must report that hospital to the Hospital Care Financing Administration (HCFA) or the Department of Mental Health (DMH). Failure to do so could result in termination of the receiving hospital from the Medicare program. Likewise, a substantiated EMTALA violation against a hospital could result in termination of Medicare funds. In 1994, EMTALA was broadened to include patients with emergent psychiatric or substance abuse conditions. A patient should never be transferred to a psychiatric facility without first calling the institution to discuss the patient's condition and obtaining the receiving hospital's approval for transfer. The name of the person accepting the transfer should be documented on the ED record. Although any ED staff member can initiate the transfer, the ED physician should speak directly to the receiving physician or mental health worker about the patient's medical or psychiatric condition. EMTALA regulations prohibit coercing a patient to agree to transfer against his or her best interest, i.e., warning that the patient will have to pay at the transferring hospital but will receive free or less expensive care at the receiving or public hospital. This is a particularly difficult area when a psychiatric patient refuses transfer to a state facility and threatens a report to Health Care Financing Administration (HCFA) or Department of Public Health (DPH) coercion against his or her best interests for insurance. An argument often can be made that the state facility is in the patient's best interest because it provides better clinical care for that patient, because it provides a more appropriate inpatient unit, better continuity for outpatient care, or both. In other instances a brief uninsured hospitalization in the ED's psychiatric unit is a better choice. In summary, EDs that give inaccurate insurance information, send patients without a transfer call, or do not provide adequate medical and psychiatric stabilization, will not only receive poor cooperation from that facility in the future when a psychiatric bed is needed, but also can be assured of an EMTALA violation against them. Preparing the patient for transfer is important. EMTALA, COBRA, or OBRA requires that a patient be medically stable such that his or her medical condition does not deteriorate during transfer to another general hospital. Patients who do not require a general hospital setting must be medically cleared prior to being transferred to a psychiatric facility. Some states have a standard transfer form to state-operated facilities, which is useful for documenting medical clearance for all psychiatric transfers. If such a form does not exist, a standard protocol and form documenting medical clearance is advised. Medical clearance should include a physical examination and focused neurologic examination. In addition, a toxicology screen, complete blood count (CBC), glucose, blood urea nitrogen (BUN), creatinine, electrolytes, and liver profile should be obtained for all psychotic patients being transferred to a psychiatric facility. All patients who are over age 45 or have a history of cardiac disease should have an electrocardiogram (ECG), because many psychotropic medications have cardiovascular effects. A legible record of the physician's psychiatric and medical assessment, laboratory tests, and treatment should be sent with the patient to the receiving psychiatric facility. Brief Holding Some EDs have an area to hold patients who cannot be safely discharged and may need up to 24 hours of observation and treatment before appropriate disposition can be made. These holding areas are most often used for patients who are intoxicated with alcohol or drugs or present with impending withdrawal states. Outpatient Referral The emergency physician should bear in mind several facts when he or she discharges a patient with an emotional problem from the ED with an outpatient referral. First, if a definite appointment with a mental health care provider is not made during the ED visit, the patient may not be seen for several days to several weeks. Second, a patient who leaves the ED may choose not to get follow-up mental health care. Third, the emergency physician will have no ongoing relationship with the patient. Fourth, the emergency physician may have little accurate information about the patient's psychiatric difficulties. Finally, the emergency physician may have little formal psychiatric training. Many EDs have psychiatrists or mental health care professionals who consult with the ED staff to evaluate psychiatric patients and decide on disposition for them. If neither a psychiatrist or mental health care professional is available, the ED physician should err on the side of safety. An outpatient disposition for the patient who has overdosed, threatens suicide or harm to others, has a serious mood disorder, or is acutely psychotic is always a risk. When the emergency physician is unsure of the proper disposition and has no psychiatric consultant available, a psychiatric evaluation is often best obtained by transferring the patient to a psychiatric facility where a psychiatrist or trained mental health care professional is available to evaluate the patient. Patients are more likely to follow up with the outpatient referral if the emergency physician is able to make a follow-up appointment with the mental health care provider. Some clinics and mental health facilities provide 24-hour services for follow-up appointments. Patients are also more likely to keep an outpatient appointment if they or their family or friends are familiar with or have been treated by the site or provider, or if the site or provider is in their neighborhood or in the same hospital as the ED. The patient should be given a card with the name, address, telephone number, contact person, and if possible, the time of appointment. If the emergency physician is unsure whether the mental health care provider is accepting outpatient referrals, two referrals should be made. As with in-hospital referrals, the patient's clinical state, physical examination, laboratory tests, and treatments should be legibly recorded and sent with the patient to the outpatient referral site.

SPECIAL PROBLEMS The Psychiatric Telephone Emergency Families with a psychiatrically disturbed member may call the ED for advice. Although a brief history may be obtained over the telephone, the main goal is to get the patient to an environment in which assessment and treatment can be provided. If the psychiatrically ill patient is committable and refuses emergency treatment, the family member may go to the mental health court and fill out a petition. This petition is presented to the court by the state's attorney. The judge may then order a 24-hour evaluation under emergency detention, which allows the police to bring the patient to the nearest ED or assist in putting the patient in an ambulance for transfer to a psychiatric hospital. “Regulars” In The ED Chronic mentally ill patients often develop a relationship with an institution and its ED. Patients who visit an ED on a regular basis may do so because the clinic they attend does not provide consistent care with one mental health professional or the patient's psychopathology prevents the patient from using non-ED services appropriately. Some character-disordered patients become lonely, depressed, and anxious at night and during weekends, when there is no access to nonemergency mental health care. When a chronic psychiatric patient becomes a “regular,” it is important to understand why the ED is being used for psychiatric care. A plan should be devised to encourage the patient to obtain more appropriate care. Discussion with the family and treating mental health professionals can greatly assist in this process. Another group of regulars in the ED include those with somatic complaints with no demonstrable organic cause. Patients with somatization disorder, hypochondriasis, and psychogenic pain disorder (briefly discussed in Chapter 120) are often unable to find a primary care physician with whom they can maintain an enduring therapeutic relationship. Because these patients view themselves as physically ill, a long-term relationship with a psychiatrist is equally problematic. As a result, the ED may become their health care provider. Every attempt should be made to refer these “regulars” to a clinic or physician who can develop an ongoing relationship with the patient. If after this referral the patient continues to visit the ED regularly, a plan should be worked out with the ongoing health provider to limit ED use. 1 “Organic” is defined as due to a medical condition (including head trauma) or a substance (alcohol or drug withdrawal or intoxication, medication side effect, vitamin deficiency, or toxin).

Suggested Readings Armitage DT, Townsend GM: Emergency medicine, psychiatry, and the law. Emerg Med Clin North Am 1993;11(4):869–887. Bacani-Oropilla G, Lippman SB: When to use psychiatric referral in the ED. Hosp Physician 1989;30:42. Beyer HA: Legal issues in a psychiatric emergency. In: Bassuk EL, Birk AW, eds. Emergency psychiatry: concepts, methods, and practices. New York: Plenum Press, 1984.

Brackel SJ: The mentally disabled and the law. 3rd ed. Brackel SJ, Perry J, Weiner B, eds. Chicago: American Bar Foundation, 1985. Citrome L, Green L: The dangerous agitated patient: what to do right now. Postgrad Med 1990;87:231. Clark P, Hafner RJ, Holme G: The brief admission unit in emergency psychiatry. J Clin Psychol 1997;53:817–823. Hughes DH: Implications of recent court rulings for crisis and psychiatric emergency services. Psychiatr Serv 1996;47:1332–1333. Monahan J, ed: The clinical prediction of violence. Washington, DC: Government Printing Office (National Institute of Mental Health), 1981. Pollard CA, Lewis LM: Managing panic at-tacks in emergency patients. J Emerg Med 1989;7:547. Shader RI, ed: Manual of psychiatric therapeutics: practical psychopharmacology and psychiatry. Boston: Little, Brown, 1981. Soreff SM: Management of the psychiatric emergency. New York: Wiley and Sons, 1981. Stoudemire A, Fogel BS: Pharmacology in the medically ill. In: Stoudemire A, ed. Principles of medical psychiatry. New York: Grune & Stratton, 1987. Strobos J: Tightening the screw: statutory and legal supervision of interhospital patient transfers. Ann Emerg Med 1991;20:302–310. Stutland NL: Refusal of medical treatment: psychiatry emergency? Am J Psychiatry 1997;154:106–108. Walker JI, ed: Psychiatric emergencies: intervention and resolution. Philadelphia: Lippincott, 1983. Patient dumping in the federal courts: expanding EMTALA without preempting state malpractice law. In Recent Developments in Law and Policy, 1992;20(3):49–252.

CHAPTER 122 ORGANIC BRAIN SYNDROMES AND DISORDERS Principles and Practice of Emergency Medicine

CHAPTER 122 ORGANIC BRAIN SYNDROMES AND DISORDERS Stephanie von Ammon Cavanaugh Capsule Definition Delirium Dementia Amnestic Disorder Mental Disorders Secondary to a Medical Condition or Substance that Mimic Primary Psychiatric Disorders Informed Consent Competency and Guardianship

CAPSULE Mental disorders due to a medical condition (including head trauma) or a substance (alcohol or drug intoxication or withdrawal, medication side effect, vitamin deficiency, or toxin) include: delirium, dementia, amnestic disorder, psychotic disorder, catatonic disorder, mood disorder, anxiety disorder, and personality change. Delirium and dementia are the most common. Amnestic disorder and disorders that mimic primary psychiatric disorder are less common. Ninety-five percent of all deliriums are reversible once the underlying cause is treated ( 1,1A). Many of the causes of delirium are life-threatening, and many patients with delirium die ( 2,2A,3 and 3A). Likewise, 35 to 40% of all patients with dementia require medical intervention; 15% have correctable disorders if treated before brain damage occurs, and for 20 to 25% with non-correctable disorders, intervention improves cognitive functioning ( 1,2A,3,4). Although similar figures are unavailable for the other “organic” 1 mental disorders, many of the causes of these disorders are treatable. Because these less common disorders, except amnestic disorder, mimic primary psychiatric disorders, an “organic” cause for psychiatric symptoms should be considered in all patients presenting with psychiatric complaints. Once a diagnosis of a delirium, dementia, amnestic syndrome, or other “organic” mental disorder is made, the emergency physician must diagnose and treat all conditions that either are life-threatening or could result in brain damage. In addition, timely follow-up care must be provided for diagnosis and treatment of less emergent causes. Finally, patients who are severely or irreversibly cognitively or behaviorally impaired and unable to care for themselves must be ensured of a disposition that provides adequate custodial care. (See also Chapter 132.)

DEFINITION The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) (5), has dropped the term “organic brain syndrome” (a constellation of signs and symptoms without reference to cause, e.g., dementia or delirium) and “organic mental disorders” (an organic brain syndrome with a known cause, e.g., alcohol withdrawal, delirium). The DSM-IV felt a false dichotomy was created between primary psychiatric disorders in which there is often evidence of a structural or functional brain abnormality (i.e., alterations in neurotransmitters in mood disorders and structural abnormalities in schizophrenia) and mental disorders caused by a medical condition (including head trauma) or substance (alcohol or drug withdrawal or intoxication, medication side effect, vitamin deficiency, or toxin). Although conceptually sound, the terminology now is quite cumbersome. Every attempt is made in this chapter to present the new terminology, except, when cumbersome, “organic” 1 is used as shorthand for mental disorders due to a medical condition or substance. Patients with delirium, dementia, and the amnestic disorder have memory deficits. Patients with delirium have dysattention (reduced ability to maintain attention to external stimuli and appropriately shift attention to new stimuli), deficits in orientation and memory, difficulties in communicating, and perceptual disturbances (illusions, hallucinations). Patients with dementia have memory deficits and evidence of deterioration of higher intellectual functioning. Patients with an amnestic disorder have recent and remote memory difficulties, without dysattention or impairment of general intellectual functioning. Patients with “organic” 1 psychotic disorder, “organic” catatonic disorder, “organic” mood disorders, “organic” anxiety disorders, and “organic” personality changes have no dysattention, little memory impairment, and no difficulty with higher intellectual functioning. Rather, these disorders mimic psychiatric disorders. In an “organic” psychotic disorder, the most prominent features are delusions, hallucinations or both. Patients with “organic” mood disorder have a depressed, expansive, or euphoric mood; patients with “organic” anxiety disorders have signs and symptoms of generalized anxiety, panic attacks, or obsessive compulsive disorder; and patients with “organic” personality disorders have changes in personality. Because patients with organic brain syndromes are unable to give an accurate history, a collateral history is essential. The onset and progression of the affective, cognitive, and behavioral and/or psychotic symptoms should be obtained. Possible “organic” 1 causes should be elicited in the history and an attempt made to relate these causes temporarily to the mental symptoms. Careful inquiry should be made as to the onset and course of physical illness; trauma; the addition, discontinuation, or change in a prescription or over-the-counter medication with central nervous system effects; illicit drug and alcohol abuse; food and fluid intake; and/or environmental toxins or poisons. A previous psychiatric illness does not rule out an “organic” 1 cause for present psychiatric symptoms. For example, a patient with a bipolar disorder may develop hypothyroidism as the result of prolonged lithium use and present with an organic mood syndrome with depression. After the history, vital signs, a physical examination including a focused neurologic examination, and a mental status examination should be performed. The medical workup depends on the specific “organic” 1 mental disorder and the possible causes and is discussed in detail under each diagnostic category.

DELIRIUM Delirium is present in 10% of all patients admitted acutely to medical and surgical wards ( 4). Clinical Features The clinical features of delirium develop over a short period (hours to days). The signs and symptoms of delirium fluctuate during the day. Many patients may have a “lucid interval,” period in which there appear to be no obvious symptoms of delirium. Delirium is often better during the day and worse at night. For the most part, delirium is caused by functional rather than structural changes in brain tissue and therefore is almost totally reversible if the causes of the delirium are treated before brain damage occurs. Table 122.1 lists common causes of delirium.

Table 122.1. Causes of Delirium

In delirium, there is evidence of wide nervous system dysfunction with disordered responsivity to sensory stimuli, dysfunction of the reticular activating system, and an inability to organize information at cortical levels ( 4,6). Delirious patients demonstrate changes in level of consciousness; altered awareness of the environment; and reduced capacity to shift, focus, and sustain attention to environmental stimuli. Clinically, these changes may be demonstrated by difficulty in obtaining or maintaining

the patient's attention during the interview. The patient may preferentially attend inappropriately to internal or external stimuli, or fall asleep while talking and need to be aroused to continue the interview. The severity of the delirium and changes in the electroencephalogram (EEG) are directly related to the severity of the changes in awareness and dysattention (6). Delirious patients may have a retarded or agitated delirium. Examples of a retarded delirium include patients with severe renal or liver failure. Alcohol withdrawal is the prototype of the agitated delirium. Patients evidence decreased responsivity to environmental stimuli in a retarded delirium and increased responsivity to stimuli in an agitated delirium. In addition, there is disruption of the sleep–wake cycle with hypersomnia in a retarded delirium and insomnia in an agitated delirium. The delirious patient shows difficulty with memory. Usually immediate and recent memory including orientation are impaired. The amount of immediate and recent memory loss is related to the severity of the delirium. In mild delirium, this memory loss may be variable; in severe delirium, it is severe. Immediate and recent memory loss are caused by impaired registration and retention of new memories, resulting from dysattention to environmental stimuli and disturbance in higher cortical functioning. Mild to significant lacunae in remote memory are often present. The severity of the remote memory loss covaries with the severity of the delirium. The delirious patient may have perceptual disturbances. Illusions and misperceptions of sensory stimuli are common in delirium. These perceptual disturbances are classically visual but often auditory. Shadows may be misinterpreted as an intruder, or a slammed door as a gunshot. Hallucinations may range from simple perceptions without relevant sensory stimuli to more complex ones. Shapes, light, animals, insects, or complex situations may be hallucinated. Somatic delusions in which the patient experiences bugs or vermin on the skin are common. Delusions usually arise in response to distorted or inaccurate perceptions. For example, a delirious patient may erroneously feel that the physician in the emergency department (ED) is trying to kill or harm him or her with diagnostic procedures. Several neurologic findings are seen in delirium. An irregular, rapid 8 to 10-cycles per minute fine to gross intention tremor may be seen ( 4,6). Asterixis and multifocal clonus also may be present. (4,6) The DSM-IV criteria for delirium are listed in Table 122.2.

Table 122.2. DSM-IV Criteria for Delirium

Differential Diagnosis Delirium may be confused with mania or schizophrenia. It is rare for a patient over age 45 to develop schizophrenia or mania. Thus, patients over age 45 without a previous psychiatric history are more likely to have a delirium. The young, healthy-appearing patient more frequently has mania, schizophrenia, or an alcohol or drug-related delirium, whereas the older, ill-appearing patient more commonly has a delirium due to a medical condition or substance. The manic patient has a history of depressive and manic episodes with periods of intact functioning between episodes, and often a euphoric mood. Irritability, however, may be seen in both mania and delirium. The distractibility of mania may be confused with the dysattention of an agitated delirium. If memory and other intellectual functions are testable, these are intact in the manic patient. Patients with delirium rarely have the grandiose delusions seen in mania. The schizophrenic has a history of schizophrenic episodes with a deterioration of social and occupational functioning that does not significantly improve between episodes. The level of consciousness is not impaired in schizophrenia. The acutely psychotic schizophrenic patient, however, may have difficulty in focusing and attending to the environment. This is sometimes confused with the dysattention of the delirium. Patients with schizophrenia often have a flat affect, bizarre delusions, and most frequently auditory hallucinations. Vivid visual hallucinations classically seen in delirium are less common in schizophrenia. Again, if testable, memory is intact in schizophrenia. Finally, asterixis and myoclonus are not symptoms of mania or schizophrenia. It sometimes is impossible to differentiate clearly between mania, schizophrenia, and delirium. In this situation, the emergency physician should proceed as if the patient is delirious, because the morbidity and mortality in untreated delirium are high. The patient with dementia does not have disturbance in the level of consciousness. Memory impairment and deterioration of higher intellectual functions are classically present. If a demented patient shows clouding of consciousness, dysattention, or psychotic symptoms, a superimposed delirium should be suspected. Demented patients can much more easily develop a delirium with a less severe physical stressor than those without dementia. For example, urinary retention, pneumonia, anticholinergic drugs, and mild dehydration can cause delirium in the demented patient. Management Once a diagnosis of a delirium is made, the emergency physician is committed to finding the cause of the delirium and treating all conditions that are life-threatening or could lead to irreversible brain damage. The brain is a sensitive indicator of systemic dysfunction, and most causes of delirium listed in Table 122.2 are life threatening or could lead to irreversible brain damage. It is important to reiterate that the most common cause of delirium is multifactorial, and a systematic search for all possible causes of delirium is essential. Drug withdrawal should always be considered as a cause of delirium and is often missed in the emergency setting. Because a delirious patient is unable to give an accurate history, a collateral history (if possible) should be obtained. A physical and neurologic examination should be performed. A CBC, glucose, BUN, creatinine, electrolytes, liver profile, urinalysis, drug screen (blood and urine), chest x ray, and ECG should be obtained. If the patient appears clinically hypoxic, blood gases should be drawn. Ongoing pulse oximetry monitoring may suggest the need for blood gases as well. If a localizing lesion is found on neurologic examination, and life-threatening central nervous system (CNS) insult is suspected, skull films, computerized cranial tomography scan, and/or magnetic resonance imaging, should be ordered emergently ( 4,6). The delirious patient is usually admitted to a medical or surgical service. Delirious patients with drug or alcohol intoxication or withdrawal may be admitted to the hospital or treated in the ED or a 24-hour holding area with careful observation. In addition to these environmental interventions, physical restraints or psychotropic medications may be required to proceed with the diagnostic work-up and prevent the patient from harming himself or herself or others. Level of consciousness may be an important indicator of deteriorating physical condition, particularly in patients with acute CNS injury. As a result, the use of psychotropic drugs should be avoided in conditions in which the level of consciousness is critical diagnostically. In these instances, physical restraints may be preferable to psychotropic drugs during the diagnostic phases. If it becomes impossible to proceed with the medical work-up without psychotropic medication, the lowest possible dosage should be used to continue with the medical work-up. After the diagnosis is made and the patient's medical condition is stable, larger doses of psychotropic medications may be used to provide adequate sedation. Medications in Delirium Benzodiazepines and/or neuroleptics are used most commonly to treat the agitation and psychosis of delirium ( 4,6,7). Short-acting benzodiazepines, such as midazolam hydrochloride, are useful in isolated instances, but require individualized dosage, constant patient supervision, and careful attention to respiratory status. In addition, most elirious patients become more confused and agitated when midazolam is metabolized. Lorazepam is an anticonvulsant; may be given orally, intramuscularly, or intravenously; has a half-life of 10 to 20 hours; and is, for the most part, safe in the medically ill. Lorazepam does not require oxidation for metabolic degradation (a process slowed by age, commonly used medications, and liver dysfunction) but only glucuronide conjugation (a process minimally affected by the factors that affect oxidation) ( 8). Oxazepam is similar to lorazepam but cannot be given intramuscularly. Other benzodiazepines that require both oxidation and conjugation may result in many active metabolites with prolonged half-lives in the elderly and medically ill. Patients with moderate to severe respiratory disease and hypercapnia are at risk even with low doses of benzodiazepines, which reduces the ventilatory response to hypoxia ( 9). In addition, if lorazepam is given too rapidly intravenously, laryngospasm can result. This can be avoided by proper, slow intravenous administration. Finally, benzodiazepines are synergistic with other CNS

depressants such as barbiturates, opiates, and alcohol. Oral, intramuscular, or intravenous lorazepam 0.5 to 2 mg is useful to control agitation. The dose depends on the age and weight of the patient and the severity of the delirium. For mild agitation, lorazepam, 0.5 to 1 mg, is recommended; for moderate agitation, lorazepam 1 to 2 mg; and for severe agitation, lorazepam 2 mg. Route of administration affects onset of action. Onset of action is almost immediate intravenously. Intramuscular or intravenous administration is preferable for more severe deliriums. If the patient is not adequately sedated, the previous or a lower dose can be administered 30 minutes later. In rare cases, lorazepam may cause paradoxic excitement in the delirious patient when not administered with haloperidol. Haloperidol also has been used extensively to treat the delirious patient and is the safest of the neuroleptics in the medically ill (usually 0.5 to 2.0 mg slow push intravenously, repeated in one-half hour as needed). Haloperidol, a butyrophenone, is a potent neuroleptic, with few anticholinergic side effects; it causes almost no orthostatic hypotension when administered orally or intramuscularly, and it has almost no cardiovascular side effects. Haloperidol does cause extrapyramidal side effects. In practice, dystonias are rare when the delirious patient is given several doses of haloperidol to provide emergency tranquilization. Dystonic reactions that may involve the tongue, jaw, neck, buccofacial movements with salivation, torticollis, oculogyric irises, and opisthotonus most rapidly respond to benztropine mesylate 1 to 2 mg intramuscularly, or diphenhydramine hydrachloride 50 mg by intravenous push. If the dystonia does not remit within 30 minutes, the dose may be repeated. Benztropine is highly anticholinergic and diphenhydramine less so. Amantadine hydrochloride 100 mg by mouth, although less rapidly acting, is less anticholinergic. Patients with Parkinson's disease may be made significantly worse by haloperidol. Haloperidol should not be used with epinephrine, because haloperidol blocks the vasopressor effect of the latter drug and may paradoxically further lower blood pressure; metaraminol, phenylephrine, or norepinephrine should be used. Neuroleptic malignant syndrome, which has been reported as a consequence of haloperidol administration, is rare during rapid tranquilization in the ED setting. Patients with a previous history of a neuroleptic malignant syndrome should never receive a neuroleptic. Haloperidol may lower the seizure threshold and should be used in combination with lorazepam in patients with risk for seizures. Finally, the half-life of haloperidol is 24 hours, and this should be taken into account when administering the drug. Agitation associated with alcohol or benzodiazepine withdrawal is preferentially treated with benzodiazepines. Agitation associated with barbiturate withdrawal is best treated with barbiturates. The agitation associated with seizures is most appropriately treated with anticonvulsants. The agitation associated with Wernicke's encephalopathy (discussed under the amnestic syndrome) is first treated with intravenous thiamine and, if alcohol withdrawal coexists, benzodiazepines.

DEMENTIA Approximately 4 to 15% of patients over age 65 have evidence of at least a mild dementing process ( 4), and approximately 2 to 5% have a severe dementing process requiring continuous custodial care ( 10). The prevalence of severe dementia increases to 15 to 20% in those over age 80, half of whom have Alzheimer's disease (10,11). As with delirium, dementia is a common finding when a patient is brought to the ED for emergent medical problems. Often a patient is brought to the ED by the family or sent from the nursing home with “mental status changes.” Less often, a demented patient is brought to the ED by the police or concerned others because the patient is unable to care for himself or herself or is found wandering in the streets or other public areas. Clinical Features The signs and symptoms of dementia develop over months to years and are relatively stable, without the rapid fluctuations seen in delirium. A more rapid deterioration of the clinical picture can occur when the patient is ill, on medications with CNS effects, fatigued, stressed, moved from a familiar environment, or when visual, auditory, or sensory stimuli input is altered or diminished ( 1,4). Although a dementia-like picture is more likely to be caused by structural changes of brain tissue and therefore is irreversible, approximately 15% have functional changes in brain tissue that are correctable if treated before brain damage occurs ( 1,3,4). Table 122.3 lists the common medical causes of dementia. The hallmarks of dementia are memory deficits and deterioration of general intellectual functioning. In mild dementia, the patient has difficulty with recent memory. Impairment in registration of new memories results in diminished ability to retain new information. Immediate memory usually remains intact until the person is more severely demented. In moderate dementia, recent memory loss is more severe, and remote memory is also impaired. In severe dementia, the patient neither understands the present nor remembers the past.

Table 122.3. Causes of Dementia

Other disturbances in higher cortical functioning become evident in moderate dementia and are severely impaired in severe dementia. The patient may exhibit various disorders in language. Aphasic difficulties become evident. The ability to use language to express or conceptualize ideas becomes impaired. Speech may be tangential, circumstantial, or rambling because of memory impairment. Apraxia, the inability to carry out motor activities despite intact comprehension and motor function, may develop. The patient may display agnosia, the failure to recognize or identify objects despite intact sensory function. Finally, the patient may have constructional difficulty, and be unable to copy three-dimensional figures. Judgment (the ability to perceive data from the environment correctly, process that data on previous experience and knowledge, and make decisions and act in a culturally appropriate manner) is generally intact in mild dementia. In moderate dementia, judgment is impaired. For example, a demented patient may give away large sums of money to relative strangers. In severe dementia, judgment is severely impaired. A severely demented patient may go outside in nightclothes and without shoes in subzero weather. Although the patient with mild to moderate dementia may have total preservation of social graces, changes in personality may become evident. There may be an accentuation or change of premorbid personality traits. A previously meticulous patient may be dirty or slovenly and not care about personal hygiene. A person who was energetic may become apathetic and show decreased interest and responsiveness to the environment. In moderate to severe dementia, the patient may show evidence of poor social judgment. The dignified elderly gentleman may make sexual advances to a stranger. The modest older woman may show no concern over showing her naked body to strangers. The patient may urinate or defecate in the bed. The previously good-natured patient may become irritable. Lability of affect (abrupt changes in affect) may also occur. Rarely, a personality change may be the presenting symptom of dementia and occur before deterioration of memory and higher intellectual functioning. Misinterpretations are common in patients with memory dysfunction and deterioration of intellectual functioning. A patient who has misplaced glasses may accuse others of stealing them. A patient whose hearing aid is not working may feel that others are talking about him or her, only to find that they are not when the hearing aid is repaired. Agitation and confusion are common when the patient cannot understand or deal effectively with the environment. Illusions, hallucinations, and delusions can accompany this agitation and occur more commonly at night. Patients with vascular dementia present with night-time agitation earlier in the dementing process than those with Alzheimer's disease ( 12). Although 25 to 30% of patients with dementia have delusions or visual hallucinations ( 4), the acute onset of hallucinations and delusions, particularly during waking hours, should alert the clinician to a superimposed delirium ( 13). The DSM-IV criteria for dementia are presented in Table 122.4.

Table 122.4. DSM-IV Criteria for Dementia

The exact presentation of the dementia depends on whether it is progressive, stable, diffuse, localized, or primarily cortical or subcortical. Patients with a degenerative process such as Alzheimer's or Pick's disease have a diffuse progressive process. Patients with vascular dementia will present with a stepwise deterioration (12). Intellectual functioning controlled by areas not damaged by the infarcts is preserved. In a stable dementia such as after brain injury or prolonged anoxia, there may be improvement of cognitive functioning for 6 months to 2 years after the structural damage as the patient adapts to the deficits. The progression of symptoms seen in subcortical dementia (Parkinson's disease, Huntington's chorea, and HIV infection) is different from that seen in cortical dementia. In early subcortical dementia, the memory loss is primarily related to retrieval of information rather than faulty registration ( 14). Recent memory loss may therefore appear “patchy.” The inability to organize a task may occur before there is any deterioration of general intellectual functioning. Apathy or decreased motivation occurs early in subcortical dementia. In moderate subcortical dementia, recent and remote memory losses are more severe, although inconsistent, again because of deficits in retrieval rather than registration. Organizational, spatial, and constructional difficulties are more evident than difficulties with language. Apathy is marked and is often confused with that of a depressive illness. Eventually, because subcortical structures project extensively to cortical areas, cortical functioning is severely impaired; severe subcortical dementia presents with the memory deficits and deterioration of general intellectual functioning found in cortical dementia. Judgment is poor, and the patient requires supervision for medical care and self-care. The causes of the dementia determine the neurologic findings, as do coexisting neurologic conditions not contributing to the dementia. The neurologic examination may be normal, or with more advanced cortical dementia there may be evidence of frontal lobe release signs. Patients with vascular dementia or dementia from brain trauma or space-occupying lesions may have focal neurologic signs. Patients with normal-pressure hydrocephalus may have incontinence and ataxia. The physical examination may be normal or abnormal, depending on the cause of the dementia or coexisting medical conditions. For example, a hypothyroid patient may present with dementia, thick edematous skin, husky voice, decreased body temperature and pulse, and hyporeflexia. Differential Diagnosis A depressed patient, because of psychomotor retardation and problems with attention and concentration, often complains of difficulties with memory ( 15). If the interviewer is persistent with the depressed patient, the mental status examination can be completed. As a rule, patients with depression complain of problems with memory, whereas patients with dementia are often unaware of memory difficulties unless confronted directly with observed deficits. Depressed patients emphasize their cognitive disabilities and draw attention to mistakes and failures. Demented patients attempt to cover cognitive deficits. Finally, although the onset of the memory deficits covaries with depressive symptoms, the onset of memory loss is gradual in demented patients ( 16). Delirium is differentiated from dementia by sudden onset, clouding of consciousness, dysattention, and acute onset of psychotic symptoms. Patients with dementia and acute mental status changes should be assumed to have a superimposed delirium. Management When dementia is diagnosed, the emergency physician is committed to seeing that all reversible causes of it are identified and treated (16), either in the ED, on a medical floor, or through referral to a primary care physician. In addition, any medical conditions or drugs that could be contributing to impaired cognitive functioning should be diagnosed and treated. Because the patient's history may be unreliable, a collateral history, if possible, is essential. A patient who presents with dementia or is brought to the ED with mental status changes should have a physical and neurologic examination, complete blood count (CBC) glucose, blood urea nitrogen (BUN) creatinine, electrolytes, liver profile, urinalysis, chest radiograph, and electrocardiogram (ECG). Thyroid battery, B 12, folate levels, human immunodeficiency virus (HIV) testing, computerized cranial tomography, or magnetic resonance imaging (MRI) may be obtained in the ED or later during the work-up in a nonemergency setting. Hypothyroidism, nutritional deficiencies, dehydration, electrolyte imbalance, failure to take medications properly, and systemic illness are common causes of deteriorating mental status in the demented patient ( 16). Patients with dementia are exquisitely sensitive to drugs with CNS effects, particularly drugs with anticholinergic effects. In addition to organic causes, other nonmedical stresses may cause deterioration of cognitive functioning and should be identified. Sensory isolation, altered visual, auditory, or sensory stimuli; fatigue; stress; an unpredictable environment; change from a familiar environment; or the loss of an important relationship can cause deterioration of cognitive functioning in the demented patient. Families may bring their demented family member to the ED because the patient has become too difficult to manage at home, or the families need additional help or a vacation from the care of the patient. Such families may be skilled at leaving the demented family member in the ED or giving a history of medical problems that require inpatient medical care. If the emergency physician sends such a demented patient home to prevent “inappropriate” use of acute medical services, the problem is not solved. Family members who are overwhelmed by the care of a demented family member may abuse or neglect the patient. At the least, the severe stress of caring for the demented patient may be detrimental to the family or the primary caregiver. If the patient is returned home, the family must be given a referral that will immediately provide help in caring for the demented family member. Referral to a nursing home, which may take months, is not adequate. The emergency physician should be aware of the resources in his or her community to assist such overburdened families, including visiting nurse services and home health care availability. The emergency physician can provide useful recommendations for families caring for the demented patient at home. Sensory isolation should be avoided. Hearing aids, glasses, and dentures should be in good working order and used by the patient throughout the day. If possible, the patient should not be left without human contact for long periods. A television or radio left on in the demented person's room provides sensory stimulation. If a patient becomes confused at night, his or her hearing aid and glasses should be left on. A night light and soft music also decrease sensory isolation at night. Night-time psychotropic medications prescribed and monitored by the demented patient's primary care physician also help to control confusion and agitation. Stimuli in the demented patient's environment should be constant, predictable, and simplified to a level the patient can cope with. Families should orient the patient to time and provide a clock or watch and calendar in the patient's room. Meals and activities should be scheduled at the same time and the same place every day. Abrupt changes in the environment should be minimized when possible.

AMNESTIC DISORDER The most common treatable presentation of the amnestic disorder is as part of Wernicke-Korsakoff's syndrome in chronic alcoholics with thiamine deficiency. Clinical Features The onset of the amnestic disorder depends on the cause. The amnestic syndrome may result from any factor that causes bilateral damage to diencephalic or medial temporal structures of the brain ( 17). Examples of acute onset include anoxia (18), head trauma (19), cerebrovascular accidents (occlusion of the postcerebral artery) (20), herpes simplex encephalitis, and temporal lobectomy (18). The onset of the amnestic disorder (Korsakoff's syndrome) as the result of thiamine deficiency is subacute (a few weeks to a few days), and usually follows Wernicke's encephalopathy in 50 to 90% of cases (21). Wernicke's encephalopathy is a delirium that presents with ophthalmoplegia, ataxia, and peripheral neuropathy. With clearing of the delirium, the amnestic disorder (Korsakoff's syndrome) becomes evident. Thiamine deficiency is seen in chronic alcoholism and is caused by poor absorption of thiamine. Alcohol interferes with the absorption of thiamine, and the lack of available thiamine is further impaired by poor nutritional status. Occasionally patients with vitamin-deficient diets or malabsorption may develop Wernicke-Korsakoff's syndrome. Patients with a deficiency of the enzyme

transketolase, for which thiamine is a cofactor, may be at greater risk of developing Wernicke-Korsakoff's syndrome. Intravenous glucose administration may use all available thiamine stores in the thiamine-deficient patient, resulting in an acute Wernicke-Korsakoff's syndrome. The major deficit in the amnestic disorder is in recent and long-term memory. Immediate memory is intact. Short-term memory is the most severely affected. This recent memory loss, also called anterograde amnesia, refers to difficulty in laying down new memories (registration) after the etiologic insult occurred. Because orientation is a memory function, amnestic patients may be disoriented. Remote memory loss or retrograde amnesia refers to the inability to retrieve memories that were laid down before the onset of the illness. Confabulation, in which the patient makes up events or haphazardly pieces fragments of the past together to fill gaps in memory, is also common. In the amnestic syndrome, there is no dysattention or clouding of consciousness, as in delirium; or deterioration of general intellectual functioning, as in dementia. The DSM-IV criteria for the amnestic disorder are listed in Table 122.5.

Table 122.5. DSM-IV Criteria for Amnestic Disorder

Management The clinical management depends on the cause of the amnestic syndrome. The amnestic syndrome caused by trauma, infarction, or anoxia usually is not reversible. Acyclovir may be useful in reversing the amnestic syndrome seen in herpes simplex encephalitis if the treatment is begun early enough. Wernicke's encephalopathy, if not treated immediately, can lead to irreversible brain damage. If Wernicke's encephalopathy is suspected, the patient should be given thiamine (4), 100 mg intravenously and 50 mg intramuscularly immediately. In addition, 50 mg intramuscularly daily or 100 mg orally three times a day should be given for 7 days. Once the amnestic syndrome (Korsakoff's syndrome) has emerged, thiamine is less successful in reversing the syndrome. After treatment, Victor et al. ( 21) found that 20% of patients with the amnestic syndrome recovered fully after 5 years, 28% were significantly improved, and 25% slightly improved; the remainder were the same or worse. Hence, when the amnestic syndrome is thought to be caused by thiamine deficiency, the patient should be given thiamine as described. In practice, every alcoholic who comes to the ED should be given thiamine to prevent the reversible brain damage associated with untreated Wernicke-Korsakoff syndrome.

MENTAL DISORDERS SECONDARY TO A MEDICAL CONDITION OR SUBSTANCE THAT MIMIC PRIMARY PSYCHIATRIC DISORDERS A patient who presents to the ED with a psychiatric disorder should be considered to have an organic cause until it is proven otherwise. Undiagnosed physical illness, prescribed or illicit drugs, or alcohol should be considered as causes. Special attention should be paid to patients who have no previous personal history of psychiatric illness, particularly if the condition appears for the first time after age 45. Sudden changes in personality are most often the result of organic causes. Psychotic Disorder Secondary to a Medical Illness or Substance Delusions and/or hallucinations caused by a specific medical condition or substance are the prominent clinical features of this disorder. Affective changes, personality changes, psychotic behavior, and psychotic speech patterns may also accompany the delusions and/or hallucinations. There may be mild cognitive impairment, but dysattention and clouding of consciousness as seen in delirium, obvious memory deficits as seen in the amnestic syndrome and dementia, and deterioration of general intellectual functioning as seen in dementia are not present in this syndrome. The DSM IV criteria for psychotic disorder due to a medical condition or substance are presented in Table 122.6.

Table 122.6. DSM-IV Criteria for Psychotic Disorder Due to a General Medical Condition or Substance

Amphetamines, cocaine, cannabis, and hallucinogens are the most common causes of “organic” 1 psychotic disorder with prominent delusions ( 5). With amphetamine and cocaine abuse, the picture may be indistinguishable from that of schizophrenia, paranoid disorders, and other nonorganic psychotic disorders ( 4). Patients with temporal lobe seizures may develop an interictal schizophrenia-like syndrome with paranoid and religious delusions one or two decades after onset of the seizures; the psychosis is inversely related to the number of seizures and is found most commonly in women with left-sided foci ( 22,23). Huntington's chorea can present with a paranoid delusional picture. Cerebral lesions, particularly nondominant lesions, may present with an organic delusional disorder ( 5). Management depends on the underlying cause of the syndrome. Symptomatic relief may be provided with haloperidol alone or combined with lorazepam, as described previously. Patients with temporal lobe seizures will require anticonvulsants ( 22). Hallucinogens are among the most common causes of “organic” 1 psychotic disorder with prominent hallucinations. Hallucinogens cause vivid visual hallucinations. With chronic use of hallucinogens, the patient may develop a persistent hallucinosis, even when the drug is no longer being used. The patient may have a schizophrenialike picture even though the capacity for human-interaction remains intact ( 4). Neuroleptics may be helpful. Alcohol is another cause of hallucinations ( 24). Delerium tremens in which vivid visual hallucinations are common, presents with the signs and symptoms of delerium and autonomic arousal. In contrast, alcoholic hallucianosis presents with vivid auditory hallucinations without a delerious picture or autonomic arousal. Because both conditions present in the same time frame following alcohol cessation an unclear diagnostic picture should be treated as an alcohol withdrawal syndrome due to the morbidity and mortality associated with delerium tremens. Other drugs such as levodopa ( 18), bromocriptine mesylate amantadine hydrochoride, ephedrine, clonidine, pentazocine, propranolol hydrochoride, and

methylphenidate hydrochloride can cause hallucinations. Discontinuing or decreasing the dosage of the medication is the treatment of choice. Catatonic Disorder Due to a Medical Condition or Substance Catatonia is characterized by immobility, negativism (resistance to being moved by the examiner) mutism, peculiar or stereotyped movements (non–goal-directed repetitive motor behavior), echolalia or echopraxia (patient mimics examiners speech or movements). Associated symptoms include posturing (maintaining a posture for a long period of time) and waxy flexibility (the patient offers initial resistance but then allows the examiner to put his or her limbs into a particular posture which is maintained). The patient does not appear to have an altered level of consciousness. The DSM-IV criteria for a catatonic disorder ( 5) due to a general medical condition or substance are presented in Table 122.7.

Table 122.7. DSM-IV Criteria for Catatonic Disorder to a General Medical Condition or Substance

The common “organic” 1 causes of this disorder are encephalitis, general paresis, epilepsy, neoplasms, cerebrovascular disease, typhoid, Wernicke's encephalopathy, pellagra, acute intermittent porphyria, glomerulonephritis, lupus erythematosus, toxic state secondary to substances (mescaline, amphetamines, PCP, cortisone, disulfiram, aspirin), and metabolic conditions (homocystinuria, hypercalcemia, diabetic ketoacidosis, hepatic encephalopathy, and uremia) ( 25,26,27 and 28). The differential diagnosis for catatonia due to a medical condition or substance includes primary psychiatric disorders. Most catatonia caused by a primary psychiatric disorder (25,26 and 27) is the result of a mood disorder (e.g., depressive disorder with psychotic features, mixed bipolar disorder, and mania), whereas less than 10% is caused by schizophrenia ( 26). Both medical conditions and primary psychiatric disorders can present with mutism, rigidity, or immobility and can be confused with catatonia. In akinetic mutism, which is caused by medical conditions affecting the diencephalon, the patient is mute and immobile, but the patient's eyes follow people around the room or respond to sound. The sudden onset of mutism can be caused by a stroke or a conversion disorder. In addition, paranoid patients may refuse to speak, and patients with petit mal and frontal lobe seizures may have periods when they appear mute. Patients with a retarded delirium may be mute and immobile. Patients with severe Parkinson's disease may have difficulty communicating and may be rigid. Neuroleptic-induced dystonias or pseudo-Parkinsonism may cause rigidity and bizarre postures. Neuroleptic malignant syndrome ( 29), a life-threatening condition, should be considered in any patient on neuroleptics who presents with rigidity and fever. When a patient presents with a catatonic picture, all possible “organic” 1 causes that are life-threatening or could cause brain damage should be ruled out in the emergency room. A collateral history is invaluable in establishing the medical, drug-related, or psychiatric events leading up to the onset of the catatonic presentation. A physical examination and a careful neurologic examination should be performed. Appropriate laboratory examinations and toxicology screen should be performed. Neuroimaging for tumors, vascular lesions, infarcts, and aneurysms may be indicated, and an electroencephalogram (EEG) may confirm an encephalopathy or seizures. Lorazepam 2 mg intravenous push or intravenous methohexital sodium or sodium amytal (in those skilled with this technique) may be helpful in the differential diagnosis of catatonia ( 28). A neurologic and psychiatric consultation may be invaluable in this difficult diagnostic area. If the diagnosis of a primary psychiatric disorder is thought to be causing the catatonia, even after careful elimination of “organic” 1 etiologies, the patient should be admitted to a psychiatric unit with medical backup. These patients often need intravenous fluids, parenteral nutrition, and electro convulsive therapy. A state facility is unable, in most cases, to provide the intensive care these patient require. Mood Disorder Secondary to a Medical Condition or Substance The distinguishing feature of this syndrome is persistent depressed, elevated, or expansive mood from an “organic” 1 cause. The severity of the mood syndrome may be mild to severe. Mild cognitive impairment may also be present. The diagnosis is not made if the mood disorder is part of a delirium. Table 122.8 outlines the DSM-IV criteria for organic mood disorder.

Table 122.8. DSM-IV Criteria for Mood Disorder Due to a General Medical Condition or Substance

A mood disorder secondary to a medical condition or substance may be indistinguishable from a depressive syndrome without an identifiable “organic” cause. As a result, common organic factors causing or contributing to depression should be ruled out in all patients who present to the ED with depression. Because patients with a family or personal history of depression may be more likely to develop depression with an “organic” 1 stressor (i.e., hypothyroidism, a-methyldopa), a previous history of depression does not rule out an “organic” cause. If the emergency physician is unable to rule out organic causes of depression in a depressed patient, this should be communicated to the physician to whom the patient is referred. Numerous illnesses and drugs have been associated with depressive symptoms (30,31,32 and 33) (Table 122.9) outlines the common “organic” causes of depression.

Table 122.9. Causes of Depression Secondary to a Medical Condition or Substance

Clinically, hypomania or mania as the result of an organic cause may be indistinguishable from bipolar disorder. Also, patients with bipolar disorder may more quickly develop a hypomanic or manic picture when stressed by an “organic” 1 factor. In addition, a manic episode must be differentiated from delirium (the differential diagnostic features of mania and delirium are discussed in the section on delirium). Thus, “organic” causes must be ruled out in all patients presenting with a hypomanic or manic episode. Again, as with the depressed patient, if organic factors are not ruled out, the emergency physician must convey this to the follow-up physician. Table 122.10 lists the “organic” causes of mania ( 31,34,35).

Table 122.10. Causes of Elevated, Irritable, or Expansive Mood Secondary to a Medical Condition or Substance

Treatment includes identifying the cause, removing the offending drug, or treating the underlying medical condition. Patients with a mood disorder secondary to a medical condition or substance may be agitated or manic and are best treated with benzodiazepines. Patients who are also psychotic are best managed with a combination of lorazepam and haloperidol. Clonazepam 1 to 2 mg, may be substituted for lorazepam and is useful for nonpsychotic hypomania or mania. Suicidal ideation may be present and carries the same risk as in the patient with a primary mood disorder. Anxiety Disorder Secondary to a Medical Condition or Substance The cardinal features of this disorder are prominent, recurrent panic attacks, generalized anxiety, or obsessive compulsive symptoms ( 5) caused by a medical condition or substance. Table 122.11 presents the DSM IV criteria for this disorder. Mild cognitive impairment may be present, usually associated with difficulties in attention and concentration. The diagnosis is not made if the panic or anxiety is part of a delirium. The syndrome may be mild to severe. The course of the syndrome depends on the cause. The etiologic factors causing “organic” 1 anxiety syndrome are listed in Table 122.12 (31,36,37).

Table 122.11. DSM-IV Criteria for Anxiety Disorder Due to a General Medical Condition or Substance

Table 122.12. Causes of Anxiety Secondary to a Medical Condition or Substance

Because an anxiety disorder secondary to a medical disorder or substance may be indistinguishable from panic attacks, generalized anxiety, or obsessions or compulsions, “organic” 1 factors must be ruled out in any patient presenting to the ED with anxiety symptoms. Hypoxia, hypoglycemia, hyperthyroidism, intoxication with stimulants (caffeine, cocaine, amphetamines) and withdrawal from sedative drugs (barbiturates, benzodiazepines, alcohol) must be diagnosed and treated in the ED. Drugs that have anxiety and jitteriness as a side effect may be temporarily discontinued if there are no medical contraindications. Other causes that involve more extensive work-up must be carried out by the follow-up physician. Symptomatic relief can be provided with benzodiazepines except for those with lung disease and hypercapnia. Benzodiazepines reduce ventilatory response to hypoxia when the respiratory center is no longer driven by hypercapnia. Lorazepam, 1 to 2 mg orally may be repeated every hour until the anxiety or panic remits. Slow intravenous administration of lorazepam, 1 to 2 mg, is useful in severe anxiety or panic. Alprazolam, 0.25 to 1 mg orally, repeated every 45 minutes to 1 hour, is also useful in aborting “organic” 1 anxiety or panic attacks. The patient may then be discharged with a benzodiazepine dosage of lorazepam, 0.5 to 2 mg orally, 3 times a day to 4 times a day or alprazolam, 0.25 to 1 mg orally, 3 to 4 times a day. Personality Change Due to a Medical Disorder or Substance The major feature of this disorder is a change or accentuation of previous personality characteristics as a result of a medical illness or substance. The personality change does not occur as part of a delirium or dementia. The DSM IV criteria for organic personality change due to a general medication condition or substance are

listed in Table 122.13 (5).

Table 122.13. DSM-IV Criteria for Personality Change Due to a General Medical Condition or Substance

“Organic” 1 personality change is usually caused by structural damage to brain tissue. The location of the lesion and the type of pathophysiologic process determine the type of personality disturbance. Head injuries involving the frontal and temporal lobes are the most frequent cause of a personality disturbance, particularly bilateral frontal lobe injuries. Two syndromes have been described with bifrontal lobe injury. The first is characterized by emotional lability, impulsivity, socially inappropriate behavior and hostility, and the second by apathy, indifference, and social withdrawal ( 38,39). Frontal lobe tumors and cerebrovascular accidents involving the middle cerebral artery are less common causes of personality changes ( 4,31). These changes also may be seen with temporal lobe epilepsy, multiple sclerosis, lupus erythematosus, and Huntington's chorea. Degenerative dementia may present with personality changes before deficits in memory and general intellectual functioning occur ( 16). Patients with a history of chronic cannabis, amphetamine, or cocaine abuse can present with personality changes ( 5). Finally, patients with heavy metal poisoning can present with personality changes ( 31). Patients are rarely brought to the ED with the presenting complaint of a personality change unless the personality change is acutely disturbing to the family. For example, a patient with head trauma may become aggressive and unmanageable or demonstrate severe lability of affect. Aggressive behavior and severe lability of affect may be controlled on an acute basis with neuroleptics, although the response is highly variable. Less potent, more sedating neuroleptics are often more efficacious than haloperidol but have more anticholinergic and orthostatic hypotensive effects than the more potent neuroleptics. Chlorpromazine, 25 to 100 mg orally or 25 to 50 mg intramuscularly; mesoridazine, 10 to 50 mg orally or 12.5 to 25 mg intramuscularly; or thiothixene, 2 to 10 mg orally, or 2 to 5 mg intramuscularly may be useful emergently for aggressive behavior and severe lability of affect. More commonly, a patient presents with other physical symptoms, and a change in personality is mentioned as part of the history.

INFORMED CONSENT A patient with a mental disorder due to a medical condition or substance, particularly delirium and dementia, may be unable to give informed consent, that is, to understand the risks benefits, or alternatives of a medical procedure or treatment. If the patient does not cognitively understand these, written consent is not valid. Informed consent is less important when the benefits are great and the risk low, but critical if the risk is high ( 40), even if the risk is for the benefit of saving the patient's life or preventing significant morbidity. In an ED, benign procedures are often performed on a cognitively impaired patient without rigorous informed consent. If a patient cannot give informed consent (even if they have signed the release form in the ED), the following should be documented on the ED record: (a) the patient was unable to understand the risks, benefits, or alternatives of the procedure because of the symptoms (list) of a mental disorder secondary to a medical condition or substance; (b) the medical procedure was explained to the family, and the family agreed verbally and in writing. Such a signature is not legal unless the family member is the legal guardian but is an extra safeguard in a malpractice suit. (c) The procedure was performed on a emergency basis and the reasons why it was emergently necessary. If the procedure or treatment carries significant risk another consulting physician should also document the need on the chart. If a family member is not available, (a) and (c) should be documented ( 36).

COMPETENCY AND GUARDIANSHIP A patient with a mental disorder secondary to a medical condition or substance, particularly dementia or delirium, may become so mentally incompetent that a guardian, usually a family member, is appointed by the court to make medical decisions, legal decisions, or both. A patient's incompetence to consent to medical procedures or manage his or her legal affairs is always a legal decision, not a medical one, although medical evidence may be used in the court's determination. Guardianship may be for legal affairs, medical decisions, or both. Guardianship may be for a limited period of time (i.e., for an acute serious illness) or for an indefinite period of time (i.e., for a severe dementia). If a patient has a legal guardian for medical decisions, that person should ideally sign the consent for ED procedures. If that person is not present, emergent diagnostic evaluation and treatment may be provided in the ED and the emergent reason for this documented on the chart ( 41).

1

“Organic” is defined as due to a medical condition (including head trauma) or a substance (alcohol or drug withdrawal or intoxication, medication side effect, vitamin deficiency, or toxin).

References 1. Detre T, Jerecki H: Organic brain syndromes. In: Detre T, Jerecki H, eds. Modern psychiatric treatment. Philadelphia: Lippincott, 1971. 1A. Wise MG, Lieberman JA. Delirium, dementia, and amnestic disorders. In: Goldman LS, Wise TN, Brodie DS, eds., Psychiatry for primary care physicians. Chicago: American Medical Association, 1998:135–154. 2. Weddington WW: The mortality of delirium: an under-appreciated problem. Psychosomatics 1982;23:1232. 2A. Hassan E, Fontaine DR, Nearman HS: Therapeutic considerations in the management of agitated or delirious critically ill patients. Pharmacotherapy 1998;18:113–129. 3. Guze SB, Cantwell DP: The prognosis in organic brain syndromes. Am J Psychiatry 1964;120:878. 3A. Jacobson S, Shreibman B: Behavioral and pharmacologic treatment of delirium. Am Fam Physician 1997;56:2005–2012. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

Wells CE: Organic syndromes: delirium. In: Kaplan HI, Saddock BJ, eds. Comprehensive textbook of Psychiatry. Baltimore: Williams & Wilkins, 1996. Mental disorders due to a general medical condition. In: Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Press, 1994. Wise MG: Delirium. In: Hales RE, Yodofsky SC, eds. Textbook of neuropsychiatry. Washington, DC: American Psychiatric Press, 1987. Slaby AE, Cullen LO: Dementia and delirium. In: Stoudemire A, Fogel BS, eds. Principles of medical psychiatry. New York: Grune & Stratton, 1987. Greenblatt DJ, Shader RI, eds. Pharmacokinetics and clinical practice. Philadelphia: WB Saunders, 1985. Lakshiminarawan S, Sahn SA, Hudson LD: Effects of diazepam on ventilatory responses. Clin Pharmacol Ther 1976;20:173. Thompson TL: II. Psychosocial and psychiatric problems of the aged. In: Schrier RW, ed. Clinical international medicine in the aged. Philadelphia: WB Saunders, 1982. Terry RD, Katzman R: Senile dementia of the Alzheimer's type. Ann Neurol 1983;14:497. Cummings JL: Multi-infarct dementia: diagnosis and management. Psychosomatics 1987;28:117. Lipowski ZJ: Differentiating delirium from dementia in the elderly. Clin Gerontol 1982;1:3. Huber SJ, Paulson GW: The concept of subcortical dementia. Am J Psychiatry 1985;142:1312. Wells CE: Pseudodementia. Am J Psychiatry 1979;136:895. Wells CE: Diagnostic evaluation and treatment in dementia. In: Wells C, eds. Dementia. 2nd ed. Philadelphia: FA Davis, 1977. Victor M: The amnestic syndrome and its anatomical basis. Can Med Assoc J 1969;100:1115. Lipowski ZJ: Organic mental disorders: introduction and review of syndromes. In: Kaplan HI, Freedman AM, Sadock BJ, eds. Comprehensive textbook of psychiatry. 3rd. ed. Edited by Baltimore: Williams & Wilkins, 1980;2.

19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41.

Kwentus JA, Hart RP, Peck ET, et al: Psychiatric complications of closed-head trauma. Psychosomatics 1985;26:8. Mathew RJ, Meyer JS: Pathogenesis and natural history of transient global amnesia. Stroke 1974;5:303. Victor M, Adams RD, Collins GH: The Wernicke-Korsakoff syndrome. In: Contemporary neurology series. Philadelphia: FA Davis, 1971;7. Blumer D, Benson DF: Psychiatric manifestations of epilepsy. In: Benson DF, Blumer D, eds. Psychiatric aspects of neurologic disease. New York: Grune & Stratton, 1982;2. Bear D, et al: Interictal behavioral changes in patients with temporal lobe epilepsy. In: Hales RE, Francis AJ, eds. Annual review. Washington, DC: American Psychiatric Press, 1985;4. Surawicz FG: Alcoholic hallucinosis, a missed diagnosis: differential diagnosis and management. Can J Psychiatry 1980;25:57. Taylor, MA Catatonia: a review of a behavioral neurologic syndrome. Neuropsychiatry, Neuropsychol Behav Neurol 1990;3(1):48–72. Abrams R, Taylor, MA: Catatonia: a prospective study. Arch Gen Psychiatry 1976;33:579–581. Carroll BT: Catatonia on the consultation-liaison service. Psychosomatics 1992;33(3):310–315. Rosebush PI, Hildebrand AM, Furlong BG, et al: Catatonic syndrome in a general psychiatric inpatient population: frequency, clinical presentation, and response to lorazepam. J Clin Psychiatry 1990;51(9):357–362. Levenson, JL: Neuroleptic malignant syndrome. Am J Psychiatry 1985;142(1):1137–1145. Stoudemire A: Depression in the medically ill. In: Cavenar J., ed. Psychiatry. New York: Basic Books, 1985. Stoudemire A: Selected organic mental disorders. In: Hales RE, Yudofsky SC, eds. Textbook of neuropsychiatry. Washington, DC: American Psychiatric Press, 1987. Katerndahl DA: Nonpsychiatric disorders associated with depression. J Fam Pract 1981;13:619. Whitlock FA, Evans, LEF: Drugs and depression. Drugs 1978;15:53. Krathammer C, Klerman GL: Secondary mania: manic syndromes associated with antecedent physical illness or drugs. Arch Gen Psychiatry 1978;35:1333. Larson EW, Richelson E: Organic causes of mania. Mayo Clin Proc 1988;63:906. Dietch JT: Diagnosis of organic anxiety disorders. Psychosomatics 1981;22:661. MacKenzie TB, Popkin MK: Organic anxiety syndrome. Am J Psychiatry 1983;140:342. Blumer D, Benson DF: Personality changes with frontal and temporal lobe lesions. In: Benson DF, Blumer D, eds. Psychiatric aspects of neurological disease. New York: Grune & Stratton, 1975;1. Alexander MP: Traumatic brain injury. In: Berson DF, Blumer D, eds. Psychiatric aspects of neurologic disease. New York: Grune & Stratton, 1982. Drane JF: Competency to give informed consent. JAMA 1984;252:925. Perr I: Many faces of competence. In: Barton WE, Sandborn CJ, eds. Law and the mental health professions. New York: International University Press, 1978.

Selected Reading Harley RA, Yudofsky SC, LaFon SG Neuropsychiatric disorders. In: Goldman LS, Wise TN, Brodie DS, eds. Psychiatry for primary care physicians. Chicago: American Medical Association, 1998:231–252.

CHAPTER 123 ANXIETY OR PANIC DISORDERS Principles and Practice of Emergency Medicine

CHAPTER 123 ANXIETY OR PANIC DISORDERS Wayne J. Katon Capsule Ed Presenting Systems Epidemiology Difficulty in Diagnosis of Panic Disorder Associated Medical Illness and Panic Disorder Medical Differential Diagnosis Psychobiology of Panic Disorder Treatment

CAPSULE Anxiety disorders are among the most frequent problems physicians diagnose and treat. One study found that, among 11% of visits to several thousand physicians in the United States, the patient's chief complaint was anxiety or nervousness ( 1). This prevalence of complaints of anxiety and nervousness is undoubtedly an underestimate because many patients present with one of the somatic symptoms of anxiety such as rapid heartbeat or a psychophysiologic symptom caused by autonomic system arousal (diarrhea or epigastric pain) ( 2). In addition to the overt complaint of nervousness, another large subset of medical patients develop pathologic anxiety as a reaction to a serious medical disorder. This secondary anxiety often leads to amplification of symptoms of that disorder ( 3). One major advance in psychiatry during the past 10 years has been the change in the concept of anxiety as a common, unidimensional symptom necessitating treatment with minor tranquilizers to that of a component of several specific, clearly delineated syndromes, each with operationally defined symptoms, time course, and treatment. These syndromes include panic disorder, generalized anxiety disorder, social phobia, agoraphobia, simple phobia, posttraumatic stress disorder, and obsessive-compulsive disorder. This chapter focuses on panic disorder, the syndrome that is most likely to be associated with use of emergency department (ED) services. Because of the sudden, severe, autonomic nervous system arousal associated with panic disorder, many patients with this disorder seek ED treatment, focusing on one of the frightening somatic components of the disorder.

ED PRESENTING SYSTEMS Patients with panic disorder frequently present to the ED because of the episodic, frightening nature of their symptoms. Cardiac, neurologic, and gastrointestinal complaints are common, and associated medical problems include labile hypertension, sinus tachycardia, hyperventilation, migraine headache, and mitral valve prolapse (4). Careful questioning about the history of autonomic symptoms of panic disorder, phobic behavior, and depressive symptoms usually allows the physician to make an accurate diagnosis. Specific psychopharmacologic treatments are effective in ameliorating anxiety, psychophysiologic symptoms (labile hypertension), and decrements in social and vocational functioning.

EPIDEMIOLOGY Panic disorder is manifested by recurrent periods of apprehension and fear and at least four of the following symptoms: palpitations; chest pain or tightness; choking or smothering sensations; dizziness; dyspnea; paresthesias; hot or cold flashes; sweating; faintness; trembling or shaking; derealization or depersonalization experiences; and a fear of dying, going crazy, or doing something uncontrolled during an attack. At least one of the attacks is followed by at least one month of one or more of the following: Persistent concern about having additional attacks. Worry about the implications of an attack (i.e., losing one's mind). A significant change in behavior related to the attacks. Recent community studies have estimated that 1.6 to 2.9% of women and 0.4 to 1.7% of men have panic disorder (3). Primary care studies have found that these patients are overrepresented in medical clinics, with approximately 6% of primary care patients suffering from panic disorder, agoraphobia or both ( 4). In clinical samples, panic disorder is significantly more common in women than in men, with a ratio between 2.5 and 3.0 ( 4). The highest 6-month prevalence is in the 25-to-44 age group (3). Panic disorder tends to be a relapsing, remitting illness. Overall, in follow-up studies of patients with panic disorder and agoraphobia, approximately 50 to 70% of patients show some degree of improvement (5). Stages in Development of Panic Disorder There are three stages in the development of panic disorder. First, several controlled studies have determined that patients with panic disorder experienced a higher frequency of stressful life events in the 6 months before the development of the syndrome than the control group experienced ( 3). These stressful events are likely to have been perceived as threatening and uncontrollable, and likely to lead to a decrease in self-esteem. After a single stressful event or series of stressful events, the patient develops one or a flurry of panic attacks. These frightening first attacks are often described by the patient as the worst experience of his or her life. With accurate diagnosis and reassurance, some of these patients may not have further attacks. More likely, the patient's attacks increase in frequency, and as the patient has more attacks, he or she begins to associate specific environments with these autonomic episodes and may begin to avoid specific situations. Thus, if the patient has an attack while driving on a freeway, he or she may begin avoiding freeway driving. These phobias tend to be of social situations, especially situations in which the patient feels that escape would be difficult because of embarrassment or humiliation. Phobias of crowds, eating in public, and riding public transportation are all common. In the second stage, patients increase their use of medical care and often present to the physician focusing on one of the specific somatic accompaniments of a panic episode. Physicians try to reassure these patients with statements such as, “It's just anxiety, stress, or your nerves.” The patient, however, is likely to have experienced significant stress and anxiety before, but never such a severe autonomic episode. These patients often perceive their anxiety or nervousness as secondary to the autonomic symptoms, and unless the diagnosis of panic disorder is made and the physician takes the time to provide careful explanation about the psychobiology of this autonomic disorder, patients are likely to seek medical consultation elsewhere. Finally, some patients move into a third stage of the disorder, agoraphobia. The patient may be fearful of going out of the house unless accompanied by a significant other. These patients are fearful of crowds and many other social situations and often become dependent on their spouse or other companions because of decrements in social and vocational functioning.

DIFFICULTY IN DIAGNOSIS OF PANIC DISORDER Patients with panic disorder have cognitive, affective, and somatic symptoms, and the attacks have social consequences (increased dependency on spouse or vocational impairment). Because of the severe episodic autonomic symptoms associated with panic disorder, most patients selectively focus on the somatic component of the episode and present with one or more of these complaints ( 2,6). In a study of 55 patients referred to psychiatric consultation by primary care physicians, who met Diagnostic and Statistical Manual, 3rd edition (DSM III) criteria for panic disorder, three clusters of presenting symptoms were seen ( 2). These presenting symptoms included cardiac symptoms (chest pain and tachycardia), gastrointestinal symptoms (epigastric distress, diarrhea, and left lower quadrant pain), and neurologic symptoms (headache, dizziness, paresthesias). The presentation of cardiologic complaints is especially common in panic disorder because the primary symptoms (chest tightness or pain, tachycardia, and dyspnea) are cardiorespiratory. These cardiac complaints are especially likely to provoke costly and sometimes invasive medical testing. Three recent studies have documented patients with chest pain and negative angiography testing as having a significantly higher prevalence of panic disorder than patients with chest pain with evidence of coronary artery disease (CAD) on angiography ( 7,8 and 9). Katon and colleagues studied 74 patients with chest pain who were referred to angiography (9). In structured psychiatric interviews blind to the angiography results, 43% of 28 patients with chest pain and normal arteriography results met criteria for panic

disorder, compared with 5% of 46 patients with chest pain who were found to have coronary artery stenosis. Patients with chest pain and normal coronary arteries were found to have significantly more autonomic symptoms (dizziness, tachycardia, shortness of breath) associated with chest pain and were significantly more likely to have atypical chest pain. In the first ED study, Wulsin and colleagues also documented a prevalence of panic disorder among patients with atypical chest pain ( 10). Forty-nine ED patients with atypical chest pain were screened with a short panic disorder screen; 43% were found to meet criteria for panic attacks. Yingling and colleagues found a 19.4% prevalence of panic disorder among patients with chest pain presenting to the ED ( 11). Several other cardiorespiratory symptoms are prominent in patients with panic disorder. These include tachycardia, shortness of breath and labile hypertension. Patients with panic disorder frequently have higher basal heart rates than the control group and episodic tachycardia associated with their anxiety attacks ( 4). These patients may be misdiagnosed as having paroxysmal atrial tachycardia (PAT) and started on cardiac medications such as digoxin or a b-adrenergic blocking agent. Careful review of electrocardiograms (ECGs) reveals sinus tachycardia with lower rates than reported in PAT. Recent studies of patients who underwent medical work-up for palpitations found a 19 to 31% rate of panic disorder ( 12,13). However, PSVT can be mistakenly diagnosed as panic disorder ( 13A). Patients with panic also can present with subjective dyspnea but actually are hyperventilating. Blood gas studies have revealed that a large subset of patients with panic disorder are chronically hyperventilating with lower carbon dioxide, bicarbonate, and phosphorus levels than the control group ( 3). Because of the chronic hyperventilation, slight stresses may lower carbon dioxide levels enough to provoke symptoms such as paresthesias, dizziness and faintness, which frighten the patient and lead to more anxiety. Thus, a vicious cycle of physiologic symptoms, fear, and catastrophic cognitions may be provoked secondary to these somatic symptoms and the subsequent worsened physiologic state.

ASSOCIATED MEDICAL ILLNESS AND PANIC DISORDER Noyes and colleagues studied the interaction between panic disorder and physical illness by following patients with panic disorder and an outpatient control group over a 6-year period ( 14). They found that patients with panic disorder had a significantly higher rate of hypertension and peptic ulcer disease over this period. Patients with panic disorder frequently develop labile hypertension with their anxiety attacks. Once these attacks are blocked by psychopharmacologic treatment, the labile hypertension usually subsides. Untreated patients with panic disorder and secondary labile hypertension may develop chronic hypertension that necessitates specific antihypertensive treatment. Approximately one-third of patients undergoing pheochromocytoma testing for labile or malignant hypertension have panic disorder, whereas only one of the 300 patients undergoing testing for this rare catecholamine-secreting tumor were found to have pheochromocytoma ( 15). Patients with panic disorder have been found to have an increased prevalence of mitral valve prolapse (MVP) ( 3,3A). A review of 17 studies found that 18% of patients with panic disorder or agoraphobia met definite criteria for MVP, and 27% met probable criteria whereas 1% of the normal control group met definite criteria for MVP, and 12% met probable criteria (16). There is also the sudden death associated with MVP, and at autopsy valvular findings may be minimal or show thickening (Chapter 3-1). Some studies have suggested that there are two groups of patients with MVP ( 17). The first consists of persons in whom the disorder is primarily an echocardiographic finding. These patients are no more symptomatic than the control group and have no higher incidence of arrhythmias and a low risk of complications. The echocardiographic findings in this group are probably anatomic normal variants and reflect the technologic advances in defining valve motion but emphasize the difficulty in differentiating variants of normal valve mobility ( 17). The second group consists of patients who typically have not only evidence of prolapse on echocardiography but also clinical findings of mitral valve regurgitation. These people have symptoms related to valvular insufficiency and appear to have an increased risk of infective endocarditis and progressive mitral regurgitation. Two useful markers have been identified to help differentiate between the first group (with trivial MVP) and the second group (with important MVP): (a) the degree of redundancy of the valve, a finding that can be defined echocardiographically; and (b) the presence of mitral regurgitation on physical examination ( 17). Nishimura and colleagues found that almost every patient with a complication of MVP had redundant valves as indicated by an increase of mitral valve leaflet thickness of 5 mm or more ( 18). MVP in patients with panic disorder is generally mild and may not be associated with thickened mitral valve leaflets (the high-risk group of MVP patients) ( 19). Patients with panic disorder and MVP also have been found to respond as well as patients with panic disorder alone to treatment with imipramine ( 20). The overall findings suggest that panic disorder is associated with an increased prevalence of MVP, but this may be a mild type that is principally an echocardiographic finding of little relevance for treatment and not necessitating prophylactic antibiotic treatment. Even in the “silent group” there are reports of ventricular fibrillation ( 20A).

MEDICAL DIFFERENTIAL DIAGNOSIS In medical patients with severe panic disorder, the physician should initially focus on any chronic medical illness that may precipitate panic (congestive heart failure, asthma) and review all pharmacologic agents the patient is taking that could cause panic as a side effect ( 21). For instance, a diabetic with a hypoglycemic episode or an asthmatic with a high serum level of aminophylline may suffer from anxiety symptoms. Medical illnesses that can cause symptoms resembling panic attacks include temporal lobe epilepsy, pheochromocytoma, hyperthyroidism, hypoglycemic episodes, mitral valve prolapse (MVP), cardiac arrhythmias, caffeinism, pulmonary embolus, electrolyte abnormalities, Cushing's syndrome, and menopausal symptoms. Screening for illicit drug use also is essential. Both cocaine and marijuana have been implicated in causing panic attacks, and withdrawal from central nervous system (CNS) depressants (e.g., alcohol, barbiturates, benzodiazepines) and opiates may cause autonomic hyperactivity and mimic panic disorder ( 3). At times, panic disorder occurs concomitantly with a chronic medical illness such as angina pectoris, hypertension, or asthma. Because of the excessive autonomic nervous system activity associated with panic disorder, the physician may see physiologic worsening of a chronic illness secondary to the anxiety attacks ( 3). These patients frequently present with increasing resistance to medications that had formerly controlled their medical symptoms.

PSYCHOBIOLOGY OF PANIC DISORDER Psychiatric research has suggested that panic disorder is associated with a biophysiologic abnormality, as demonstrated by the observed familial predisposition, the positive treatment response to specific psychopharmacologic agents, and the specificity of response to provocative agents (lactate, Co 2, clonidine, yohimbine, isoproteronol, and caffeine) ( 3). Both normal fear and abnormal anxiety responses involve deep brain structures more than the cerebral cortex, specifically: (a) the limbic system (hypothalamus, septum, hippocampus, amygdala, and cingulum); (b) other neuronal bodies including the thalamus, locus ceruleus, median nuclei raphes, and dental/interposital nuclei of the cerebellum; and (c) connections between these structures ( 22). Research using positron emission tomography (PET) scan, magnetic resonance imaging (MRI) brain imaging techniques, and brain electrical activity mapping have implicated temporal lobe abnormalities in panic disorder as well as temporal lobe blood flow changes during normal fear ( 3). Research has resulted in several competing theories about the genesis of panic attacks, including (a) the locus ceruleus theory, (b) the benzodiazepine–GABA model, (c) the lactate theory, and (d) the CO 2 theory. Locus Ceruleus Theory The locus ceruleus is located in the dorsolateral tegmentum of the pons and contains nearly half of the noradrenergic neurons of the brain. The locus ceruleus is believed to control the sympathetic nervous system and to represent the area of the brain that is associated with alarm reactions to external threatening stimuli ( 3). Activation of the locus ceruleus has been associated with alarm and fear reactions in monkeys, and bilateral lesions of the locus ceruleus were associated with failure to show normal cardiorespiratory responses to threatening stimuli ( 23). Provocative challenge tests with clonidine (which decreases locus ceruleus activity) and yohimbine (which increases locus ceruleus activity) demonstrated an increased oscillatory range in noradrenergic activity among patients with panic disorder compared with a control group ( 24). These medications are agonists (clonidine) and antagonists (yohimbine) of the inhibitory a 2 adrenergic receptory of the locus ceruleus, leading several researchers to postulate that patients with panic disorder may have abnormalities of their a 2 noradrenergic receptor system (24).

Gamma-Aminobutyric Acid–Benzodiazepine Hypothesis Researchers have discovered brain benzodiazepine receptors that are linked to a receptor of the inhibitory neurotransmitter (GABA) ( 25). Binding of a benzodiazepine (Bz) to the Bz receptor facilitates the action of GABA, which is known to increase the permeability of chloride ions through the chloride ion channel. The heightened permeability of the cell to chloride ions decreases neuronal excitability by hyperpolarizing the neuronal membrane. These diffuse, inhibitory short GABA-ergic circuits and associated Bz receptors are present throughout the brain and spinal cord. GABA and benzodiazepines have inhibitory effects on the locus ceruleus and also may decrease anxiety by modulating the ascending activating systems (serotonergic, noradrenergic, and probably dopaminergic) that are implicated in the expression of fear ( 3). There also appear to be endogenous anxiogenic compounds that act on Bz receptors ( 26). Thus, these receptors may mediate both increases and decreases in anxiety. Research has found that panic disorder patients may be less sensitive to the catecholamine-reducing effects of anxiolytic benzodiazepines and more sensitive to the effect of benzodiazepines with anxiogenic properties ( 26). These results suggest that an abnormality of the Bz receptor may be present in some patients with panic disorder. Lactate and Carbon Dioxide Theories Early research in the 1940s and 1950s found that patients with panic disorder could be distinguished from the control group by their higher oxygen consumption with vigorous exercise and greater serum lactate production ( 4). This finding led to speculation that patients with panic attacks were more sensitive to the effects of lactate. Subsequently, patients with panic disorder have been repeatedly shown to be more sensitive to infusions of 10 mg/kg of 0.5 molar sodium lactate infusions than the control group (27). Approximately 75% of panic disorder patients have anxiety attacks provoked by these infusions, compared with 5% of the control group. Interpretation of these findings in explaining an overall theory of the genesis of panic attacks remains controversial, however ( 27). Carbon Dioxide Theory Panic attacks with Co 2-provocative tests are associated with exaggerated ventilatory responses and increases in plasma norepinephrine and diastolic blood pressure (28). Patients with panic disorder have been postulated to have hypersensitive Co 2 receptors or Co2 receptors with low set points. When triggered by increasing Co 2, these receptors evoke a subjective anxiety attack associated with an exaggerated ventilatory response and subsequent hypocapnic alkalosis. Patients may “learn” to hyperventilate to maintain low levels of Co 2 and avoid triggering their Co 2 sensors, thus explaining the repeated finding that many patients with panic disorder are chronic hyperventilators (28). It is not yet clear which of these theories is correct. Brain neurophysiologic research in the next decade, aided by innovations in brain imaging, promises to help unravel the enigmatic cause of severe anxiety.

TREATMENT In the context of the ED, where the patient has often presented with a frightening somatic complaint such as tachycardia or chest pain, the first step in treatment is education and negotiation of differing explanatory models ( 3). It is often helpful for the physician to describe panic attacks as caused by dysfunction of the autonomic nervous system in which a burst of catecholamines is released into the peripheral circulation, causing symptoms such as tachycardia, chest pain, dyspnea, and dizziness. A further analogy about panic attacks being similar to the flight-or-fight response may help. The patient can be provided with the following explanation: “If you were walking down a dimly lit street and heard a sudden sound behind you, your heart would begin to race; your breathing rate would increase; you would feel warm, tense, and shaky; and you would be prepared to either flee or fight for your life. These attacks that you are having are caused by dysregulation of the same area of the brain that controls the fight-or-flight response, but you are having this alarm or danger response at inappropriate times when there is no danger.” This explanation also leads naturally into a discussion of medications that dampen or alleviate the dysregulation of the autonomic nervous system. Double-blind, placebo-controlled studies have documented that four pharmacologic classes of medication are equally effective and significantly more effective than placebo in the treatment of panic disorder: 1. 2. 3. 4.

Serotonin reuptake inhibitors (SRIs) Tricyclic antidepressants High-potency benzodiazepines Monoamine oxidase inhibitors (29)

In medical patients the first line of treatment of panic disorder should be the SRIs. Paroxetine HCl, sertraline HCl, and fluoxetine HCl all appear to be effective. These should be started at a lower dosage in patients with panic (paroxetine HCl 10 mg, sertraline HCl 25 mg, and fluoxetine HCl 5 mg) because of their tendency to cause jitteriness in early stages of treatment. They should be gradually increased to dosages needed to treat major depression. In medical patients, the next line of treatment of panic disorder should be the tricyclic antidepressants. Imipramine HCl is the best-studied medication in the treatment of panic disorder, with at least 10 double-blind controlled studies demonstrating its efficacy ( 29). Studies have also documented that other tricyclics such as desipramine, nortriptyline, amitriptyline, clomipramine, and doxepin are also effective ( 29,30). Patients with panic disorder can be started on 25 mg of imipramine or desipramine, with an increase of 25 mg every 2 to 3 days. The endpoint of treatment should be when the patient's panic attacks are completely ameliorated. This usually requires a 100 to 300 mg dosage. A subgroup of patients with panic disorder develop intolerable side effects on all serotonin reuptake inhibitors and tricyclic antidepressants. Some of these patients can be treated with minute dosages of tricyclics, (5 to 10 mg initially) or Fluoxetine (2 to 4 mg of liquid) with a gradual increase in dosage. Another alternative is to add a low dosage of alprazolam, lorazepam, or clonazepam with the tricyclic, which often decreases the initial anxiety and jitteriness that can be transient side effects of tricyclics. A small subgroup of patients, however, do not tolerate SRIs or tricyclic antidepressants, and the high-potency benzodiazepines represent an effective time-tested treatment. Alprazolam, lorazepam, and clonazepam have all been demonstrated to be more effective than placebo in the treatment of panic disorder. Patients should be started on 0.5 mg of alprazolam 2 times a day, with a gradual increase by 0.5 mg increments every 2 to 3 days until panic attacks cease. Equivalent dosages of lorazepam and clonazepam to 0.5 mg of alprazolam are 1.0 mg of lorazepam and 0.25 mg of clonazepam ( 3). One caveat is that patients with prior histories of abuse with multiple drugs or alcohol, personality disorder, or chronic benign pain probably should not be treated with benzodiazepines because of potential problems with abuse. Monoamine oxidase inhibitors are potentially the most effective medications for panic disorder, but the unfamiliarity of most physicians with these medications and the potential “hypertensive crisis” that can ensue when the patient does not follow a low-tyramine diet preclude their regular use in primary care. In a patient who has not responded to an SRI or a tricyclic antidepressant or benzodiazepine, psychiatric consultation may be helpful. References 1. Schurman RA, Kramer PD, Mitchel JB: The hidden mental health network: treatment of mental illness by nonpsychiatrist physicians. Arch Gen Psychiatry 1985;42:89–94. 2. Katon W: Panic disorder and somatization: a review of 55 cases. Am J Med 1984;77:101–106. 3. Katon W: Panic disorder in the medical setting. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Alcohol, Drug Abuse and Mental Health Administration, 1989. 3A. Albert MA, Mukerji V, Sabeti M, et al: Mitral valve prolapse, panic disorder and chest pain. Med Clin North Am 1991;45:1119–1131. 4. 5. 6. 7. 8. 9. 10. 11.

Zaubler T, Katon W: Panic disorder and medical comorbidity: a review of the medical and psychiatric literature. Bull Menninger Clin 1996;60:12–38. Reich J: The epidemiology of anxiety. J Nerv Ment Dis 1986;174:129–136. Clancy J, Noyes R: Anxiety neurosis: a disease for the medical model. Psychosomatics 1976;17:90–93. Bass C, Wade C: Chest pain with normal coronary arteries: a comparative study of psychiatric and social morbidity. Psychosom Med 1984;14:51–61. Katon W, Hall ML, Russo J, et al: Chest pain: relationship of psychiatric illness to coronary arteriographic results. Am J Med 1988;84:1–9. Beitman BD, Basha I, Flaker G, et al: Atypical or nonanginal chest pain: panic disorder or coronary artery disease. Arch Intern Med 1987;147:1548–1552. Wulsin LR, Hillard JR, Geier P, et al: Screening emergency room patients with atypical chest pain for depression and panic disorder. Int J Psychiatry Med 1988;18:315–323. Yingling KW, Wulsin LR, Arnold LM, et al: Estimated prevalence of panic disorder and depression among consecutive patients seen in an emergency department with acute chest pain. J Gen

Internal Med 1993;8:231–235. 12. Weber BE, Kapoor WN: Evaluation and outcomes of patients with palpitations. Am J Med 1996;100:138–148. 13. Barsky AJ, Cleary PD, Coeytaux RR, et al: The clinical course of palpitations in medical outpatients. Arch Intern Med 1995;155:1782–1788. 13A. McCrank E, Schurmans K, Lefcoe D: Paroxysmal supraventricular tachycardia misdiagnosed as panic disorder. Arch Intern Med 1998;158:297–303. 14. 15. 16. 17. 18. 19. 20.

Noyes R, Clancy J: Anxiety neurosis: a 5-year follow-up. J Nerv Ment Dis 1976;162:200–205. Fogarty J, Engel CC, Russo J, et al: Hypertension and pheochromocytoma testing: the association with anxiety disorders. Arch Fam Med 1994;3:55–60. Margraff J, Ehlers A, Roth WT: Mitral valve prolapse and panic disorder: a review of their relationship. Psychosom Med 1988;40:93–113. Wynne J: Mitral valve prolapse. N Engl J Med 1986;314:577–578. Nishimura RA, McGoon MD, Shub C, et al: Echocardiographically documented mitral-valve prolapse: long-term follow-up of 237 patients. N Engl J Med 1985;313:1305–1309. Gorman JM, Geotz RR, Fyer M, et al: The mitral valve prolapse-panic disorder connection. Psychosom Med 1988;50:114–122. Gorman JM, Fyer AF, Gliklick J, et al: Effect of imipramine on prolapsed mitral valves of patients with panic disorder. Am J Psychiatry 1981;138:977–978.

20A. Strasberg B, Casp A, Kusniec J, et al: Ventricular fibrillation in a patient with silent mitral valve prolapse. Cardiology 1988;75:149–153. 21. Rosenbaum JF: The drug treatment of anxiety. N Eng J Med 1982;7:401–404. 22. Marks IM: Fear, phobias and rituals: panic, anxiety and their disorders. New York: Oxford University Press, 1987:190–191. 23. Svensson TH: Peripheral, autonomic regulation of locus ceruleus noradrenergic neurons in brain: putative implications for psychiatry and psychopharmacology. Psychopharmacology 1987;92:1–7. 24. Charney DS, Heninger GR: Abnormal regulation of noradrenergic function in panic disorders. Arch Gen Psychiatry 1986;43:1042–1054. 25. Insel TR, Ninan PT, Aloi J, et al: A benzodiazepie receptor mediated model of anxiety. Arch Gen Psychiatry 1984;41:741–750. 26. Roy-Byrne PP, Cowley D: Panic disorder. biological aspects. Psychiatric Ann 1988;18:457–462. 27. Margraf J, Anke E, Roth WT: Sodium lactate infusions and panic attacks: a review and critique. Psychosom Med 1986;48:23–51. 28. Gorman JM, Fyer MR, Goetz, R, et al: Ventilatory physiology of patients with panic disorder. Arch Gen Psychiatry 1988;45:31–39. 29. Roy-Byrne P: Integrated treatment of panic disorder. Am J Med 1992;92(supp 1A):49–54. 30. Gorman J: The use of newer antidepressants for panic disorder. J Clin Psychiatry 1997;58:54–58.

CHAPTER 124 SOMATOFORM DISORDERS* Principles and Practice of Emergency Medicine

CHAPTER 124 SOMATOFORM DISORDERS* Beverly Fauman Capsule Definitions and Evaluation of Somatoform Disorders Pathophysiology and Anatomy Prehospital Assessment and Stabilization Clinical Presentation and Examination Differential Diagnosis Initial Stabilization Laboratory and Other Procedures Management and Indications for Admission Pitfalls Medicolegal Pearls

CAPSULE The somatoform disorders are a group of illnesses characterized by physical complaints for which the etiology ultimately appears to be psychological. Presentations are often complex and the diagnosis may be difficult to confirm. Patients often present to the emergency department (ED) and may be well known to the ED staff. Somatoform disorders can occur alone or in combination with other physical illnesses, can be exacerbated by emotional stress, and often occur in patients who at other times have serious physical illnesses. These are patients about whom the anecdote of the tombstone epitaph, “I told you I was sick,” leaves the physician unsure and uncomfortable about the diagnosis. Confrontation is not curative. The best prognosis is associated with early detection and aggressive treatment. If the ED physician suspects one of the somatoform disorders, they should refer the patient to (or back to) a primary care physician. In the ED, where judgement must be rapid, it is wise to consider the diagnosis of a somatoform disorder and refer for additional nonemergency evaluation once life-threatening disease is ruled out.

DEFINITIONS AND EVALUATION OF SOMATOFORM DISORDERS Somatoform disorders are illnesses in which the patient's symptoms and idea of what is wrong are physical, but responsible and thorough physical, laboratory, and psychiatric evaluation determine that the illness is psychologically based ( Table 124.1). The three elements of this diagnostic group are: (a) persistent or recurring physical complaints unconfirmed on physical examination, (b) persistent worry about a physical illness despite no physical findings, or (c) exaggerated concern about nonexistent or minor physical defects in an otherwise normal-looking person ( 1). Patients with somatoform disorders frequently also have a history of significant physical illness. In some disorders, the patient complains of or feigns symptoms that are under his or her voluntary control. These are called factitious disorders. Sometimes, such conditions are actually created or simulated (Munchausen syndrome). Somatoform disorders, on the other hand, are not under the patient's voluntary control.

Table 124.1. The Somatoform Disorders

A conversion reaction is commonly thought to be the conversion of a psychologic idea or wish that is uncomfortable for the patient to acknowledge consciously into a physical symptom that accomplishes the dual purposes of expressing the conflicting wish and relieving the psychologic conflict. Somatization disorders are less discrete episodes of illness than conversion disorders are. They involve various organ systems, are less bizarre than conversion symptoms, and may lead the physician to perform expensive diagnostic tests or procedures. Because a patient who is prone to somatization disorder generally has different somatic complaints at different times and may consult multiple specialists, it may take some time for one physician to pull the whole picture together ( 2). Hypochondriasis differs from somatization disorder in that the patient generally focuses on only one organ system, with a persistent, almost delusional conviction that something is wrong with that system. The hypochondriac appears to misinterpret or exaggerate normal bodily sensations. A patient with somatization disorder may consult physicians in multiple specialties, whereas the hypochondriac patient is more likely to consult, for example, a succession of cardiologists. Occasionally, one can identify a family member from whom the patient has “inherited” the symptom. A relative may have died of colon cancer or myocardial infarct, and the patient demands repeated barium studies or electrocardiograms (ECGs) for reassurance about normal variations in stool or pulse ( 3). In body dysmorphic disorder, the patient has an excessive preoccupation with an imagined defect, or exaggerated concern about a minor defect; for example, one breast being slightly larger than the other. Although these patients more commonly seek out plastic surgeons, they also may request emergency consultation regarding their concern over a body part ( 4). Pain disorder is considered to be psychologically based when a patient has complaints of chronic, unremitting pain for which thorough evaluation cannot provide a sufficient explanation. A patient who has had an organic cause for the pain, but for whom the pain persists long after it should, is also diagnosed as having pain disorder. These patients are difficult to treat because they may become addicted to narcotics and fear the recurrence of pain. They become demanding, prompting caregivers to feel that they are being manipulative. Patients with lawsuits pending related to the original injury that caused the pain lend further suspicion that the patient is feigning the pain. Some authors believe that pain disorder is a manifestation of depression, because some of these patients respond to antidepressants (5,6). Undifferentiated somatoform disorder is a diagnosis that is used when a patient has persistent physical complaints, which are not explained by physical and laboratory examinations, and/or the degree of complaint far exceeds any physical findings, yet none of the diagnoses described seem to apply.

PATHOPHYSIOLOGY AND ANATOMY The somatoform disorders affect every body part and organ system, which is why it can be so problematic to diagnose. A patient with somatoform disorder may have different somatic complaints at different times. One clue to conversion reaction or psychologic pain disorder is a discrepancy between the described symptom and what we know about physiology and anatomy: the symptom “cannot be.” A conversion symptom must be related to a perceived sensation to be able to serve as a conversion; therefore, gastric secretions, blood pressure, or other silent physiologic processes generally are not part of a conversion disorder. The conversion symptom may, however, give rise to corresponding motor and physiologic changes, termed conversion complications.

Somatization disorder is defined as recurrent complaints of symptoms over time, beginning before age 30, and involving many organ systems. Many of these complaints suggest serious illness, but occur in a patient who simply does not look that sick. Common complaints in somatization disorder include difficulty in swallowing, fainting, nausea, shortness of breath, palpitations, and dizziness ( 1). These are not pathognomonic for somatization disorder, nor are they the only symptoms. The diagnosis is made from the whole picture. The hypochondriac patient appears to be exquisitely sensitive, or to overreact to ordinary physiologic functions. This patient may regularly check his or her own blood pressure, pulse, stool, or urine stream for reassurance. As with somatization disorder, certain organ systems are more likely than others to be the focus of the hypochondriac patient's concern, but fixed, chronic concern with any organ system or body site may occur. A patient who has body dysmorphic disorder becomes obsessed with the idea that there is something grossly awry with a body part or facial feature. The patient with this disorder frequently checks themself in the mirror to assess whether there is reason for concern, as for example with one breast that is larger than the other, an ear that sticks out, or an eye that is slightly lower than the other. The asymmetry is not striking and may not even be detectable by others. Pain disorder includes pain of sufficient severity, intensity, and duration to warrant attention; and it may be associated solely with psychologic factors, a combination of psychologic and general medical problems, or associated only with a general medical condition. Some examples include menstrual pain that the patient believes is more frequent or more severe than most women experience, pain during intercourse, persistent pain following severe injuries, long since healed, and pain without any associated insult.

PREHOSPITAL ASSESSMENT AND STABILIZATION Somatoform disorders are difficult to diagnose in the field, particularly if they present as emergencies. Instructions to the field should be to assume that the patient is organically ill, stabilizing his or her as needed. The important thing to remember is that these patients are best managed over the long term by a primary care physician, and unusual or invasive diagnostic tests or procedures should be kept to a minimum. If possible, the patient's primary care provider should be contacted before invasive or risky diagnostic or therapeutic measures are undertaken ( 6).

CLINICAL PRESENTATION AND EXAMINATION The somatoform disorders present much like regular medical illnesses. The patient believes that he or she has a serious organic disorder and is unlikely to volunteer information that would lead the physician to recognize the emotional basis of the symptoms. Certain presentations are more suggestive of one of the somatoform disorders. These include serious or worrisome symptoms without accompanying signs; a patient under age 30 or with recurrent or ongoing symptoms starting before age 30; and symptoms often revolving around breathing, urination, eating, elimination, or activity of the voluntary muscles. Palpitations, neurologic symptoms, or symptoms related to the sexual organs are also common. The onset of a conversion reaction is sudden, usually in reaction to a particular event and in an emotionally charged setting. The patient appears healthy and less concerned about the symptom than one would expect. The family does not appear insightful and often is oversolicitous, in contrast to the patient's lack of concern. There is often a history of a curious undiagnosed illness in the past that subsided spontaneously or even “miraculously.” Recurrence is not unusual, and it may or may not be manifested by the same symptom. Conversion symptoms are culture bound; therefore, today we rarely see the dramatic, discrete, “obvious” conversions described by Freud, Janet, and Charcot. A good history and physical examination, a thorough neurologic examination, and the physician's ability to recognize an ill patient are the best diagnostic tools. The sooner a conversion reaction is identified, the more amenable it is to treatment. Conversely, multiple laboratory tests, specialty consultations, and other delays in defining the illness make it more entrenched and harder to treat. Conversion symptoms typically involve voluntary muscles, although they may take virtually any form. Pain is not a common conversion symptom, and if this is a major part of the patient's presentation the physician should consider a pain disorder as the diagnosis. The most frequent complaints are motor disturbances and sensory abnormalities. The symtpoms may mimic physical illness or complicate existing physical illness. The patient experiencing a conversion reaction is not feigning; that is, he or she does not have conscious control over the symptom, did not choose it, and is not aware or willing to accept the idea that it is psychologic. Questioning must proceed gently, for the purpose of gathering information and not to confront the patient or to try to get him or her to admit what is happening. The physician is trying to determine what psychologic conflict might be resolved by the patient's symptom. Conversion can exist when a conflict cannot be discovered, but the diagnosis cannot be established with confidence. Questions should focus on what was happening when the symptoms began, and what the symptom prevents the patient from doing. The conversion symptom serves an adaptive function for the patient. The conversion process is believed to spare the patient the anxiety, guilt, or shame that would otherwise have been engendered by the unacceptable idea, which constitutes the primary gain. Secondary gain is achieved by the sick role. The patient with hypochondriasis, psychogenic pain disorder, or somatization disorder has an extensive history of physician contact ( 7); the patient with conversion reaction may have much more episodic medical intervention. Although the conversion disorder patient is often relatively unconcerned about his or her symptoms, the other disorders carry with them a great deal of worry and concern, as well as outrage if the complaints are not taken seriously. The hypochondriac has developed a fixed, almost delusional preoccupation with a body part or a body function. He or she has not been well for some time and may have suffered real illness between hypochondriac episodes. These real illnesses have two effects: (a) they relieve the hypochondriac complaints for weeks to months, and (b) they confirm for the patient that he or she was justified to be concerned. The hypochondriac patient may be a man or woman, usually middle aged or older. His or her relationship with family, friends, and physicians is characterized by the focus on symptoms, medications, and illness. In contrast to the other disorders discussed here, the malady is usually relatively constant, and the patient may stay with one physician, even though all treatment efforts have been ineffective ( 2,3). Body dysmorphic disorder is similar to hypochondriasis in the fixed preoccupation with a body part. Relationships with others may also be characterized by this preoccupation, although there is no relief of symptoms by experiencing a real illness. The preoccupation may wax and wane over time. Signs and laboratory findings do not correspond to the patient's symptoms. The physician should not proceed with any invasive or risky diagnostic tests that are not dictated by clinical judgment. Whenever possible, a single primary care provider should be identified for these patients, to oversee and determine the necessary diagnostic and therepeutic measures indicated.

DIFFERENTIAL DIAGNOSIS The primary diagnoses to exclude are imminently life-threatening ones (Table 124.2), for example, myocardial infarct, stroke, hyperglycemia, hypoglycemia, or pulmonary embolism. Depression, hyperventilation, the anxiety disorders, and conversion disorder may respond to rapid intervention; therefore, a psychiatric consultation in the ED may be useful. Panic disorder may be associated with mitral valve prolapse and sudden death. An early manifestation of a schizophrenic disorder may be bizarre or obsessive concern about bodily functions; here also, a psychiatric evaluation may establish the correct diagnosis. Patients who are victims of domestic violence, or who are themselves abusive parents, may present to an ED with vague, unusual, or hypochondriacal complaints, often between episodes of violence. It is unclear whether this is a conscious cry for help, a manifestation of depression, or an unconscious wish to be discovered or stopped. The physician should make it a practice to evaluate all patients who appear to have a somatoform disorder for a domestic violence history. Other distorders that may be considered should be evaluated only to the extent needed to rule out acute illness. The patient should then be referred to a primary care physician.

Table 124.2. The Somatoform Disorders: Differential Diagnosis in the Emergency Department

In the past, hypochondriacal patients often presented to the ED hoping that repeated evaluations would incidentually uncover the cancer they were sure they had. In the present era, similar patients carry the conviction that they will have acquired immunodeficiency syndrome (AIDS).

INITIAL STABILIZATION The patient with a somatoform disorder stabilizes initially with reassurance that the physician is taking the complaints seriously and will evaluate them. Vital signs should be obtained, and any deviation from them explored. Remember that ketoacidosis may present only as slightly rapid respirations; hypothyroidism as only slightly depressed temperature, blood pressure, or heart rate.

LABORATORY AND OTHER PROCEDURES To facilitate appropriate treatment of a patient with any of the somatoform disorders, limit evaluation to the symptoms and signs that suggest acute physical illness. If the patient is knowledgeable or insistent about some obscure or risky test or treatment, make a note of it; this is probably not a naïve patient or one without a medical history. In the ED, you should not order tests for rare or unlikely disorders that are not imminently serious. Refer the patient instead to a primary care physician. Patients with somatoform disorders experience much of their morbidity from procedures and laboratory tests, often unnecessary ones.

MANAGEMENT AND INDICATIONS FOR ADMISSION Reassurance is necessary but short-lived. Perform only those laboratory tests needed to confirm absence of significant acute illness. Consult other physicians and further evaluate or hospitalize the patient if you have significant concerns, but not if you merely feel pressured by the patient to do more. A patient with conversion disorder may need to be hospitalized because the symptoms greatly impair function, although conversion reactions are often treated effectively in the ED. A psychiatric consultation may be useful to help with management or a decision to admit. Any indication of suicidal intent requires psychiatric consultation.

PITFALLS The problems that arise when the patient with somatoform disorder is misdiagnosed or mismanaged in the ED are frustrating at best and life-threatening at worst. The frustration comes from feeling that you have been manipulated by the patient. Frustration can be minimized by: (a) relying on your medical judgment and objective findings to determine the need for further tests or treatment; (b) obtaining a consultation or second opinion when you are uncertain; and (c) recognizing that the patient is really helpless to control his or her symptoms and the accompanying anxiety. A particular problem in the treatment of these disorders is getting the patient to agree to see a psychiatrist. Potential life-threatening problems are addressed by: (a) not ordering or performing risky tests or procedues that can be postponed, and (b) referring the patient to a primary care physician who can oversee and coordinate further management.

MEDICOLEGAL PEARLS Patients who eventually are found to have a psychologic basis for their symptoms may anger the physician, who is eager to identify and treat “real” diseases. There is the potential for at least two adverse outcomes: first, the physician may do or say something to express this anger, which may provoke a lawsuit; second, the physician may do or say something to ensure that no diagnosis is overlooked, leading to excessive testing with its inherent costs and risks ( 6). There are several ways to minimize legal risk. Most important, realize that the patient does not have conscious control over his or her symptoms and is not trying to take advantage of the system or harass you. This is the patient's poor adaption to life, and the patient is helpless. Many patients with psychogenic pain disorder are involved in lawsuits, and the pain may actually disappear when the lawsuit is settled. This does not prove that the pain was factitious or under the patient's willful control. If the patient comes in with a complaint that suggests serious illness, indicate in your note how you explained that symptom, or why you do not believe the patient is experiencing a stroke, myocardial infarct, or other life-threatening disease. Avoid using of pejorative or derogatory descriptions in the record, but explain in the chart your reasons for not performing particular laboratory tests. Beware of the somatizing patient who has a long history of negative work-ups but eventually becomes very ill. Such patients require reevaluation. Numerous lawsuits have resulted, for example, from pain-medication-seeking patients who develop a perforated ulcer but who are dismissed as having just another episode of craving medications. * Previously termed “psychosomatics.”

References 1. 2. 3. 4. 5.

Fauman MA: Study guide to the DSM IV. Washington, DC: American Psychiatric Press 1994:241–258. Barsky AJ, Wyshak G, Klerman GL, et al: The prevalence of hypochondriacs in medical outpatients. Soc Psychiatry Psychiatr Epidemiol 1990;25:89–94. Brown HN, Vaillant GE: Hypochondriasis. Arch Intern Med 1981;141:723–724. Phillips KA, McElroy SL, Keck PE, et al: Body dysmorphic disorder: 30 cases of imagined ugliness. Am J Psychiatry 1993;150:302–308. Escobar JI, Swartz M, Rubio-Stipec M, et al: Medically unexplained symptoms: distribution, risk factors, and comorbidity. In: Kirmayer LJ, Robbins JM, eds. Current concepts of somatization: research and clinical perspectives. Washington, DC: American Psychiatric Press, 1991:63–78. 6. Emerson J, Pankratz L, Joos S, et al: Personality disorders in problematic medical patients. Psychosomatics 1994;35:469–473. 7. Lipowski ZJ: Somatization: the concept and its clinical application. Am J Psychiatry 1988;145:1358–1368.

Selected Readings Fauman, BJ, Fauman MA: Emergency psychiatry for the house officer. Baltimore: Williams & Wilkins, 1981. Ford CV: The somatizing disorders: illness as a way of life. New York: Elsevier Scientific Publishing, 1983. Kirmayer LJ, Robins JM: Current concepts of somatization: research and clinical perspectives. Washington, DC: American Psychiatric Press, 1991. McKinney IR, Epstein RM, Freeman TR: Re-thinking somatization. Ann Intern Med 1997;126:747–750. Tomb DA: Psychiatry for the house officer, 4th ed. Baltimore: Williams & Wilkins, 1995.

CHAPTER 125 DOMESTIC ABUSE, ELDER ABUSE, AND THE ABUSED, ASSAULTED ADULT Principles and Practice of Emergency Medicine

CHAPTER 125 DOMESTIC ABUSE, ELDER ABUSE, AND THE ABUSED, ASSAULTED ADULT Susan V. McLeer and Margo J. Krasnoff Capsule Introduction Clinical Presentation Initial Identification Clinical Evaluation Initial Stabilization and Management Pitfalls National Contacts

CAPSULE Each year more than 23,000 people die from interpersonal violence in the United States ( 1). Because of under reporting, official crime statistics do not begin to reflect the true extent of violence in our society. Estimates indicate that for each reported death there are at least 100 nonfatal assaults ( 1). Hospitals, and specifically emergency departments (EDs), see large numbers of patients presenting with injuries caused by interpersonal violence ( 2). The medical evaluation and care provided for abused and assaulted adults must extend beyond the specifically identified medical or surgical problems. It is essential for physicians to determine if injuries were caused by a mode of assault or abuse that is likely to recur, as in adult domestic violence and abuse of the elderly. If recurrence appears likely, then ED staff must determine the patient's need for protection against further assault or abuse. It is also important that emergency physicians understand the behavioral, cognitive, and neurophysiologic changes that can be precipitated by severe stress in order to guide the patient as to when he or she should seek treatment for the probable psychologic sequelae of assault or abuse.

INTRODUCTION Adult domestic violence, by far the most prevalent of the recurrent forms of assault or abuse, is defined as the use of physical force by one partner against the other in an intimate relationship, regardless of marital status or cohabitation. Elder abuse is the willful infliction of physical pain or injury, debilitating mental anguish, or financial exploitation of an older person. It also includes active and passive neglect. Active neglect is the failure of a caretaker of an older person to intervene or resolve a significant need despite the awareness of available resources; passive neglect includes unintentional neglect, resulting from either ignorance or genuine inability to provide care. Although some studies have indicated that physical force is used against men as often as, if not more than, against women ( 3,4), the physical abuse of men does not appear to be a widespread clinical problem ( 5). Three factors account for this phenomenon: (a) The strength differential between men and women is sufficiently great that men are less apt to be injured; (b) the means of physical force used by women has been demonstrated to be less serious than those used by men (hitting and throwing things versus use of fists and weapons); and (c) the studies indicating that women frequently use physical force against men do not address issues of motivation, e.g., the use of physical force in self-defense during a battering episode. Physical abuse of women, however, has become a problem of crisis proportion, with 20 to 25% of adult women in the United States having been abused at one time or another by a male intimate ( 2,4). Data from regional studies, including a random sample survey of 2,020 older persons in the Boston metropolitan area, indicate an abuse rate of 32:1000 ( 6). Of the abusers, two-thirds were spouses and the remainder were adult caregivers, the majority of whom were adult children. Although a national study has yet to be done, it is estimated that about 1.5 to 2 million older Americans are victims of elder abuse each year ( 7,8), with women being at greatest risk (9). Both elder abuse and spousal abuse rarely resolve spontaneously without intervention or a major change in the victim's environment.

CLINICAL PRESENTATION Domestic Violence Domestic violence perpetrated against women may be the single most common cause of injuries presented by women to the health care system, accounting for more injury episodes than automobile accidents, muggings, and rapes combined ( 10). As many as 30 to 40% of injured women seeking care in ED settings may have injuries caused by battering ( 2,11,12 and 13). In addition, significant numbers of battered women seek care in ED settings with non–trauma-related complaints. In a study of women seeking emergency care in Denver (13), one of nine women (12%) spontaneously requested services as victims of acute domestic violence. Among these women, nontrauma complaints predominated. In this study, 54% of women seeking care in the ED, including those with and without trauma-related chief complaints, reported that they had experienced assault, been threatened, or made to feel afraid by their domestic partners at some point in their lives. Battering is a chronic problem, with the severity and frequency of beatings increasing over time ( 14,15 and 16). Seventy-five to eighty-six percent of those first injured experience ongoing abuse (16 and 17). Battering accounts for one of every five women seeking medical care ( 10), with most battered women seeking care not for injuries, but for general medical, behavioral or psychiatric problems. Studies of pregnant women indicate that 10 to 17% have been physically or sexually abused during their current pregnancy ( 2,18,19), and for most battered, pregnant women the abuse intensifies while they are pregnant ( 19). Compared with women who are not battered, battered women are more likely to present with depression, anxiety, family/marital, or sexual problems (19% versus 8%) or vague medical complaints (12% versus 3%) ( 17). Drug and alcohol abuse is even more prevalent, with battered women having 16 times the risk of abusing alcohol and 9 times the risk of drug abuse, compared with other women ( 17). As many as 26% of women who attempt suicide have a history of having been battered ( 10), and of those who make an initial attempt, 50% will do so again ( 17). In 1984, 1310 women and 806 men were killed during acts of domestic violence ( 20). Clearly, domestic violence is a source of great morbidity and significant mortality in our society. Elder Abuse Although it is unknown how many elder abuse victims seek emergency care, it is known that older persons are in more frequent contact with health care providers than younger persons because of the greater likelihood of both chronic and acute illness ( 21). Diagnosing abuse or mistreatment in this population is particularly challenging in that signs and symptoms can affect multiple systems ( Table 125.1). In addition with the increased prevalence of chronic disease in the elderly, it is important to anticipate the possibility of comorbidity, abuse coexisting with underlying disease. Implausible explanations for an injury are suggestive of maltreatment; however, diagnosis of elder mistreatment is challenging, because the elderly are injured more frequently than the general population as a result of age-associated factors (e.g., increased falls, osteoporosis, osteomalacia).

Table 125.1. Indicators of Elder Abuse and Mistreatment

Elderly with cognitive changes, such as dementia or confusion, may have limited communicative skills and increased vulnerability. Because it has been demonstrated that delirious and demented patients have an increased incidence of neglect, unsolicited reports of abuse by elderly patients should be taken seriously rather than dismissed as paranoid ideation ( 22). Such reports may accurately reflect an abusive environment.

INITIAL IDENTIFICATION If asked, battered women almost always admit to having been battered (10). Without systematic use of protocols designed to identify and diagnose victims of domestic violence, physicians have been found to identify only 1 abuse victim in 35 ( 17,23). Mental health professionals, charged with asking intimate questions of clients, identify only 1 abuse victim out of 30 (24). Therefore, routine screening for domestic violence is advised for all patients. Refer to Table 125.2 for a suggested screening strategy.

Table 125.2. Screening Adult Women for Domestic Violence

Health professionals can easily be trained to identify victims of domestic violence through the use of brief protocols ( 12,25,26,27 and 28). Unless an institutionalized system exists for ensuring the use of such protocols, however, it appears that professionals will not continue to diagnose battering systematically. In a study conducted in a Philadelphia teaching hospital, introduction of an ED protocol designed to detect injuries caused by battering increased the identification of battered women from 5.6% of female trauma patients to 30%. An 8-year follow-up study in the same hospital found that, without continued monitoring and use of protocols, the identification of battering decreased to preprotocol levels ( 29). Children in violent families suffer considerably. On the basis of clinical reports and published empirical studies, it appears that children who witness domestic violence are at increased risk for developing emotional, social, and behavioral problems ( 30,31). Wolfe et al. (32), in a study of 198 children from violent and nonviolent families, found that among 102 children from violent families, 34% of boys and 20% of girls fell into the clinical range of behavioral problems. These levels of behavioral and emotional dysfunction also have reported by other investigators ( 33,34). In addition to the indirect effects of witnessing parental violence, children are at heightened risk for being physically abused themselves. In a national epidemiologic study of family violence, a 129% greater chance of child abuse was found among families in which a husband had hit his wife ( 3). In clinical populations the coexistence of child physical abuse and adult domestic violence may be even more prevalent. Hilberman and Munson ( 24) reported finding physical abuse in one-third of children of battered women in a rural setting, and Bowker ( 35) identified 70% of the children of a volunteer sample of battered women as having been physically abused by the batterer. Stark and Flitcraft ( 36,37) reported that among a population of women whose children had been reported as cases of suspected abuse, 45% reported being beaten by their partner. The implications of these findings are significant for health providers. Whenever a child is identified as being abused, one should ask if the child's mother is being battered. Likewise, whenever a battered woman is identified, one needs to determine if there are children in the family and if they also are being abused. As with domestic violence, there is gross underrecognition of elder abuse ( 38,39). The absence of brief, easily usable, and well-validated screening protocols has been identified as a major barrier for health care professionals in the detection of elder abuse ( 40,41). EDs of hospitals that have implemented elder abuse protocols have found a substantial improvement in the way elder abuse cases are processed and documented ( 42,43 and 44). There is also much better long-term follow-up (40,43). Suggested screening questions for elder abuse are listed in Table 125.3. When clinicians ask an elderly patient about abuse, they may not get truthful answers because of the patient's fears of not being believed, embarrassment, and shame (especially if the perpetrator is a family member). Fear of reprisal, abandonment, or institutionalization also may discourage disclosure. Denials of abuse by the patient or the caregiver does not preclude the diagnosis.

Table 125.3. Screening Elders for Mistreatment

CLINICAL EVALUATION The emergency physician's role with adult victims of assault or abuse is complex, and the ED may provide the first opportunity for a traumatized victim to find support and assistance. The emergency physician bears the ultimate responsibility for the quality of the medical care provided and must ensure that necessary protocols are followed. Given limited time, certain tasks can be delegated to other health care professionals. The seven general steps to follow with suspected woman or elder abuse are described in the following sections. Step 1. Obtain Trauma and Psychosocial History ADULT VICTIMS OF DOMESTIC VIOLENCE The emergency physician should routinely ask all women direct, specific questions about domestic violence in a private setting without any partners or friends

present. Establishing that the woman's injuries are secondary to battering is the first task. When asked directly about how the injury occurred, 16 to 30% of female trauma patients reported that they had been battered. Some women, however, do not admit that they have been battered. Any trauma or burn that seems incompatible with a history of the injury suggests battering or abuse and indicates the need for gentle probing about how things are at home, the presence of undue stress, frequent disagreements, and so on. Asking more about disagreements and whether they have escalated to shouting, loss of temper, or slapping, aid in eliciting a history of battering. Information must be collected to facilitate a comprehensive assessment of the battered woman's needs, resources, and priorities to develop immediate and long-range plans designed to minimize or eliminate future abusive episodes. Table 125.4 outlines a structured interview that can be used to obtain the necessary information for treatment planning. The initial identification of a battered woman can be achieved by a triage nurse, as long as the patient is interviewed alone in a private environment. A more detailed history takes 30 to 40 minutes and may require a social worker or trained domestic violence volunteer. Some institutions have a multidisciplinary domestic violence team to help provide services to the victim. If an interpreter is required, an interpreter outside the family is essential.

Table 125.4. Structured Interview for Victims of Domestic Violence

VICTIMS OF ELDER ABUSE Older adults and their caregivers must be interviewed separately and alone in order to obtain honest information about the clinical presentation and the home environment. If the two sources provide a disparate history, this should trigger a more detailed exploration of the circumstances. All elderly patients should be asked “Do you feel safe where you live?” and asked about who assists them when help is needed ( 45,46). The elderly person who is at risk for abuse is frequently dependent on the abuser for basic needs such as food, shelter, clothing, medical care, and social stimulation. Consequently, the abused older person may be terrified of disclosing abuse. Studies indicate that elder abuse is recurrent in up to 80% of cases ( 47). The abuser is a relative 86% of the time and lives with the elderly person in 75% of cases (47). In a study of elder abuse presenting in an ED, only 33% of abuse victims stated outright that they were being abused, and 6% were reported by neighbors and nonabusive relatives. Another 61% were detected by medical professionals during the course of evaluation or hospitalization. This underscores the need for clear protocols for identifying victims of elder abuse ( 44). In most cases, abuse was inferred from the physical appearance of the patient (42%) and findings from the social service evaluation of the patient's living conditions (19%). Several risk factors have been identified as associated with elder abuse and underscore the need to obtain historic information from multiple sources ( Table 125.5). These risk factors indicate that abuse is apt to occur in families where there is a history of violence or substance abuse or a discrepancy between family needs and resources. It is of utmost importance to gather clinical data regarding the living circumstances of the elderly patient and those of the caretaker and his or her family. The American Medical Association (AMA) has recommended that all physicians incorporate routine questions about elder abuse into their daily practice, during an interview conducted away from the caregiver or suspected abuser ( 46).

Table 125.5. Risk Factors for Abuse of the Elderly

As with other forms of domestic violence and abuse, a history of previous injuries or physical deterioration suggests abuse or neglect. Likewise, because evidence of physical trauma is found in 50% of elder abuse cases, a careful physical and functional assessment is of utmost importance. Protocols have been developed for EDs to aid in the clinical assessment of the elderly patient ( 46,47). Step 2. Diagnose and Treat Medical and Surgical Problems This step becomes the first priority when a patient is severely injured or medically compromised. Assessment for both battered women and victims of elder abuse, however, requires careful attention to the patterns of injury and signs of physical neglect. Both battered women and abused elderly patients may show physical signs of sexual abuse or rape, and all should be asked whether sexual assault has occurred. A body map of injuries is particularly helpful for all victims of violence ( Fig. 125.1).

Figure 125.1. Body map and indications of elder abuse. (Reproduced with permission from Jones J, Dougherty D, Schelble D, et al. Emergency department protocol

for the diagnosis and evaluation of geriatric abuse. Ann Emerg Med 1988;17:1012.)

A battered woman may present to the ED with repeated physical injuries, medical complaints, or mental health problems. A finding among injured women that is highly correlated with adult domestic violence is the lack of consistency between the nature and extent of the patient's injury and the explanation given for the injury. Other indicators suggestive of battering are listed in Table 125.6.

Table 125.6. Indicators of Domestic Violence

Dehydration and malnutrition, inappropriate or soiled clothing, poor hygiene, old and uncared-for injuries, or other signs of medical neglect are apt to be suggestive of elder abuse. Additional clinical indicators are listed in Table 125.1. When altered mental status is encountered without a plausible explanation, consider overmedication with psychotropic drugs and order toxicology testing. In cases of suspected elder mistreatment, the threshold for ordering radiographs should be lower because of the tendency of the elderly to minimize their injuries, the unreliability of the history, and the higher prevalence of osteopenia ( 48). Step 3. Evaluate the Emotional Status of the Assaulted or Abused Patient The emotional status of all assaulted or abused adults needs determination. Studies have indicated that assaulted adults, particularly sexually assaulted adults, are at extreme risk for the development of posttraumatic stress disorder (PTSD) ( 49). PTSD is an anxiety disorder caused by exposure to an event that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others. The person's response to the event must have involved intense fear, helplessness, or horror. Patients with PTSD undergo behavioral and cognitive changes as well as neurophysiologic changes. Studies have demonstrated that the autonomic nervous system is hyperreactive, with peripheral evidence of heightened adrenergic activity. In the early phase of PTSD, there is an additional increase in the release of adrenal corticosteroids, but as a more chronic coarse develops, the adrenal activity decreases, resulting in a reverse ratio of peripheral markers of adrenergic activity and adrenal cortical activity. The behavioral and cognitive components of the posttraumatic stress response are organized around efforts to cope with or avoid increased anxiety. Stimuli that are reminiscent of the original trauma can precipitate severe anxiety attacks. Consequently, patients develop behavioral patterns designed to avoid places, persons, and situations that are reminiscent of the trauma. Table 125.7 lists diagnostic criteria for PTSD.

Table 125.7. Diagnostic Criteria for Posttraumatic Stress Disorder

Many patients who initially give evidence of PTSD following assault develop persistent posttraumatic stress symptoms. These symptoms may meet partial or full criteria for PTSD and can be most disruptive to normal life. They may persist for months, if not years, after the original assault. Patients with PTSD experience difficulties in interpersonal, intimate relationships and may develop a variety of phobic behaviors, including agoraphobia, which prevent participation in many job-related activities as well as social activities that were once experienced as enjoyable. The possibility of an intense and prolonged stress response should be discussed with the assaulted patient so that he or she may understand different signs and symptoms of stress and seek appropriate help when needed. The development of a posttraumatic stress response needs evaluation and discussion with all victims of assault or abuse, including stranger assault. In forms of assault that are recurrent, e.g., domestic violence and elder abuse, the evaluation of emotional status is more complicated. Three additional areas must be evaluated: (a) the specific coping mechanisms being used, (b) the presence or absence of a serious psychiatric disorder, and (c) the potential for suicidal or homicidal behaviors. Each of these provides vital information for assessing a person's functional ability as well as the intensity of the strain on coping skills. The assessment of coping skills in victims of assault or abuse can be determined during the collection of the basic clinical history with a few additional questions ( Table 125.8). The other two categories require assessment by a mental health professional who is knowledgeable about the adaptive and psychologic sequelae following chronic victimization and battering.

Table 125.8. Assessment of Coping Skills

The need to use a mental health professional with clinical experience and familiarity with the research in domestic violence and elder abuse cannot be overestimated. Victim's emotional responses are all too frequently misinterpreted using standard psychologic and psychiatric techniques without considering what would be a normative response to the most serious stress of chronic victimization. Research has demonstrated that battered and abused people respond to domestic stress much like other individuals in life-threatening situations. Studies with both civil disasters and war victims have indicated that, during the impact phase when the threat of danger is perceived as a reality, victims respond with feelings of shock, denial, disbelief, and fear. Confusion and dazed apathetic behaviors are common. Theorists have offered the explanation that, as the level of danger increases, new defensive strategies are used that increasingly involve an internal focus with decreased external activity and appearance of extreme apathy. This phenomenon has been noted repeatedly among crime victims. Adult victims of domestic violence and elder abuse also demonstrate most, if not all, of these same reactions. In the absence of a clear history and clinical experience with disaster victims, however, victims of domestic violence and elder abuse are often misdiagnosed and improperly treated. SUICIDE RISK IN DOMESTIC VIOLENCE Victims of domestic violence and elder abuse must be evaluated for suicidal and homicidal potential. One of every 10 battered women attempts suicide. Of those, 50% try more than once. Another way of expressing the risk of suicide among victims of domestic violence is that 26% of all female suicide attempts are preceded by physical abuse. This is even higher among black women, for whom 50% of all suicide attempts are preceded by abuse. Although empirical studies have not been carried out regarding the likelihood of suicidal or homicidal behavior among victims of elder abuse, it should be noted that the age group at highest risk for successful suicide is the elderly population (over 65 years of age). Therefore, this becomes a most important area of assessment in elderly patients. Both adult victims of domestic violence and victims of elder abuse can also have serious psychiatric disorders independent of the experience of having been clinically abused. It is important to diagnose and treat these major psychiatric disorders in this population because appropriate treatment will aid the individual in gaining more control and enhanced coping abilities. Nonetheless, one cannot overemphasize the need to be careful regarding specific psychiatric diagnoses: In the assaulted and abused adult, it is easy to misinterpret symptoms that occur secondary to the severe stress of chronic, unremitting battering or abuse and attribute them to other disorders.

INITIAL STABILIZATION AND MANAGEMENT Step 4. Determine Risk to the Abused or Assaulted Patient In recurrent forms of abuse or assault, it is essential to assess the patient's need for protection from further abuse. For women who are being battered in the home, it is essential not only to assess the risk for the woman herself, but also to determine if she has children and if they are at heightened risk for physical abuse. Table 125.9 lists risk factors associated with increased injury or death.

Table 125.9. Risk Factors for Escalating Violence

The most immediate need for the battered woman and her children may be for an immediate, safe shelter that provides protection from the batterer. The act of revealing to health care professionals that she has been battered may increase her risk of being severely battered on return to her home. The woman herself is the best judge of how dangerous it would be for her to return immediately. Most community organizations working with adult victims of domestic violence maintain shelters at undisclosed locations. Hotline workers can help the woman gain access to a shelter. Unfortunately, there are insufficient shelters in the United States; hence, if the shelters are filled, one should not overlook the battered woman's friends and relatives as potential resources. Hotel rooms also can be used to provide temporary shelter for women at high risk. With elderly patients who are being abused or neglected, it is essential to involve the social service department in the hospital to assess the patient's home environment and determine the resources available for the patient and the caregiver. Step 5. Determine the Need for Legal Information The legal systems for providing aid to adult victims of domestic violence and victims of elder abuse have developed independent of each other. Systems for battered women are targeted toward protecting the woman against further abuse, but in most states do not involve mandated reporting. However, laws requiring mandated reporting are being enacted increasingly on a state-by-state basis; therefore, it is necessary to ensure that ED policies and procedures are consistent with local laws regarding the reporting of suspected domestic violence. Table 125.10 outlines the protocol for determining the need for legal information for victims of domestic violence.

Table 125.10. Assessment of Legal Needs

Almost all states in the United States have responded aggressively and enacted legislation designed to protect victims of domestic violence. The battered woman can use the civil laws for protection against abuse or institute criminal action. Alternatively, she can initiate both civil and criminal actions. The protection against abuse laws provide the opportunity for a woman to obtain a court order stating that the abuser cannot come near her or her property. The court order also can indicate that

the batterer must stay away from her place of work. The court order does not give the batterer a criminal record; violation of the order does. Should the batterer appear at the woman's home or directly threaten her, she can call the police, who theoretically can then arrest the batterer and file criminal charges. A Protection Against Abuse Order is sufficient to provide the necessary structure to protect the battered woman in some instances. In other instances, it helps not at all. The batterer may be so violent that he escalates his attack on finding out that a court protection order has been obtained. He may break through doors or windows, hide in closets with weapons and so on to gain access to the woman. When under such direct attack, it may be impossible for the woman to call the police. In such instances, it is helpful for the battered woman to speak to neighbors and ask them to call the police if the batterer is seen near the property or if trouble is feared. Children can be instructed to dial 911. Assault is a crime whether it occurs in the street or in the privacy of a person's home. Hence, battered women can choose to petition the district attorney's office to initiate criminal charges against the batterer. This can be done in tandem with a Protection Against Abuse Order. The risk to the battered woman may be great unless the batterer is held in jail pending trial; however, the more frequent scenario, is a pretrial hearing, bail set, and the man released on bail. Hence, the batterer once again has access to the woman. The batterer's rage over facing criminal charges may be great, thereby significantly increasing the woman's risk. The decision to initiate criminal charges against a batterer should be discussed with community experts on domestic violence, and activity should be carefully coordinated to ensure that the woman will be safe. There is no federal legislation to define the problem of elder abuse. Consequently, each state has established its own definition and reporting mechanism. Emergency physicians need to become familiar with the legislation regarding elder abuse and adult protective services in their state ( 50). Adult protective services may be able to offer significant resources to older adults with clear or suspected impairments in states with mandatory or voluntary reporting. Elderly patients seen in the ED frequently have medical problems that require increased home support for convalescence. Social work staff members can assess family and community services and arrange for additional skilled help when necessary. EDs should have directories of community resources available for referral ( 50). Printed material for victims and potential victims of domestic violence and elder abuse to read should be available in the waiting room, as well as in the bathrooms, where they can be privately and discreetly accessed. For all adult victims of domestic violence, the value in providing the patient with concrete information, including names and phone numbers, cannot be overemphasized. Most communities have staff members associated with Women Against Abuse, Women in Crisis, and community agencies working with the abused elderly, who can provide legal counseling and advocacy. These resources are of enormous value to abused patients who might not use the resource immediately after an ED visit, but may find a need for services later. Step 6. Develop a Follow-Up Plan This process takes considerable time in the ED setting, yet it is essential if a serious effort is to be directed toward interrupting the cycle of violence and minimizing, if not preventing, future violence. Physicians need to be aware of the community resources that can provide safety, advocacy, and support for victims of violence. Table 125.11 outlines the essential tasks. Because of the interrelationship between a woman's being battered in the family system and a heightened risk of child abuse in the home, there must be a coordinated effort between the ED team working with battered women and the institutionalized system for reporting and intervening in cases of suspected child abuse.

Table 125.11. Follow-Up Planning for Victims of Domestic Violence

With elder abuse, unless there is a life-threatening injury or imminent danger of serious harm, the proper evaluation can be performed by the primary physician with the assistance of the official state adult protective services program. A report of suspected elder abuse or neglect usually triggers an unannounced visit to the home of the elderly person with the goal of substantiating whether abuse or neglect have occurred and determining which services might benefit the patient in their home environment. Step 7. Document Findings and Recommendations in the Medical Record The medical record is an invaluable document for all adult victims of assault or abuse. The documentation of the patient's injuries and emotional status may assist victims seeking orders of protection or prosecution of their assailants. The medical record should include verbatim descriptions of events, drawings or photographs of injuries, and a full-body examination for the location and size of skin lesions.

PITFALLS 1. Avoid blaming the victim. Battered women are a heterogeneous group and do not have a characteristic profile of psychologic features that lead them to victimization. 2. Do not assume that the situation is less serious if the woman abuses drugs or alcohol. Battered women are at 16 times the risk of abusing alcohol and at 9 times the risk of abusing drugs compared with women who are not battered. The abuse of substances by battered women is most frequently a secondary problem precipitated by chronic battering and victimization. 3. Do not expect a “quick fix.” The entrapment by the batterer is considerable from both an emotional viewpoint and an economic one. Children in the home may make it even more difficult for the battered woman to extricate herself from the situation. Early in the process, the woman experiences shock and disbelief that the man who loves her could do such things to her. Coping skills during this phase of the relationship are hence directed toward decreasing the violence while preserving the relationship. This coping strategy is doomed to fail because the victim has no control over the batterer's violence. At a point when the woman perceives that she cannot control the batterer's violence, her coping strategy shifts toward the development of escape skills. Battered women have been found to be at greatly increased risk for injury or death when they decide to leave the batterer once and for all. The persistence and violence of the batterer's effort to maintain contact with the woman makes leaving most difficult. Health care professionals should not give up if the battered woman does not leave immediately. The process of leaving is difficult, dangerous, and frightening. Continued support through the escape phase is essential, and women who do not leave immediately should not be viewed as noncompliant. 4. Do not dismiss signs of elder abuse as evidence of the aging process. Poor nutrition, multiple bruises, and injuries may well be physical markers suggesting that the patient is receiving inadequate and abusive care. Patterns of injury as well as patterns of medical relapse should be examined carefully to ensure that abuse or neglect is not the cause. Frequent exacerbations of medical illness may indicate that the patient is not being provided with needed medication. These findings in the elderly do not definitively “prove” the presence of abuse, but should be signals for initiating a thorough and careful social service evaluation to determine if there are patterns of abuse or neglect in the elderly person's life.

NATIONAL CONTACTS

National Coalition Against Domestic Violence, P.O. Box 18749, Denver, Colorado 80218; 303-839-1852. National Aging Resource Center on Elder Abuse, 810 First Street, NE, Suite 500, Washington, DC 20002-4205; 202-682-2470. National Domestic Violence Hotline: 800-799-SAFE; 24-hour counseling, crisis assistance, and linkage to local domestic violence agency. National Hotline for the Hearing Impaired: 800-787-3224. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50.

U.S. Department of Justice, Federal Bureau of Investigation. Uniform crime reports: crime in the United States, 1994. Washington, DC: U.S. Department of Justice, 1995. Wilt S, Olson S: Prevalence of domestic violence in the United States. J Am Med Wom Assoc 1996;51:77–82. Straus MA, Gelles RJ, Steinmetz SK: Behind closed doors: violence in the American family. Garden City, New York: Doubleday Anchor Press, 1980. Straus MA, Gelles RJ: Societal change and changes in family violence from 1975 to 1985 as revealed by two national surveys. J Marriage Fam 1986;48:465–479. Steinmetz S: “The battered husband syndrome.” Victimology: An Internat J 1977;2:499–509. Pillemer K, Finkelhor D: The prevalence of elder abuse: a random sample survey. Gerontologist 1988;28:51–57. U.S. Congress, House Select Committee on Aging, Subcommittee on Health and Longterm Care. Elder abuse: a Decade of shame and inaction. 101st Congress, second session, 1990. American Medical Association. Diagnostic and treatment guidelines on elder abuse and neglect. Chicago: AMA, 1992. Kosberg JI: Preventing elder abuse: identification of high risk factors prior to placement decisions. Gerontologist 1988;28:43–50. Stark E, Flitcraft AH: “Spouse abuse.” In: Surgeon General's workshop on violence and public health source book. Leesburg, Virginia. October 27–29, 1985. Washington, DC: National Center on Child Abuse and Neglect, 1985. Flitcraft A: Battered women: an emergency room epidemiology. M.D. thesis. New Haven, CT: Yale School of Medicine, 1977. McLeer SV, Anwar R: A study of battered women presenting in an emergency department. Am J Public Health 1989;79:65–66. Abbott J, Johnson R, Koziol-McLain J, et al: Domestic violence against women: incidence & prevalence in an emergency department population. JAMA 1995;273:1763–1767. Dobash RE, Dobash RP: The case of wife beating. J Fam Issues 1981;2:439–470. Walker LE: The battered woman's syndrome. New York: Springer, 1984. Berrios DC, Grady D: Domestic violence: risk factors and outcomes. West J Med 1991;155:133–135. Stark E, Flitcraft AH: Wife abuse in the medical setting: Introduction for health personnel. Monograph #7. Washington, DC: Office of Domestic Violence, 1981. McFarlane J, Parker B, Soeken K, et al: Assessing for abuse during pregnancy: severity & frequency of injuries & associated entry into prenatal care. JAMA 1992;267:3176–3178. Stewart DE, Cecutti A: Physical abuse in pregnancy. Can Med Assoc J 1993;149:1257–1263. Browne A: When battered women kill. New York: MacMillan/Free Press, 1987. Capezuti E: Preventing elder abuse and neglect. In: Lavizzo-Mourey R, Day S, Diserens D, et al. eds. Practicing prevention for the elderly. Philadelphia: Hanley & Belfus, 1989;167–181. Fulmer T, McMahon DJ, Baer-Hines M, et al: (1992) Abuse, neglect and abandonment: an analysis of all elderly patients seen in one emergency department during a six-month period. J Emerg Nurs 1992;18:505–510. Stark E, Flitcraft A, Frazier W: Medicine and patriarchal violence: the social construction of a private event. Int J Health Serv 1979;9:461–493. Hilberman E, Munson K: Sixty battered women. Victimology: An Internat J 1978;2:460–470. Kurz D: Emergency department responses to battered women: resistance to medicalization. Soc Problems 1987;34:69–81. Issac NE, Sanchez RL: Emergency department response to battered women in Massachusetts. Ann Emerg Med 1994;13:855–858. McFarlane J, Greenberg L, Weltge A, et al: Identification of abuse in emergency departments: effectiveness of a two-question screening tool. J Emerg Nurs 1995;21:391–394. Olson L, Anctil C, Fullerton L, et al: Increasing emergency physician recognition of domestic violence. Ann Emerg Med 1996;27:741–746. McLeer SV, Anwar RAH, Herman S, et al: Education is not enough: a system's failure in protecting battered women. Ann Emerg Med 1989;18:651–653. Hughes HM: Psychological and behavioral correlates of family violence and child witnesses and victims. Am J Orthopsychiatry 1988;58:77–90. Jaffe PG, Wolfe DA, Wilson SK: Children of battered women: development, clinical psychology and psychiatry. Newbury Park, CA: Sage Publications, 1990. Wolfe DA, Jaffe, P, Wilson S, et al: Children of battered women: the relation of child behavior to family violence and maternal stress. J Consult Clin Psychol 1985;53:657–665. Sternberg KJ, Lamb ME, Greenbaum C, et al: Effects of domestic violence on children's behavior problems & depression. Dev Psychol 1993;29:44–52. Jouriles EN, Norwood WD: Physical aggression toward boys and girls in families characterized by the battering of women. J Fam Psych 1995;9:69–78. Bowker LH: On the relationship between wife-beating and child abuse. In: Yillo K, Bograd M, eds. Feminist perspectives on wife abuse. Beverly Hills, CA: Sage 1988;158–174. Stark E, Flitcraft A: Women-battering, child abuse and social heredity: what is the relationship? Sociological Rev Monograph 1985;31:147–171. Stark E, Flitcraft A: Violence among intimates: an epidemiological review. In: Van Hasselt V, Morrison RL, Bellack AS, Hersen M, eds. Handbook of family violence. New York: Plenum Press, 1988;293–317. Callahan JJ: Elder abuse: some questions for policy makers. Gerontologist 1988;28:453–458. Appleton W: Elder abuse: diagnose, treat, cure. Ann Emerg Med 1988;17:1104–1105. Rathbone-McCuan E, Voyles B: Case detection of abused elderly parents. Am J Psychiatry 1982;139:189–192. Rosenblatt DE, Cho KH, Durance PW: Reporting mistreatment of older adults: the role of physicians. J Am Geriatric Soc 1996;44:65–70. Beth Israel Hospital Elder Assessment Team: An elder abuse assessment team in an acute hospital setting. Gerontologist 1986;26:115–118. Fulmer T: Toward the development of a social policy statement on elder abuse. OASIS 1988;5:1–3. Jones J, Dougherty J, Schelble T, et al: Emergency department protocol for the diagnosis and evaluation of geriatric abuse. Ann Emerg Med 1988;17:1006–1015. Lach MS, Pillemer K: Abuse and neglect of elderly persons. New Engl J Med 1995;332:437–443. Aravanis SC, Adelman RD, Breckman R, et al: Diagnostic and treatment guidelines on elder abuse and neglect. Chicago: AMA, 1992;1–42. American Medical Association Council on Scientific Affairs: Elder abuse and neglect. JAMA 1987;257:966–971. Lachs MS, Fulmer T: Recognizing elder abuse and neglect. Clin Geriatric Med 1993;9:665–681. American Psychiatric Association: Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC: American Psychiatric Association, 1994. Jones JS: Elder abuse and neglect: responding to a national problem. Ann Emerg Med 1994;23:845–848.

Suggested Readings American Medical Association: Diagnostic and treatment guidelines on domestic violence. Chicago: AMA, 1992;1–19. American Medical Association: Diagnostic and treatment guidelines on elder abuse and neglect. Chicago: AMA, 1992. Berry DB: Domestic violence sourcebook: everything you need to know. Ralph Lowe Publisher, 1996. Davidhizar R: Elder abuse: the American experience. Elder Care 1997;9:12–14. Jones JS, Holstege C, Holstege H: Elder abuse and neglect: understanding the causes and potential risk factors. Am J Emerg Med 1997;15:579–583. Jones JS, Veenstra TR, Seamen JP: Elder mistreatment: National survey of emergency physicians. Ann Emerg Med 1997;30:473–479. Kleinschmidt KC: Elder abuse: a review. Ann Emerg Med 1997;30:463–472. Kurz D: Emergency department responses to battered women: resistance to medicalization. Soc Problems 1987;34:69–81. McLeer SV, Anwar RAH: The role of the emergency physician in the prevention of domestic violence. Ann Emerg Med 1987;16:1155–1161. Pillemer K, Finkelhor D: The prevalence of elder abuse: a random sample survey. Gerontologist 1988;28:51–57. U.S. Department of Justice, Federal Bureau of Investigation. Uniform crime reports: crime in the United States, 1994. Washington, DC: U.S. Department of Justice, 1995.

Chapter 126.1 Approach to the Pediatric Emergency Patient Principles and Practice of Emergency Medicine

CHAPTER 126 EVALUATION

1 Approach to the Pediatric Emergency Patient Thom A. Mayer, Robert C. Luten and Michael F. Altieri The Patient: Recognition of Serious Illness The At-Risk Child The Process: Role of Observation Importance of Close Follow-Up

THE PATIENT: RECOGNITION OF SERIOUS ILLNESS Of the thousands of children that an emergency physician sees each year, the primary task is to pick out the children with potentially serious disease from this otherwise undifferentiated group of patients. Equally important, emergency physicians must be able to recognize when specific pediatric patients are beginning to deteriorate into shock or respiratory failure, requiring immediate intervention to stop the progression toward cardiopulmonary arrest. Shock and respiratory failure are the primary syndromes responsible for death or permanent disability of children ( 1,2).

THE AT-RISK CHILD The at-risk child has an illness or injury of such nature or magnitude that the potential exists for progression to a serious outcome if left untreated. For example, most patients presenting to the emergency department (ED) with diarrhea and dehydration are not critically ill. Some, however, present with such severity or duration of symptoms that they fall into the category of at-risk children because their disease can progress further toward a shock syndrome. Several types of children can easily be excluded from the at-risk category. Children with minor illnesses or injuries who are active, alert, and interacting appropriately with their parents are one example. At the opposite end are children who are obviously critically ill and may in fact be moribund. These children not only are easily recognized, but also usually have appropriate early interventions because of the severity of their illnesses or injuries. An additional group that can be excluded from the at-risk category are patients who might initially appear well, but are at risk because of serious diseases or risk factors. In most cases, these children can be recognized easily on the basis of their history or clinical presentation. For example, a child with factor VIII deficiency who falls several feet onto his or her side is clearly at risk regardless of how active and alert he or she may be during the initial clinical presentation. Similarly, whatever the level of activity or dehydration, a child under 8 weeks of age with even a low-grade fever is widely recognized as being at risk, regardless of the initial clinical presentation ( 3). The key to this concept is recognizing that any disease process in a child is a part of a natural progression. Although most children with infectious diseases, including gastroenteritis, appear only mildly ill, the potential progression of the patient and the duration and severity of the symptoms are such that these children may develop frank shock or respiratory failure, or even progress to cardiopulmonary arrest. In general, patients who are categorized by emergency physicians as at risk generally fall into one of three categories: 1. A common, usually benign disease, such as gastroenteritis, that can rapidly progress to a more severe form with severe dehydration and shock. For these patients, early recognition of the disease is critical with appropriate interventions to interrupt the disease cycle and its further progression. 2. An early form of a potentially serious disease. The child appears ill from a clinical standpoint and requires further diagnostic efforts to clarify whether a potentially serious disease is present. For example, patients with meningitis fall into this category, in which observation and specific diagnostic tests, in this case a lumbar puncture or computed tomography scan are necessary. An additional example are patients considered at risk because of an early form of a serious disease, including the group with so-called “occult bacteremia.” 3. Children who initially appear clinically ill, but in whom the possibility of a serious disease can be ruled out by additional observation and evaluation. One example would be children who initially appear fussy or lethargic and, therefore, receive blood tests and a lumbar puncture to rule out meningitis. An additional example would be children with inspiratory stridor, in whom a lateral neck radiograph is necessary to rule out epiglottitis. One concept essential to the evaluation of ill and injured children is ensuring that a systematic approach is taken to every pediatric patient. For example, experienced emergency physicians are well aware that careful observation of the vital signs in the initial evaluation of the patient can be critical. The dictum, “It takes evaluation of 1000 normal children to recognize 1 abnormal child” is valid for the emergency physician ( 4). Judicious observation of children can be extremely helpful in distinguishing children at risk from otherwise undifferentiated pediatric patients in the ED. McCarthy has described a technique referred to as “optimal observation,” in which febrile infants are given antipyretics to lower temperature and then placed in the lap of the mother and reevaluated. The scale developed by McCarthy et al. allows the clinician to quantify the interaction of the patient with the environment. This has been found to correlate with the risk of severe infectious diseases, including occult bacteremia and meningitis ( 5,6 and 7).

THE PROCESS: ROLE OF OBSERVATION Studies have shown that observation of the acutely ill child may be more predictive of serious disease than are historical variables ( 6,7 and 8). More important, continued observation and reevaluation of the pediatric patient is essential in providing optimal care. Although this is also true for adult patients, the degree to which ongoing observation is necessary for pediatric emergency care is much more dramatic than for adult emergency medicine. Thus, the observation process in pediatric emergency medicine is concurrent but discrete from elements of the history, physical examination, and laboratory tests.

IMPORTANCE OF CLOSE FOLLOW-UP It is essential to recognize that the role of follow-up care for patients discharged from the ED is accentuated in pediatric patients, particularly among those on the borderline between undifferentiated pediatric patients and those at risk. For example, if a mildly dehydrated child presents to the ED who tolerates oral fluids well and defervescence occurs during the stay in the ED, it is appropriate to discharge the child with instructions for close observation at home. The ongoing observation and response to therapy in such a child is critical, however, because the dehydration may progress if the child is vomiting and unable to tolerate oral fluids at home. For this reason, it is important to have close telephone follow-up and ensure that the family understands the need for follow-up medical care during the following 12 to 24 hours or sooner if there is rapid deterioration. Equipment Needs An additional aspect of pediatric emergency care that differs from adult emergency care is the equipment need for optimal care of the child and weight-per-kilogram medication dosing (see Appendix B). In addition, the size of equipment used during a cardiopulmonary resuscitation depends on the child's age and/or size. For that reason, researchers have sought an alternate way to ensure appropriate medication dosages and equipment sizes during the acute care of children. Recognizing the correlation between length and lean body mass, a multicenter study was taken to compare the correlation in pediatric emergency patients between length and the child's total mass. This correlation was found to be highly significant and paved the way for development of the Broselow length-based resuscitation system ( 9). Simply stated, the correlation between lean body weight and length allows calculation of appropriate drug dosages according to the child's overall length. In addition, appropriate equipment sizes can be calculated according to the child's overall length, with considerable overlap among children of the same general size. Application of this logic in the operating suite setting has shown a strong correlation between the tube size selected by the Broselow system and that which would be selected by an experienced anesthesiologist ( 10). In addition, study of field and ED resuscitations indicate a high correlation between the Broselow length-based system and the medication and equipment that would be selected if there were sufficient time to allow weights and measurements to be taken (TA Mayer, October 1991, Presentation to AAP Annual Mtg., Boston, MA).

Because of its simplicity and accuracy, the length-based resuscitation system should be used in all general EDs. Special equipment should also be available ( Table 126–1.1).

Table 126–1.1. Equipment Needs in Pediatric Emergency Medicine: Pediatric Equipment Checklist

References 1. Halton N, et al: Routine emergency department use for sick care for children in the U.S. Pediatrics 1996;98:28. 2. Mayer TA: Diagnosis and treatment of hemorrhagic shock. In: Harwood Nuss A, Linden C, Luten RC, et al. eds. The clinical practice of emergency medicine. Philadelphia: JB Lippincott, 1991;814. 3. McLellan D, Giebink GS: Perspectives on occult bacteremia in children. J Pediatr 1986;109:18. 4. Mayer TA: Approach to the pediatric multiple trauma patient. In: Harwood Nuss A, Linden C, Luten RC, et al., eds. The clinical practice of emergency medicine. Philadelphia: JB Lippincott, 1991;800. 5. McCarthy PL, Jekel JF: Further definition of history and observation variables in assessing febrile children. Pediatrics 1981;67:5. 6. McCarthy PL: Controversies in pediatrics: what tests are indicated for the child under two with fever? Pediatr Rev 1979;1:2. 7. McCarthy PL, Sharpe MR, Spiesel SZ, et al: Observation scales to identify serious illness in febrile children. Pediatrics 1982;70:802. 8. McCarthy PL, Lembo RM, Fink HD, et al: Observation, history, and physical examination in diagnosis of serious illness in febrile children £ 24 months. J Pediatr 1987;110:26. 9. Lubitz VS, Seidel JS, Chameides L, et al: A rapid method for estimating weight and resuscitation drug dosages from length in the pediatric age group. Ann Emerg Med 1988;17:576. 10. Luten RC, Wears RL, Broselow J, et al: Length-based endotracheal tube size for pediatric resuscitation. (Abstract) Ann Emerg Med 1990;19:476.

Chapter 126.2 Altered Mental Status in Children Principles and Practice of Emergency Medicine

CHAPTER 126 EVALUATION

2 Altered Mental Status in Children Daniel J. Isaacman Capsule

CAPSULE The child presenting with an altered mental status is one of the most distressing situations in pediatric emergency medicine. Although many of the causes of coma in the infant and child are similar to those in adults, some are unique to the pediatric age group. Table 126–2.1 illustrates the mnemonic commonly used to recall those etiologies responsible for adult coma. “Pediatric diagnoses” that must be added to this list include ingestion, lead encephalopathy, child abuse, intussusception, ketotic hypoglycemia, Reye's syndrome, and inborn errors of metabolism.

Table 126–2.1. TIPS from the Vowels (AEIOU)

The differential diagnosis of altered mental status changes with age. Table 126–2.2 lists the common diagnostic considerations by age.

Table 126–2.2. Common Considerations of Altered Mental Status at Various Ages

Although a complete history and physical examination should eventually be done, the urgency of the situation demands a rapid, organized approach to determine the immediate severity of the illness and to identify a rapidly remediable condition. Laboratory testing should be tailored to the history and physical obtained. The approach to the child presenting with altered mental status is illustrated in Figure 126–2.1.

Figure 126–2.1. Altered Mental Status.

Approach to the child with altered mental status: 1. The best and most universal way of quantifying this alteration is through the application of the Glasgow coma scale, an ordinal scale based on numerical scores given for best eye opening, verbal response, and motor response. In preverbal children an alteration of the verbal score is frequently made to reflect the neurologic immaturity of the child. 2. Signs of herniation in children include a unilateral dilated pupil (uncal herniation), alterations in respiratory pattern, and either decorticate or decerebrate posturing. The complete Cushing's triad (hypertension, bradycardia, and an altered respiratory pattern) is often a late finding. 3. Signs of increased intracranial pressure include headache, vomiting, high pitched cry, bulging fontanelle, and difficulty with balance. 4. Computed tomography (CT) scans in patients with suspected trauma can be done without contrast. A good fundoscopic examination should be performed prior to CT scan to look for retinal hemorrhages, a physical finding suggestive of child abuse. 5. Nuchal rigidity is a reliable sign of meningitis only in children 18 months of age or older. In younger children, the clinical signs of meningitis are based more on the general appearance of the child and include irritability, lethargy, high pitched cry or ful/bulging fontanelle. 6. Glucose should be given either as 4 m/kg of D25 or 10 m/kg of D10. D50 should not be used in infants and young children because of its high osmotic load. 7. Response to naloxone does not necessarily confirm the presence of opiates. Naloxone can also temporarily reverse the sedation caused by other agents. 8. For the vast majority of ED cases, noncontrast CT scans should suffice for adequate visualization. Those cases, which merit additional resolution, are best visualized using magnetic resonance imaging (MRI). 9. Laboratory results that may be useful include: toxicology screens (suspected ingestion), arterial blood gases (concern regarding anoxic injury), electrolytes

(helpful when patient has altered intake or output by history), glucose (suspected diabetic ketoacidosis or hypoglycemia), liver function tests (hepatic encephalopathy from infectious causes or Reye's syndrome), serum ammonia level (Reye's syndrome or suspected metabolic defect), serum organic or amino acids (metabolic defect). Rectal exam should be performed in all patients under 2 years of age (intussusception). Lead levels and free erythrocyte protoporphyrin levels and abdominal flat plates should be considered in patients with a history of pica and in patients living in older dwellings (lead intoxication). Hemoglobin and hematocrit should be considered in any patient with suspected acute blood loss. 10. Chronic subdurals without antecedent history of trauma should prompt the investigation of child abuse. Selected Readings Choi SC, Barnes TY, Bullock R, et al: Temporal profile of outcomes in severe head injury. J Neurosurg 1994;81:169–173. Davis RL, Mullen N, Makela M, et al: Cranial computed tomography scans in children after minimal head injury with loss of consciousness. Ann Emerg Med 1994;24:640–645. Kraus J, Fife D, Conroy C: Pediatric brain injuries: the nature, clinical course, and early outcomes in a defined United States population. Pediatrics 1987;79:501–507. Levin HS, Aldrich EF, Saydjari C, et al: Severe head injury in children: experience of the Traumatic Coma Data Bank. Neurosurgery 1992;31:435–443. Mahoney WJ, D'Souza BJ, Haller JA, et al: Long term outcome of children with severe outcome and prolonged coma. Pediatrics 1983;71:756–762. Morray J, Tyler D, Jones T: Coma scale for use in brain-injured children. Crit Care Med 1984;12:1018–1020. Seshia S, Johnston B, Kasian G: Non-traumatic coma in childhood: clinical variables in prediction of outcome. Dev Med Child Neurol 1983;25:493–501.

Chapter 127.1 Neonatal Resuscitation and Selected Neonatal Emergencies Principles and Practice of Emergency Medicine

CHAPTER 127 RESUSCITATION

1 Neonatal Resuscitation and Selected Neonatal Emergencies Kent F. Argubright and Kristi Watterberg Capsule Resuscitation Cardiopulmonary Transition Apnea Neonatal Thermoregulation Seizures Resuscitative Equipment Medications Resuscitation Procedures Special Problems The Premature Neonate Techniques Other Neonatal Emergencies

CAPSULE Principles of pediatric advanced life support (ALS) important in the organized approach to neonatal resuscitation, include basic ABCs, venous access, warmth, dextrose, cultures; and antibiotics, fluids, and naloxone hydrochloride, if needed. The most common situation requiring neonatal resuscitation in the emergency department (ED) is a precipitous delivery before or after arrival. These neonates usually require simple resuscitative measures. Neonates who are the product of a planned home delivery are brought in because of failure to respond to simple resuscitative efforts. These infants often suffer severe respiratory and circulatory depression. Rapid and appropriate action on the part of the emergency physician is needed in such cases. Resuscitative efforts should not be withheld because of prolonged depressed states or prematurity.

RESUSCITATION Table 127–1.1 demonstrates survival-rate improvement from 1978 to 1991. According to the National Institute of Child Health, during 1991 and 1992 the overall survival for infants weighing 501 to 1500 g at birth was 81%, compared with 74% in 1987 and 1988. The survival rates were 44% at birth weight 501 to 750 g; 81% at 751 to 1000 g; 92% at 1001 to 1250 g; and 95% at 1251 to 1500 g. Female infants had a significantly greater chance of surviving than did male infants at similar birth weights and gestational ages. Major morbidity increased with decreasing birth weight and included late-onset septicemia 22%, chronic lung disease (oxygen dependence at 36 weeks' corrected age) 18%, severe intraventricular hemorrhage (grades III and IV) 11%, and necrotizing enterocolitis 5%. Twelve percent of all infants were treated with corticosteroids for chronic lung disease, including 36% of infants who were oxygen dependent at age 28 days ( 1).

Table 127–1.1. Weight-Specific Survival Rates (%) in the University of New Mexico Hospital Newborn Intensive Care Unit

CARDIOPULMONARY TRANSITION Birth requires dramatic changes in cardiopulmonary function. Inflation of the lungs and rearrangement of the central circulatory pathways must take place to ensure successful oxygenation and an appropriate acid–base balance ( 2). The primary site of oxygenation in the fetus is the placenta. Approximately 40% of the fetal cardiac output flows out of the umbilical arteries from the fetal descending aorta to the placenta. This blood is oxygenated and returns to the fetus by way of the umbilical vein. Disruption of fetal respiratory gas exchange or oxygen transport can occur at several sites in this pathway. They include inadequate maternal uterine blood flow (e.g., maternal hypotension or uterine artery vasospasm), inadequate diffusion from the maternal circulation to the fetal circulation (e.g., abruption, placental insufficiency), or inadequate fetal transport (e.g., fetal anemia, cord occlusion). The fetal circulation ( Fig. 127–1.1) depends on several right-to-left shunts. Oxygenated blood returning through the umbilical vein passes through the portal vein and into the inferior vena cava (IVC) by way of the ductus venosus. On entering the right atrium, this blood is directed through the foramen ovale to the left atrium. Deoxygenated blood returning by the superior vena cava (and a fraction by the IVC) passes from the right atrium to the right ventricle and out of the pulmonary artery. Only a small portion of this blood enters the pulmonary circulation, whereas the majority passes through the ductus arteriosus to the descending aorta. Pulmonary vascular resistance (PVR) in the fetus is high secondary to pulmonary vasoconstriction. Because of the relatively low resistance of the placental vascular bed, systemic vascular resistance (SVR) in the fetus is low. This differential (PVR >> SVR) shunts blood away from the pulmonary circulation through the ductus arteriosus to the descending aorta and out to the placenta. The fully developed fetal lung at term contains thousands of alveoli in close approximation to pulmonary capillaries. These alveoli contain adequate amounts of surfactant to maintain alveolar patency once ventilation and respiration begin ( 3). The fetal lung at term contains approximately 100 to 120 mL of fluid. Birth initiates the cardiopulmonary changes necessary for neonatal survival ( Fig. 127–1.2). Pulmonary fluid is expelled through the mouth and nose as the fetus passes down the birth canal. Residual fluid is forced down the airways with the infant's initial breaths and is absorbed from the alveoli by the interstitial lymphatics. With the onset of regular respirations, functional residual capacity is established and oxygen tension rises. Expansion of the lungs causes PVR to decrease. Increasing umbilical vessel occlusion (by either cord clamping or vasospasm) initiates conversion from fetal to neonatal circulatory patterns. Cutaneous vasoconstriction augments this increase in SVR. Over the following days, oxygenation results in closure of the ductus arteriosus. The left and right atrial pressures gradually equalize, and the foramen ovale closes. The neonate converts to a circulatory pattern consistent with survival in its new air-breathing state.

Figure 127–1.1. Fetal circulation. Oxygenated blood from the placenta (a) enters the inferior vena cava (b) and preferentially passes through the foramen ovale (c). This mixes with a small amount of blood from the pulmonary veins (d) and passes to the left ventricle (e) and out the ascending aorta. Deoxygenated blood returning from the brain and upper body (f) enters the right atrium from the superior vena cava, passes through the right ventricle to the ductus arteriosus and the descending aorta. Only a small amount of this flow enters the pulmonary artery (g). (Reproduced with permission from Sciarra JJ, Eschenbach DA, eds. Gynecology and obstetrics: maternal-fetal medicine, rev ed. Philadelphia: Harper & Row, 1983;3:2.)

Figure 127–1.2. Neonatal circulation. With expansion of the lungs (a), pulmonary vascular resistance (PVR) diminishes and pulmonary flow increases. Occlusion of the umbilical arteries (b) causes systemic vascular resistance (SVR) to increase. Right and left atrial pressures equilibrate, causing functional closure of the foramen ovale (c). Continued oxygenation maintains this flow pattern and causes the ductus arteriosus (d) to close. (Reproduced with permission from Sciarra JJ, Eschenbach DA, eds. Gynecology and obstetrics: maternal-fetal medicine, rev ed. Philadelphia: Harper & Row, 1983;3:2.)

These patterns of circulatory change all depend on the establishment of adequate ventilation. If it is disrupted or prevented, fetal circulatory patterns persist or resume. Persistent fetal circulatory patterns may be seen in the neonate with birth asphyxia or meconium aspiration syndrome. Asphyxia causes PVR to remain elevated; this results in diminished pulmonary flow, which causes further hypoxia and acidosis and maintains the patency of fetal shunts (i.e., foramen ovale and ductus arteriosus). A vicious cycle is initiated. Fetal acidosis and hypoxia result in a pattern of persistent pulmonary hypertension and circulatory shunting, which prolongs and even worsens acidosis and hypoxia ( Fig. 127–1.3).

Figure 127–1.3. Asphyxia-induced circulatory pattern. Poor lung expansion (a) leads to hypoxia, acidosis, and increased pulmonary vascular resistance (PVR), causing diminished pulmonary flow. Hypoxia causes maintenance of a patent ductus arteriosus with continued right-to-left shunting (b). The foramen ovale (c) also continues to shunt right to left because of low left atrial pressures from diminished pulmonary flow. (Reproduced with permission from Sciarra JJ, Eschenbach DA, eds. Gynecology and obstetrics: maternal-fetal medicine, rev ed. Philadelphia: Harper & Row, 1983;3:3.)

Aspiration of meconium causes ventilation–perfusion inequalities in the lung. This may result in acidosis and hypoxemia, causing increased PVR and initiation of the cycle just described. Fetal hypotension also may cause persistence of the fetal pattern of right-to-left shunting. Hypotension can result from direct fetal blood loss, which may be apparent (e.g., fetal laceration, hematoma, hemorrhage from the cord vessels), or from occult fetal blood loss (e.g., placenta previa, abruption, maternal–fetal hemorrhage, or fetal hemolysis).

APNEA 1. If apnea is encountered, resuscitation should be instituted immediately, with the presumption of a severe asphyxial episode and secondary apnea. Only in retrospect will it be possible to decide whether asphyxia was present or whether the apnea was due to other causes (e.g., maternal medications). 2. If secondary apnea is present, resuscitative efforts may have to be quite prolonged before spontaneous respirations are seen. Meconium Aspiration Gasping efforts during asphyxial episodes may cause in utero aspiration of amniotic fluid containing meconium or vernix. This may severely compromise initial ventilatory function and complicate resuscitation, with ventilation-perfusion abnormalities, increased pulmonary vascular resistance, hypoxemia, and acidosis.

NEONATAL THERMOREGULATION The maintenance of an appropriate thermal environment has profound effects on the survival of the low–birth-weight or asphyxiated infant. As early as 1907, Pierre Budin, writing in The Nursling, noted that mortality increased from 33 to 90% when the rectal temperature was allowed to drop from 36–37°C to 32.5–33.5°C (96.8–98.6°F to 90.5–92.3°F). Neonates lose heat by evaporation, conduction and convection, radiation. Evaporative heat losses can be substantial if the neonate is not dried immediately after delivery. Approximately 0.5 calorie of body heat is lost for every gram of water that evaporates. Conduction involves heat transfer from one solid object to another (i.e., neonate to blanket or neonate to mother). This can be reduced if contact is limited to warmed surfaces. Convection is heat transfer from a solid object (e.g., neonate) to the gaseous surroundings. Heat loss by convection can be limited by warming the ambient air and eliminating drafts. Radiant heat loss is direct infrared transfer from a warm object (e.g., neonate) to any surrounding cooler one (e.g., walls, carpet, chairs). This effect can be overcome with a radiant

heater. The neonate responds to the sudden environmental temperature change at birth in several ways. In the normal situation, this stimulus causes the initial breath. In addition, cutaneous vasoconstriction adds to the increased SVR, aiding in normal neonatal cardiopulmonary transition. Although neonates are homothermal, their thermal regulatory capacity is limited. The neonate depends primarily on chemical thermogenesis for maintenance of body temperature. This heat is generated from brown fat stores. The ability to combat cold stress is limited further by prematurity, asphyxia, and low glucose. The thermoregulatory range is narrow in the neonate. Thus, minimal cold stress can cause hypothermia. Because the primary mechanism of thermogenesis is consumption of brown fat, oxygen consumption increases dramatically with decreasing environmental temperature ( Fig. 127–1.4). This increased oxygen demand may result in substrate depletion and acidosis in the premature or asphyxiated neonate. Asphyxia also may directly compromise thermoregulation (3), by reducing the duration of primary apnea and hastening the onset of the much more ominous secondary apnea.

Figure 127–1.4. Oxygen consumption and thermoregulation. Changes in oxygen consumption with decreasing or increasing environmental temperatures (breathing room air [20%] or a hypoxic [12%] mixture). (Reproduced with permission from Klaus M, Fanaroff A, eds. Care of the high-risk neonate, 2nd ed. Philadelphia: WB Saunders Company, 1979;95.)

SEIZURES Neonates felt to be at highest risk for seizures exhibit the following risk factors: (a) a low 5-minute Apgar score (less than 5), (b) need for intubation in delivery room, and (c) severe acidemia (4).

RESUSCITATIVE EQUIPMENT The basic equipment needed for neonatal resuscitation in the ED is listed in Table 127–1.2. It should be organized in its own area to reduce confusion with adult resuscitation equipment. The radiant warmer should be kept on at all times. This reduces conduction heat loss. Blankets should be placed in the warmer. A large, flat, stable area is most appropriate for neonatal resuscitation.

Table 127–1.2. Recommended Equipment for Neonatal Resuscitation

MEDICATIONS Only a limited number of medications are needed for neonatal resuscitation. Listed, along with dosages and routes of administration, in Table 127–1.3, these include sodium bicarbonate, dextrose solutions, epinephrine, human serum albumin, and naloxone hydrochloride. Although previously atropine sulfate and calcium were recommended, there is no current evidence that they are useful in the acute phase of neonatal resuscitation.

Table 127–1.3. Medications for Neonatal Resuscitation

Sodium Bicarbonate Because the normal-term neonate has a mixed respiratory and metabolic acidosis at birth ( Table 127–1.4), care must be taken in the interpretation of blood gases. Administration of alkali must be approached judiciously. Several studies have shown a correlation between hypernatremia secondary to alkali administration and intracranial hemorrhage, whereas other studies have not. Clearly, adequate ventilation must be established before administration of sodium bicarbonate or P CO2 rises and acidosis worsens.

Table 127–1.4. Changes in Blood Gases Between Fetus and Neonate

Use of alkali may be appropriate under the following conditions: 1. 2. 3. 4. 5.

When the infant is intubated and adequate ventilation is documented. When the infant is severely acidotic (arterial pH £ 7.10). When the situation is life-threatening. When blood gases are available to assess the effect of administration before a second dose of alkali is given. When a central line (umbilical venous catheter) is in place through which the alkali can be infused.

Naloxone The need for naloxone hydrochloride in the ED is rare, but it can save lives. Narcotic depression may be seen in the neonate whose nonaddicted mother received narcotic analgesics within 60 to 90 minutes of delivery. In truly narcotic-depressed neonates, 1-minute Apgar scores are usually normal, but 5-minute and 10-minute Apgar scores are depressed because of inadequate respirations. Naloxone may be necessary to reverse narcotic-induced respiratory depression. Infants of narcotic-addicted mothers are addicted themselves and should not be acutely withdrawn with naloxone. Acute narcotic withdrawal in addicted neonates can have severe consequences. In addition, naloxone administration in nonaddicted neonates may not be innocuous because b-endorphins may play a role in transition to neonatal life, and naloxone may block these beneficial effects. Dextrose Some neonates will experience marked distress due to hypoglycemia. Particularly if labor has been hard or with prematurity, this is more likely. Dextrose solution can be given after heel puncture for blood glucose.

RESUSCITATION (5,6 and 7) The emergency physician may commonly face three situations requiring resuscitation of a neonate: (a) precipitous delivery in the ED, (b) unexpected delivery on the way to the hospital, and (c) planned home delivery with unexpected complications ( 8). In any of these situations, the infant should be evaluated immediately with the Apgar score (Table 127–1.5). Although the Apgar score is usually awarded at 1 and 5 minutes, this evaluation should be made whenever the infant is first seen. If the first Apgar score awarded is 7 or less, the infant should be reevaluated and additional Apgar scores awarded at 5-minute intervals throughout the resuscitation. Keep in mind that premature infants may have lower Apgar scores than term infants because of decreased muscle tone and reflex irritability.

Table 127–1.5. The Apgar Scoring System

The following sections describe resuscitation procedures, according to the initial Apgar score awarded, then discuss techniques needed for resuscitation. Prophylactic intratracheal surfactant therapy ( 9) is new, and each ED should meet with the obstetrics and pediatrics departments to develop a protocol for its use in out-of-hospital or ED delivery.

PROCEDURES Note: If the amniotic fluid is meconium stained and the infant has not yet been delivered, follow the procedure outlined in the Meconium section (under Special Problems) before proceeding to further resuscitation. All neonates regardless of Apgar score, must first be dried off and kept warm. Hypothermia can severely compromise the neonate, causing acidosis, reduced perfusion, and increased oxygen consumption. The principles of resuscitation—airway, breathing, circulation—are the same for the neonate as for the older child or adult. In the asphyxiated infant, good ventilation is critical and can be more difficult to attain than in larger humans. Keep in mind the length of time that can be required to establish adequate respiratory effort in the asphyxiated newborn and the surprisingly good prognosis for survivors if adequate ventilation can be established. If the Apgar score is 8 to 10, suction the nose and oropharynx with a bulb syringe, towel the neonate dry, keep him or her warm, return him or her to the mother (wrapped in a warm blanket), and observe. If the Apgar score is 5 to 7, suction the nose and oropharynx with a bulb syringe. Stimulate breathing by vigorously rubbing the back. Toweling the neonate dry is excellent for stimulating breathing. If the neonate is slow to respond, or does not maintain regular respirations after stimulation is stopped, initiate bag-and-mask ventilation until good respirations are established. Continue ventilation until the neonate is pink. After withdrawal of respiratory support, observe carefully for deterioration. If the neonate is stable, return the baby to the mother in warm blankets and continue to observe. If the Apgar score is 0 to 4, suction the nose and oropharynx and quickly rub dry. Insert an orogastric tube, begin bag-and-mask ventilation immediately, and assess heart rate. As resuscitation begins, one individual should review the history, especially for acute blood loss. At 1 minute, if the heart rate is below 80 or if the neonate

is making no respiratory effort, prepare to intubate while continuing bag-and-mask ventilation and start intravenous (umbilical) line after taking a blood/glucose test. Once the neonate is intubated and good air exchange is achieved, reassess the heart rate. If it is above 60, continue vigorous bagging at 40 to 60 breaths per minute until the neonate is pink and the heart rate is above 100 and stable. Watch for the onset of gasping. Most infants respond well to ventilation alone. If, however, the heart rate remains below 60 after good air exchange has been established, begin cardiac compressions at a rate of 120, with a ventilatory rate of 40. Administer 0.1 mL/kg of 1:10,000 epinephrine either through the endotracheal tube or an umbilical venous (UVC) line. Never inject epinephrine subcutaneously in an asphyxiated infant. Then, through the UVC, administer 1 to 2 mEq/kg, of NaHCO 3, diluted as shown in Table 127–1.3. No bicarbonate should be given until adequate ventilation is established, and bicarbonate should be given only with extreme caution in premature infants. Flush the line with 3 to 4 mL of saline. Inject a dose of epinephrine and flush the line again. If the heart rate does not respond, infuse 10 mL/kg of 5% human serum albumin (one part 25% albumin to 4 parts normal saline). Alternatives to 5% human serum albumin include whole blood (rarely available), normal saline and Ringer's lactate. After an initial trial of these measures, reassess the neonate. If the heart rate has not responded to resuscitation, the most common reason is inadequate ventilation. Recheck the adequacy of ventilation and all oxygen delivery equipment. Absent or decreased breath sounds on the left may be from intubation of the right main stem bronchus. If the endotracheal tube is in proper position and breath sounds are still unequal, consider the possibility of a tension pneumothorax. Perform needle aspiration if necessary. Try to obtain arterial blood gases, either through an umbilical artery catheter (if an experienced person is present to insert one) or peripherally. Blood gases document the adequacy of ventilation and show whether additional bicarbonate is necessary. Obtain a radiograph if possible. Continue the resuscitation.

SPECIAL PROBLEMS Meconium Adequate suctioning of the mouth, nares, and hypopharynx after delivery of the infant's head but before delivery of the shoulders may prevent meconium aspiration syndrome (although in utero asphyxia may cause grasping and inhalation of meconium before delivery). For all infants delivered through meconium stained fluid, suction the mouth, pharynx and both nares using a 10F or larger suction catheter. Controversy exists concerning the management of infants after delivery. If meconium is thin and watery and contains no particles, and if the infant is vigorous (Apgar score ³ 7), no further therapy may be necessary. However, for thick or particulate meconium and for all depressed infants, the following procedure should be performed. Place the infant on a warmer. Visualize the hypopharynx with a laryngoscope and suction out remaining meconium, then intubate the trachea and suction meconium from the airways. This procedure may be accomplished by directly suctioning the trachea with a 10 or 12F suction catheter or by intubating with an endotracheal tube, then attaching meconium aspirator to the tube and withdrawing the tube under suction. Meconium should not be evacuated by passing a suction catheter through the endotrachael tube, because the catheter will be too small (8F) to remove large particles of meconium. Repeat intubation may be necessary if meconium is found below the vocal cords; however, prolonged, repeated intubation and suctioning may further compromise the resuscitation of a depressed infant. After this procedure, the newborn infant frequently needs brief bag-and-mask ventilation to help inflate the lungs. ( Fig. 127-1.5)

Figure 127–1.5. Equipment for neonatal resuscitation. Illustrated are an aneroid manometer, continuous positive airway pressure (CPAP) ventilation bag, term and premature masks, bulb syringe, DeLee suction suction trap, laryngoscope with a Miller No. 0 blade, endotracheal tube with stylet, and suction catheter with glove.

THE PREMATURE NEONATE The pediatrician should be called as soon as possible for all expected premature deliveries. These infants are more susceptible to all stresses surrounding birth. They lose heat quickly; therefore, great care must be taken to keep them warm. Air exchange can be more difficult to achieve with bag and mask, especially for very low–birth-weight neonates, and they must be intubated quickly if chest expansion is not adequate with bagging or if they do not respond to bag-and-mask ventilation. The ED, especially during an unexpected precipitous delivery, is not a good place to make a decision about the potential viability of a very premature neonate. All neonates should be supported if possible until a person experienced in the evaluation of premature neonates can arrive and make any necessary decisions about viability and further care. Intratracheal surfactant can make a difference in survival of the most premature neonates. Suitable protocols for its use should be prepared.

TECHNIQUES Bag-and-Mask Ventilation If assisted ventilation is needed, bag-and-mask ventilation should have continuous positive airway pressure (CPAP) capability and should allow interposition of an aneroid manometer to monitor the pressure delivered to the neonate. A No. 8F feeding tube should be placed into the stomach during CPAP or bag-and-mask ventilation to prevent abdominal distention, which can interfere with adequate ventilation. Adjust the CPAP valve to deliver 5 cm H 2O pressure, with enough flow to reinflate the bag quickly. Place the mask over the neonate's nose and mouth. Cup two or three fingers under the neonate's chin and extend the head slightly to obtain a good seal. Allow the bag to fill, and check the CPAP pressure on the manometer. Begin bagging at about 4 to 60 breaths per minute, watching the manometer to keep inflating pressure at 20 to 24 cm H 2O. Look at chest wall movement and listen to breath sounds to assess the adequacy of ventilation. If chest wall movement or breath sounds are inadequate, increase inflating pressures slightly. If ventilation is still inadequate, intubate the neonate rather than using higher pressures with bag-and-mask ventilation. Because of their small size, premature neonates may be difficult to ventilate with bag and mask. One technique that may help is to turn the face mask around 180° and cover the infant's entire face. Proceed quickly to intubation if bag-and-mask ventilation does not result in adequate ventilation. Endotracheal Intubation A laryngoscope with a No. 0 Miller blade ( Fig. 127–1.5) allows good visualization of the glottis ( Fig. 127–1.6). The tube should slide through the cords easily. Too large a tube can cause pressure necrosis, and a tube that is forced through the cords can cause significant trauma ( Table 127–1.6). A flexible Teflon introducer, or stylet, can be used to give stability to the endotracheal tube. Care must be taken that the introducer does not protrude from the end of the endotracheal tube.

Figure 127–1.6. Neonatal intubation. (Reproduced with permission from Klaus M, Fanaroff A, eds. Care of the high-risk neonate, 2nd ed. Philadelphia: WB Saunders, 1979;33.)

Table 127–1.6. Endotracheal Tube Sizes

Oropharyngeal intubation is the procedure of choice in emergency situations. Nasopharyngeal intubation can be more difficult and more time-consuming and should be considered an elective procedure rather than an emergency procedure. The neonates neck should not be hyperextended. The neonate may lie flat, or a towel or diaper may be placed under the head to bring it forward into the “sniffing” position. A feeding tube placed into the stomach can help by identifying the esophagus. The laryngoscope is introduced into the right side of the neonate's mouth and brought across the tongue as it is advanced, sweeping the tongue out of the way. The side of the hand can be held against the neonate's cheek to stabilize the laryngoscope. The fourth and fifth fingers can be held under the neonate's chin for additional stabilization and, if necessary, can provide slight pressure on the cords to bring them into view. The laryngoscope is frequently inserted down the esophagus past the vocal cords. If the vocal cords are not initially visualized, the laryngoscope should be withdrawn slowly. When the vocal cords drop into view, the laryngoscope is advanced into the vallecula, and the endotracheal tube is inserted 1 to 2 cm below the vocal cords. To avoid uncertainty about the success of the intubation, visualize the cords after the tube has been inserted. The tube can be palpated at the sternal notch and advanced about 1 cm farther for correct placement. Ventilate at pressures of 20/4, increasing as necessary to 30/4. Adequacy of air exchange and quality of breath sounds should be ascertained and the tube taped firmly into position. Heart Massage (Chest Compressions) Although the principles behind heart massage in the infant are the same as those in older children and adults, the procedure requires modification because of the neonate's smaller size. The force used for compressions must be decreased, and the number of compressions per minute must be increased. Both hands are placed around the neonate's chest, and the thumbs are positioned on the midsternum. The neonate's chest should not be squeezed by the hands; instead, the fingers should act as a backboard while the thumbs apply force to the sternum. The presence of a femoral pulse indicates adequacy of compressions. Compressions should be about 90/minute. The person doing cardiac compressions should count them aloud (i.e., 1,2,3; 1,2,3) so that the lungs can be inflated after every third compression. Compressions can be discontinued after the heart rate is above 100. Umbilical Venous Catheterization Emergency vascular access in the asphyxiated newborn is most easily obtained through the umbilical vein, which is usually easy to see through the translucent umbilical cord. Its normal position is cephalad to the umbilical arteries. Encircle the umbilicus with umbilical tape and tie loosely so that any bleeding can be controlled. Cut through the umbilical stump (approximately 1 cm above the skin) only far enough to open the vein, trying not to disturb the arteries. Advance a 5F catheter 5 cm only (even less in a small, premature neonate) and check for blood return. Advancing the catheter any farther may position it in the liver or other undesirable location. Suture into position and tape onto the abdomen to secure. The line can be kept open with D5W running slowly (2 mI/hour) to avoid overload. Intraosseous infusion can be used when venous access is difficult. The tibial region is often used in emergencies, and intraosseous infusions may find more use in prehospital care ( 10). Needle Aspiration of Pneumothorax If the neonate has not responded to resuscitative measures, and if breath sounds are asymmetric (not caused by low endotracheal tube position), the possibility of pneumothorax, either spontaneous or from resuscitative measures, must be considered. Chest radiograph, although exceedingly helpful in making the diagnosis (and in differentiating pneumothorax from diaphragmatic hernia), is not always immediately available. If the neonate has convincing clinical evidence of pneumothorax—diminished breath sounds that are not corrected with changing the endotracheal tube position, muffled heart sounds or shifted heart location, asymmetric chest or chest motion—and the neonate's condition is critical, needle aspiration can be performed, using a 23- or 25-gauge butterfly intravenous needle connected to a three-way stopcock and a syringe. Prepare the chest wall midway between clavicle and nipple and insert the needle in the nipple line, maintaining suction with the syringe. A tension pneumothorax is immediately evident, and release of air should improve the neonate's appearance. If a collection of air is found, withdraw air until a physician experienced in chest tube insertion in neonates arrives. If no air is found, withdraw the needle while continuing to maintain suction with the syringe.

OTHER NEONATAL EMERGENCIES The chief role of the emergency physician in other neonatal emergency conditions is recognition and suitable referral. Table 127–1.7 lists the most common conditions encountered and can serve as a brief guide to their evaluation. Any of these conditions can be associated with an urgent need for resuscitation on the basis of principles discussed in this chapter.

Table 127–1.7. Selected Neonatal Emergencies

References 1. Fanaroff AA, Wright LL, Stevenson DK, et al: Very-low-birth-weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, May 1991 through December 1992. Am J Obstet Gynecol 1995;173:5, 1423–1431. 2. Bowen FW: Management issues for the neonatal patient. Clin Perinatol 1996;23:1, 1–30. 3. Notter RH, Shapiro DL: Lung surfactants for replacement therapy: biochemical biophysical and clinical aspects. Clin. Perinatol. 1987;14:433. 4. Perlman JM, Risser R: Can asphyxiated infants at risk for neonatal seizures be rapidly identified by current high-risk markers? Pediatrics 1996;97:4, 456–462. 5. Davis D: How aggressive should delivery room cardiopulmonary resuscitation be for extremely low birth weight neonates? Pediatrics 1993;92:447. 6. Sinkin RA, Davis JM: CPR of the newborn. Pediatr Rev 1990;12:136. 7. Bloom RS, Cropley C: Textbook of neonatal resuscitation. Dallas: American Academy of Pediatrics and American Heart Association, 1994. 8. Brunette DD, Sterner SP: Prehospital and emergency department delivery: review of eight years' experience. Ann Emerg Med 1989;18:1116. 9. Kendig JW, Notter RH, Cox C, et al: A comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks' gestation. N Engl J Med 1991;324:865. 10. Miner WF: Prehospital use of intraosseous infusions by paramedics. Pediatr Emerg Care 1989;5:5.

Chapter 127.2 Pediatric Cardiopulmonary Resuscitation Principles and Practice of Emergency Medicine

CHAPTER 127 RESUSCITATION

2 Pediatric Cardiopulmonary Resuscitation Paula C. Fink Clinical Presentation and Examination History Clinical Presentation Laboratory Tests Initial Stabilization: Use Protocols Sequence of Cardiopulmonary Resuscitation Postarrest Care Cardiac Rhythm Abnormalities

CLINICAL PRESENTATION AND EXAMINATION The presentation of a child in frank cardiopulmonary arrest is obvious; however, the child in impending arrest may have a more confusing clinical presentation. With the exception of trauma and a few other catastrophic events, cardiopulmonary arrest in children is not sudden but is usually the result of a progressive deterioration of the respiratory and circulatory systems. Unlike cardiac arrest in adults, it is usually preceded by respiratory failure. The key to preventing cardiopulmonary arrest is recognizing the signs and symptoms of respiratory distress in a child and intervening to stop the progression to cardiopulmonary failure.

HISTORY The history of the illness is paramount in diagnosis and treatment and should be tailored to the specific age of the patient. Infants An infant can deteriorate rapidly within 8 hours, and the pertinent history should reflect this short time course. Feeding patterns should be determined. Did the child refuse to drink? What have they been fed: formula or water? Has honey or any “home remedies” been given? What medications is the child taking? Have they been irritable, vomiting, or febrile? The past medical history, though short, is also important. The perinatal history regarding the gestational age at birth and the length of time the child needed to stay in the hospital after birth is valuable information. Did the child require advanced medical care after birth? A family history is important in specific areas. Has there been a sudden infant death syndrome (SIDS) victim in the family? Are there any congenital illnesses or syndromes in the family, including sickle cell disease, Down syndrome, or congenital heart disease? Is anyone in the family currently ill or hospitalized? Children The specific concerns of the toddler and young child's history address the fact that this age group has mobility but minimal judgment. Information concerning possible toxins and exposures can hold the key to the cause of cardiopulmonary arrest. Drowning and near-drowning are a major cause of arrest at this age, and the time under water, the water temperature, and the care given at the scene are important information that can help in the approach to treatment of the arrest. Again, a past medical history may be helpful in treating or evaluating an arrest. A child with a history of asthma on chronic steroids has a different response to stress than a previously healthy child.

CLINICAL PRESENTATION Shock, or imminent shock, in infants and children has certain clinical features. Defined at the cellular level as the failure to deliver adequate substrates to and remove waste from the cell, shock can result from many conditions. In children, shock is usually the direct result of inadequate oxygenation of vital organs. The clinical manifestations of hypoxia begin subtly with air hunger and increased respiratory and heart rate. The child then exhibits lethargy, a decreasing level of consciousness, and confusion. The skin becomes peripherally cyanotic, then progresses to central cyanosis, mottling, and prolonged capillary refill. If the condition remains unchecked, there is further deterioration, with bradycardia, apnea, hypotension, and finally asystole and death. Because of the poor glucose stores in infants and children, hypoglycemia secondary to sepsis and stress can also cause deterioration and eventual cardiopulmonary arrest. Like hypoxia, hypoglycemia has a profound effect on the central nervous system (CNS), producing confusion, lethargy, and progression to coma. Pure circulatory failure without respiratory failure is uncommon but can be seen in some patients with cardiac abnormalities, ingestions, sepsis, or severe dehydration. In these cases, the patient may have a rapid heart rate and hypotension. Respiratory failure can also be caused by the mechanical obstruction of the airway by foreign-body aspiration, epiglottitis, or croup, but, if appreciated early, this type of respiratory arrest can be avoided.

LABORATORY TESTS Laboratory values, with a few exceptions, are seldom helpful in the diagnosis of cardiopulmonary arrest because of the delay in getting the results and the blatant physical signs of the patient. A few “bedside” tests can be performed that can affect treatment. The bedside glucose level, which can be obtained in 2 minutes, is of great value in diagnosing hypoglycemic seizures, diabetic ketoacidosis (DKA), and complications of ethanol ingestion. The pulse oximetry monitor has improved pediatric acute care, but it is useless in patients with hypotension or poor digital perfusion. The dipstick urinalysis can detect hematuria, glycosuria, or ketonuria. A table-top hematocrit centrifuge allows for a fast estimate of circulating red cell mass. Occult blood testing of the feces in the rectum can inform the physician of gastrointestinal bleeding. Emergent laboratory values to obtain and have run immediately (Stat) include an arterial blood gas, complete blood count (CBC) blood glucose, and electrolytes. Appropriate drug levels and toxicologic screens should be drawn. Emergent radiographs of the cervical spine in trauma and chest are of great value as long as they can be obtained without obstructing the care of the patient and are of good quality.

INITIAL STABILIZATION: USE PROTOCOLS Pediatric Advanced Life Support guidelines were updated in 1992 following a conference on cardiopulmonary resuscitation (CPR) and emergency cardiac care convened by the American Heart Association ( 1). The protocols in Figure 127–2.1 and Figure 127–2.2 are based on guidelines that have evolved from this conference.

Figure 127–2.1. Protocol for bradycardia.

Figure 127–2.2. Protocol for asystole/pulseless electrical activity/electromechanical dissociation (EMD).

SEQUENCE OF CARDIOPULMONARY RESUSCITATION Impending cardiopulmonary arrest symptoms, as described earlier in this chapter, can identify a child as being in need of emergent supportive care, but CPR should not be instituted until unresponsiveness is demonstrated ( Table 127–2.1). The level of consciousness can be determined by verbal or painful stimuli, being careful to keep the head and neck aligned in case of cervical injury. If there is no response to touch or verbal stimulus, one must assume that the victim is unconscious, and assessment of the airway, breathing, and circulation should be done with speed and accuracy.

Table 127–2.1. Signs of Cardiopulmonary Arrest

Airway The simplest solution to cardiopulmonary distress caused by an obstructed airway is to remove the obstruction. In pediatrics, this is especially important because most pediatric arrests are the result of respiratory compromise. Often the obstruction is caused by the tongue falling back and blocking the oropharynx. Positioning the patient to open the airway is the first step. If trauma is known to be the cause of the arrest, or if the mode of injury is unknown, manual in-line cervical immobilization must be maintained until the neck is stabilized. If the mode of injury is known not to involve trauma, “head tilt” without hyperextension of the neck can open the airway. Breathing If the patient does not respond with spontaneous breathing to airway positioning, artificial respirations must be started. In the field, mouth-to-mouth ventilation is appropriate. In a health care facility, the rescuer should use bag-mask equipment supplying 100% oxygen. Pocket masks have been a boon to resuscitation, allowing the rescuer to be protected from communicable diseases while still being able to supply emergent ventilations to patients. The first assisted ventilations should be two slow breaths to allow the rescuer to assess the patency of the airway, to determine the pressure required to raise the chest of the patient, and to oxygenate the patient. If the chest does not rise, the rescuer should reposition the airway and repeat the ventilations. If this still does not allow good ventilation, obstruction secondary to a foreign body should be suspected ( Chapter 9–6). Ninety percent of deaths from aspiration occur in children younger than 5 years, and the most commonly aspirated materials are food or balloons. Airway obstruction from a foreign body should be suspected in infants and children who exhibit a sudden onset of respiratory distress. Unconscious patients who are difficult to ventilate or cannot be ventilated should be evaluated for foreign-body airway obstruction. Relief of airway obstruction in an infant can be attempted by holding the infant straddling the rescuers arm, with the infant lying on their abdomen, and the rescuer supporting the infant's head with one hand, holding the head lower than the body (see Chapter 1). The rescuer then delivers five forceful blows to the back between the shoulder blades with the heel of the hand. If the obstruction is not relieved, the child is turned over and placed between the rescuer's arm supporting the infant's head, neck, and back and the opposite hand placed on the infant's chest. Five chest thrusts are delivered in the same position as CPR chest compressions but at a slower rate. These maneuvers are repeated with frequent assessment of airway patency until the obstruction is relieved. Subdiaphragmatic abdominal thrusts (Heimlich maneuver) may be used for older children, 1 to 8 years old, with choking or airway obstruction ( Table 127–2.2).

Table 127–2.2. Cardiopulmonary Resuscitation Guidelines

Circulation After airway and breathing have been established, the presence or absence of cardiac contractions or their efficacy must be evaluated. In an infant, the precordial impulse often can be felt on the chest, but without peripheral pulses, the circulation is ineffective. The pulses that are easily palpated in an infant or young child are the brachial or femoral arteries because the carotid artery is often obscured by fat. In older children and adults, the carotid artery is the best pulse to use to determine adequate circulation. Hypothermia, cyanotic heart disease, and methemoglobinemia can produce an ashen color in a patient with adequate circulation. Poor peripheral circulation as indicated by an ashen color and cyanosis can be misleading, and CPR should not be started if the patient has strong pulses but poor color. Without palpable pulses, external cardiac compressions must accompany artificial respirations. If the patient does not respond to the initial two breaths, CPR should be performed for 1 min prior to calling for help. The majority of pediatric arrests are respiratory in cause and 1 min of immediate, appropriate CPR may revive the patient. This is unlike an adult arrest where “Call First”, after the initial two breaths activates the emergency medical system (EMS) and encourages the use of early defibrillation. The infant or young child should be placed on a firm surface, and support to the upper thoracic cage should be given by a towel to remove dead space and allow for effective compressions (2). Finger placement for the compressions is just below the intermammary line where it intersects with the sternum. The rescuer should use two to three fingers and compress to a depth of 0.5 to 1 inch at a rate of 100 times/min. The compressions should be smooth and in a steady rhythm, with full release of the pressure on the chest without removing the fingers from the chest so as not to lose the landmarks. In a child older than 1 year, the heel of one hand is used for compressions. Positioning is found by following the costal margins of the ribs to the sternum; two fingerbreadths above their intersection on the sternum is the position for compressions. Compressions should again be smooth and rhythmic to a depth of 1 to 1.5 inches and a rate of 100 times/min. If the child is older than 8 years or is the size of an adult, adult CPR procedures should be used. The positioning for compressions is the same as in a child, using the heel of the hand and compressing the lower third of the sternum rostral to the xiphoid process. Compressions should be to a depth of 1.5 to 2.0 inches and at a rate of 80 to 100 times/min. Coordination with breathing in the infant should be with a minimal pause in compressions at a ratio of five compressions to one breath. In older children, there can be a slight pause at the end of every fifth compression (1 to 1.5 seconds). Evaluation of the child by assessing the pulse and looking for spontaneous breathing should be done every 10 cycles. Refer to Table 127–2.2 for ventilation and compression rates. INTRAOSSEOUS INFUSIONS Circulatory support often requires fluid administration, and intravenous line placement is often technically difficult and time-consuming. Intraosseous (IO) infusions were used extensively in the 1940s and subsequently fell out of favor with improvements in intravascular catheters ( 3). The procedure offers vascular access within the first 5 minutes to pediatric patients with vascular collapse. It has been shown that injections into the bone marrow are absorbed almost immediately into the circulation. The rates of infusion compare favorably with central line delivery and can be faster than peripheral intravenous administration ( 4). No medications have been found to be absolutely contraindicated by IO infusion; however, there is a risk of fluid extravasation into the subcutaneous tissue. Medications that can cause tissue damage, such as phenytoin, sodium bicarbonate, and calcium should be given with care. Because these lines are usually placed during resuscitation efforts and sterile technique often is not used, infection is a rare but possible complication. Relative contraindications to IO placement are repeated attempts in the same limb and placing the needle through a burn or infection ( 5). Absolute contraindications include osteogenesis imperfecta and an ipsilateral fracture of the bone because of fluid extravasation through the fracture. Technique The choice of the site of infusion should be made with consideration of the patient's age, size, and illness. Limbs with cellulitis or major burns should be avoided to reduce the chance of infection. As stated previously, a broken bone or a bone that had a previous attempt at IO placement should also be avoided. The optimal site in children is the proximal tibia, with the distal tibia and distal femur in infants as other choices. In adults, the sternum is an alternate site, but in children under 3 years the sternal marrow space is thought to be too small. That site also may inhibit chest compressions during resuscitation. Complications from sternal puncture have included mediastinitis, hydrothorax, and injury to the heart. Care must be taken with long bone IO placement to avoid damaging the growth plate by directing the needle away from the growth plate at about 10 to 15°. Currently, 13- to 18-gauge disposable bone-marrow aspiration needles are available. These should have a stylet to keep the bone cortex from plugging the needle, an adjustable screw guard to vary the needle length, a flange guard to allow the needle to be secured to the skin, and short length to allow for ease in placement. Any bone marrow needle or 18-gauge spinal needle can be used in an emergency. To place the needle in the proximal tibia, the anteromedial surface of the tibia is sterilely prepared about 1 to 3 cm below the tibial tuberosity ( Fig. 127–2.3). The needle is inserted at an angle of 10 to 15° from vertical slanting away from the growth plate with a boring, rotary motion. If the angle is vertical to the bone, the needle has less chance of glancing off the cortex of the bone and missing the marrow (see also Chapter 10).

Figure 127–2.3. Technique for infusion into proximal tibia.

The needle entry into the bone marrow is indicated by a sudden lack of resistance, the upright standing of the needle without support, and the free flow of fluid without extravasation into soft tissue. Bone marrow usually can be aspirated from the needle to confirm placement. This fluid can be used for laboratory studies such as glucose level or bacterial culture. Sometimes you may not be able to aspirate bone marrow into the needle because of the narrow gauge of the needle, but placement can be confirmed by flushing the needle with saline before attaching the intravenous line. Once the vascular volume has improved to allow conventional vascular access, the IO should be removed. The longer it is allowed to stay in place, the higher the risk of infection.

POSTARREST CARE Once the patient has been resuscitated, care must be taken to prevent a recurrent arrest. The specific therapy used should reflect the probable cause of the initial arrest. Constant attention to the Airway, Breathing, and Circulation (ABCs) often maintains the patient until transport to an adequate care facility. Maintaining the airway is paramount, and care in securing the endotracheal tube, if placed, is key. A chest radiograph should be obtained to check for tube

placement. Sedation may be needed if the patient is agitated. If the patient appears highly agitated and has good respiratory effort, you may consider extubation, but reintubation may be difficult in the face of airway edema. Ventilation can be continued by bag-mask in the nonbreathing patient, and a ventilator should be considered. Cardiac perfusion should be constantly monitored by blood pressure and peripheral circulation assessment. Often the postarrest patient has an intravascular fluid deficit and may need volume. The injured heart may not be able to support circulation without a vasopressor such as dopamine hydrochloride and their administration should be considered. If the patient had an arrhythmia, the antiarrhythmic medication used to correct it may have to be given as a constant infusion. Fluids and Medications FLUIDS Cardiopulmonary arrest from hypovolemic shock is common in pediatrics and can result from medical or traumatic causes. In the treatment of these conditions, fluid therapy should resemble the fluids lost. Shock from dehydration should be treated with boluses of an isotonic crystalloid solution; shock from hemorrhage should be treated with blood transfusions after an initial crystalloid bolus; and shock from sepsis may be treated with colloids. In an emergent situation, the exact fluid given does not matter as long as it is isotonic. The initial volume of fluid is 20 mL/kg given as soon as vascular access is obtained and “pushed” in manually by syringe. The patient should then be reassessed for signs of improvement because subsequent boluses may be necessary. A decrease in heart rate, improvement of peripheral circulation, or increased level of consciousness are signs of response to fluid therapy. One should be aware that a patient in hypovolemic shock may need a total of 60 mL/kg fluid to stabilize. Boluses of dextrose-containing fluids should be avoided because hyperglycemia may produce an osmotic diuresis. MEDICATIONS AND DEFIBRILLATION The following sections describe the differences in dosage and use of resuscitation medications in pediatrics. Please refer to the other sections in the text for the pharmacology of these medications and to Table 127–2.3 for pediatric doses and concentrations.

Table 127–2.3. Pediatric Cardiopulmonary Arrest Medications

Epinephrine Epinephrine is a catecholamine with both a and b adrenergic receptor stimulating actions. The alpha action is primarily vasoconstriction and causes a rise in systolic and diastolic blood pressure. Beta action produces an increase in myocardial contractility and heart rate. Epinephrine is indicated for treatment of asystole, electromechanical dissociation (EMD), and pulseless electrical activity (PEA), and to render the heart more susceptible to defibrillation. Infants and children are sensitive to epinephrine, with few side effects. The first dose given intravenously or via IO should be 0.01 mg/kg of a 1:10,000 solution. Subsequent doses of epinephrine should be increased tenfold to 0.1 mg/kg. Ideally, a higher concentration of epinephrine (1:1,000) should be used to limit the volume of fluid. The first dose of epinephrine given intratracheal via endotracheal tube should be the higher 0.1 mg/kg dose to ensure the maximal delivery of the drug. Often a child with hypotension responds to epinephrine, and administration as an infusion is indicated. The infusion rate for this is 1 µg/kg per minute, increasing as necessary to a maximum of 20 µg/kg (1). Atropine Sulfate Atropine sulfate is a parasympatholytic drug with central and peripheral actions. Its central action is to stimulate the medullary vagal nucleus and, with low doses of atropine, this produces bradycardia. The peripheral effects of blocking the vagal nerve and increasing the heart rate are desired when giving atropine. Low doses of atropine can cause a paradoxic bradycardia. Atropine should be given at a dose of 0.02 mg/kg, with a minimum dose of 0.1–0.2 mg. The maximum total dose for a child is 1.0 mg, and that for adolescents and adults is 2.0 mg. Sodium Bicarbonate Retention of carbon dioxide results from respiratory arrest and causes respiratory acidosis. This can be treated best with adequate ventilation. If the arrest is allowed to continue with lack of circulation, cell death occurs, producing lactic acid, which results in a metabolic acidosis. Sodium bicarbonate can correct this acidosis by combining with hydrogen to form carbon dioxide, which can be eliminated by ventilation. The administration of sodium bicarbonate is not recommended indiscriminately during cardiac arrest because it does not reverse intramyocardial acidosis ( 6). When the circumstances surrounding the arrest indicate metabolic acidosis (a long period of inadequate ventilation or prolonged arrest), the administration of sodium bicarbonate can be indicated as guided by arterial blood gas results. The indiscrimate use of sodium bicarbonate may cause hypernatremia or a metabolic alkalosis. Large boluses of sodium bicarbonate infused into the central circulation of infants can produce a hyperosmolar state that can cause intraventricular hemorrhage. The dose of sodium bicarbonate is 1 to 2 mEq/kg. Calcium salts precipitate out if given with sodium bicarbonate, and catecholamines are inactivated when given with them. Being hyperosmolar, sodium bicarbonate can sclerose small veins and cause chemical burns if it extravasates into subcutaneous tissue; therefore, it cannot be given intratracheally. Defibrillation The largest possible electrode that will not lose contact with the chest wall but will not touch the other electrode should be used. In small infants, the paddles may be placed on either side of the chest to ensure optimal chest contact. There are available infant paddles with a diameter of 4.5 cm and paddles for children of 8.0 cm and 13.0 cm in diameter. Two joules (J) per kilogram is the initial dose to be used. The voltage is delivered with firm pressure on the paddles and, if defibrillation is not successful, the voltage should be doubled and the shock repeated. If still no response, another shock should be delivered at the doubled dose of 4 J/kg. If there is no response again, CPR should be continued and the patient evaluated for adequacy of oxygenation and ventilation before a standard 0.01 mg/kg dose of epinephrine is given and a repeat attempt of defibrillation ( Fig. 127–2.2).

CARDIAC RHYTHM ABNORMALITIES The cardiac rhythm abnormalities of a child with impending cardiopulmonary arrest are much less complicated than those in adults. Myocardial damage from coronary artery disease, the cause of most adult cardiac arrests, is rarely the cause of a child's abnormal rhythms. In all arrhythmias, the patient must be evaluated to

determine if the rhythm is compromising the cardiac output or could degenerate into a lethal rhythm. If there is no compromise or risk of degeneration, no emergent treatment of the rhythm abnormality is indicated, and the patient should be observed for complications. The response of the heart to the causes of a child's cardiopulmonary arrest is usually an attempt to increase cardiac output by increasing its heart rate. This can cause tachyarrhythmias, which compromise the diastolic filling and reduce stroke volume. The most common tachyarrhythmias found in children are sinus, supraventricular, and ventricular tachycardia. Once the heart begins to fail because of toxins or hypoxia, bradyarrhythmias may result. These also reduce cardiac output by reducing the heart rate. Finally, when the heart has failed, asystole occurs. Please refer to the subchapter Pediatric Cardiac Emergencies ( Chapter 130–1) for normal heart rate ranges and discussions of the pathophysiology and pharmacologic treatment of these arrhythmias atrioventricular block, supraventricular tachycardia [SVT], atrial flutter and fibrillation, ventricular tachycardia, and fibrillation). Electromechanical dissociation (EMD) is a cause of cardiopulmonary arrest in children as in adults. The heart has normal electrical activity, but its mechanical function is ineffective for circulation. The causes of EMD are the same in children and adults with special emphasis on hypoxia, acidosis, and hypovolemia in children. Treatment of this rhythm requires diagnosis of the cause and then specific directed treatment ( Table 127–2.4).

Table 127–2.4. Causes of Electromechanical Dissociation (EMD)

Causes of Pediatric Cardiopulmonary Arrest The annual incidence of cardiac arrest in children and adolescents is about 12:100,000 ( 7,11). The most common cause in infants is usually respiratory in origin rather than cardiac as in adults. As the child ages, the causes change from disease-oriented to trauma. The leading cause of death in children aged 1 to 14 years is trauma, with more than 23,000 deaths per year (8). Table 127–2.5 lists the most common causes of cardiac arrest.

Table 127–2.5. Causes of Pediatric Cardiac Arrest

Sudden infant death syndrome (SIDS), the leading cause of cardiac arrest and death in infants, is defined as the sudden death of an infant that is unexplained by history and for which a thorough postmortem examination fails to demonstrate the cause of death (see Chapter 129–3). Outcome Out-of-hospital cardiac arrest in children has a poor prognosis with neurologic morbidity such as vegetative state in many who survive ( 9). This has led to attempted guidelines for cessation for CPR such as discontinuing efforts after 25 minutes if there is no spontaneous circulation ( 10). Schindler et al. (11) found 15% survival to discharge in children requiring CPR in the ED. This is in agreement with prior studies ( 12). The most recent studies use larger doses of epinephrine, with increased return of spontaneous circulation. Regardless, no patients in the Schnidler et al. series who had more than 20 minutes of ED CPR survived. The only exception might be with profound hypothermia (13). Clearly we need more on-scene interventions to improve these dismal statistics. References 1. Emergency Cardiac Care Committee and Subcommittees, American Heart Association: Guidelines for cardiopulmonary resuscitation and emergency cardiac care (part IV). JAMA 1992;268:2262–2275. 2. Orlowski JP: Optimum position for external cardiac compression in infants and young children. Ann Emerg Med 1986;15:667–673. 3. Heinild S, Sondergaard T, Tudvad F: Bone marrow infusions in childhood: experiences from a thousand infusions. J Pediatr 1947;30:400–411. 4. Getschman SJ, Dietrich AM, Franklin WH, et al: Intraosseous adenosine: as effective as peripheral or central venous administration? Arch Pediatr Adolesc Med 1994;148:616–619. 5. Simmons CM, Johnson NE, Perkin RM, et al: Intraosseous extravasation complication reports. Ann Emerg Med 1994;23:363–366. 6. Kette F, Weil MH, von Planta M, et al: Buffer agents do not reverse intramyocardial acidosis during cardiac resuscitation. Circulation 1990;81:1660–1666. 7. Eisenberg M, Bergner L, Hallstrom A: Epidemiology of cardiac arrest and resuscitation in children. Ann Emerg Med 1983;12:672–674. 8. Bushore M: Children with multiple injuries. Pediatr Rev 1988;10:49–57. 9. Fields AL, Coble DH, Pollack MM, et al: Outcomes of children in a persistent vegetative state. Crit Care Med 1993;21:1890–1894. 10. Bonnin MJ, Pepe, Kimball KT, et al: Distinct criteria for termination of resuscitation in the out-of-hospital setting. JAMA 1993;270:1433–1436. 11. Schindler MB, Bohn D, Cox PN, et al: Outcome of out-of-hospital cardiac or respiratory arrest in children. N Engl J Med 1996;335:1474–1479. 12. Sheikh A, Brogan T: Outcome and cost of open- and closed-chest cardiopulmonary resuscitation in pediatric cardiac arrests. Pediatrics 1994;93:392–398. 13. Corneli HM: Accidental hypothermia: J Pediatr 1992;120:671–679.

Selected Readings APLS: the pediatric emergency medicine course. American Academy of Pediatrics, Elk Grove Village IL, and American College of Emergency Physicians, Dallas, TX, 1993. National Conference on Cardiopulmonary Resuscitation and Emergency Cardiac Care. Standards and Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care. JAMA 1992;255. Seidel J: Pediatric cardiopulmonary resuscitation: an update based on the new American Heart Association guidelines. Pediatr Emerg Care 1993;9:98–103. Textbook of pediatric advanced life support. American Heart Association, Dallas, TX, and American Academy of Pediatrics, Elk Grove Village, IL, 1994.

Chapter 128.1 Management of the Pediatric Airway Principles and Practice of Emergency Medicine

CHAPTER 128 AIRWAYS

1 Management of the Pediatric Airway Thom A. Mayer Introduction Pediatric Airway Anatomy Evaluation of the Pediatric Airway Airway Intervention Rapid-Sequence Intubation Surgical Management of the Airway Prehospital Care

INTRODUCTION In critically ill or injured children, the most important aspect of management is appropriate and aggressive treatment of the airway. In children, the primary reason to initiate resuscitation is primary respiratory failure; the next reason is secondary cardiac arrest. This has given rise to the dictum, “Adults drop dead—children droop dead,” meaning that most children have a progression of respiratory failure that results in hypoxia and acidosis, with secondary cardiac arrest as a result of their primary respiratory arrest.

PEDIATRIC AIRWAY ANATOMY There are numerous differences between the anatomy of the airway in the child and the adult. Proper positioning of the airway differs in adults and children because of anatomic features. In children, the head is larger and occupies a larger total body surface area and mass than in adults. In addition, the occiput is more prominent in children. The larynx in the child is more anterior and more cephalad than in adults. The epiglottis is more cartilaginous and sits at roughly a 45° angle, effectively obscuring the vocal cords unless appropriate airway maneuvers are undertaken. The epiglottis is also more “spoon-shaped” than in the adult, which can make intubation and interpretation of lateral neck radiographs more difficult ( 1). Although the narrowest portion of the adult airway is at the level of the vocal cords (or glottis), the limiting area of the pediatric airway up until the age of 10 to 12 years is the cricoid cartilage ( 2). The cricoid cartilage is also the site of abundant, loose areolar columnar epithelium in the child, which is sensitive to traumatic injury and infection. The columnar epithelium is also reactive. Thus, it is far more prone to the development of subglottic scarring than in adults. In addition, because the child's airway is smaller, narrowing of the airway causes a significant increase in airway resistance. Particularly in young children, the chest wall is far more compliant than in adults and less-well protected by muscle and fat, rendering it more susceptible to injury. In addition, forces applied to the chest wall are more likely to be transmitted to the underlying pulmonary parenchyma. The diaphragm in children is also more compliant and inserts at more of a horizontal angle. In cases in which the stomach or bowel is distended, significant respiratory compromise can occur because the diaphragm distends up into the chest more easily in children. Children use their abdominal musculature for the mechanics of breathing to a greater extent than do adults. For that reason, any forces that cause splinting of the abdominal muscles may also cause respiratory compromise.

EVALUATION OF THE PEDIATRIC AIRWAY The first assessment to make is the overall rate of respirations, which varies according to a child's age. In most cases, children in respiratory distress are tachypneic, although those with major trauma or prolonged hypoxia may be apneic. An attempt should also be made to assess the depth of respirations. Hyperpnea may indicate significant respiratory disease or underlying acidosis. Shallow respirations may reflect splinting of the chest or abdominal wall or simply the inability to move air. Following the initial determination of the rate and depth of respirations, a clinician should determine the overall work of breathing. This involves numerous factors, all of which result in the overall sense of how difficult it is for the patient to move air. In patients with significant respiratory compromise, a cascade of events occurs that reflects the body's attempt to recruit additional respiratory muscles to assist in the work of breathing. One of the earliest signs is nasal flaring, manifesting as widening of the nostrils on inspiration. This is particularly noticeable in young children with airway compromise, but it may be seen in older children ( 3). Retractions are the visible reflection of the use of additional airway muscles required to move air. This includes suprasternal, infraclavicular, subdiaphragmatic, and intercostal muscles. Although intercostal retractions have traditionally been discussed extensively, suprasternal, infraclavicular, and subdiaphragmatic retractions also are common. Most ominous is the simultaneous presence of all forms of retractions, reflecting the extreme amount of work that the child must do to move air effectively (4). After assessing the overall work of breathing, care should be taken to determine that there is bilateral, symmetric chest wall rise with inspiration. Failure of one side of the chest wall to move may mean that the child has a pneumothorax, hemothorax, tension pneumothorax, chest wall splinting, or airway obstruction. Auscultation of the chest should always be undertaken, but can be notoriously inaccurate in children, particularly if done with an adult stethoscope. For example, it is common for a child to have a pneumothorax with breath sounds that can be heard over each hemithorax. Similarly, even in children with complete lobar consolidation from pneumonia, it may be difficult to hear rales or adventitial sounds. This occurs because the child's chest wall transmits sounds so easily that airway movement through normal segments often transmits to the chest wall, obscuring what might normally be heard in adult patients. This problem can be obviated somewhat by the use of pediatrics stethoscopes, but it is still difficult to rely solely on auscultation to determine the extent or presence of pulmonary disease in children ( 1). When present, wheezing is an important finding, although some children with extensive bronchospastic disease move so little air that wheezing is not present. In addition, in normal children and young adults, the narrowness of the pediatric airway can cause minor amounts of wheezing with forced inspiration and expiration, which can be mistaken for bronchospastic diseases ( 5). Although some pediatric pulmonologists believe that egophony can be an important finding in children, it is difficult to reproduce reliably in the emergency department (ED) setting and, therefore, has limited utility. The presence or absence of cyanosis is an important finding indicating significant desaturation of hemoglobin. When prehospital care and ED triage personnel see a cyanotic patient, oxygen should be started immediately. Cyanosis is seen less commonly because of appropriate field interventions. Pulse oximetry is an extremely important adjunct in the management of the pediatric patient with a potentially compromised airway and should be used on all patients with suspected or confirmed respiratory failure. This allows for real-time data that can be helpful in the management of the pediatric patient. In addition, pulse oximetry should be used as a monitoring device for any child in whom either sedation or significant radiographic imaging is undertaken ( 6).

AIRWAY INTERVENTION Airway Positioning The prone position usually assumed by a child precludes the ability to maintain an open airway. Under these circumstances, the “mandibular block” of tissue, comprising the mandible, tongue, and associated muscle structures falls posteriorly producing near total airway obstruction. Instead, patients should be placed in the “sniffing position,” which consists of a slight amount of flexion of the neck on the long axis of the body and a slight amount of extension of the head on the neck. This can be accomplished by placing a towel or the physician's hand under the occiput of the child. At the same time, a jaw thrust maneuver should be done to elevate the mandibular block of tissue. From a practical standpoint, this results in a position in which the nares and the tip of the mandible are at the same level. Even when endotracheal intubation is performed, it is imperative to maintain the child in the sniffing position because the relatively soft tubes used in children can be compressed

by failure to maintain an adequate position of the airway. Oxygen Therapy Oxygen should properly be considered a drug in ill or injured pediatric patients, but it is a drug with an extremely wide tolerance and few or no side effects in pediatric emergency patients. One common failing of EDs is the failure to provide adequate oxygen therapy to the patient in a rapid fashion. Any child who is undergoing any form of respiratory distress should be given oxygen immediately. This includes providing oxygen at the triage station. Theoretic concerns in adult patients such as chronic hypercapnia decreasing the oxygen drive are rarely a factor in pediatric patients ( 7). For this reason, humidified oxygen at high-flow rates should be administered to any child in respiratory distress. Foreign Body Obstruction Fortunately, complete foreign body obstruction in children is not common. Partial airway obstruction caused by foreign bodies, however, is a common problem in the ED. In this circumstance, the child should be rapidly placed in the sniffing position and the pharynx should be suctioned and digitally swept for potential foreign bodies. Attempts should be made to ventilate the child by the bag-valve-mask technique. If airway obstruction persists, the procedure should be repeated. With significant foreign body obstruction in children under 1 year, the child may be turned upside down and four sharp back blows delivered in an attempt to dislodge the foreign body (8). In older children, the Heimlich maneuver may be used. If these measures fail, direct visualization of the airway and removal of foreign bodies may be attempted with Magill forceps. Care should be taken during such manipulations, however, because inexperienced operators may drive the foreign body deeper into the airway. Nonetheless, careful attempts to visualize and extract the foreign body should be undertaken. If this fails, airway control may require cricothyroidotomy to achieve transtracheal flow if the obstruction cannot be removed. Bag Valve Mask Ventilation The easiest form of assisted ventilation in a child is bag-valve-mask ventilation. This technique can be difficult in adults, owing to the difficulty to obtain a proper airway seal and sufficient pressures to generate tidal volume. These are of less concern in children. Obtaining a proper airway seal in a child usually is easy with an appropriate-sized mask. These masks can be chosen by use of the length-based resuscitation system or by ensuring that the mask fits snugly from the bony bridge of the nose to the midpoint of the symphysis of the mandible. Because of the child's smaller size, it is easier to obtain an adequate seal with minimal air leak in the child. Similarly, automatic-refilling resuscitation bags generate sufficient pressure to deliver adequate tidal volume of 15 mL/kg to the child. From a practical standpoint, this means that there should be bilateral, symmetric chest wall rise with each ventilation. Because of the possibility of gastric distention, a nasogastric tube should be placed in all patients undergoing assisted ventilation so that the stomach can be decompressed ( 1). This prevents potential distention of the diaphragms and airway compromise. Even in cases in which there is relatively high-grade airway obstruction, bag-valve-mask ventilation usually can be used to oxygenate the patient. In significant epiglottitis, it is possible to temporize with bag-valve-mask ventilation until endotracheal intubation can be accomplished. In high-grade obstruction from epiglottitis, it may be necessary to use an anesthesia bag to allow generation of higher peak airway pressures to overcome such obstruction. Unfortunately, most EDs are not equipped with anesthesia bags, but instead rely on some form of self-filling bag. Endotracheal Intubation Indications for endotracheal intubation in the ill or injured pediatric patient include the following: Inability to ventilate the child by bag-valve-mask methods to maintain oxygenation. The need for prolonged control of the airway, including prevention of aspiration. Maximization of oxygen and ventilation in children in shock. Need for controlled hyperventilation in head injured patients ( 9). Regardless of the reason for endotracheal intubation, ventilation with high-flow oxygen is recognized as the most important aspect of this procedure. First, the child should be aggressively preoxygenated using the bag-valve-mask technique before any attempt at endotracheal intubation. Because bag-valve-mask ventilation is almost always successful as a temporizing measure in the ED, it should always be done before attempts at endotracheal intubation. Second, the child should be placed in an appropriate airway position, as indicated previously. Third, the appropriate equipment should be selected and prepared for intubation. Length-based resuscitation systems allow selection of an adequate-sized tube, although some EDs prefer to use either anatomic indicators or tables or charts. A stylet should be placed in the airway, but care should be taken to insure that it does not extend past “Murphy's eye” because perforation of the trachea can occur if the stylet is allowed to advance outside the end of the endotracheal tube. The laryngoscope blade and light should be tested quickly to ensure that it is functioning. Adequate suctioning equipment, including a rigid tonsillar or Yankauer suction tip, should be provided. Because of the differences in the pediatric airway, most experienced intubators prefer to use a straight blade in children because it allows easier visualization of the vocal cords. When “standard” adult technique is used with a curved blade, the tip of the blade lodges in the vallecula. When the laryngoscope blade is elevated in the same way as in the adult patient, the epiglottis is not sufficiently elevated to visualize the vocal cords. For intubators who prefer using a curved blade in children, it is usually preferable to use the tip of the blade to elevate the epiglottis, similar to the technique that would be used with a straight blade. If length-based resuscitation systems or tables are not used, a simple way of choosing the appropriate tube size is to select a tube that is the same size as the child's external naris or the distal tip of the fifth finger. Both of these anatomic sites approximate the size of the cricoid ring until approximately 10 years of age ( 10). Care should be taken to advance the tube gently, but firmly past the cords once they have been visualized. The tube should be positioned so that there is bilateral, symmetric chest wall rise with appropriate ventilation once the stylet has been removed. Tube position should be verified by chest radiograph but it is essential to continue to watch for bilateral symmetric chest wall rise throughout the child's resuscitation. While breath sounds are often used in the adult patient, they can be strikingly deceiving in the pediatric patient. It is not uncommon to hear breath sounds when the tube has been placed in the esophagus. Similarly, it is possible to hear breath sounds on the left-hand side when the tube is placed down the right main stem bronchus. This is because of the ability of the child's chest wall to transmit sound easily, as mentioned previously.

RAPID-SEQUENCE INTUBATION In most EDs, rapid-sequence intubation commonly is used to ensure that the airway is handled in an efficient, rapid, and atraumatic fashion in adult and pediatric patients (Table 128–1.1, Table 128–1.2 and Table 128–1.3). The goals of rapid sequence intubation are:

Table 128–1.1. Rapid-Sequence Intubation: Paralyzing Agents

Table 128–1.2. Rapid-Sequence Intubation: Adjunctive Agents

Table 128–1.3. Medications for Rapid-Sequence Intubation

Rapid airway control with minimal physical and psychological trauma. Prevention of regurgitation and aspiration. Prevention of rises in intracranial pressure in head-injured or ischemic patients. The technique consists of using a muscle relaxant to induce paralysis and cricoid pressure to prevent regurgitation (Sellick maneuver) ( 11). In many cases, additional adjunctive agents are used to perform rapid-sequence intubation. These include sedatives to produce unconsciousness, vagolytic agents to decrease airway secretions, and lidocaine to decrease intracranial pressure. In many cases, however, the need for immediate control of the airway is such that a muscle relaxant to paralyze the patient is the only pharmacologic intervention possible. Nonetheless, the use of additional adjunctive agents is discussed. Two caveats are critical to remember throughout this procedure. First, it must be assumed that the patient has a full stomach and that aspiration is imminent unless adequate precautions are taken. Nasogastric intubation and aspiration of gastric air, secretions, and particulate matter should be undertaken whenever possible. Sellick maneuver, consisting of firm cricoid pressure with additional pressure lateral to the larynx against the spinal column, may prevent regurgitation and aspiration and should be used whenever rapid–sequence intubation is performed. Care should be taken to avoid occluding the carotid arteries during this procedure. If the patient is actively vomiting, the maneuver should be released to avoid tears of the esophagus. Second, in patients with suspected or clear evidence of cervical spine injury, the pharmacologic paralysis induced during this procedure relaxes the physical splinting offered by cervical muscular spasm. Therefore, extreme caution should be used to maintain adequate in-line cervical immobilization during this procedure. Because of these factors, rapid-sequence intubation always involves at least a two-rescuer approach. Ideally, three rescuers are used: one to intubate the patient, one to maintain cervical immobilization, and one to apply the Sellick maneuver. Muscle Relaxants for Intubation The agent selected to induce paralysis for rapid-sequence intubation should have rapid onset and short duration, be reversible, and have the fewest possible side effects. Such agents may be either depolarizing or nondepolarizing muscle relaxants. The muscle relaxant used most in the ED setting is succinylcholine, a depolarizing muscle relaxant, which acts by combining with the neuromuscular endplate, producing widespread fasciculation that proceeds predictably ( 12). These fasciculations begin over the chest and abdomen; proceed to the neck, arm, and leg; and are followed by facial, pharyngeal, and laryngeal fasciculations. Finally, the intercostal and diaphragmatic muscles fasciculate before complete paralysis. Succinylcholine's onset of action occurs at approximately 1 minute and peaks at 1½ to 2 minutes with a duration of action of approximately 7 to 8 minutes. To induce paralysis, a dose of 1 to 1.5 mg/kg should be given ( 13). There are several potential problems with neuromuscular blockade by means of succinylcholine. This drug causes a rise in intraocular, intragastric, and intracranial pressure, although it is not contraindicated in head-injured patients. Because of the rise in intraocular pressure seen with succinylcholine, it should never be used in penetrating eye injuries. With use of a prophylactic nasogastric tube and the Sellick maneuver (cricoid pressure), the rise in intragastric pressure (presumably caused by fasciculations of the gastric smooth muscle) can be obviated. Although succinylcholine does cause a brief and transient rise in intracranial pressure, it is commonly used in rapid sequence intubation in patients with severe head injuries ( 14). Succinylcholine should not be given to patients with neuromuscular disease, crush injuries, paraplegia, or burns of more than 1-week duration. Nonetheless, the drug can be safely used in patients immediately after the onset of either burns or spinal cord injury. Although bradycardia and excessive bronchial secretions have been reported with succinylcholine, this can be prevented by premedicating the patient with atropine. The nondepolarizing muscle relaxants include pancuronium, vecuronium, atracurium, and several other agents that are rarely used. Atracurium, however, can cause significant histamine release, resulting in profound hypotension, and rarely is used in either the ED or the operating suite ( 15). Vecuronium has an intermediate onset and duration. Onset times vary from 90 seconds to 2 minutes, with a duration of action of 25 to 60 minutes. There are few cardiovascular side effects with this drug, and it has a low risk for histamine release. Because it is a nondepolarizing muscle relaxant, it is reversible with cholinergic agonists such as edrophonium or

neostigmine. Vecuronium is available only as a powder and must be reconstituted at the time of use, although does not require refrigeration as does the preconstituted form of succinylcholine ( 16). Pancuronium bromide is a longer-acting nondepolarizing agent with an onset of action from 1 to 5 minutes and a duration from 30 to 80 minutes ( 17). The prolonged paralysis produced by the drug limits its usefulness in the immediate airway control of the pediatric patient in the ED, particularly when ongoing neurologic examinations must be performed. It is used primarily in those patients in whom succinylcholine or vecuronium is contraindicated, intubated patients who are fighting the ventilator, or patients requiring computed tomographic (CT) scans where patient movement is a problem and prolonged duration of action is not a problem. Selection of a muscle relaxant depends on the individual patient's needs and the experience of the physician with each of the drugs. In most cases, immediate airway control can be provided easily with succinylcholine or vecuronium. The potential complications of succinylcholine, although extensive, are infrequent in practical experience. For this reason, as well as its rapid onset and short duration, it is a common choice among experienced ED physicians providing rapid sequence intubation. Because of its potential side effects, however, an increasing number of physicians have used vecuronium, even though it must be constituted at the time of its use. Because it does not need to be refrigerated, it is often used by helicopter flight crews for rapid-sequence intubation. The side effects with this agent are extremely limited, and it is used frequently in ED airway management. Pancuronium bromide usually is given only to patients in whom long-term paralysis for airway control is indicated, although it remains a safe and reasonable alternative. Adjunctive Medications for Intubation When elective intubation is performed, it is common for the physician to use some form of sedative agent to induce unconsciousness. These agents should ideally have rapid onset, short duration, and limited side effects. The commonly used agent is thiopental, a short-acting barbiturate with an onset of action of 10 to 20 seconds. Thiopental may reduce intracranial pressure and has the potential of decreasing metabolic and oxygen demands. In addition, as with all barbiturates, it may cause hypotension resulting from myocardial depression and peripheral vasodilation ( 18). For this reason, its usefulness in the ED is somewhat limited because many patients needing emergency airway control also have some element of cardiovascular instability. It is important to remember that thiopental is an extremely poor analgesic and, therefore, does not ensure that the patient will be pain-free during airway procedures. An excellent alternative to thiopental is etomidate, an imidazole derivative that rapidly produces unconsciousness. A dose of 0.3 mg/kg is well tolerated, even in patients with potential cardiovascular instability. There are minimal side effects from this agent and it is frequently used by pediatric anesthesiologists and pediatric emergency physicians ( 19). While there are a number of newer agents that can be used as sedative-hypnotic agents (e.g., propofol) in the pediatric patient in the ED, the majority of these agents have relatively thin margins for error, do not offer clear-cut advantages to the agents listed previously, and are frequently more costly than other agents. For these reasons, utilization of these agents needs to be examined carefully for distinct clinical and cost-effective advantages prior to widespread use ( 20). Fentanyl is a short-acting, synthetic narcotic analgesic with a high degree of potency. The duration of action varies from 30 minutes to approximately 3½ hours, depending on the dose given. Fentanyl does produce postrespiratory depression and may not be the ideal agent for induction of unconsciousness during rapid sequence intubation ( 21). Diazepam and midazolam are benzodiazepine derivatives producing sedation of somewhat slower onset than the previously mentioned agents. Although cardiovascular and respiratory side effects are infrequent compared with barbiturates, the degree of unconsciousness produced is somewhat irregular. Midazolam produces a faster onset of unconsciousness and a shorter duration of action and is considerably more amnestic. It has gained wide use in rapid-sequence intubation. Ketamine is a highly disassociative anesthetic that produces rapid sedation and amnesia. In patients with documented hypovolemia, it causes a mild increase in systemic blood pressure through its sympathomimetic action. It also, however, produces intracranial pressure elevation, intraocular pressure elevation, and may produce excessive airway secretions. Because of its disassociative effects, it is usually not the agent of choice in awake and alert patients although it remains an excellent agent for deep sedations. Because it causes excessive secretions, premedication with atropine is recommended ( 22). It also has a bronchodilating effect and can be of benefit in patients with asthma who require intubation. Atropine is a vagolytic agent familiar to all ED physicians that is useful in blocking vagal stimulation during laryngoscopy, which helps prevent bradycardia and excessive secretions. However, it must be given several minutes before the induction of muscle relaxation to be effective. Choice of Medication for Rapid-Sequence Intubation Given this armamentarium of agents, what is the most effective way to proceed with rapid-sequence intubation? The ED physician should use the agents with which they are most familiar. Numerous agents in various combinations can be used. Generally, it is important to be able to induce muscle relaxation in an extremely rapid fashion without absolute dependence on adjunctive agents to produce unconsciousness or decrease secretions. Because of the nature of pediatric emergency medicine, often there is no time to perform a semi-elective rapid-sequence intubation, and the situation requires crash induction. Under these circumstances, succinylcholine, vercuronium or the newer agent rocuronium is a reasonable alternative ( 23). Because succinylcholine can be preconstituted in a refrigerated form, it is often the agent of choice ( 23) because it is a simple matter to draw it up and give it by intravenous push. Nonetheless, vecuronium or rocuronium are also reasonable choices under such circumstances, provided the nurses are adequately instructed in reconstituting the solution in a rapid and timely fashion ( Table 128–1.1) (23A). It is also critical that not only the ED physicians, but the respiratory therapists and nurses in the ED are familiar with performing the Sellick maneuver to prevent regurgitation and aspiration. All of the details of emergency airway management in children should be discussed in educational programs for the ED staff. While it is important to be able to accomplish emergency or “crash” for ET intubation, ED physicians should also be familiar with adjunctive agents, particularly those that rapidly and safely induce unconsciousness. Under circumstances in which time allows a semi-elective rapid-sequence intubation, thiopental, etomidate, or other agents may be helpful in inducing unconsciousness. In a patient with status asthmaticus in whom intubation is required because of impending respiratory failure, it is important to render the patient unconscious before intubation. In such circumstances, etomidate, ketamine, diazepam, and midazolam are reasonable alternatives because thiopental is contraindicated in status asthmaticus. If there is time to produce unconsciousness by any of the mentioned agents, it is also reasonable to assume that the patient may also be pretreated with atropine. In addition, patients with severe head injuries in whom intracranial pressure may be elevated can be treated with lidocaine in a dose of 1 mg/kg to attempt to prevent a rise in intracranial pressure and decrease the incidence of laryngospasm. This agent, however, must be given 3 to 5 minutes before airway manipulation for maximum effect. Regardless of what agents are chosen to provide rapid-sequence intubation, it is essential that the patient be effectively preoxygenated and suctioned before any attempt at airway manipulation. Although all ED staff caring for ill or injured children should be capable of providing rapid-sequence intubation, effective instruction should be given to all staff members to ensure that they are familiar with this technique and the need for maintenance of appropriate maneuvers during airway manipulation.

SURGICAL MANAGEMENT OF THE AIRWAY In rare circumstances, children may have direct injury to the larynx or trachea as a result of bicycle or snowmobiling accidents, running into a fixed object that strikes them in the larynx, etc. These injuries, however, are unusual in children, rendering cricothyroidotomy or tracheostomy a rare necessity. The dictum “ventilate—don't operate!” applies best to children ( 24). Almost all children can be adequately ventilated and oxygenated without surgical intervention. In patients with direct laryngeal injury, the preferred surgical method for airway control is needle cricothyroidotomy, which can provide up to 30 minutes of airway control when used with jet ventilation (25). Needle cricothyroidotomy (see Chapter 1) should be performed with the patient's head in a neutral position with adequate in-line cervical immobilization. After preparing the neck with antiseptic solution, one finger should be used to palpate the cricothyroid membrane in the midline, between the thyroid and the cricoid cartilage. It is critical to stay precisely in the midline during this procedure to ensure that the airway is appropriately cannulated and significant bleeding is avoided. An assistant should always be present to hold the child's head and neck and facilitate this midline position. Once the cricothyroid membrane has been identified, a 10-mL syringe should be attached to a large, 14-gauge catheter. While palpating the cricothyroid cartilage in the midline, insert a catheter just below the midpoint of the

cricothyroid membrane with a needle angled 45° caudally. Rapid aspiration of air into the syringe indicates entry into the tracheal lumen. The stylet should be carefully withdrawn while the plastic catheter is advanced caudally into the trachea, taking care not to perforate the posterior tracheal wall. The position of the catheter should be rechecked by aspirating on the syringe. The hub of the catheter should be attached to a 3.5-mm pediatric endotracheal tube adapter. Bag ventilation can be delivered by this means or by connecting a high-flow oxygen source with a wide connector between the oxygen and cannula. Intermittent ventilation can be delivered by occluding the open port of the wide connector with the thumb. This technique allows 30 to 45 minutes of airway control under duress, and an additional 14-gauge needle may be placed adjacent to the initial one to allow venting of the airway and blowing off carbon dioxide.

PREHOSPITAL CARE The most important aspect of prehospital care of the pediatric patient is to ensure that all prehospital care providers are adequately instructed in assessment of the pediatric airway and as bag-valve-mask ventilation. Although endotracheal intubation of children is an important skill for paramedics, prehospital care providers often need training in assessment and initial management of the airway bag and mask ventilation. References 1. Mayer T: Emergency management of pediatric trauma. Philadelphia: WB Saunders Co., 1985. 2. Mayer T: Initial evaluation and management of the injured child. In: Mayer T, ed. Emergency management of pediatric trauma. Philadelphia: WB Saunders Co., 1985:1–38. 3. Cohen DE, Broennle AM: Emergency department anesthetic management. In: Fleisher GR, Ludwig SL, eds. Textbook of pediatric emergency medicine. 2nd ed. Baltimore: Williams & Wilkins, 1988:53–65. 4. Backofen JE, Roger MC: Emergency management of the airway. In: Roger MC, ed. Textbook of pediatric intensive care. Baltimore: Williams & Wilkins, 1987:22–38. 5. Steuart RD: Endotracheal intubation. In: Hallaham ML, ed. Current therapy in emergency medicine. Toronto: BC Decker, 1987:11–21. 6. Kulick RM: Pulse oximetry. Pediatr Emerg Care 1987;3:127–132. 7. Hedges JR, Amsterdam JT, Cionni DJ, et al: Oxygen saturation as a marker for admission or relapse with acute bronchospasm. Am J Emerg Med 1987;5:192–202. 8. Bushore M, Fleisher G, Siedel J, et al: Advanced pediatric life support course. Dallas: American College of Emergency Physicians, 1990. 9. American College of Surgeons-Committee on Trauma. Advanced Trauma Life Support Course. Chicago: American College of Surgeons, 1988. 10. Yamamoto LG, Yim GK, Britten AG: Rapid sequence anesthesia induction for emergency intubation. Pediatr Emerg Care 1990;6:200–205. 11. Sellick BA: Cricoid pressure to control regurgitation of stomach contents during induction of anesthesia. Lancet 1961;2:404–408. 12. Roberts DJ, Clinton JE, Ruiz E: Neuromuscular blockade for critical patients in the emergency department. Ann Emerg Med 1986;15:152–158. 13. Thompson JD, Fish S, Ruiz E: Succinylcholine for endotracheal intubation. Ann Emerg Med 1982;11:526–532. 14. Minton MD, Grosslight K, Stirt JA, et al: Increases in intracranial pressure from succinylcholine: prevention by prior non-depolarizing blockade. Anesthesiology 1986;65:165–172. 15. Lennon RL, Olson RA, Gronert GA: Atracurium or vecuronium for rapid sequence endotracheal intubation. Anesthesiology 1986;64:510–517. 16. Casson WR, Jones RM: Vecuronium induced neuromuscular blockade: the effect of increasing dose on speed of onset. Anesthesia 1986;41:354–360. 17. Shanks CA: What's new in skeletal muscular relaxants and their antagonists? Anesth Clin North Am 1988;6:335–341. 18. Hudson RJ, Stanski DR, Burch PG: Pharmacokinetics of methohexital and thiopental in surgical patients. Anesthesiology 1983;59:215–219. 19. Capan LM, Miller SM, Turnborg H, eds: Trauma anesthesia and intensive care. Philadelphia: JB Lippincott, 1991. 20. Nelson WE, Behrman DE, Dleigman RM: Pediatric critical care. In: Nelson's textbook of pediatrics. 25th ed. Philadelphia: WB Saunders and Co., 1996. 21. Shudnofsky CR, Wright SW, Dronen SC, et al: The safety of fentanyl use in the emergency department. Ann Emerg Med 1989;18:635–642. 22. White PF, Way WL, Trevor AJ: Ketamine—its pharmacology and therapeutic uses. Anesthesiology 1982;56:119–126. 23. Reeves ST, Turcasso NM: Nondepolarizing neuromuscular blocking drugs in the ICU. South Med J 1997;90:769–774. 23A. Nelson JM, Morell RC, Butterworth JF: Rocuronium vs. succinylcholine for rapid sequence intubation. J Clin Anaesth 1997;9:317–320. 24. Mayer T: Initial evaluation and management of the injured child. In: Mayer T, ed. Emergency management of pediatric trauma. Philadelphia: WB Saunders Co., 1985:1–38. 25. Mayer TA: Emergency pediatric tracheostomy: a technique in search of an indication. Ann Emerg Med 1987;16:606–607.

Chapter 128.2 Pediatric Asthma Principles and Practice of Emergency Medicine

CHAPTER 128 AIRWAYS

2 Pediatric Asthma Robert G. Bolte Introduction Adrenaline Albuterol Laboratory Studies Intubation Metered-Dose Inhaler Ipratropium Need for Early Corticosteroids Magnesium Medicolegal Pearls

INTRODUCTION Asthma is characterized by bronchial hyperreactivity, airway inflammation, and reversible airway obstruction ( 1). Asthma is one of the most common diseases of childhood, with a prevalence of 4.1% in the pediatric population ( 2). Despite a variety of new therapeutic modalities for the management of asthma, the incidence, hospitalization rate, and mortality rate for pediatric asthma has increased in the United States during the past two decades ( 3). In the past decade, the inhaled beta-adrenergic agents have become the mainstay of acute asthma therapy, supplanting more nonspecific parenteral agents (e.g., adrenaline and aminophylline. For initial treatment of asthma, beta 2-agonists produce more rapid and potent bronchodilation than does intravenous theophylline. In cases of acute asthma, if emergency department (ED) beta 2-aerosol therapy is optimized, the additional use of theophylline (oral or intravenous) increases side effects but not bronchodilation. Studies in hospitalized adult and pediatric patients demonstrate that intravenous aminophylline provides no additional benefit but does increase adverse effects when added to routine inhaled beta-aerosols. Intravenous isoproterenol is no longer recommended due to the dangers of cardiac toxicity.

ADRENALINE Adrenaline still has an occasional use in children rapidly deteriorating on beta 2-agonist inhalation therapy (.01 mg/kg of 1:1000 adrenaline subcutaneously) who may be unresponsive to albuterol or metaproterenol. Also in the struggling toddler who is unable to use the nebulizer or who is resisting it, a subcutaneous injection of adrenaline may result in clinical improvement and subsequent ease in using the nebulizer. In cases of severe asthma with substantial diminution in tidal volume, hypoventilation, or obstruction, the delivery of nebulized medication may be inadequate. In such instances, one may also be dealing with anaphylaxis. Use of adrenaline may result in sufficient relief to avoid endotracheal intubation. Intravenous terbutaline can also be used in this situation, but requires a delay in gaining intravenous access. (For terbutaline, use 10 mg/kg over 30 minutes followed by a continuous infusion of 0.1 µg/kg per minute.)

ALBUTEROL Albuterol is currently the beta-agonist of choice for delivery by the inhaled route in the treatment of acute pediatric asthma (2.5 mg per dose in saline). Frequent high-dose nebulizations are the standard method of delivery (with oxygen at 6 to 8 L/min). If respiratory failure is impending, continuous albuterol nebulization (0.5 mg/kg/hr) should be promptly initiated, possibly avoiding the need for mechanical ventilation. Electrolytes must be monitored, however, because hypokalemia results from albuterol treatment.

LABORATORY STUDIES Because of their ventilation/perfusion characteristics, children are prone to the development of hypoxia during an asthmatic exacerbation. Therefore, administration of oxygen and continuous monitoring of oxygen saturation in the asthmatic child with moderate to severe distress is essential. If feasible, capillary or arterial blood gas measurements should be obtained in any child with a severe exacerbation of asthma initially unresponsive to treatment. P CO2 is the best parameter of ventilation. As respiratory drive is typically increased with an asthmatic exacerbation, a normal P CO2 (38 to 42 mmHg) in an asthmatic child with obvious respiratory distress is an early sign of impending respiratory failure. Peak flow measurements should be incorporated whenever possible into the clinical evaluation of the child, 5 years of age or greater, with an asthmatic exacerbation. Although not a part of the routine assessment of the asthmatic child in the ED, it is prudent to obtain a chest radiograph in any asthmatic child considered severe enough to be transported for a higher level of care if the transport itself is not delayed by this process.

INTUBATION In cases of rising P CO2, falling P O 2, along with exhaustion, agitation, sometimes cyanosis, and change in mental status, respiratory failure is imminent. Intubation may be required as a life-saving intervention, along with mechanical ventilation. Skill in intubation is imperative in such cases. Rarely, in status asthmaticus oxygenation cannot be maintained. One report demonstrates the use of emergency extracorporeal life support in three such cases in Japan.

METERED-DOSE INHALER Some pediatric studies in EDs have suggested that a metered-dose inhaler (MDI) combined with a spacer device can deliver inhaled beta-agonists with effectiveness comparable to nebulization. Depending on the practice setting, the more routine use of MDIs with spacers may result in significant cost reductions. None of the MDI studies published to date have large numbers of children who are young and, therefore, less cooperative or critically ill in severe distress.

IPRATROPIUM Cholinergic-mediated bronchoconstriction can be blocked by anticholinergic agents, such as ipratropium, which competitively antagonize acetylcholine at its receptor sites. Ipratropium is a synthetic derivative of atropine. Because of its poor gastrointestinal absorption and lack of central nervous system effects, nebulized ipratropium produces no significant systemic toxic effects. The use of repeated doses of ipratropium (250 µg) added to frequent high-dose albuterol nebulizations has been shown to be safe and more effective than albuterol alone. Moreover, the additive use of ipratropium was shown to reduce hospitalization rates in the subgroup of children whose asthmatic exacerbations were most severe (forced expiratory volume in 1 second < 30% of predicted).

NEED FOR EARLY CORTICOSTEROIDS An asthmatic exacerbation has a significant inflammatory component and corticosteroids are the mainstay of acute anti-inflammatory treatment. Data suggests that the anti-inflammatory effects of oral and parenteral corticosteroids have a relatively rapid onset, with significant clinical improvement seen as early as 2 to 4 hours after administration. Studies highlight the importance of early administration of parenteral steroids in the ED treatment of the child with moderate to severe disease, who has the potential for hospital admission if not improved with ED treatment. A reasonable management approach would also incorporate a 3 to 4 hour “poststeroid administration ED observation period” to allow time for the potential clinical improvement to become apparent and, therefore, possibly avoid hospitalization. The oral route offers the advantages of cost savings as well as minimizing pain for the child when compared to intravenous therapy. (For intravenous, methylprednisolone 2

mg/kg orally, 1 to 2 mg/kg prednisone given once daily for 3 to 7 days. No tapering is needed.) For the child with an acute asthmatic exacerbation who responds to ED treatment and is able to be discharged to home, a short course of high-dose oral steroid should be strongly considered to help prevent clinical relapse with the potential for additional ED visits and/or hospitalization. Extensive clinical experience has shown that short courses of high-dose oral steroids without tapering are safe and effective (prednisone 2 mg/kg/day up to 60 mg in two divided doses). They are indicated if the child with a moderate to severe exacerbation required significant ED treatment or if the exacerbation was incompletely responsive to reasonable home bronchodilator therapy prior to ED intervention. A history of frequent hospital admissions or repeated ED visits may also influence the decision toward prescribing a short course of steroids at discharge. If the child is hospitalized, steroids are indicated to facilitate more rapid improvement of airway obstruction. For intravenous use, methylprednisolone (2 mg/kg) is a reasonable choice on the basis of its short duration of pituitary-adrenal suppression and minimal effects on sodium retention.

MAGNESIUM Magnesium sulfate has received attention as a possible treatment modality in the acute management of the asthmatic patient. There is no clear consensus in the adult literature regarding the utility of magnesium sulfate infusion with recent clinical trials reaching conflicting conclusions. In the pediatric age group, two recent randomized, placebo-controlled trials suggest efficacy, particularly in the severe pediatric exacerbation. In the child with severe exacerbation (e.g., potential intensive care unit admission, impending respiratory failure) not responding to aggressive conventional treatment regimens (continuous albuterol inhalation, multiple ipratropium nebulizations), intravenous magnesium appears to be a prudent modality to expeditiously implement. Toxicity appears to be minimal and clinical response is relatively rapid (25 mg/kg—no more than 2 g mixed with 100 to 200 mL of saline and given over 20 min).

MEDICOLEGAL PEARLS One case resulting in a large settlement involved a 4-year-old child with progressive asthma admitted to the hospital. He would not take oral medications, intravenous access was difficult, and agitation made nebulization difficult. He suffered a cardiac arrest (in asystole) after a respiratory arrest. References 1. Guidelines for the diagnosis and management of asthma. National Asthma Education Program, Expert Panel Report. U.S. Department of Health and Human Services, National Institutes of Health. Publication No. 97-4051, pp. 59–70. April 1997. 2. Weitzman M, Gortmaker SL, Sobol AM, et al.: Recent trends in the prevalence and severity of childhood asthma. JAMA 1992;268:2673. 3. Centers for Disease Control and Prevention. Asthma—United States, 1982–1992. MMWR 1995;43:952.

Suggested Readings Appel DA, Karpel JP, Sherman M: Epinephrine improves expiratory flow rates in patients with asthma who do not respond to inhaled metaproterenol sulfate. J Allerg Clin Immunol 1989;84:90–98. Beck R, Robertson C, Galdes-Sebaldt M, et al: Clinical and laboratory observations—Combined salbutamol and ipratropium bromide by inhalation in the treatment of severe acute asthma. J Pediatr 1985;107:606. Becker AB, Nelson NA, Simons FER: Inhaled salbutamol (albuterol) vs injected epinephrine in the treatment of acute asthma in children. J Pediatr 1983;102:465. Benton G, Thomas RC, Nickerson BG, et al: Experience with a metered-dose inhaler with a spacer in the pediatric emergency department. AJDC 1989;143:678. Bloch H, Silverman R, Mancherje N, et al: Intravenous magnesium as an adjunct in the treatment of acute asthma. Chest 1995;107:1576. Bodenhamer MD, Bergstrom R, Brown D, et al: Frequently nebulized beta-agonists for asthma: effects on serum electrolytes. Ann Emerg Med 1992;21:1337. Bowton DL, Goldsmith RRT, Haponik EF: Substitution of metered-dose inhalers for hand-held nebulizers: success and cost savings in a large acute-care hospital. Chest 1992;101:305. Brain JD, Valberg PA: Deposition of aerosol in the respiratory tract. Am Rev Respir Dis 1979;120:1325. Brunette MG, Lands C, Thibodeau LP: Childhood asthma: prevention of attacks with short-term corticosteroid treatment of upper respiratory tract infection. Pediatrics 1988;81:624. Carryer HM, Koelsche GA, Prickman LE, et al: Effects of cortisone on bronchial asthma and hay fever occurring in subjects sensitive to ragweed pollen. Mayo Clin Proc 1950;25:482. Carter E, Cruz M, Chesrown S, et al: Efficacy of intravenously administered theophylline in children hospitalized with severe asthma. J Pediatr 1993;122:470. Chamberlin P, Meyer WJ III: Management of pituitary-adrenal suppression secondary to corticosteroid therapy. Pediatrics 1981;67:245. Chick TW, Nicholson DP, Johnson RL: Effects of isoproterenol on distribution of ventilation and perfusion in asthma. Am Rev Respir Dis 1973;107:869. Chou KJ, Cunningham SJ, Crain EF: Metered-dose inhalers with spacers vs nebulizers for pediatric asthma. Arch Pediatr Adolesc Med 1995;149:201. Ciarallo L, Sauer AH, Shannon M: Intravenous magnesium therapy for moderate to severe pediatric asthma: results of a randomized, placebo-controlled trial. J Pediatr 1996;129:809. Craig VL, Bigos D, Brilli RJ: Efficacy and safety of continuous albuterol nebulization in children with severe status asthmaticus. Pediatr Emerg Care 1996;12:1. Crain ER, Weiss KB, Fagan MJ: Pediatric asthma care in US emergency departments: current practice in the context of the NIH guidelines. Arch Pediatr Adolesc Med 1995;149:893. Cugell DW: Clinical pharmacology and toxicology of ipratropium bromide. Am J Med 1986;81:18. Cydulka RK, Emerman CL: A pilot study of steroid therapy after ED treatment of acute asthma. Is a taper necessary? J Emerg Med 1998;16:15–21. Davies DS: Pharmacokinetics of inhaled substances. Scand J Respir Dis 1979;103:44. Davis A, Vickerson F, Worsley G, et al: Clinical and laboratory observations: determination of dose-response relationship for nebulized ipratropium in asthmatic children. J Pediatr 1984;105:1002. DeNicola LK, Monem GF, Gayle MO, et al: Treatment of critical status asthmaticus in children. Pediatr Clin North Am 1994;41:1293. DeStefano G, Bonetti S, Bonizzato C, et al: Additive effect of albuterol and ipratropium in the treatment of bronchospasm in children. Ann Allergy 1990;65:260. DiGiulio GA, Kercsmar CM, Krug SE, et al: Hospitalized treatment of asthma: lack of benefit from theophylline given in addition to nebulized albuterol and intravenously administered corticosteroid. Pediatr 1993;122:464.

J

Fanta CH, Rossing TH, McFadden ER, Jr: Emergency room treatment of asthma. Relationships among therapeutic combinations, severity of obstruction and time course of response. Am J Med 1982;72:416. Fiel SB: Should corticosteroids be used in the treatment of acute, severe asthma? I. A case for the use of corticosteroids in acute, severe asthma. Pharmacotherapy 1985;5:327. Fiel SB, Swartz MA, Glanz K, et al: Efficacy of short-term corticosteroid therapy in outpatient treatment of acute bronchial asthma. Am J Med 1983;75:259. Fuglsang G, Pedersen S, Borgstrom L: Dose-response relationships of intravenously administered terbutaline in children with asthma. J Pediatr 1989;114:315. Galant SP: Current status of b-adrenergic agonists in bronchial asthma. Pediatr Clin North Am 1983;30:931. Gandevia B: Historical review of the use of parasympatholytic agents in the treatment of respiratory disorders. Postgrad Med J 1975;51:13. Garra B, Shapiro GG, Dorsett CS, et al: A double-blind evaluation of the use of nebulized metaproterenol and isoproterenol in hospitalized asthmatic children and adolescents. J Allergy Clin Immunol

1977;60:36. Gazioglu K, Condemi JJ, Hyde RW, et al: Effect of isoproterenol on gas exchange during air and oxygen breathing in patients with asthma. Am J Med 1971;50:185. Geelhoed GC, Landau LI, LeSouef: Evaluation of SaO 2 as a predictor of outcome in 280 children presenting with acute asthma. Ann Emerg Med 1994;23:1236. Geelhoed GC, Landau LI, LeSouef PN: Oximetry and peak expiratory flow in assessment of acute childhood asthma. J Pediatr 1990;117:907. Green SM, Rothrock RG: Intravenous magnesium for acute asthma: failure to decrease emergency treatment duration or need for hospitalization. Ann Emerg Med 1992;21:260. Gross NJ. Sch 1000: a new anticholinergic bronchodilator. Am Rev Respir Dis 1975;112:823. Gross NJ, Skorodin MS: Anticholinergic, antimuscarinic bronchodilators. Am Rev Respir Dis 1984;129:856. Hales CA, Kazemi H: Hypoxic vascular response of the lung. Effect of aminophylline and epinephrine. Am Rev Respir Dis 1974;110:126. Harfi H, Hanissian AS, Crawford LV: Treatment of status asthmaticus in children with high doses and conventional doses of methylprednisolone. Pediatrics 1979;61:829. Harris JB, Weinberger MM, Nassif E, et al: Early intervention with short courses of prednisone to prevent progression of asthma in ambulatory patients incompletely responsive to bronchodilators. J Pediatr 1987;110:627. Harris L: Comparison of the effects on blood gases, ventilation, and perfusion of isoproterenolphenylephrine and salbutamol aerosols in chronic bronchitis with asthma. J Allergy Clin Immunol 1972;49:63. Haskell RJ, Wong BM, Hansen JE: A double-blind, randomized clinical trial of methylprednisolone in status asthmaticus. Arch Intern Med 1983;143:1324. Hurwitz ME, Burney RE, Howatt WF, et al: Clinical scoring does not accurately assess hypoxemia in pediatric asthma patients. Ann Emerg Med 1984;13:1040. Jannum DR, Mickel SF: Anisocoria and aerosolized anticholinerigics. Chest 1986;90:148. Jezek V, Ourednick A, Stepanek J, et al: The effect of aminophylline on the respiration and pulmonary circulation. Clin Sci 1970;38:549. Kaliner M: Human lung tissue and anaphylaxis: the role of cyclic GMP as a modulator of the immunologically induced secretory process. J Allergy Clin Immunol 1977;60:204. Kattan M: Management of acute asthma: a continuing challenge. J Pediatr 1996;129:783. Katz RW, Kelly HW, Crowley MR, et al: Safety of continuous nebulized albuterol for bronchospasm in infants and children. Pediatrics 1993;92:666. Kelly HW: Controversies in asthma therapy and the b2-adrenergic agonists. Clin Pharm 1984;3:386. Kerem E, Levison H, Schuh S, et al: Efficacy of albuterol administered by nebulizer versus spacer in children with acute asthma. J Pediatr 1993;123:313. Konig P: Asthma: a pediatric pulmonary disease and a changing concept. Pediatr Pulmonol 1987;3:264. Kukitu I, Okamoto K, Satut T, et al: Emergency extracorporeal life support for patients with near-fatal status asthmaticus. Am J Emerg Med 1997;15:566–569. Kulick RM: Pulse oximetry. Pediatr Emerg Care 1987;3:127. Landau LI: Outpatient evaluation and management of asthma. Pediatr Clin North Am 1979;26:581. Lee H, Evans HE: Lack of cardiac effect from repeated doses of albuterol aerosol. Clin Pediatr 1986;25:349. Levitt MA, Gambrioli EF, Fink JB: Comparative trial of continuous nebulization versus metered-dose inhaler in the treatment of acute bronchospasm. Ann Emerg Med 1995;26:273. Lin RY, Sauter D, Newman T, et al: Continuous versus intermittent albuterol in the treatment of acute asthma. Ann Emerg Med 1993;22:1847. Littenberg B, Gluck EH: A controlled trial of methylprednisolone in the emergency treatment of acute asthma. N Engl J Med 1986;314:150. Malani JT, Robinson GM, Seneviratne EL: Ipratropium bromide induced angle closure glaucoma. N Z Med J 1982;95:749. Letter. McFadden ER, Lyons HA: Arterial-blood gas tension in asthma. N Engl J Med 1968;278:1027. Mikhail MS, Hunsinger SY, Goodwin SR, et al: Myocardial ischemia complicating therapy of status asthmaticus. Clin Pediatr 1987;26:419. Molho M, Benzaray S, Lidji M, et al: Salbutamol versus atropine. Site of bronchodilatation in asthmatic patients. Respiration 1987;51:26. Monem GF, Kissoon N, DeNicola L: Use of magnesium sulfate in asthma in childhood. Pediatric Annals 1996;25:136. Myers JH, Shook JE, Ward MA: Intravenous magnesium for moderate to severe childhood asthma. Pediatr Emerg Care 1995;11:325. Abstract. Newhouse MT, Dolovich MB: Current concepts, control of asthma by aerosols. N Engl J Med 1986;315:870. Newman SP, Pavia D, Moren F, et al: Deposition of pressurized aerosols in the human respiratory tract. Thorax 1981;36:52. Olshaker J, Jerrard D, Barish RA, et al: The efficacy and safety of a continuous albuterol protocol for the treatment of acute adult asthma attacks. Am J Emerg Med 1993;11:131. Pabon H, Monem G, Kissoon N: Safety and efficacy of magnesium sulfate in children with status asthmaticus. Pediatr Emerg Care 1994;10:200. Pain MC, Read J: Patterns of response to bronchodilator in young patients with asthma. Aust Ann Med 1963;12:216. Papo MC, Frank J, Thompson SE: A prospective, randomized study of continuous versus intermittent nebulized albuterol for severe status asthmaticus in children. Crit Care Med. 1993;21:1479. Pavia D, Thomson M, Shannon HS: Aerosol inhalation and depth of deposition in the human lung. Arch Environ Health 1977;16:131. Peerless AG, Rachelefsky GS, Mickey MR, et al: Bronchodilator characteristics of nebulized metaproterenol sulfate, isoetharine, and atropine in chronic asthma. J Allergy Clin Immunol 1963;72:702. Qureshi F, Zaritsky A, Lakkis H: Efficacy of nebulizes ipratropium in severely asthmatic children. Ann Emerg Med 1997;29:2205–211. Ratto D, Alfaro C, Sipsey J, et al: Are intravenous corticosteroids required in status asthmaticus? JAMA 1988;260:527. Rebuck AS, Chapman KR, Abboud R, et al: Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room. Am J Med 1987;82:59. Rebuck MB, Read J: Assessment and management of severe asthma. Am J Med 1971;51:788. Reilly PA, Yahav J, Mindorff C, et al: Dose-response characteristics of nebulized fenoterol in asthmatic children. J Pediatr 1983;103:121. Reisman J, Galdes-Sebalt M, Kazim F, et al: Frequent administration of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children. 1988;81:16.

J Allergy Clin Immunol

Robertson CF, Smith F, Beck R, et al: Response to frequent low doses of nebulized salbutamol in acute asthma. J Pediatr 1985;106:672. Rossing TH, Fanta CH, Goldstein DH, et al: Emergency therapy of asthma: comparison of the acute effects of parenteral and inhaled sympathomimetics and infused aminophylline. Am Rev Respir Dis 1980;122:365.

Rudnitsky GS, Eberlein RS, Schoffstall JM, et al: Comparison of intermittent and continuously nebulized albuterol for treatment of asthma in an urban emergency department. 1993;22:1842.

Ann Emerg Med

Scarfone RJ, Fuchs SM, Nager AL, et al: Controlled trial of oral prednisone in the emergency department treatment of children with acute asthma. Pediatrics 1993;92:513. Scarfone RJ, Loiselle JM, Wiley JF, et al: Nebulized dexamethasone versus oral prednisone in the emergency treatment of asthmatic children. Ann Emerg Med 1995;26:480. Schiermeyer RP, Finkelstein JA: Rapid infusion of magnesium sulfate obviates need for intubation in status asthmaticus. Am J Emerg Med 1994;12:164. Schuh S, Johnson D, Callahan S, et al: Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose therapy in severe childhood asthma. J Pediatr 1995;126:639. Schuh S, Parkin P, Rajan A, et al: High-versus low-dose, frequently administered, nebulized albuterol in children with severe acute asthma. Pediatrics 1989;83:513. Schuh S, Reider MJ, Canny G, et al: Nebulized albuterol in an acute childhood asthma: comparison of two doses. Pediatrics 1990;86:509. Self TH, Abou-Shala N, Burns R, et al: Inhaled albuterol and oral prednisone therapy in hospitalized adult asthmatics: does aminophylline add any benefit? Chest 1990;98:1317. Shah P, Dhurjon L, Metcalfe T, et al: Acute angle closure glaucoma associated with nebulized ipratropium bromide and salbutamol. Br Med J 1992;304:40. Siegel D, Sheppard D, Gelb A, et al: Aminophylline increases the toxicity but not the efficacy of an inhaled beta-adrenergic agonist in the treatment of acute exacerbations of asthma. Dis 1985;132:283. Skobeloff EM, Spivey VH, McNamara RM, et al: Intravenous magnesium sulfate for the treatment of acute asthma in the emergency department.

Am Rev Respir

JAMA 1989;262:1210.

Strauss RE, Wertheim DL, Bonagura VR, et al: Aminophylline therapy does not improve outcome and increases adverse effects in children hospitalized with acute asthmatic exacerbation. Pediatrics 1994;93:205. Streck WF, Lockwood DH: Pituitary adrenal recovery following short-term suppression with corticosteroids. Am J Med 1979;66:910. Tal A, Levy N, Bearman JE: Methylprednisolone therapy for acute asthma in infants and toddlers: a controlled clinical trial. Pediatrics 1990;86:350. Tal A, Pasterkamp H, Leahy F. Arterial oxygen desaturation following salbutamol inhalation in acute asthma. Chest 1984;86:868. Tiffany BR, Berk WA, Keir I, et al: Magnesium bolus or infusion fails to improve expiratory flow in acute asthma exacerbations. Chest 1993;104:831. Walters EH, Cockroft A, Griffiths T, et al: Optimal doses of salbutamol respiratory solution: comparison of three doses with plasma levels. Thorax 1981;36:625. Williams JR, Bothner JP, Swanton RD: Delivery of albuterol in a pediatric emergency department. Pediatr Emerg Care 1996;12:263. Younger RE, Gerber PS, Herrod HG, et al: Intravenous methylprednisolone efficacy in status asthmaticus of childhood. Pediatrics 1987;80:225.

Chapter 129.1 Infection and Bacteremia: Management of the Febrile Child Under Two Years Principles and Practice of Emergency Medicine

CHAPTER 129 INFECTIONS

1 Infection and Bacteremia: Management of the Febrile Child Under Two Years Daniel J. Isaacman and Paul N. Seward Capsule Definitions Epidemiology Clinical Presentation Laboratory Evaluation Search for Focus of Infection Hospital Management Conclusion Medicolegal Pearls

CAPSULE Perhaps nothing in emergency medicine is quite so alarming as a febrile child. Surely for the anxious or angry parents who appear at the emergency department (ED) with the child at midnight, it is a difficult time. Considering the diagnostic uncertainties and the devastating outcome of missing the diagnosis of sepsis or meningitis, even the most experienced and courageous of clinicians may occasionally reach past the chart of a febrile toddler for the next chart in the stack. All is not hopeless, however, there are reasonable ways to approach this problem. The approach to the febrile child is not fundamentally technologic. Instead, it is one that emphasizes the human qualities of medicine: basic clinical skills, communication with parents and families, and the integration of the patient into systems for continuity of care.

DEFINITIONS Fever is defined as an abnormal elevation of body temperature. In deriving normal values from a healthy population of infants and young children, investigators have noted that temperatures of 38.0° C (100.4°F) and above fall two standard deviations above the norm. Are all measuring devices equivalent? As many of the current practice guidelines for the evaluation of fever in infants and small children are based upon the height of fever, it is important to obtain an accurate body temperature measurement. Maternal ability to detect fever in children over 3 months of age by tactile assessment was shown to have a sensitivity of approximately 75%, whereas the sensitivity is lower in neonates ( 1). Rectal temperatures remain the gold standard for the determination of body temperature in these children. Tympanic membrane thermometry offers the advantage of being a rapid and noninvasive method of temperature measurement but can differ from rectal measurements by up to 1.0°F. The sensitivity of tympanic thermometry to detect clinically significant fever is low and ranges from 63 to 80% ( 2). For all children less than 36 months of age, a rectal temperature measurement should be obtained whenever management decisions will be based upon the presence or height of fever. Pascoe and Grossman (3), define the critical terms as follows: Bacteremia: The presence of bacteria in the blood. Septicemia: The presence and persistence of bacteria and their toxins in the blood, associated with systemic symptoms of fever and prostration. These definitions emphasize a critical and sometimes overlooked point: bacteremia and septicemia are not the same. Septicemic children are sick. They are always in danger and usually appear significantly ill. These are children who represent the bulk of the potentially poor outcomes and whose clinical presentation is generally suspicious. Bacteremic children, however, may appear transiently ill only during the acute showering of bacteria and otherwise may appear relatively well. Also, it is probable that many of these children might cope with their infection and do well. An unknown number of them, however, if untreated, may develop focal infections, septicemia, or meningitis. These children represent the principal diagnostic problem that renders this area of pediatrics so particularly challenging.

EPIDEMIOLOGY One of the best ways to approach diagnostic problems is to identify which patients one needs to worry about. Unfortunately, except to tell us that the younger the child the greater the risk, the epidemiologist has little to offer in the way of prediction of bacteremia. First, it does not matter where one practices: there is no socioeconomic predilection for bacteremia. The child of the suburbs has the same likelihood of problems and presents the same diagnostic dilemmas as the child of the inner city ( 4,5 and 6): 1. Two to eight percent of febrile children between 3 and 24 months have blood cultures that test positive for bacteria ( 3,5,7,8 and 9). 2. Routine immunization against Haemophilus influenzae has dramatically reduced the incidence of disease caused by this organism. Currently, 85 to 90% of occult bacteremia is caused by Streptococcus pneumoniae. A significant percentage of pneumococci (up to 35% in certain regions in the US) have developed moderate to high resistance to penicillins and cephalosporins, therefore, changing the approach to the treatment of disease caused by this organism. The other major etiologic agents include Neisseria meningitidus, Streptococcus pyogenes, Haemophilus influenzae, and Salmonella species. Staphylococcal bacteremia is commonly associated with bone or joint infection. 3. Four to ten percent of untreated children with bacteremia develop meningitis, even if the result of the lumbar puncture at initial presentation was negative ( 3). Children with fevers above 40.0°C (104°F) have an increased risk of having bacteria in the cerebrospinal fluid ( 3,10).

CLINICAL PRESENTATION Even though a systematic history (including parental observations) and physical examination by an experienced clinician are the best tests available to identify the bacteremic child, they are nonetheless unreliable predictors of who is sick and who is not ( 8,11). Research, to date, has shown variable sensitivity in the history and physical for the detection of bacteremia. However, Crocker and associates ( 12) examined 201 febrile infants of ages 6 months to 2 years, 21 of whom had blood cultures positive for the presence of bacteria. They noted no correlation between bacteremia and increasing temperature or parental perceptions of “irritability” or “lethargy.” Similarly, Dershewitz and colleagues ( 6) found that no level of training enabled a practitioner to identify bacteremic children clearly. Teach and Fleisher ( 13) showed poor sensitivity of the Yale Observation score in detecting occult bacteremia in febrile ambulatory pediatric patients. However, Schwartz and Wientzer ( 4) examined 52 children between 2 and 36 months of age who appeared to the pediatrician to have toxic symptoms and had temperatures higher than 38.8°C (101.8°F). Six of the toxic infants, but none of the nontoxic infants, had culture-positive bacteremia ( 4). Similarly, Waskerwitz and Berkelhamer (14) studied 25 pediatricians at all levels in a pediatric training program and their evaluations of 292 febrile children under 24 months of age. They showed that no single finding was absolutely predictive of bacteremia and that combining findings did not improve predictive accuracy. The physician's assessment, however, was the most useful factor in prediction. Most important, the physician's assessment reliably identified all patients with serious complications. The

researchers comment, “This study supports the notion that a good history and physical examination are essential components of the evaluation of each child. No other procedures should be considered ‘routine'” ( 14). Given that the examination is critical, if unreliable, what factors in the examination, history and physical, are the most useful? These are described in the following sections. Age The evaluation of a febrile infant, 0 to 3 months of age, differs from that for the older child, 3 to 36 months. The temperature cutoff used to determine the presence of fever as well as the incidence of serious bacterial infection (SBI) are different. Generally, this includes meningitis, bacteremia, pneumonia, VTI, bone joint infections and bacterial gastroenteritis. Additionally, the neurologic immaturity of the neonate makes the physical examination much less reliable in this age group. Current guidelines further subdivide the 0- to 3-month age group into two subpopulations: infants 0 to 28 days of life and those 29 to 90 days of life. Infants show decreased immune function due to deficiencies in humoral and cellular immunity and their examinations are often more difficult due to their relative neurologic immaturity. Fever in the young infant is also less common than in the older infant and young child. The physician is, therefore, cautioned to pay close attention to the infant in the first 3 months of life with this symptom. A documented fever in a young infant, therefore, generally mandates a battery of laboratory testing to rule out SBI. Several investigators evaluated the utility of a battery of laboratory tests to screen for SBI in this age group. The most extensively tested screening exam was developed by Dagan et al. (The Rochester criteria) ( 15). Experts in pediatric infectious diseases and pediatric emergency medicine generated a set of guidelines for the management of fever in this age group. This group utilized the Rochester criteria to develop the algorithm presented in Fig. 129–1.1.

Figure 129–1.1. Practice guideline for the management of a previously healthy infant 0 to 90 days of age with fever without source greater or equal to 38.0°C. (Reproduced with permission from Pediatrics 1993;92:1–12.)

Current recommendations for the evaluation of fever in this age group suggest a complete physical examination as well as a complete blood count, blood culture, urinalysis and urine culture. Febrile children under 1 month of age require a spinal tap as part of the evaluation and are generally hospitalized. Studies are underway evaluating the efficacy of outpatient management for children in this age group with normal physical examination and laboratory findings. Children between 28 and 90 days are felt to be at increased risk for SBI if they appear toxic on physical examination or if their laboratory findings are abnormal. These high-risk infants have approximately an 8 to 10% chance of harboring an SBI. They are typically hospitalized for parenteral antibiotic therapy while awaiting the return of culture results. Children who fall into the low-risk category have a 0 to 2% chance of having SBI and are, therefore, felt to be candidates for outpatient management (either with or without prophylactic antibiotic therapy). Outpatient management should only be considered if the child can be reexamined by a physician the following day and if the caretaker is reliable. While the guidelines have been the source of extensive debate, they form a reasonable starting point for attempting to identify infants at low risk for SBI. In general, the clinician must search for a means of identifying children at low risk who can be managed safely as outpatients. The more secure the follow-up, the more latitude offered to the clinician. For the child 91 days to 36 months who appears toxic, the following is suggested ( Fig. 129–1.2).

Figure 129–1.2. Practice guideline for the management of a previously healthy child 91 days to 36 months of age with fever without source. (Reproduced with permission from Pediatrics 1993;92:1–12.)

Vital Signs Any child under 2 years with a temperature above 39°C (103°F), even one who does not appear particularly ill, must be evaluated carefully. Although no age-specific standards exist for heart and respiratory rates in febrile children, tachycardias and tachypneas that seem out of proportion to the degree of fever require close evaluation and management. “General Appearance” This item is in quotes because it is the most important and least quantifiable factor considered in the examination. Regardless of temperature, febrile children who appear ill must be watched with concern. Moreover, their appearance should be assessed, not only in an initial examination but also during a period of time ( 3,5,7). During this time, the most important considerations are: Appearance: Color, tone, presence of respiratory difficulty, grunting, or flaring of the nostrils. Behavior: Does the child interact normally with the parents? Is the child interested in toys or a bottle? Does the child interact normally with the examiner? Most important, if irritable or unhappy, can the child be consoled by the parents ( 3,8,10)? Source of Infection Is there an otitis, a pharyngitis, an upper respiratory infection? Is there evidence of pneumonia or urinary tract infection? Similarly, the absence of a focus of infection

in a significantly febrile or ill-appearing child requires additional evaluation ( 3). Table 129–1.1 lists infectious agents that may be found in certain conditions.

Table 129–1.1. Common Infectious Agents

LABORATORY EVALUATION Significance of the White Blood Cell Count In most studies, approximately three-fourths of children over 3 months of age with Streptococcus pneumoniae bacteremia and one-half of children with Haemophilus influenzae infection have a white blood cell count of more than 15,000 per mm 3 (3,5,7,8,12) or a polymorphonuclear neutrophil count of more than 9000 per mm 3 (12). In addition, Crain and Shelov ( 16) studied 175 infants under 8 weeks of age and found that the clinical impression of sepsis, a white blood cell count of more than 15,000 per mm3, or an erythrocyte sedimentation rate of 30 or more identified all infants with bacteremia and excluded 82% of those without ( 16). Other laboratory indicators, including erythrocyte sedimentation rate and absolute polymorphonuclear neutrophil count, have seemed helpful in some studies, but none are absolute predictors (7). Studies over 2 decades have concluded that the variability of white blood counts is too great to be predictive ( 9,17,18). Finally, Bausher and Baker (18) note that patients who prove to have meningococcemia with low white blood cell counts and no meningeal signs may have a worse prognosis than those with higher white cell counts.

SEARCH FOR FOCUS OF INFECTION Provided that a thorough history and physical examination are unable to indicate a source for the fever and the white blood cell count is nonspecific the next step in the search for occult infection is laboratory testing. While some suggest that pneumonia can be difficult to detect clinically, there seems to be little utility in routinely ordering chest radiographs in young febrile children who do not have cough, tachypnea, or focal findings or auscultation of the chest ( 19). The common occult infections in this age group are urinary tract infection (UTI) and bacteremia. UTI occurs in approximately 5% of infants and young girls between the ages of 1 and 24 months of age with fever greater than 38.5°C (101.1°F) and no source. Groups at greatest risk for UTI include caucasian females under 1 year of age and uncircumcised males. Children in this age group with fever greater than 38.5°C (101.1°F) and no source should be screened for UTI. Specimens should be collected by catheterization or suprapubic aspiration and refrigerated if more than 10 minutes will elapse prior to the processing of the specimen. The decision to order a complete blood count on the febrile patient with fever and no focus of infection is linked to one's philosophy regarding the use of prophylactic antibiotics for the treatment of this disease. Studies have shown that an absolute white blood count of greater than 15,000/mm 3 is helpful in distinguishing febrile children with a better than 10% chance of bacteremia from those with a much lower chance (less than 3%) ( 19A). Studies suggest that the absolute neutrophil count may be another important predictor of bacteremia. Clinicians that subscribe to the belief that prophylactic antibiotics are effective in the prevention of serious sequelae of bacteremia may utilize the white count to help select a population of patients that merits presumptive treatment ( 19,20), with due respect to the phenomena of leukopenia with some infections—notably meningococcus and pseudomonas sp. Blood Culture The blood culture remains the gold standard for diagnostic tests—not so much as a test that is immediately useful, but the test with which others are compared. It is worth noting, however, that beyond simply defining disease, there is some evidence that the blood culture may be useful in quantifying it. Sullivan and associates ( 21) studied the relationship between the degree of clinical disease that eventually developed and the organism count on initial blood culture. They found that for Streptococcus pneumoniae and Haemophilus influenzae 92% of 25 patients with initial bacterial counts greater than 100 organisms/mL developed meningitis or epiglottitis; however, only 10% of 42 patients with lower counts developed serious disease. No difference was noted for Neisseria meningitidis (21). Bell et al. (22) noted that patients with occult bacteremia caused by S pneumoniae would often show low-density bacteremia when compared to patients with bacteremia caused by H influenzae or N menigitidus. It is also important to know how long blood cultures must be observed. Over a 3-year period in Children's Hospital of Pittsburgh, Rowley and Wald ( 23) reviewed 268 blood cultures yielding positive results; they noted that only four specimens became positive after 48 hours and that all of these were from patients with a previously identified infective focus. They concluded that empiric antibiotic therapy may be discontinued in immunocompetent patients without a focus of infection and with blood cultures that are negative after 48 hours ( 23). The volume of blood collected greatly affects the sensitivity of the blood culture. Information suggests that collecting at least 3 mL of blood per culture vial improves sensitivity of the test (24). Newer automated surveillance systems allow culture detection 24 hours per day and have speeded the time to the detection of positive growth. Contamination of blood cultures can be greatly reduced by careful attention to skin preparation, particularly by letting betadine dry on the skin for 60 seconds prior to venipuncture.

HOSPITAL MANAGEMENT The diagnosis of the febrile child is far from exact. The basic rule of emergency medicine must always come into play. In situations of diagnostic uncertainty, the physicians must do their best to estimate the risk that a given patient could have a bad outcome related to the presenting symptoms and protect those deemed to be at significant risk for this outcome. For the febrile child between 3 months and 2 years of age the following steps should be taken: 1. A thorough history and physical examination should guide the evaluation. A period of observation is often a helpful adjunct to resolve diagnostic uncertainty. 2. Any identified illness should be treated. It must be remembered, however, that the discovery of a specific focus of infection does not rule out a more disseminated infection as well. 3. Preexisting illness that compromises immune function may require presumptive treatment for sepsis. 4. Screening laboratories should include a urinalysis and culture for boys less than 6 months of age and girls less than 2 years of age. A complete blood count with differential and a blood culture should be considered for all children with fevers greater than 39°C (102.2°F). 5. A blood culture can be used to screen children with high fevers for bacteremia. If obtained, a minimum of 3 mL per culture vial is recommended. All children ill enough to merit a blood culture should receive follow-up within 24 hours. 6. All children whose blood culture yield positive results consistent with pathogenic bacteria must be reevaluated. If S pneumoniae or group A streptococcus are

identified and the patient is afebrile and appears well, the patient may be managed as an outpatient. If the preliminary results suggest H influenzae, Salmonella, or N meningitidus, the patient should be admitted to the hospital for additional evaluation and treatment. 7. The reliability of follow-up will play a major role in determining the optimal management strategy for each patient.

CONCLUSION The febrile infant or toddler presents a problem that will always concern the physician who treats sick children. In the midst of diagnostic uncertainties, however, the following basic principles of medical care hold true: Thorough clinical evaluation is the mainstay of diagnosis. Err on the side of caution. A combination of close follow-up and preventative therapy for patients at significant risk for occult bacteremia should be a sufficient safeguard to protect patients who are well enough to go home but still present diagnostic uncertainty.

MEDICOLEGAL PEARLS Insidious presentations of meningitis should be watched for, particularly in children under 1 year. Extremely high fever (e.g., 41.1°C [106°F]) has a high correlation with serious illness. Purpuric skin rashes can be an early sign of the Waterhouse-Friderichsen syndrome caused by meningococcemia. Interhospital transfers of severely ill children should not be made by private vehicles. Suitable personnel should be available in case of complications. References 1. 2. 3. 4. 5. 6. 7.

Banco L, Veltri D: Ability of mothers to subjectively assess the presence of fever in their children. Am J Dis Child 1984;138:976–978. Brennan D, Falk J, Rothrock S, et al: Reliability of infrared tympanic thermometry in the detection of rectal fever in children. Ann Emerg Med 1995;25:21–25. Grossman M: Bacteremia in the febrile child. In: Pascoe DL, Grossman M, eds. Quick reference to pediatric emergencies. Philadelphia: JB Lippincott Co., 1984:417–418. Schwartz RH, Wientzen RL: Occult bacteremia in toxic-appearing, febrile infants. Clin Pediatr 1982;21:659–663. Brook I, Gruenwald LD: Occurrence of bacteremia in febrile children seen in a hospital outpatient department and private practice. South Med J 1984;77:1240–1242. Dershewitz RA, Posner MK, Paichel W: Comparative study of the prevalence outcome, and prediction of bacteremia in children. J Pediatr 1983;103:352–358. Soman M: Diagnostic workup of febrile children under 24 months of age: a clinical review. West J Med 1982;137:1–12.

7A. Lorin MI, Feigin RD: Fever without localizing signs. In: Feigin RD, Cherry RD, eds. Textbook of pediatric infectious disease. 4th ed. Philadelphia: WB Saunders, 1998:157–168. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.

Fleisher GR, Ludwig S: Textbook of pediatric emergency medicine. Baltimore: Williams & Wilkins Co., 1994. Murray DL, Zonana J, Seidel IS, et al: Relative importance of bacteremia and viremia in the course of acute fevers of unknown origin in outpatient children. Pediatrics 1981;68:157–160. Lorin MI: Fever: pathogenesis and treatment. In: Feigin RD, Cherry RD, eds. Textbook of pediatric infectious disease. 4th ed. Philadelphia: WB Saunders, 1998:89–94. McCarthy PL, Lembo RM, Baron MA, et al: Predictive value of abnormal physical examination findings in ill-appearing and well-appearing febrile children. Pediatrics 1985;76:167–171. Crocker PJ, Quick G, McCombs W: Occult bacteremia in the emergency department: diagnostic criteria for the young febrile child. Ann Emerg Med 1985;14:1172–1177. Teach S, Fleisher G: Efficacy of an observation scale in detecting bacteremia in febrile children three to thirty-six months of age, treated as outpatients. J Pediatr 1995;126:877–881. Waskerwitz S, Berkelhamer JE: Outpatient bacteremia: clinical findings in children under two years with initial temperatures of 39.5°C or higher. J Pediatr 1981;99:231–233. Dagan R, Powell KR, Hall CB, et al: Identification of infants unlikely to have serious bacterial infection although hospitalized for suspected sepsis. J Pediatr 1985;107:855–860. Crain EF, Shelov SP: Febrile infants: predictors of bacteremia. J Pediatr 1982;101:686–689. Morens DM: WBC count and differential: value in predicting bacterial disease in children. Am J Dis Child 1979;133:25–27. Bausher JC, Baker RC: Early prognostic indicators in acute meningococcemia: implications for management. Pediatr Emerg Care 1986;2:176–179. Baraff LJ, Bass JW, Fleisher GW: Practice guidelines for the management of infants and children 0–36 months of age with fever without source. Pediatrics 1993;92:1–12, Ann Emer Med 1993;22:1198–1209.

19A. Bass LW, Steel R, Wittler R, et al: Antimicrobial treatment of occult bacteremia: a multicenter cooperative study.

Pediatr Infect Dis J 1993;12:466– 473.

20. Fleisher GR, Rosenberg N, Vinci R, et al: Intramuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young febrile children at risk for occult bacteremia. J Pediatr 1994;124:504–512. 21. Sullivan TD, LaScolea LJ, Neter E: Relationship between the magnitude of bacteremia in children and the clinical disease. Pediatrics 1982;69:699–702. 22. Bell L, Alpert G, Campos J, et al: Routine quantitative blood cultures in children with Haemophilus influenzed of streptococcus pneumoniae bacteremia. Pediatrics 1985;76:901–904. 23. Rowley AH, Wald ER: The incubation period necessary for detection of bacteremia in immunocompetent children with fever. Clin Pediatr 1986;25:485–489. 24. Isaacman DJ, Karasic RB, Reynolds EA, et al: Effect of volume of blood cultures and number of blood cultures and volume of blood on the detection of bacteremia in children. J Pediatr 1996;128:190–195.

Suggested Readings Adams WG, Deaver KA, Cochi SL, et al: Decline of childhood Haemophilus influenzae type b (Hib disease) in the Hib vaccine era. JAMA 1993;269:221–226. Baker MD, Bell LM, Avner JR: Outpatient management without antibiotics of fever in selected infants. N Engl J Med 1993;329:1437–1441. Baskin MN, O'Rourke EJ, Fleisher GR: Outpatient management of febrile infants 28 to 89 days of age with intramuscular administration of cefriaxone. J Pediatr 1992;120:22–27. Callaham M: Inaccuracy and expense of the leucocyte count in making clinical decisions. Ann Emerg Med 1986;15:774. Dagan R, Sofer S, Phillip M, et al: Ambulatory care of febrile infants younger than 2 months of age classified as being at low risk for having serious bacterial infections. J Pediatr 1988;112:355–360. Long S: Antibiotic therapy in febrile children: “best laid schemes.” J Pediatr 1994;124:585–588. McCarthy P, Sharpe M, Spiesel S: Observation scales to identify serious illness in febrile children. Pediatrics 1982;70:802–809. McLellan D, Giebink GS: Perspectives on occult bacteremia in children. J Pediatr 1986;109:1–8. Morbidity and Mortality Weekly Report. Progress toward elimination of Haemophilus influenzae type b disease among infants and children—United States. MMWR 1995;28:545–550. Plouffe JF, Breiman RF, Facklam RR: Bacteremia with Streptococcus pneumoniae. Implications for therapy and prevention. JAMA 1996;275:194–198. Wald E, Dashefsky B: Cautionary note on the use of empiric ceftriaxone for suspected bacteremia. Arch Dis Child 1991;145:1359–1361.

Chapter 129.2 Acute Respiratory Emergencies in Children: Croup, Epiglottitis, Bronchiolitis, Pneumonia Principles and Practice of Emergency Medicine

CHAPTER 129 INFECTIONS

2 Acute Respiratory Emergencies in Children: Croup, Epiglottitis, Bronchiolitis, Pneumonia Michael F. Altieri and Thom A. Mayer Croup (Laryngotracheobronchitis) Epiglottitis Bronchiolitis Pneumonia

CROUP (LARYNGOTRACHEOBRONCHITIS) Croup is a viral illness that usually affects children from 6 months to 4 years of age ( 1). It is usually a non-life-threatening illness, but can become severe enough to require airway support when airway inflammation is significant enough to cause respiratory compromise. Croup is usually seen between November and March, but may occur in other months as well. The most common etiologic agent is the parainfluenza virus or respiratory syncytial virus (RSV) ( 2,2A). Pathophysiology Croup affects the vocal cords and the mucosa of the subglottic area. It causes edema of the mucosa and an increase in secretion of mucus. The edema and secretions inhibit the flow of air through the vocal cords and the subglottic area. Because the inflammation may variably affect the airway from the level of the vocal cords down to and including the bronchi, the term “laryngotracheobronchitis” is technically more accurate than “croup.” In general, the severity of the illness can be closely correlated with the degree of airway narrowing caused by the combination of edema and an increase in mucus production ( 3). Clinical Presentation Croup usually begins with an upper respiratory infection type of prodrome, including low-grade fever and runny nose. A cough soon develops, then becomes increasingly severe and sounds like the barking of a seal. The child then develops stridor with sternal, suprasternal, and substernal retractions. The illness usually peaks between the third and fifth days ( 4). A second entity, called spasmodic croup, may be seen independently of infectious croup (laryngotracheobronchitis) or in conjunction with it. It is caused by spasm of the larynx. In spasmodic croup, there is a sudden onset of stridor with a croupy cough, and fever may or may not be associated with this cough. It is typically seen in the child with mild infectious croup who becomes acutely worse when put to bed. Spasmodic croup often responds dramatically to exposure to humidity and/or the cool night air. The child's symptoms often resolve before presentation to the emergency department (ED). Physical Examination Children with croup usually are nontoxic in appearance and have mild rhinorrhea, variable degrees of inspiratory stridor, and a characteristic barking cough. Depending on the degree of inflammation and mucous secretion, the child may have different degrees of tachypnea, sternal or substernal retractions, and inspiratory stridor. Most children present with low-grade fever. There is 2:1 male:female ratio ( 5). In general, stridor does not become audible until approximately 75 to 90% of the airway has become occluded. Cyanosis only occurs in extremely severe cases in which the airway has become significantly compromised. Prehospital Management Prehospital management should include the following: 1. 2. 3. 4. 5.

Humidified oxygen; pulse oximetry if available. Call results to ED. Consider 0.5 mL of racemic epinephrine in 2.5 mL of normal saline by nebulization if moderate to severe respiratory distress. Transport If the child has severe respiratory distress and shows signs of respiratory failure, assist with bag-valve-mask ventilation. Severe cases may need intubation or needle cricothyroidotomy.

ED Management EVALUATION The initial evaluation of the ED patient presenting with croup should be an overall assessment of the child's difficulty in breathing. The clinical croup score is helpful in this regard because it assesses inspiratory breath sounds, stridor, cough, retractions, cyanosis, and central nervous system function in a numeral fashion ( Table 129–2.1).

Table 129–2.1. Clinical Croup Score

CHEST RADIOGRAPH In cases in which the clinical diagnosis is evident based on the history and physical findings, a chest radiograph may not be needed. In cases in which there is a question regarding involvement of the lower airway, a chest radiograph is appropriate. Croup can often be associated with a concomitant pneumonia and such cases have longer hospitalizations and increased morbidity ( 2A,6). LATERAL NECK RADIOGRAPH Portable lateral neck radiographs are generally restricted to patients in whom the diagnosis of epiglottitis or foreign body is being seriously considered. The diagnosis

of croup is virtually ensured by the history, physical findings, and response to treatment. Lateral neck films in patients with croup typically show “ballooning” of the airway above the level of obstruction on the lateral film and “steepling” at the level of obstruction on the anterioposterior (AP) film ( Fig. 129–2.1) (see subsequent section Radiologic Diagnosis of Epiglottitis .)

Figure 129–2.1. (A) Lateral neck radiograph in a child with croup demonstrates a normal epiglottis, a deep air shadow anterior to the epiglottis, indicating no inflammation, and “ballooning” of the hypopharynx above the level of obstruction at the cricoid cartilage. (B) AP radiograph in a child with croup demonstrates “steepling” of the airway, reflecting narrowing in a concentric and progressive fashion that mimics that of a church steeple. This reflects the narrowing of the cricoid cartilage from inflammation.

PULSE OXIMETRY MONITORING Pulse oximeter readings should be obtained on all patients in whom there is potential airway compromise. It is wise to continue to monitor the patient throughout therapy in the ED because partial airway obstruction may progress. Hypoxia on admission is associated with increased morbidity ( 2A). ARTERIAL BLOOD GAS Arterial blood gases usually are restricted to patients in whom significant respiratory failure is suspected. Even patients to be hospitalized because of severe illness may not need arterial blood gases unless impending respiratory failure is suspected or there are signs of C O2 retention or deterioration. Treatment Humidified oxygen should be provided to all children presenting to the ED with clinical signs or symptoms consistent with laryngotracheobronchitis. In patients with minimal signs of disease, humidified room air still allows better liquefaction and mobilization of secretions and decreased threat of airway obstruction. In cases in which cyanosis is present or the croup score indicates significant disease, high-flow oxygen should be provided. In patients in whom the croup score in the clinical evaluation indicates relatively mild disease, overall assessment of the patient and improvement of the hydrational status, both with humidified oxygen and through the gastrointestinal tract, may be all that is required in the ED management phase. Parents should be given specific discharge instructions regarding continuation of mist-vaporization treatments, close observation, and appropriate follow-up. Racemic epinephrine (Vapo-Nephrine) should be considered for children with croup scores at or above 5. These are usually children with significant respiratory compromise, often those with either sufficient severity of illness or duration of symptoms to require relief of airway obstruction. The medication is usually given in a dose of 0.5 mL in 2.5 mL of normal saline given by nebulized mist ( 6). It has been shown that L-epinephrine is at least as effective as racemic epinephrine in the treatment of croup. It is also more available, less expensive, and does not carry the risk of additional adverse effects ( 7). Significant controversy exists as to whether children who have been given racemic epinephrine require admission to the hospital. In the past, such children usually have been admitted to the hospital because racemic epinephrine usually is restricted to children whose clinical evaluation and croup score place them in a significant at risk category. In addition, a “rebound” phenomenon has been described in children receiving racemic epinephrine. In this phenomenon, clinical symptoms may dramatically worsen once the medication has worn off, resulting in what can present as dramatic airway compromise after an initial response to therapy. This response has been described as occurring as long as 6 hours after the initial treatment. Studies have suggested that when racemic epinephrine is combined with steroid treatment, systemic and inhalational hospital admission may be avoided and patients safely discharged home after 3 hours of ED observation (8,9). In all cases in which racemic epinephrine has been used, the patient's private pediatrician or the pediatrician on call should be consulted regarding such a decision. Rarely, a pediatrician or a gatekeeper physician for a managed care program may recommend discharge after suitable patient evaluation. Although this practice should be discouraged, no such patient should be discharged from the ED without 3 to 6 hours of observation, during which clinical improvement should be clearly documented. Some physicians in clinical practice use racemic epinephrine in children with mild croup. While there are few side effects of such treatment, the practice has led to an unfortunate and misleading corollary—that children treated with racemic epinephrine can be safely discharged from the ED after brief periods of observation. (This practice should not be encouraged.) From a clinical standpoint, a croup score of greater than 5 correlates with a child who has rhonchi, a hoarse cry, inspiratory stridor, use of accessory muscles (flaring or retractions), and evidence of desaturation (cyanosis or room air pulse oximetry readings of less than or equal to 92% or agitation). When racemic (or L-epinephrine) treatments are restricted to such patients, observation periods of 3 to 6 hours should be required prior to consideration of discharge from the ED. Some of the literature suggests that steroids may be of significant benefit in laryngotracheobronchitis if given early in the course of the disease. The effect seems to be independent of the degree of severity of the illness. In general, patients seen within the first 3 to 4 days of illness probably benefit from administration of steroids. These may be given orally (prednisone 2 mg/kg per dose every 8 hours times three doses) or as dexamethasone (0.6 mg/kg in a single intramuscular dose) ( 10). However, some studies have been less encouraging about steroid use in bronchiolitis ( 10A,10B). While nebulized dexamethasone is not of consistent benefit in the treatment of acute croup, nebulized budesonide may be more effective ( 11,12 and 13). When to Hospitalize the Child with Croup Hospitalization should be considered in any patient who has received racemic epinephrine and has not clearly improved or in whom clinical deterioration occurs within 3 hours of the treatment. In rare circumstances, intubation may be required to maintain the airway in a child with croup. In these cases, it is critical to remember that the cricoid area of the child's airway is the narrowest portion of the airway and the site of active inflammation in croup. For this reason, it is usually necessary to select a tube size that is somewhat smaller than the child could normally accommodate, which helps to ensure minimal trauma to the mucosa of the cricoid cartilage while the endotracheal tube is in place. In all children who are discharged from the ED, careful discharge instructions should be given, including specific instructions to return if airway obstruction worsens during therapy. Differential Diagnosis Epiglottitis usually has a more abrupt onset, results in a more toxic appearance and a higher fever, and produces supraglottic, rather than subglottic airway

compromise. In any case in which there is a question regarding the diagnosis, a lateral neck radiograph ( Fig. 129–2.1) should be obtained. Upper airway foreign body usually can be distinguished by the abrupt onset of symptoms after the child has placed something in his or her mouth. Foreign bodies may lodge at any point in the airway, either above or below the level of the vocal cords. In many cases of airway foreign bodies, wheezing is present on a unilateral basis, which assists in making the diagnosis. Radiographs of the airway or decubitus films may also be helpful in identifying the foreign body including inspiratory and expiratory radiographs (See Chapter 9–6). Tonsilar hypertrophy usually can be distinguished on physical examination. In cases in which there is some question, lateral neck radiographs and a chest radiograph usually distinguish croup based on the findings listed previously. Posterior pharyngeal abscesses usually can be distinguished on physical examination or by radiographs and computed tomography (CT) scans ( Fig. 129–2.2, Fig. 129–2.3).

Figure 129–2.2. (A) Lateral neck radiograph in a child with a posterior pharyngeal abscess shows straightening of the cervical spine, increased diameter in the retropharyngeal space, and loculation of fluid. (B) Xeroradiograph of child with posterior pharyngeal abscess.

Figure 129–2.3. CT scan of the head and neck, showing a large retropharyngeal abscess, just in front of the spinal column. Loculated areas are well visualized in several areas.

Pitfalls Consider admission for any child who needs racemic epinephrine because a significant rebound phenomenon can be seen anywhere from 2 to 4 hours after its administration. Any child with a croup score of more than 4 in the first 2 days of the illness should probably be considered for admission because this child will most likely get worse before getting better. Antibiotics are not necessary with croup unless there is a concomitant pneumonia, and even at this time the pneumonia is probably viral.

EPIGLOTTITIS Epiglottitis is a life-threatening infection that carries the potential of complete and sudden airway obstruction. It is a rapidly progressing illness usually seen in the preschool age group (between 2 and 5 years). Epiglottitis can clearly be seen at any age, however, from infancy to adulthood ( 9). Unlike croup, it has no seasonal propensity. Since the advent of the HB vaccine, there has been a great decrease in the incidence of epiglottitis nationwide ( 14). Pathophysiology Epiglottitis is an infection of the upper respiratory tract involving the epiglottis and the aryepiglottal tissue. It is exclusively a supraglottic infection. In the past, most cases were caused by Hemophilus influenzae type B. Other agents that may cause this illness include Staphylococcus aureus, Neisseria catarrhalis, and S. pneumoniae (15,16). This bacterial infection causes massive swelling and edema of the epiglottis and the entire supraglottic area. This swelling in the airway of a small child can lead rapidly to complete airway obstruction. Clinical Presentation Unlike croup, epiglottitis has no prodrome phase. The child presents acutely ill with a body temperature often elevated to 40.0° C (104.0° F), is toxic-appearing, and usually has significant stridor. Because of the severe dysphagia of epiglottitis, the child is often drooling and will not swallow secretions. The child speaks with a muffled voice and is often seen “tripoding,” sitting on the edge of the bed with the arms on the bed behind them and throwing the neck and mandible forward to maximize the airway. Often the child refuses to lie down because the dyspnea becomes worse in a supine position. Physical Examination Children with epiglottitis usually have a high fever, appear toxic, and have stridorous respirations. If the epiglottis is visualized, it is enlarged and cherry red in color. Attempts at visualization of the epiglottis should not be done. Even with extreme care, respiratory obstruction may occur, and such examination is discouraged in contemporary emergency medical practice. Physicians should rely instead initially on clinical findings and the lateral neck radiograph ( Fig. 129–2.4) for diagnosis.

Figure 129–2.4. Lateral neck radiograph taken in a patient with epiglottitis show a classic “thumbprint”-shaped epiglottis, minimal to no airway shadow anterior to the epiglottis, and hyperaeration of the area proximal to the epiglottis.

Physical examination may also demonstrate concomitant otitis media or pneumonia, but attention must first be directed to the cause of respiratory distress. Prehospital Management Prehospital management should include the following: 1. 2. 3. 4. 5. 6.

Keep the child calm. Do not instrument the oral pharynx. Use caution in starting an intravenous line. Transport the child in the sitting position. Do not force them to lie down as it may exacerbate their respiratory distress. Supplemental oxygen by blow-by or mask is advised. If the child suffers complete airway obstruction during transport, the following three methods are recommended to establish an airway: A. A bag-valve-mask using high pressure and occluding the pop-off valve. B. Oral tracheal intubation. C. Needle cricothyroidotomy. 7. Notify the receiving hospital before the patient's arrival. When complete airway obstruction occurs during transport, the prehospital care provider is faced with an extremely difficult situation. In all cases, an initial attempt should be made to ventilate the child through bag-valve-mask ventilation. Even in patients with a high degree of airway obstruction, it is sometimes possible to generate enough pressure through appropriate airway seal to oxygenate or ventilate the child until he or she can be transported to the hospital. In all such cases, there should be evidence of bilateral chest wall rise during ventilation and evidence of improvement of oxygenation via pulse oximetry. If this cannot be obtained, a single cautious attempt at intubation may be attempted if the prehospital care provider has the experience and technical expertise to intubate and the estimated time to arrival at the hospital is more than a few minutes. Manipulation of the inflamed epiglottis, however, may cause significant laryngospasm, and this should be done only by experienced intubators and in the most extreme circumstances. If these techniques fail or the emergency medical technician is not experienced in intubation, needle cricothyroidotomy may be necessary to ensure that oxygenation and ventilation can be performed until an airway can be established in the hospital. ED Management EVALUATION If the diagnosis of epiglottitis is in doubt, i.e., if croup or foreign body aspiration is a serious consideration, airway films and chest radiographs are indicated. These films should initially be done in the ED, where the ED physician is available to handle endotracheal intubation and/or provision of a surgical airway. Equipment for endotracheal intubation and cricothyrotomy should be kept at the bedside. As soon as the ED is aware of the potential of receiving a child with epiglottitis, the support services of anesthesiology and ENT should be mobilized. If at all possible, an operating room (OR) should be prepared so that the patient may be transported there for intubation. Subsequently, the child should be monitored in an intensive care unit. Many centers have a protocol for epiglottitis. SECURING THE AIRWAY Optimally, the person in the institution most experienced in endotracheal intubation should be summoned to perform the intubation. This is usually an anesthesiologist. Preferably, the intubation should be done in the OR under general anesthesia. A person capable of supplying a surgical airway should be standing by. In an emergency situation of sudden respiratory obstruction, however, there should be no delay in attempting to provide even a temporary airway. Even a needle (the largest available) cricothyrotomy can provide a temporary airway with minimal morbidity. If the airway is obstructed in the ED, endotracheal intubation, needle cricothyrotomy, and bag-valve-mask ventilation are the three methods that can be used to attempt emergency ventilation of the patient. After the airway is secured, an intravenous line should be placed, the patient should be kept sedated (midazolam 0.1 to 0.3 mg/kg and/or morphine infusion 0.1 to 0.2 mg/kg per hour). In some cases, paralysis (vecuronium 0.1 mg/kg every hour) needs to be used (with a ventilator). Antibiotics should be started intravenously after blood culture and culture of the local area. Ceftriaxone (50 to 100 mg/kg per day) given twice daily has become common. However, because H. influenzea has decreased significantly, epiglottitis in immunized children might be from another bacterial cause. The occasional S aureus (needing vancomycin) or Corynebacterium diphtheria (requiring erythromycin) can, therefore, be detected. Cefuroxime or cefotaxime may substitute for ceftriaxone. Differential Diagnosis The differential diagnosis of epiglottitis should include the following: 1. 2. 3. 4. 5. 6.

Croup Upper airway foreign body Bacterial tracheitis Diphtheria Tonsillar hypertrophy Peritonsillar/retropharyngeal abscess

In general, children with epiglottitis have more severe airway obstruction than those with croup, a more rapid onset of illness, higher fevers, and do not respond to efforts at humidification of the airway. Radiologic Diagnosis of Epiglottitis Soft tissue lateral neck radiographs can play an important role in subacute diagnosis. CT and magnetic resonance imaging (MRI) scanning have limited use because

of time delays and need for isolation. Interpretation of standard lateral neck radiographs may be difficult, but certain findings can be useful: 1. 2. 3. 4. 5.

Ballooned hypopharynx Increased epiglottic and aryepiglottic fold widths Narrowed tracheal air column Prevertebral soft tissue swelling Obliteration of the vallecula and pyriform sinuses

Figure 129–2.4 and Figure 129–2.5 demonstrate findings on lateral neck radiographs. Interpretation is often difficult. Future developments in CT and MRI scanning will be welcome in assisting in diagnosis of these conditions.

Figure 129–2.5. Close-up view of the lateral airway in a child with epiglottitis shows the classic findings of a large epiglottis and a minimal shadow anterior to the epiglottis.

A study by Rothrock et al. (17) attempted to define objective radiologic parameters on soft tissue lateral neck radiographs. Ratios of soft-tissue structures of children with known epiglottitis were compared with those of children without it but with pharyngitis or croup. These investigators found that accuracy of diagnosis was enhanced although measurements in the acute setting are different. While more reliable direct information can be obtained by CT scan, the time delays and need for longer periods of positioning, are impediments to the use of this tool in the acute diagnosis of epiglottitis. The primary use of radiologic evaluation should be reserved for patients in whom the diagnosis is not clinically obvious and in which the condition has not progressed to an extreme state. Some cases of epiglottitis never progress to complete respiratory obstruction, particularly when diagnosis and treatment are started early.

BRONCHIOLITIS Bronchiolitis is a viral infection of the lower airways usually caused by RSV (respiratory synctial virus). It can be caused by influenza virus, parainfluenza virus, and adenovirus (18). Bronchiolitis is usually seen in children under 2 years, but is mostly seen in those under 1 year. It has a seasonal propensity and is mostly seen in the winter months (between November and March) when RSV is at its peak. RSV bronchiolitis during the first year of life seems to be an important risk factor for the development of asthma and the sensitization to common allergies during the subsequent 2 years, particularly in children with hereditary factors for atopy/asthma ( 19). Pathophysiology This viral infection of the lower airway (bronchioles) produces edema of the mucosa and significantly increases the mucouslike secretions. It also causes spasm of the peribronchiolar muscles, which are underdeveloped but present in young children. In most cases of bronchiolitis, there is actual mucus over the epithelium, which not only decreases the airway's ability to offer a normal defense mechanism but may also cause plugging of the airway. Fortunately, the epithelium of the airway usually regenerates in a brief time, usually 2 to 3 days, although return of the functional capacity of the cilia may take up to 2 weeks ( 20). Clinical Presentation The degree of symptoms present in children with bronchiolitis depends on the extent of pathophysiologic changes present in the ciliated epithelium. The child usually starts with symptoms of an upper respiratory infection, including nasal congestion, nasal discharge, and fever. Lower respiratory symptoms such as a tight cough and wheezing usually develop over a day or two (slower than in asthma). The child can then develop varying degrees of respiratory distress. The symptoms include tachypnea, retractions (mainly intracostal), nasal flaring, and signs of hypoxia such as cyanosis and pallor. Caution: young babies infected with RSV can develop periods of apnea along with the symptoms of bronchiolitis (21). Bronchiolitis usually lasts for 1 to 2 weeks, although improvement can be noted within several days, mirroring the cellular changes and regeneration mentioned previously. Physical Examination The examination of a child with bronchiolitis usually reveals a low-grade fever (38 to 39° C [101 to 102° F]), tachypnea, nasal flaring, intercostal retractions, expiratory wheezes, and rales. In severe cases, the child may be noted to be cyanotic. The degree of respiratory difficulty depends on the combination of involvement of bronchiolar smooth muscular involvement, airway inflammation, mucous production, and mucous plugging. In young children, apnea may be present as well. The increased respiratory rate and inability to take fluids by mouth because of the tachypnea often results in clinical dehydration. Prehospital Management Prehospital management should include the following: 1. Administer humidified oxygen. 2. Nebulization treatments as per standing orders and on-line medical control. a. Albuterol—weight less than 10 kg, 1.25 mg; weight over 10 kg, 2.5 mg, or b. Terbutaline by nebulization—less than or equal to 10 kg of weight, 2 mg; weight over 10 kg, 4 mg, or c. Metaproterenol by nebulization (5% solution)—weight less than or equal to 10 kg, 0.15 mL; weight over or equal to 10 kg, 3 mL; or d. Subcutaneous epinephrine (1:1000 dilution)—0.01 mL/kg, maximum 0.3 mL. 3. Assist ventilation with bag-valve-mask or endotracheal intubation if necessary. ED Management

EVALUATION The ED evaluation may include the following: 1. 2. 3. 4. 5. 6.

Overall assessment of difficulty in breathing. Pulse oximetry. Arterial blood gases (if there are signs of respiratory decompensation). Chest radiograph. CBC. Electrolyte and blood urea nitrogen (BUN), as well as routine “chemistries,” if the patient has a history of decreased oral intake or vomiting or there are signs of dehydration. 7. A nasal smear for RSV for patients requiring hospitalization. TREATMENT Treatment in the ED is based on clinical evaluation of severity and should include: 1. Humidified oxygen. 2. Beta-adrenergic drugs such as albuterol, terbutaline, metaproterenol, or epinephrine, as detailed previously ( 22). The addition of iprotropium bromide is not effective in the treatment of bronchiolitis ( 22,23). Recent data has suggested that nebulized racemic epinephrine may be more beneficial than b 2 agonists in the treatment of bronchiolitis (24,25). The use of steroids can also be considered using methylprednisolone 1 mg/kg per dose given every 4 hours. Recent studies have questioned whether steroids are beneficial ( 10,10B). Consider the use of antiinflammatory therapy with nebulized cromolin sodium or inhaled corticosteroids ( 26). 3. Fluids should be encouraged, given orally if tolerated; if not, by intravenous hydration at approximately 1 ½ times maintenance. 4. Bolus fluid therapy should be considered if the child is significantly dehydrated. The boluses administered should be 10 to 20 mL/kg per bolus of normal saline solution. In general, slow rehydration is preferable, guided by electrolytes and renal function measures. 5. Assist ventilation if necessary by endotracheal tube. 6. Ribavirin, an antiviral agent used for the treatment of severe RSV, can be used, but is usually administered to in hospital patients. Similarly, RSV immune globulin has been given to children at high risk of severe RSV disease with benefit ( 17A). 7. The etiologic agents in bronchiolitis are invariably viruses. In children with areas of opacity on the chest radiograph, however, the clinician is faced with a dilemma. Does this represent atelectasis or pneumonia? In all likelihood, these opacities, which are not uncommon, represent atelectasis caused by mucus plugging. Some clinicians, however, recommend that antibiotic coverage be instituted whenever such abnormal chest radiographs are noted. All children under 6 months of age with clinical symptoms consistent and bronchiolitis should be tested for RSV. If they test positive, they are at greater risk for apnea episodes with bronchiolitis and should be considered for hospitalization, especially if they are premature, have preexisting cardiovascular problems, are younger than 3 months old, or have prior history of “ALTE” (apparent life-threatening event usually apneic episodes). Differential Diagnosis The differential diagnosis of bronchiolitis should include asthma, congestive heart failure secondary to any congenital heart disease, cystic fibrosis, chronic or acute aspiration, pneumonia, and lower airway foreign body. Pitfalls and Medicolegal Pearls A patient should be considered for admission if: (a) there is severe respiratory distress (RR greater than 60 with evidence of accessory muscle use), (b) periods of apnea are noted, (c) a pulse oximeter shows oxygen saturation consistently below 90% on room air or arterial blood gases show a P O2 of less than 60 on room air, and (d) intolerance is shown to fluids by mouth. If there is any doubt, a period of observation is warranted, with close monitoring.

PNEUMONIA Pneumonia is an infection of the lung parenchyma that can involve the alveoli or be an interstitial process. It is a common infection in children, and the etiologic agents vary according to the age of the patient. Pathophysiology Table 129–2.2 categorizes the infectious etiologic agents by the age of the patient ( 27). Streptococcus pneumoniae is now the leading cause of fatal bacterial pneumonia in young children ( 29). Some organisms are less commonly found in pediatric pneumonia. These include pertussis, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and anaerobes such as peptostreptococcus ( 28).

Table 129–2.2. Infectious Agents in Relation to Age

Clinical Presentation Pneumonia usually presents as a febrile illness with tachypnea and cough and signs of lower respiratory illness (nasal flaring, intercostal retractions). In severe cases, cyanosis and pallor can be seen. Lower lobe pneumonia often presents in a young child as abdominal pain and vomiting and is often confused with gastroenteritis. The young infant may present with only irritability and poor feeding. Chlamydia pneumoniae is often seen in conjunction with conjunctivitis. The child is often afebrile, but usually has a severe cough and tachypnea. Physical Examination Physical examination should assess the following: 1. Fever 2. Tachypnea (30)

3. 4. 5. 6. 7. 8. 9.

Toxic appearance (variable) Nasal flaring Retractions (mainly intercostal) Cyanosis or pallor Rales and wheezes in the lung fields (difficult to hear in children) Decreased breath sounds or egophony Conjunctivitis (infants with chlamydia)

Prehospital Management Prehospital management should include the following: 1. Supplemental oxygen by mask, nasal prongs, or blow-by 2. Assist with ventilation if necessary 3. Transport ED Management EVALUATION Laboratory tests to consider should include CBC, arterial blood gas (in severe respiratory distress), pulse oximetry, chest radiograph, blood culture, and chlamydial culture, and sputum culture (difficult to obtain in a small child—can be obtained through endotracheal suctioning if a child is intubated) ( Fig. 129–2.6 and Fig. 129–2.7).

Figure 129–2.6. (A) PA radiograph of the chest in a patient presenting with cough and tachypnea shows an extremely ill-defined area in the right upper lobe, opposite the area of the aortic knob, which is difficult to visualize on the PA film (B) Lateral radiograph in the same patient shows a well-defined round pneumonia posteriorly just behind the thoracic spine.

Figure 129–2.7. PA radiograph in a child presenting simply with fever and tachypnea shows a discrete right middle lobe infiltrate. As is typical of children, the chest was totally clear to auscultation, including the right middle lobe.

TREATMENT Treatment should be by supplemental oxygen mask, nasal prongs, or blow-by. Assist ventilation if necessary. ANTIBIOTICS Table 129–2.2 lists likely organisms. In neonates, ampicillin and gentamycin are necessary. Over that age clinical signs need to dictate therapy. Amoxicillin davulanate (Augmentin) is a reasonable choice for the child between 2 months and 5 years. After this age coverage for mycoplasma should be added, therefore, pedizole, clarithromycin, or azithromycin are reasonable choices. In the ED the trend has been to start ill-appearing patients on parenteral medications with close follow-up (e.g., ceftriaxone 50 mg/kg). Differential Diagnosis Differential diagnosis should include lower airway foreign body, reactive airway disease, congestive heart failure, and aspiration. References 1. Krilov LR, Cooper DJ: Respiratory syncytial virus. Residual Staff Physician 1996;April:33. 2. Goldhagen JL. Croup: pathogenesis in management.J Emerg Med 1984;1:3. 2A. Wang EE, Lamb J, Stephens D: Pediatric investigators collaborative network on risk factors and outcomes in patients hospitalized with RSV lower respiratory tract infection. J Pediatr 1995;126:212–216. 3. 4. 5. 6. 7.

Battaglia JD: Severe croup: the child with fever and upper airway obstruction. Pediatr Rev 1986;7:227. Davis HW, Gartner JC, Galvis AG, et al: Acute upper respiratory obstruction: croup and epiglottis. Pediatr Clin North Am 1981;28:859. Stankiewicz JA, Bowes AK: Croup and epiglottitis: a radiologic study. Laryngoscope 1985;95:1159. Barkin RM, Rosen P, eds: Emergency pediatrics: a guide to ambulatory care. St. Louis: CV Mosby, 1990:644. Waisman Y, Klein BL, Boenning DA, et al: Prospective randomized double-blind study comparing L-epinephrine and racemic epinephrine aerosols in the treatment of laryngotracheitis (croup). Pediatrics 1992;89(2):302–306. 8. Ledwith CA, Shea LM, Mauro RD: Safety and efficacy of nebulized racemic epinephrine in conjunction with oral dexamethasone and mist in the outpatient treatment of croup. Ann Emerg Med 1995;25(3):331–337. 9. Pendergast M, Jones JS, Hartman D: Racemic epinephrine in the treatment of laryngotracheitis: can we identify children for outpatient therapy? Am J Emerg Med 1994;12(6):613–661.

10. Kairys SW, Olmstead EM, O'Conner GT: Steroid treatment of laryngotracheitis: a meta-analysis of the evidence from randomized trials. Pediatrics 1989;83:683. 10A. Roosevelt G, Sheehan K, Grupp-Phelan J, et al: Dexamethasone in bronchiolitis—a randomized controlled trial. Lancet 1996;348:292–295. 10B. Klassen TP, Sutcliffe T, Waters LK, et al: Dexamethasone in salbutamol-treated in patients with acute bronchiolitis. J Pediatr 1997;130:191–196. 11. 12. 13. 14. 15. 16. 17.

Johnson DW, Schuh S, Koren G, et al: Outpatient treatment of croup with nebulized dexamethasone. Arch Pediatr Adolesc Med 1996;150(4):349–355. Fitzgerald D, Mellis C, Johnson M, et al: Nebulized budesonide is as effective as nebulized adrenaline in moderately severe croup. Pediatrics 1996;97(5):722–725. Husby S, Agestoft L, Mortensen S, et al: Treatment of croup with nebulised steroid (budesonide): a double blind placebo controlled study. Arch Dis Child 1993;68(3):352–355. Hickerson SL, Kirby RS, Wheeler JG, et al: Epiglottitis: a 9-year case review. South Med J 1996;89(5):487–490. Lazoritz S, Sanders BS, Bason WM: Management of acute epiglottitis. Crit Care Med 1979;7:285. Brilli RJ, Benzing G, Cotcamp DH: Epiglottitis infants less than two years of age. Pediatr Emerg Care 1989;5:16. Rothrock SG, Pignatello GA, Howard RM: Radiologic diagnosis of epiglottitis: objective criteria for all ages. Ann Emerg Med 1990;19:978.

17A. Groothuis JR: Role of antibody and use of RSV immune globulin to prevent severe RSV disease in high-rise children. J Pediatr 1994;124:S28–32. 18. Wright PF: Bronchiolitis. Pediatr Rev 1986;7:219. 19. Sigurs N, Bjarnason R, Sigurbergsson F, et al: Asthma and immunoglobin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls. Pediatrics 1995;95(4):500–550. 20. Wolfram RW: Bronchiolitis. In: Harwood-Nuss A, Linden C, Luten RC, et al., eds. The Clinical Practice of Emergency Medicine. Philadelphia: JB Lippincott, 1991. 21. Burhn FW, Mokrohisky ST, McIntosh K: Apnea associated with RSV infection in young infants. J Pediatr 1987;3:382. 22. Schuh S, Canny G, Reisman JJ, et al: Nebulized albuterol and acute bronchiolitis. J Pediatr 1990;117:633. 23. Schuh S, Johnson D, Canny G, et al: Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis. Pediatrics 1992;90(6):920–923. 24. Sanchez I, DeKoster J: Effect of racemic epinephrine and salbutamol on clinical score and pulmonary mechanics in infants with bronchiolitis. J Pediatr 1993;122(1):145–151. 25. Krisjansson S, Lodrup, Carlsen KC, et al: Nebulized racemic adrenaline in the treatment of acute bronchiolitis in infants and toddlers. Arch Dis Child 1993;69(6):650–654. 26. Reijonen T, Korppi M, Kuikka L, et al: Anti-inflammatory therapy reduces wheezing after bronchiolitis. Arch Pediatr Adolesc Med 1996;150(5):512–517. 27. Turner RB, Lande AE, Chase P, et al: Pneumonia in pediatric outpatients. Cause and clinical manifestations. J Pediatr 1987;111:194. 28. Denny FW, Clyde WA: Acute lower respiratory tract infections in non-hospitalized children. J Pediatr 1986;108:635. 29. Sniadack DH, Schwartz B, Lipman H, et al: Potential interventions for the prevention childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children—implications for vaccine strategies. Pediatr Infect Dis J 1995;14(6):503–510. 30. Taylor JA, DelBeccaro M, Done S, et al: Establishing clinically relevant standards for tachypnea in febrile children younger than two years. Arch Pediatr Adolesc Med 1995;149(3):283–287.

Chapter 129.3 Pediatric Viral Infections: Measles, Mumps, Rubella, “Fifth” Disease, Roseola, Chicken Pox, Herpes Virus, Cytomegalovirus, Infectious Mononucleosis, Rotavirus, Adenovirus, Polio, Conjunctivitis, Gingivostomatitis, Rabies Principles and Practice of Emergency Medicine

CHAPTER 129 INFECTIONS

3 Pediatric Viral Infections: Measles, Mumps, Rubella, “Fifth” Disease, Roseola, Chicken Pox, Herpes Virus, Cytomegalovirus, Infectious Mononucleosis, Rotavirus, Adenovirus, Polio, Conjunctivitis, Gingivostomatitis, Rabies Michael R. Sayre and George R. Schwartz Maculopapular Exanthem Agents Vesicular Exanthem Agents Systemic Viral Infections without Rash Viral Gastroenteritis Small Round Structured Virus Ophthalmia Neonatorum Conjunctivitis Beyond the Neonatal Period Gingivostomatitis Central Nervous System Agents

MACULOPAPULAR EXANTHEM AGENTS Vaccination has significantly changed the landscape of viral diseases. The oral polio and MMR (measles, mumps, rubella) vaccines have made these diseases so rare that newly graduated doctors may not ever have seen a case. However, worldwide, the situation is still quite different with thousands of deaths yearly ( 1,2). Measles (Rubeola) Measles is an acute epidemic disease caused by an RNA virus and characterized by cough, coryza, conjunctivitis (especially palpebral), a confluent erythematous maculopapular rash, and a pathognomonic exanthem in the mouth called Koplik's spots. It is a highly contagious disease transmitted by infectious droplets or, less commonly, by airborne spread (1). The incubation period lasts 8 to 12 days from exposure to onset of symptoms. The patient typically has 2 to 3 days of nonproductive cough, rhinorrhea, sore throat, and significant fever. The rash usually starts on the back of the neck and then spreads to involve all the body surfaces. The palpebral conjunctival injection is most significant in the lower lids. Koplik's spots are bright red inflamed spots on the buccal and lingual mucosa. The patient may have right lower quadrant abdominal pain; and the diagnosis of measles is sometimes made by a pathologist who finds multinucleated giant cells in the appendix, confirming the diagnosis before the rash is present. Complications of measles commonly include otitis media and pneumonia. Encephalitis occurs in 1 of every 2000 cases reported in the United States, and survivors of this complication frequently have permanent brain damage. Death, predominantly from respiratory and neurologic complications, occurs in 1 of every 3000 cases reported in the United States. The differential diagnosis before onset of the rash includes other viral causes of upper respiratory symptoms, streptococcal pharyngitis, Mycoplasma infection, chlamydia, and infectious mononucleosis. The treatment is supportive because no specific antiviral therapy is available. The introduction of a vaccine in the 1960s, with additional improvement occurring in the 1970s, led to a dramatic reduction in the number of cases of measles. The number of cases reported annually dropped from 26,871 in 1978 to an all-time low of 1,497 in 1983. An increase occurred in 1986 (6,282), with a decrease again in 1987 and 1988, but the number of cases rose again in 1989, when more than 14,000 cases were reported (3) and this has remained high with increases from 1991 to 1994 ( 4). Increased concentration on immunization from 1994 to 1998 is expected to reverse this trend. Many cases are now thought to be from “imported” sources. The goal of eliminating measles in the United States has not been reached because of failure to implement the current vaccination recommendations, resulting in large numbers of unvaccinated preschool-age children in some areas and vaccine failure ( 2). An intensive vaccination program can be initiated in the emergency department (ED) (5). Immunosuppressed patients such as those with leukemia, lymphoma, or generalized malignancy or those undergoing therapy with immunosuppressive drugs or radiation should not be given live measles virus vaccine. Patients with human immunodeficiency virus (HIV) infection, including the acquired immunodeficiency syndrome (AIDS) should be vaccinated unless severely immunocompromised. Refer these cases to a specialist in infectious disease. Rubella Rubella in the postnatal period is usually a mild disease characterized by a few days of malaise and low-grade fever, followed by a pink maculopapular rash lasting 2 to 3 days and associated with postauricular and suboccipital lymphadenopathy. The disease is commonly accompanied by transient polyarthralgia and polyarthritis in older individuals. Rare complications include encephalitis and thrombocytopenia. Transmission is through direct or droplet contact with nasopharyngeal secretions. The peak incidence of infection is late winter and early spring. Before widespread use of the rubella vaccine, rubella was an epidemic disease with 6- to 9-year cycles. Because the vaccine is effective, the incidence of rubella has declined by more than 99% when compared to the prevaccine era. Outbreaks do still occur, usually in young adults. Serologic surveys have indicated that 10 to 20% of young adults are susceptible to rubella, predominantly because of underutilization of the vaccine and not because of waning immunity in immunized persons (1). The rates depend on the vaccination programs in force. With heightened concern, the rates can be reduced to 3 to 5% (5A). The most severe complication of rubella is transmission to unborn children (congenital rubella). It is acquired by transplacental infection of the fetus and is a devastating disease. A discussion of this syndrome is beyond the scope of this text, but the important point is that patients with rubella should be advised to stay away from any woman who may be pregnant. Contact isolation is required for 7 days after onset of the rash. When a pregnant woman is exposed to rubella, a blood specimen should be obtained as soon as possible and tested for rubella antibody. The presence of antibody indicates that the individual is immune and not at risk. Those previously determined to be immune can also be reassured. If antibody is not detectable, additional testing must be done 3 and 6 weeks after exposure to determine accurately whether or not infection has occurred. The routine use of immunoglobulin (IG) for postexposure prophylaxis in early pregnancy is not recommended because studies have shown that infants with congenital rubella have been born to mothers who were given IG shortly after exposure. Congenital rubella can only be prevented by adequate immunization of the general population with live rubella virus vaccine ( Table 129–3.1). Available data indicate that one dose confers long-term immunity.

Table 129–3.1. Indications and Contraindications for Rubella Immunization

Special efforts must continue to immunize postpubertal adolescents and adults, including college students and military recruits who have not been previously immunized or have not been proven serologically to be immune. For a detailed discussion of the recommended immunization guidelines for rubella, see Report of the Committee on Infectious Diseases, by the American Academy of Pediatrics, affectionately known as The Red Book (1). Erythema Infectiosum (Fifth Disease) Erythema infectiosum is characterized by 1- to 4-day history of mild systemic symptoms followed by a characteristic rash, which may erupt in three stages. The typical first phase consists of intensely red cheeks with circumoral pallor, giving use to the descriptive term “slapped cheek.” This is followed by a maculopapular lacelike rash on the arms. The rash then moves to the trunk, buttocks, and thighs. Reappearance of the rash may occur for several weeks after nonspecific stimuli such as a change in temperature, sunlight, or emotional stress. Arthralgia and arthritis are commonly reported. Joints in the hands are frequently involved, followed by joints in the knees and wrists. Joint symptoms are reported to be common in adults and may occur as the sole manifestation of the infection. In 1975, erythema infectiosum was found to be caused by human parvovirus B19. This virus has also been shown to be the primary cause of transient aplastic crisis in patients with chronic hemolytic anemias and chronic anemia with immunodeficiency, and it has been associated with fetal death. In addition to patients with chronic hemolytic anemias (e.g., sickle-cell disease, hemoglobin SC disease, hereditary spherocytosis, b-thalassemia, and autoimmune hemolytic anemia), this virus can also cause transient aplastic crises in other conditions in which increased red cell production is necessary to maintain stable red cell indices, as may occur in anemia from blood loss. Chronic B19 infection can cause a severe anemia associated with red cell aplasia in patients with immune deficiency diseases, including HIV-related immune deficiency as well as leukemias and congenital immune deficiencies ( 6). Erythema infectiosum outbreaks often occur from late winter to early spring and may persist until school recesses for summer. The incubation period is usually 4 to 14 days. Transmission is probably by respiratory secretions from viremic patients. There is no vaccine to prevent B19 virus infection, and the role of IG in patients with immunodeficiency syndromes needs additional study. Exanthem Subitum (Roseola) Human herpesvirus 6 (HHV 6), also called the human B-lymphotropic virus (HBLV), was first isolated in 1986 ( 7). It was not clear what illness this agent caused until 1988, when HHV 6 was shown to be the cause of a common childhood illness formally called exanthem subitum and informally roseola ( 8). Because HHV 6 is a herpesvirus, one might expect that it can reactivate under certain conditions, and indeed some patients with AIDS do have high levels of the virus in their serum ( 9). HHV 6 may also cause clinical illness in the form of lymphadenopathy syndromes ( 10). At least 25% of the population has detectible antibody to HHV 6 ( 10). Exanthem subitum is a disease of children between 6 months and 3 years. It is the most common exanthem in children under 2 years of age ( 11). The clinical course begins with the abrupt onset of a high fever, often to 40°C (104°F). The child usually does not appear particularly ill despite the high temperature. Febrile seizures are not uncommon, however. After 3 days, the fever ends, and a fine macular erythematous rash appears over the face, trunk, and extremities. This characteristic exanthem consists of small, pale pink, discrete macules or maculopapules. Periorbital edema is a common finding. The rash fades over the next 12 to 24 hours. HHV 6 can cause a similar febrile illness but without the characteristic rash ( 11). There are no known sequelae of HHV 6 infection, but research into the life cycle of this virus has just begun. The diagnosis of HHV 6 infection is based on the characteristic clinical course of the illness. There is an IgG antibody test available for research purposes (Cappel Laboratories, Cochranville, PA USA) to document seroconversion after a clinical illness ( 11). No data exists to estimate the infectivity of HHV 6, but given the fact that cases are sporadic, it seems that it is low. A roseolalike illness has been associated with several other viral agents including enterovirus, echovirus, and several adenoviruses. Exanthem subitum is a benign illness that requires no therapy other than comfort measures and reassurance. The principal challenge is differentiation from other more serious causes of high fever in infants. Frequently, therefore, it is a diagnosis of exclusion, used when pneumonia and occult bacteremia have been ruled out. A clue to the correct diagnosis is the relatively well appearance of the child despite the elevation in temperature. Table 129–3.2 compares the common maculopapular exanthems discussed in this section.

Table 129–3.2. Common Maculopapular Exanthems

VESICULAR EXANTHEM AGENTS Many of the agents that cause vesicular exanthems are members of the Herpes viridiae family. Herpesviruses are relatively complicated. They have a double-stranded, linear DNA with a regular icosahedral protein shell surrounded by a lipid, carbohydrate, and protein envelope. Generally, herpesviruses produce a pronounced primary infection and then a period of latency. At some point there can be reactivation with variability between infected individuals as well as species of

herpesviruses. Chickenpox Varicella-zoster virus (VZV) causes chickenpox. The same virus has been shown by restriction endonuclease mapping to cause herpes zoster. There are about 2.8 million cases of chickenpox in the United States each year ( 12). Most cases occur from November through May. One-half of all cases happen in 5- to 9-year-olds ( Fig. 129–3.1). Therefore, by age 15, less than 10% of Americans remain susceptible.

Figure 129–3.1. Age distribution of chickenpox and its complications. (Adapted from Preblud SR D'Angelo LJ. Chickenpox in the United States, 1972–1977. J Infect Dis 1979;140:257–260.)

Once the virus is introduced into a household, the attack rate for susceptible contacts is 87% ( 13). Transmission of chickenpox is by respiratory droplet spread, but transmission by direct contact with infected vesicles or rarely on the hands of hospital personnel has also been reported ( 14). VZV cannot be recovered from vesicular crusts or room dust (15). After a person inhales the respiratory droplets, primary replication begins in the nasopharynx. In a few days, a primary viremia seeds the reticuloendothelial system. The virus replicates there until the secondary viremia, beginning about 14 days after initial viral acquisition, infects the skin. As the secondary viremia begins, the patient often has mild fever, myalgias, and malaise. Within a day, the rash begins with small red macules, followed by development over 12 to 24 hours of the vesicle filled with clear fluid containing infectious virus, lymphocytes, and cellular debris. Initially, the rash appears on the trunk and spreads to the extremities. Then the vesicle becomes cloudy, ruptures, and forms a crust within 12 to 24 hours. Crusts can last up to 1 to 3 weeks. The secondary viremia continues about 5 days, and the patient with chickenpox remains contagious until all the vesicles have crusts. Itching is a prominent symptom. Complications from chickenpox are unusual in the immune competent host. They include bacterial superinfection of the skin, acute cerebellar ataxia, Reye's syndrome and death. Recently, an increased association between Group A hemolytic strep bacteremia has been noted in children with varicella. Up to 33% of adults with chickenpox have radiographic evidence of pneumonitis ( 16). If the pneumonia is to become clinically evident, it will do so about 3 to 5 days after the onset of the rash. Many mothers of patients with chickenpox say, “I am pregnant. Will chickenpox hurt my baby?” Because most adult Americans are immune to chickenpox, it is unlikely that the expectant mother will become infected. If she does, however, chickenpox in pregnant women is usually no more severe than in other adults although it was once thought to be so. Chickenpox with pneumonia in pregnant women, however, has led to reported deaths ( 17). There is a congenital varicella syndrome characterized by hypoplastic limbs and severe fetal scarring, but this is rare, even when the mother gets chickenpox late in first trimester. However, if virus is acquired transplacentally just before birth, i.e., if the mother's rash appears 5 days before through 2 days after delivery, the resulting perinatal disease is severe. In these cases, the baby has up to a 30% chance of death ( 18). In nearly all cases, the diagnosis of chickenpox can be made by the characteristic appearance of the rash. A Tzanck prep can be performed to demonstrate multinucleated giant cells. In addition, antibody tests can establish whether past infection was present. This is important for the management of nosocomial outbreaks (19). Acetaminophen generally has been recommended; however, this treatment was recently shown to be of no benefit and may prolong the illness ( 20). Aspirin should not be used because of the risk of Reye's syndrome. Simple measures such as trimming the fingernails and oatmeal baths in lukewarm water often help. If the patient is not an infant, antihistamines such as diphenhydramine (Benadryl) may be prescribed to help control itching. There has been a great deal of interest in the use of acyclovir for the treatment of chickenpox. It is useful in immunocompromised children in preventing dissemination of the infection throughout the body ( 21), and has a role in fulminating varicella. Acyclovir has been tested in normal children, and studies have shown that it shortens the clinical course and reduces morbidity ( 22). Its ability to reduce the rare serious complications is not proven. Maternal varicella pneumonia can be treated with intravenous acyclovir ( 23,24). Until better antiviral agents are developed, there is little specific therapy for the ordinary varicella sufferer. Widespread immunization has been initiated and will likely alter the epidemiologic landscape significantly due to its high immunogenicity after a single dose (greater than 96%) ( 24A). However, this view of the need for widespread immunization has some forceful critics ( 24B). Patients who are immunocompromised can be treated with continuous infusion acyclovir at high dose, 10 mg/kg every 8 hours ( 24C). Most nonimmunized people are exposed before a rash is present on the source (because viral shedding begins up to 24 hours before the rash). Partial temporary immunity is available in the form of varicella-zoster immune globulin for patients at high risk for disseminated disease ( 25). Live varicella vaccine should eliminate most wild virus disease (26). One study demonstrated a lower incidence of zoster in children with leukemia who received the live attenuated varicella vaccine ( 27). Current recommendations include varicella vaccination ( 1). Herpes Simplex Herpes simplex virus (HSV) is the cause of several clinical illnesses characterized by localized ulcerations, typically on the oral or genital mucosa. Herpes simplex is divided into two antigenic types: Herpes simplex virus 1 and 2. Infection begins with invasion of cells not resulting in cell death. A typical herpesvirus latency period ensues, much shorter than that of other herpesviruses. Later reactivation happens. Herpes simplex infection is common. About 40% of Americans between ages 25 and 29 have antibodies to HSV 1. Visits to physicians for genital herpes has increased. HSV 2 antibodies do not appear until puberty, and their prevalence correlates with the past sexual activity of the individual. Up to 80% of female prostitutes have antibodies against HSV 2. Interestingly, only about one-third of individuals with antibodies against HSV 2 have a history of genital ulcerations. HSV is usually acquired after direct contact with virus from another person's mucosa. About 5% of adults have asymptomatic salivary excretion of HSV 1. HSV, however, is likely to be transmitted when the source has lesions. Herpes infections have been found nearly everywhere on the body. After initial acquisition of the infection, there is an incubation period of about 1 week (range 1 to 26 days). Frequently, first episodes of the infection are accompanied by systemic symptoms. Both strains of the virus can infect the genital and oral regions. Each virus, however, is more severe in its preferred site. Oral-facial HSV infection is commonly referred to as a “cold sore.” Usually these infections are caused by the HSV 1 serotype. First episodes of the infection are manifested by gingivostomatitis and pharyngitis. Systemic symptoms include fever, malaise, myalgias, irritability, and cervical adenopathy; and these may last between 3 and 14 days. The differential diagnosis includes bacterial pharyngitis, Stevens-Johnson syndrome, and other viral stomatitis (coxsackievirus, etc.) The patient may never have a recurrence or may experience reactivation with a range from asymptomatic viral excretion to severe buccal ulcerations. The complications of oral-facial herpes simplex infections include generalization of infection in the immunocompromised host, superinfection, and

erythema multiforme. Herpetic whitlow is characterized by the abrupt onset of edema, erythema, and localized tenderness around the base of the fingernail. These vascular and pustular lesions may appear like a bacterial paronychia. Fever and systemic symptoms are common. Surgical treatment of lesions mistaken for bacterial paronychia is thought to lead to delayed healing. Herpes simplex infections of the first branch of the trigeminal nerve can lead to herpetic keratoconjunctivitis, which is the common cause of corneal blindness in the United States. Steroid treatment of such lesions allows spread of the disease. Proper treatment includes prompt ophthalmologic referral and antiviral therapy. HSV can also infect the central nervous system (CNS), either as a complication of oral-facial or genital disease or spontaneously. Herpes simplex encephalitis is the common cause of acute, sporadic viral encephalitis in the United States with 2 cases per 1,000,000 population each year; nearly all are HSV 1. It generally spreads from exogenously acquired virus by way of the olfactory bulb. This disorder is characterized by fever and focal temporal lobe signs. Polymerase chain reaction (PCR) testing can confirm the diagnosis (28). (see Chapter 61–7). When HSV is acquired during delivery, it can be devastating. Neonatal herpes simplex affects about 17 in 100,000 live births ( 29). About 70% of infants with untreated neonatal herpes have CNS involvement, and if the CNS is involved, the mortality rate approaches 65% ( 30). Between 55 and 70% of neonatal herpes simplex is caused by HSV 2 (29), but the risk of acquiring infection at time of vaginal delivery is less than 50% ( 31). The newborn can also acquire HSV 1 spread from family members or medical personnel. Antiviral chemotherapy has reduced the mortality to a still-high 14% ( 32). The clinical diagnosis of HSV infection is accurate when classic findings are present. The best laboratory test is the tissue culture. It is usually positive 2 to 4 days after inoculation. Serologic testing for antibodies against HSV is not clinically useful. The benefits of acyclovir for oral herpes simplex infections are much less pronounced. It has some benefit when administered orally for initial infections ( 32A). Acyclovir can be given intravenously for severe infections. This therapy is needed in cases of disseminated infection or when the patient's cellular immunity is impaired. Intravenous acyclovir is also used for CNS infections. Resistance to acyclovir is becoming a problem ( 33,33A). When resistance occurs, higher doses may be needed, or another antiviral agent, foscarnet, appears to be effective, famciclovir is as effective as acyclovir, but offers convenience of twice daily dosage ( 34).

SYSTEMIC VIRAL INFECTIONS WITHOUT RASH Cytomegalovirus Cytomegalovirus (CMV) is another herpesvirus that can cause either a lytic (active) or latent infection. Microscopically, CMV-infected cells appear as giant cells, and so the virus was named. Cytomegalovirus is found worldwide. Approximately 1% of newborns in the United States are infected with CMV. The virus is transmitted because it is shed in milk, saliva, feces, and urine. It is not as easily transmitted as varicella, however. Cytomegalovirus infection is common in some groups. For example, viral shedding is noted in 50 to 100% of 2 year olds in day care centers ( 35). Antibody titers approach 100% in female prostitutes and homosexual men. Sixty-three percent of the tested employees of the Children's Hospital of Alabama had antibody to CMV (36). Once acquired, CMV persists for life but normally remains latent. Reactivation, however, can occur in the presence of impaired T-lymphocyte immunity. When CMV infects certain types of patients, it can have severe consequences. One feared complication of CMV is fetal deformity. The clinical features of congenital CMV include petechiae, hepatosplenomegaly, jaundice, microcephaly, deafness, intrauterine growth retardation, prematurity, inguinal hernias, and chorioretinitis. If an infant is severely affected it has about a 20 to 30% mortality risk. Perinatal CMV is not as severe as congenitally acquired disease. About one-half of newborns breast-fed from seropositive mothers are infected within 1 month of birth. Usually the infection is asymptomatic, but some infants develop interstitial pneumonitis. After the newborn period, CMV mononucleosis is the most common presentation. The typical patient is a sexually active young adult. Illness begins 20 to 60 days after acquisition of the virus, and it lasts from 2 to 6 weeks. The illness is characterized by myalgias, headaches, and splenomegaly. Unlike mononucleosis caused by Epstein-Barr virus, exudative pharyngitis is unusual. On diagnostic testing, there are frequently more than ten atypical lymphocytes on the differential white cell count, but the heterophil-antibody test is negative. After primary infection, low-grade viral shedding may last for years. Complications of CMV infection include reactivation and dissemination during periods of impaired cellular immunity, as well as possible atherosclerosis ( 37). CMV is the most important viral pathogen complicating organ transplants. CMV infection in AIDS patients is nearly universal and may worsen T-lymphocyte deficiency. Each of the several diagnostic techniques for CMV has a pitfall. A positive culture of urine, blood, or genital secretions confirms infection, but does not prove that CMV is the cause of the patient's symptoms. Seroconversion of IgG antibody from negative to positive is diagnostic of primary infection, but it is not a rapid diagnostic technique. IgM antibody is usually indicative of primary infection in the immune competent patient but is highly unreliable in the immunocompromised. Finding CMV inclusion bodies on microscopic examination is diagnostic of infection, but the study is not sensitive ( 38). There is another test under development called the granulocyte-associated immunoglobulin test that will reportedly rapidly diagnose CMV infection ( 39). Because its specificity is only 82%, however, its clinical utility has been questioned (40). There is no treatment required for the majority of patients with CMV. These patients have intact immune systems and handle the virus well. If the patient has depressed cellular immunity, ganciclovir has shown promise ( 41), and can be used for treatment or prophylaxis (5 mg/kg IV twice daily for 2 weeks) (42). A live virus vaccine against CMV is undergoing clinical evaluation. It does not prevent disease, at least in renal transplant recipients, but it does seem to attenuate its severity (43). Infectious Mononucleosis Infectious mononucleosis, a common illness among American teenagers, is caused by the Epstein-Barr virus. Epstein-Barr virus is transmitted primarily by saliva (kissing). In poor populations, primary infection frequently occurs at an earlier age. These early infections are mild and appear like most other upper respiratory viral illnesses. The peak incidence in the United States is between 14 and 18 for boys. The virus is shed continuously in the oropharynx for up to 18 months after primary infection. Then it is shed periodically without clinical illness. When it is transmitted by saliva, the initial site of replication of the Epstein-Barr virus is in the oropharynx. Epstein-Barr virus infects B lymphocytes. In addition, oropharyngeal epithelial cells contain virus in infectious mononucleosis. Within 24 hours after entry into B lymphocytes, Epstein-Barr nuclear antigens (EBNA) become detectable. Then Epstein-Barr virus stimulates these B lymphocytes to produce immunoglobulins, which react with sheep red blood cells (heterophil antibodies). Eventually some cells lyse and release virus, which infects other B lymphocytes. The immune system produces antibody to viral capsid antigen and the nuclear antigen. In addition, there is a cellular immune response with T suppressor-cytotoxic lymphocytes (CD8). The Epstein-Barr virus remains in a small number of B lymphocytes for life, and it can reactivate during periods of depressed cellular immunity such as organ transplantation, iatrogenic immunosuppression, or AIDS. After an incubation period of about 4 to 8 weeks, the patient develops nonspecific symptoms including malaise, anorexia, and chills. Fatigue is often a prominent complaint. Physical findings include pharyngitis (often exudative), fever, and lymphadenopathy. Ninety percent of patients have fever up to 39°C or 40°C (102.2°F or 104.0°F), and 50% have splenomegaly. Sometimes the diagnosis is made when the patient is given ampicillin to treat presumed streptococcal pharyngitis. Administration of ampicillin to a patient with infectious mononucleosis frequently results in a pruritic, maculopapular eruption. The pharyngitis generally lasts about 5 to 7 days, the fever 7 to 14 days, and the lymphadenopathy 3 weeks. The malaise is persistent. Most patients restart work or school in about 3 to 4 weeks. Antibodies to sheep erythrocytes that can be removed by prior absorption with beef red cells, but not with guinea pig kidney cells, are termed heterophil antibodies. Heterophil antibodies are present in 50% of young children and 90 to 95% of adolescents and adults with infectious mononucleosis. Up to 15% of patients with

infectious mononucleosis are heterophil-negative during the first 5 days of the illness. The monospot test is a rapidly performed and accurate substitute for the standard heterophil differential antibody test. The heterophil antibody test remains positive for 9 to 12 months after the illness. In addition to the antibody tests, the differential white cell count may show a relative and absolute lymphocytosis in 75% of cases. Frequently, a large number (10% or more) are atypical in appearance. Also, specific antibody tests can be performed, but are of limited utility in the ED. IgM antibodies to viral capsid antigen are diagnostic of primary Epstein-Barr virus infection. IgG antibodies appear early in the course of the illness and are present for life. There are few complications to a primary infection with the Epstein-Barr virus. About one-half of patients with infectious mononucleosis have mild thrombocytopenia. Spontaneous splenic rupture does occur rarely, usually in the second or third week of the illness ( 44). Other complications include autoimmune hemolytic anemia, severe granulocytopenia, cranial nerve palsies, encephalitis, persistent headaches ( 45), hepatitis, pericarditis, myocarditis, interstitial pneumonitis ( 46), Burkitt's lymphoma, and B-cell lymphoma. The diagnosis of infectious mononucleosis is usually made clinically with laboratory confirmation by way of a positive differential heterophil antibody test or positive monospot test. Severe pharyngitis may be caused by another virus (herpes simplex) or b-hemolytic streptococci. Streptococci may be found in up to 30% of patients with infectious mononucleosis. In addition, atypical lymphocytosis is sometimes found in rubella, hepatitis, toxoplasmosis, mumps, and drug reactions. The management of infectious mononucleosis is chiefly supportive. There is no evidence that bed rest hastens recovery, and the patient should be allowed to return to usual activities as tolerated. The patient should be advised to avoid contact sports for 6 to 8 weeks to decrease the risk of splenic rupture. No medications have yet been shown to influence the course of the illness. Mumps Mumps is caused by a paramyxovirus. Since live virus mumps vaccine was released in 1967, the incidence of mumps in the United States has fallen dramatically. Almost 13,000 cases occurred in the United States in 1987, however, among those cases were those not vaccinated and in whom the vaccine failed. The vaccine has an efficacy of about 80% (47). Mumps is characterized by painful swelling of the parotid gland lasting at least 2 days. Many cases are subclinical. Frequently the swelling is unilateral, and is usually followed by a moderate temperature. Other salivary glands may be involved. The illness usually lasts less than a week. Mumps virus has been transmitted up to 24 hours before the onset of the swelling, and the patient remains capable of transmitting virus as long as 3 days after symptomatic improvement. The incubation period is about 18 days. Complications of mumps include meningoencephalitis, deafness, and orchitis ( 48). The orchitis is usually unilateral and occurs in 20 to 30% of postpubertal males, but sterility is rare ( 48). Death is also rare, but one-half of the deaths have been in adults ( 48). If the patient with mumps has any contact with someone who has not been vaccinated or is unsure of immune status and the contact was born before 1956, mumps vaccine should be administered to that contact ( 48). No other treatment is available.

VIRAL GASTROENTERITIS Rotavirus Rotavirus, the most common cause of diarrhea in infants and children, causes up to one-half of the cases of diarrhea between October and April ( 49) and is responsible for most hospitalizations for diarrhea among American children ( 50). Because the peak incidence of illness begins each year in the southwestern United States and travels northeast, transmission may be by means other than fecal contamination of food or water ( 50). Rotavirus infection is characterized by frequent diarrheal stools in children between 6 months and 3 years of age. Illness typically begins after an incubation period of 2 days. The patient usually has vomiting and a low-grade fever. About one-fifth of children have red tympanic membranes with loss of landmarks ( 51). The illness lasts from 1 to 5 days and usually resolves spontaneously. The diarrhea can be quite severe, and the patient may become significantly volume depleted. Dehydration and subsequent circulatory collapse is the mechanism of death in patients with severe untreated diarrhea. The diagnosis of rotavirus infection depends on laboratory isolation of the virus from stool samples. Several rapid tests for rotavirus detection in the stool are now available ( 52). In adults, in whom rotavirus infection is unusual, the presence of fecal white blood cells or fecal occult blood is helpful, but it is a poor screen in children for a bacterial cause of the diarrheal illness because about one-third of rotavirus infections have fecal white blood cells or occult blood ( 53). Serum electrolytes may reveal reduced plasma bicarbonate concentration, signifying the development of acidosis. The treatment of rotavirus infection involves preventing or treating dehydration. Most children can be treated with oral rehydration. A few require intravenous fluids, either because of associated vomiting or because of the degree of volume depletion. The risk of death from diarrheal illness is closely related to an admission weight less than the third percentile for age ( 54). For children who are less than 5% dehydrated, oral rehydration therapy with a glucose-electrolyte solution is nearly always as effective as intravenous therapy ( 55). The oral rehydration solution is a balanced glucose and Na + mixture with a Na+ concentration between 40 and 90 mEq/L. These solutions serve only to maintain fluid balance and have no effect on stool volume or the patient's nutritional status. Early feeding may help to resolve the illness. Drug therapy with either antibiotics or antidiarrheals is not recommended. As with many of the other serious viral illnesses, a rotavirus vaccine has been developed and offers some efficacy in endemic areas ( 56). However, there is a good deal of debate regarding use, cost, and possible interaction with polio vaccine (56A).

SMALL ROUND STRUCTURED VIRUS The Norwalk agent is one of a group of viruses termed small round structured viruses, which can cause gastroenteritis. Many of these infectious agents have been found because of their link to food-borne outbreaks ( 57). Norwalk agent in particular has been associated with shellfish contamination. Snow Mountain agent is another small round structured virus that causes disease apparently spread by contaminated food ( 58). Airborne transmission of Norwalk virus in an ED has also been implicated (59). There is no treatment for these infections that are self-limited (i.e., “the 24-hour bug”). However, the public health implications include regarding food handlers and health care workers as potentially secreting virus until 48 hours after clinical recovery ( 59,60). Adenovirus Adenovirus group F has been shown to be a cause of diarrhea in all age groups. Adenovirus may be as common as rotavirus among hospitalized children in the 1- to 6-month age group (61). Watery and nonbloody diarrhea begins after an 8- to 10-day incubation period and lasts up to 1 week. Most patients have some vomiting and a fever. No special treatment other than maintenance of hydration is required ( 62). Conjuctivitis Pediatric conjunctivitis is divided into infections that occur in the newborn (“ophthalmia neonatorum”) and those that occur in older children. This distinction is made because the pathogens and management differ between the two groups. In children, as in adults, conjunctivitis may be the result of a viral or bacterial infection, exposure to an allergen or chemical irritation, or associated with a dermatitis. In the ED often patients early in an infection before all the symptoms and physical findings have developed are seen. It is best to err on the side of treatment with antimicrobials if a bacterial source is suspected. Newborns acquire eye pathogens during vaginal delivery from the mother. Chlamydia trachomatis, Neisseria gonorrheae, Escherichia coli, and herpes simplex are all capable of producing neonatal conjunctivitis. Neisseria gonorrheae is the most serious of these. Untreated, this infection can cause corneal perforation in just a few days. Any newborn with conjunctivitis should have Gram stain, Giemsa stain, and culture of the discharge performed. In the older child, most conjunctivitis is a result of a viral infection, but the bacterial conjunctivitis that does develop results from the bacteria that normally inhabit the eyelashes. Staphylococcus epidermidis and Staphylococcus aureus comprise 65 to 90% of these organisms, followed by Corynebacterium, pneumococcus, and

hemophilus.

OPHTHALMIA NEONATORUM (Table 129–3.3)

Table 129–3.3. Management of Conjunction in Newborn Ophthalmia Neonatorum

Chlamydia Trachomatis CLINICAL PRESENTATION AND EXAMINATION Most cases of ophthalmia neonatorum are now caused by Chlamydia trachomatis infection acquired from the mother. It is a bilateral infection with purulent discharge seen in the second week of life. The follicular response on the underside of the eyelids normally seen in chlamydial infections is absent in the newborn. The cornea is clear. Diagnosis is made by Giemsa staining for intracellular inclusions and also by culture. Chlamydia conjunctivitis is a self-limited infection without serious sequelae to the eye. The significance in its diagnosis is the associated pneumonia that develops in 10 to 20% of exposed infants. Chlamydia trachomatis is responsible for 30 to 40% of the pneumonias that occur in the first 6 months of life. The prevention of pneumonia is the reason treatment is necessary. If a diagnosis of chlamydia conjunctivitis is made, both the mother and her sexual partner should also be treated. MANAGEMENT Newborns with chlamydia conjunctivitis should be treated with topical and oral erythromycin (50 mg/kg per day) for 7 weeks. Newborns with suspected Chlamydia pneumonia may require admission for intravenous antibiotics, hydration, and supplemental oxygen, depending on the severity of respiratory distress. Neisseria Gonorrheae CLINICAL PRESENTATION AND EXAMINATION Gonococcal conjunctivitis causes a severe bilateral infection marked by copious purulent discharge. The onset is in the first 3 days of life. The cornea may appear cloudy. If left untreated, the infection causes corneal perforation in less than a week. Diagnosis is made by culture and Gram stain. MANAGEMENT Infants with gonococcal conjunctivitis require admission for intravenous penicillin and topical antimicrobials. Ceftriaxone may be used if the organism is resistant to penicillin. Viral Conjunctivitis in the Newborn CLINICAL PRESENTATION AND EXAMINATION Viral infections of the eye are uncommon in the neonatal period. Primary herpetic conjunctivitis is the usual viral infection at this time, and is acquired during delivery. The eye is reddened, tearing but without purulent drainage. Fluorescein staining of the cornea may only reveal what appears to be an abrasion or the characteristic dendritic appearance of the herpes infection may be obvious. Any newborn examined and felt to have a corneal abrasion should be evaluated in 24 hours to ensure normal healing. Patients at risk of a herpes infection should be managed with ophthalmology consultation.

CONJUNCTIVITIS BEYOND THE NEONATAL PERIOD (Table 129–3.4)

Table 129–3.4. Management of Conjunctivitis Beyond the Newborn Period

Viral Infections CLINICAL PRESENTATION AND EXAMINATION Viral infections cause most of the pediatric conjunctivitis seen in EDs. Viral conjunctivitis usually accompanies other upper respiratory symptoms but may also occur in isolation. The eye is reddened and irritated. There may be tearing but no purulent discharge. These mild infections are self-limited and need not be treated except for symptomatic relief with cool compresses. Epidermic keratoconjunctivitis is the true contagious “pink eye,” which spreads rapidly through families and schools. It is caused by adenovirus types 8 and 19. It causes the most severe conjunctivitis. Infection normally begins in one eye but soon the other becomes involved, often to a lesser extent. The eye is injected, with heavy tearing. There may be minimal mucopurulent discharge. Eyelids are swollen and ecchymotic, giving the appearance of trauma. A keratitis often develops between days 5 and 12, causing intense pain, photophobia, and foreign body sensation. Subepithelial infiltrates develop after day 10, leading to diminished vision.

Corneal staining with fluorescein reveals fine punctate uptake of stain. The patient also often has preauricular adenopathy and associated viral illness with sore throat, fever, and myalgias. The course of the infection is long, lasting up to 4 weeks. A similar but less severe infection is seen with adenovirus 3 and 7. MANAGEMENT Treatment of epidemic keratoconjunctivitis consists of prophylactic broad-spectrum topical antibiotics, cool compresses, and strict hand-to-eye hygiene. Referral to ophthalmology is necessary because steroids may help to improve the subepithelial infiltrates and subsequent diminished vision. Herpes Simplex CLINICAL PRESENTATION AND EXAMINATION Herpex simplex conjunctivitis is a unilateral infection. The eye is injected with slight mucoid discharge. The patient complains of pain and photophobia. Herpetic vesicles on the eyelid margin may be seen. The cornea should be stained looking for the characteristic dendritic appearance of the herpes lesions. Slit lamp examination should be performed if the patient is able to cooperate. MANAGEMENT Patch the eye and refer to ophthalmology immediately. The ophthalmologist will use topical and oral antiviral agents and follow these patients closely because they may eventually require corneal transplants. If there are doubts or the child is too young to be adequately assessed in the ED, an immediate ophthalmologic consultation should be obtained (see Chapter 96).

GINGIVOSTOMATITIS Introduction Gingivostomatitis is a herpes simplex infection of the oral cavity. It is often the primary herpes infection seen in young children. It recurs later as cold sores into adulthood. Pathophysiology and Anatomy The HSV invades the oral cavity through direct contact with someone with the active virus or something with the virus on its surface. The characteristic painful vesicles develop on the lips, tongue, and buccal mucosa. Unlike herpangina (coxsackievirus), which involves the posterior pharynx, gingivostomatitis affects the anterior oral cavity more severely ( 28). Most cases of gingivostomatitis are self-limited and without complication. The main problems are pain control and maintaining hydration. There have been several reported cases of the virus spreading locally to involve the epiglottis and aryepiglottic folds. Clinical Presentation and Examination Gingivostomatitis occurs in children aged 1 to 4. Symptoms include fever and painful oral ulcerations. Cervical lymphadenopathy is common. The child may appear dehydrated from fever and poor oral intake, which may require hospitalization. The lesions in the oral cavity can extend to the area surrounding the lips and can be severe. Differential Diagnosis The differential diagnosis includes herpangina, Stevens-Johnson syndrome, Kawasaki syndrome, aphthous ulcers, and severe viral or streptococcal pharyngitis (Table 129–3.5). Herpangina affects the posterior pharynx with characteristic small ulcerations with white centers. There may be similar lesions on the palms of the hands and soles of the feet. It is caused by coxsackievirus, and the children generally appear less toxic and better hydrated than children with gingivostomatitis. Children with Stevens-Johnson syndrome are toxic, and although their oral findings may appear similar to a severe gingivostomatitis, they also have a characteristic diffuse rash. Kawasaki disease, like Stevens-Johnson syndrome, is associated with a severe rash as well as swelling of the hands and feet and a conjunctivitis, and again the children appear more toxic. Aphthous ulcers and pharyngitis normally have localized findings and are easily distinguishable from a gingivostomatitis.

Table 129–3.5. Differential Diagnosis

Management (Table 129–3.6)

Table 129–3.6. Management of Gingivostomatitis

Gingivostomatitis in the immunocompetent child is usually a self-limited infection. Parents should be encouraged to push fluids. Ice pops (Popsicles) are soothing and a good source of fluids. Hot or irritating foods should be avoided. An oral mixture of liquid antacid and benadryl mixed 1:1 provides significant relief. Parents must be advised of dose and frequency, however, to avoid overdosing the child. Using a cotton swab with viscous xylocaine can allow much relief in the ED. Indications for Admission Children who are significantly dehydrated and unable to take oral fluids should be admitted to the hospital. If there is doubt as to the diagnosis and the child appears toxic, they should be admitted to the hospital for additional workup. Beware of misdiagnosis of Kawasaki disease or Stevens-Johnson syndrome as gingivostomatitis; failure to admit children who are dehydrated and unable to take oral fluids; and failure to provide adequate analgesia.

CENTRAL NERVOUS SYSTEM AGENTS Poliovirus Poliovirus infection is increasingly uncommon. In 1988, only 335 confirmed cases of poliovirus infection were reported in the Americas, and there appears to be a reasonable chance that wild poliovirus can be eliminated from the hemisphere by the end of the 1990s ( 63). Poliomyelitis is characterized by the development of fever, headache, and myalgias followed by acute paralysis. The paralysis may be severe and cause respiratory insufficiency. Treatment is supportive, and many patients recover some or all of their motor function. A syndrome of delayed weakness is sometimes found years after the initial poliomyelitis. The disease is vaccine-preventable, but whether killed or live virus is preferable remains controversial ( 64). In some areas, both vaccines are given in combination (65). Live polio vaccine can apparently be given to pregnant women without an increase in fetal malformation ( 66). Poliovirus infection can occur in immunocompromised contacts of normal children immunized with live oral poliovirus vaccine ( 67). Rabies Rabies is an acute viral encephalitis caused by a rhabdovirus that is capable of producing infection in animals as well as humans. The virus cannot penetrate intact skin, and except for rare cases of infection by means of inhalation or corneal transplant, the virus requires a break in the skin or mucous membrane to establish local infection. Only 40 to 50% of victims of bites from rabid animals develop rabies, but the disease is almost uniformly fatal. The average interval between exposure and clinical disease in humans is 1 to 2 months, but may vary from 10 days to well over a year. Variables affecting the length of the incubation period include the age of the patient (shorter in children than adults), the size of the inoculum, the severity of the bite, and the location of the bite (shorter for wounds of the face and neck than for the extremities). “Classic” rabies usually presents with a prodromal phase. Symptoms include fever, chills, malaise, and myalgias, and may also include nonspecific gastrointestinal and upper respiratory symptoms. This prodrome may begin with proximal radiation of pain, paresthesias, and pruritus from the site of the bite. This is followed by the symptoms of encephalitis, which include excessive motor activity and altered mental status followed shortly thereafter by spasm of the laryngeal and pharyngeal muscles. It is this last sign that led to the disease being called “hydrophobia.” Facial grimacing, opisthotonos, and seizures also occur. During the latter stages of the illness, autonomic overactivity is common, along with cardiac dysrhythmias, cranial nerve palsies, syndrome of inappropriate antidiuretic hormone, and hallucinations. Cortical function is maintained until late in the disease, but ultimately the patient becomes comatose and soon dies. The differential diagnosis of classic rabies includes tetanus, delirium tremens, other viral encephalitis and hysteria. The diagnosis of rabies is not made without a high index of suspicion. The Centers for Disease Control and Prevention (CDC) in Atlanta should be consulted concerning any patient suspected of having rabies. The most important issue for ED physicians is the appropriate use of vaccines for the prevention of the disease. The method of administration of the vaccine is simple (Table 129–3.7). The difficult task, however, is determining whether or not the vaccine is needed ( Fig. 129–3.2). The ED physician must determine the patient's risk of developing rabies. Several points should be considered in making this decision: (a) the species of the animal, (b) its vaccination status, (c) its condition at the time of the bite, (d) whether the attack was provoked or unprovoked, and (e) the local rabies epidemiology.

Table 129–3.7. Steps in Post Exposure Prophylaxis for Rabies

Figure 129–3.2. Indication for rabies prophylaxis in animal bites. (+) = positive result; (–) = negative result. (Reproduced with permission from Kauffman FH, Goldman B. Rabies. Am J Emerg Med 1986;4:529.)

Good local wound care cannot be overemphasized as the beginning of postexposure prophylaxis. The wound should be washed with copious amounts of soap and water and debrided of devitalized tissue. Consideration should be given to not closing the wound primarily. Tetanus immunization should be administered, based on the patient's immunization history. After local wound care, simultaneous passive and active immunization should be instituted. The human diploid cell vaccine now available is much safer than older

vaccines. Immunization is most effective when performed immediately after exposure to rabies. Table 129–3.3 outlines the regimen for this prophylaxis ( 68). References 1. 2. 3. 4. 5.

Report of the Committee on Infectious Diseases. 22nd ed. American Academy of Pediatrics, 1994. Centers for Disease Control. International task force for disease eradication. MMWR 1990;39:209. Centers for Disease Control. Measles prevention: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1989;38:1. CDC Health Information for International Travel 1996–1997. Washington, DC: US Dept HHS, 1997. Schlenker TL, Risk I, Harris H: Emergency department vaccination of preschool-age children during a measles outbreak. Ann Emerg Med 1995;26(3):320–323.

5A. Cherry JD: Rubella virus. In: Feigin RD, Cherry JD, eds. Textbook of pediatric infectious disease. Philadelphia: WB Saunders Co., 1998:1922–1949. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

Centers for Disease Control. Risks associated with human parvovirus infection B19. MMWR 1989;38:81. Salahuddin SZ, Ablashi DV, Markham PD, et al: Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 1986;234:596. Yamanishi K, Okuno T, Shiraki K, et al: Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet 1988;1:1065. Ablashi DV, Josephs SF, Buchbinder A, et al: Human B-lymphotropic virus (human herpesvirus-6). J Virol Methods 1988;21:29. Eizuru Y, Minematsu T, Minamishima Y, et al: Human herpesvirus 6 in lymph node. Lancet 1989;1:40 Letter. Suga S, Yoshikawa T, Asano Y, et al: Human herpesvirus-6 infection (exanthem subitum) without rash. Pediatrics 1989;83:1003. Preblud SR: Age-specific risks of varicella complications. Pediatrics 1981;68:14. Ross AH: Modification of chickenpox in family contacts by administration of gamma globulin. N Engl J Med 1962;67:369. Leclair JM, Zaia JA, Levin MJ, et al: Airborne transmission of chickenpox in a hospital. N Engl J Med 1980;302:450. Weller TH: Varicella-herpes zoster virus. In: Evans AS, ed. Viral infections of humans: epidemiology and control. 2nd ed. New York: Plenum Publishers, 1982;569–595. Preblud SR: Age-specific risks of varicella complications. Pediatrics 1981;68:14. Fox GN, Strangarity JW: Varicella-zoster virus infections in pregnancy. Am Fam Phys 1989;39:89. Preblud SR, Orenstein WA, Bart KJ: Varicella: clinical manifestations, epidemiology and health impact in children. Pediatr Infect Dis 1984;3:505. Sayre MR, Lucid EJ: Management of varicella-zoster virus-exposed hospital employees. Ann Emerg Med 1987;16:421. Doran TF, De Angelis C, Baumgardner RA, et al: Acetaminophen: more harm than good for chickenpox? J Pediatr 1989;114:1045. Novelli VM, Marshall WC, Yeo J, et al: High dose oral acyclovir for children at risk of disseminated herpes virus infections. J Infect Dis 1985;151:372. Dunkle LM, Arvin AA, Whitley RS, et al: A controlled trial of acyclovir for chickenpox in normal children. N Engl J Med 1991;325:1539. Davidson RN, Lynn W, Savage P, et al: Chickenpox pneumonia: experience with antiviral treatment. Thorax 1988;43:827. Brown ZA, Baker DA: Acyclovir therapy during pregnancy. Obstet Gynecol 1989;73:526.

24A. Dennehy PH, Jost EE, Peter G: Active immunizing agents. In: Feigin RD, Cherry RD, eds. Textbook of pediatric infectious disease. Philadelphia: WB Saunders Co., 1998:2731–2769. 24B. Spingarn RW, Benjamin JA: Universal vaccinations against varicella (letter). N Engl J Med 1998;338:683. 24C. Krolewiecki AJ, Braffman M: More on continuous-infusion acyclovir for severe varicella. N Engl J Med 1997;337:203–204. 25. 26. 27. 28. 29. 30. 31.

Immunization Practices Advisory Committee (ACIP). Varicella-zoster immune globulin for the prevention of chickenpox. MMWR 1984;33:84. Weibel RE, Neff BJ, Kuter BJ, et al: Live attenuated varicella virus vaccine: efficacy trial in healthy children. N Engl J Med 1984;310:1409. Hardy I, Gershon AA, Steinberg SP, et al: The incidence of zoster after immunization with live attenuated varicella vaccine. N Engl J Med 1991;325:1545. Connelly BL, Stanberry LR: Herpes simplex virus infections in children. Curr Opin Pediatr 1995;7(1):19–23. Selin LK, Hammond GW, Aoki FY: Neonatal herpes simplex virus infection in Manitoba, 1980 to 1986, and implications for preventive strategies. Pediatr Infect Dis J 1988;7:733. Stagno H, Whitley RJ: Herpes virus infections of pregnancy. N Engl J Med 1985;313:1327. Prober CG, Sullender WM, Yasukawa LL, et al: Low risk of herpes simplex virus infections in neonates exposed to the virus at the time of vaginal delivery to mothers with recurrent genital herpes simplex virus infections. N Engl J Med 1987;316:240. 32. Koskiniemi M, Happonen J-M, Järvenpää A-L, et al: Neonatal herpes simplex virus infection: a report of 43 patients. Pediatr Infect Dis J 1989;8:30. 32A. Guinan ME. Oral acyclovir for the treatment and suppression of genital herpes simplex virus infection. JAMA 1986;255:1747. 33. Davis EA, Sayre MR. The use of oral acyclovir in the treatment of herpetic whitlow abstract. Ann Emerg Med 1989;18:471. 33A. Erlich KS, Mills J, Chatis P, et al: Acyclovir-resistant herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989;20:293. 34. Chatis PA, Miller LE, Schrager LE, et al: Successful treatment with foscarnet of an acyclovirresistant mucocutaneous infection with herpes simplex virus in a patient with acquired immunodeficiency syndrome. N Engl J Med 1989;320:297. 35. Pass RF, Hutto C. Group day care and cytomegalovirus infections of mothers and children. Rev Infect Dis 1986;8:599. 36. Balcarek KB, Bagley R, Cloud GA, et al: Cytomegalovirus infection among employees of a children's hospital: no evidence for increased risk associated with patient care. JAMA 1990;263:840. 37. Melnick JL, Adam E, DeBakey ME: Possible role of cytomegalovirus in atherogenesis. JAMA 1990;263:2204. 38. Drew WL: Diagnosis of cytomegalovirus infection. Rev Infect Dis 1988;10:S468. 39. Debure A, Celton JL, Cartron J, et al: Granulocyte-associated immunoglobulins in renal transplant recipients with cytomegalovirus infection. Lancet 1988;2:1338. 40. Morris DJ: Rapid diagnosis of cytomegalovirus infection in renal transplant recipients. Lancet 1989;1:332. 41. Buhles WC Jr, Mastre BJ, Tinker AJ, et al: Syntex Collaborative Ganciclovir Treatment Study group. Ganciclovir treatment of life- or sight-threatening infection: Experience in 314 immunocompromised patients. Rev Infect Dis 1988;10:S495. 42. Schmidt GM, Norak DA, Niland JC, et al: A randomized controlled trial of prophylactic gancyclovir for CMV infection (pulmonary) in recipients of allogenic bone marrow transplants. N Engl J Med 1991;324:1005. 43. Brayman KL, Dafoe DC, Smythe WR, et al: Prophylaxis of serious cytomegalovirus infection in renal transplant candidates using live human cytomegalovirus vaccine: interim results of a randomized controlled trial. Arch Surg 1988;123:1502. 44. Konvolinka CW, Wyatt DB: Splenic rupture and infectious mononucleosis. J Emerg Med 1989;7:471. 45. Diaz-Mitoma F, Vanast WJ, Tyrrell DLJ: Increased frequency of Epstein-Barr virus excretion in patients with new daily persistent headaches. Lancet 1987;1:411. 46. Schooley RT, Carey RW, Miller G, et al: Chronic Epstein-Barr virus infection associated with fever and interstitial pneumonitis. Ann Intern Med 1986;104:636. 47. Wharton M, Cochi SL, Hutcheson RH, et al: A large outbreak of mumps in the postvaccine era. J Infect Dis 1988;158:1253. 48. Centers for Disease Control. Mumps prevention. MMWR 1989;38:388–397. 49. Bartlett AV 3d, Reves RR, Pickering LK: Rotavirus in infant-toddler day care centers: epidemiology relevant to disease control strategies. J Pediatr 1988;113:435. 50. Ho MS, Glass RI, Pinsky PF, et al: Rotavirus as a cause of diarrheal morbidity and mortality in the United States. J Infect Dis 1988;158:1112. 51. Rodriguez WJ: Viral enteritis in the 1980s: perspective, diagnosis and outlook for prevention. Pediatr Infect Dis J 1989;8:570. 52. Prey MU, Lorelle CA, Taff TA, et al: Evaluation of three commercially available rotavirus detection methods for neonatal specimens. Am J Clin Pathol 1988;89:675. 53. Paccagnini S, Fontana M, Ceriani R, et al: Occult blood and faecal leukocyte tests in acute infectious diarrhoea in children. Lancet 1987;1:442. 54. Hay IT: Age and admission weight as predictors of mortality in gastro-enteritis. S Afr Med J 1989;76:483. 55. Santosham M, Daum RS, Dillman L, et al: Oral rehydration therapy in infantile diarrhea: a controlled study of well nourished children hospitalized in the United States and Panama. N Engl J Med 1982;306:1070. 56. Lanata CF, Black RE, del Aguila R, et al: Protection of Peruvian children against rotavirus diarrhea of specific serotypes by one, two, or three doses of the RIT 4237 attenuated bovine rotavirus vaccine. J Infect Dis 1989;159:452. 56A. O'Ryan ML, Matson DO: A quadrivalent rotavirus vaccine. N Engl J Med 1998;338:620–621. 57. Iversen AM, Gill M, Bartlett CL, et al: Two outbreaks of foodborne gastroenteritis caused by a small round structured virus: evidence of prolonged infectivity in a food handler. Lancet 1987;2:556. 58. Guest C, Spitalny KC, Madore HP, et al: Foodborne Snow Mountain agent gastroenteritis in a school cafeteria. Pediatrics 1987;79:559. 59. Sawyer LA, Murphy JJ, Kaplan JE, et al: 25- to 30-nm virus particle associated with a hospital outbreak of acute gastroenteritis with evidence for airborne transmission. Am J Epidemiol 1988;127:1261. 60. Reid JA, Caul EO, White DG, et al: Role of infected food handler in hotel outbreak of Norwalk-like viral gastroenteritis: implications for control. Lancet 1988;2:321. 61. Wood DJ, Longhurst D, Killough RI, et al: One-year prospective cross-sectional study to assess the importance of group F adenovirus infections in children under 2 years admitted to hospital. J Med Virol 1988;26:429. 62. Wood DJ: Adenovirus gastroenteritis. Br Med J [Clin Res] 1988;296:229. 63. Centers for Disease Control: Progress toward eradicating poliomyelitis from the Americas. MMWR 1989;262:1443. 64. Moulia-Palat JP, Garanna M, Schlumbergar M, et al: Is inactivated polio vaccine more expensive? Letter. Lancet 1988;2:1424. 65. Tulchinsky T, Abed Y, Shaheen S, et al: A ten-year experience in control of poliomyelitis through a combination of live and killed vaccines in two developing areas. Am J Public Health 1989;79:1648. 66. Harjulehto T, Aro T, Hovi T, et al: Congenital malformations and oral poliovirus vaccination during pregnancy. Lancet 1989;1:771. 67. Nkowane BM, Wassilak SG, Orenstein WA, et al: Vaccine-associated paralytic poliomyelitis. United States: 1973 through 1984. JAMA 1987;257:1335. 68. Kauffman FJ, Goldmann BJ: Rabies. Am J Emerg Med 1986;4:525.

Chapter 130.1 Pediatric Cardiac Emergencies Principles and Practice of Emergency Medicine

CHAPTER 130 SYSTEMS

1 Pediatric Cardiac Emergencies Karen S. Rheuban Congenital Heart Disease Cyanotic Heart Disease Acyanotic Heart Disease Congestive Heart Failure Acquired Heart Disease Dysrhythmias

CONGENITAL HEART DISEASE Structural congenital cardiovascular abnormalities may become hemodynamically significant in the neonatal period and often require early intervention. The transition from fetal life to that of the normal newborn is a complex process, and derangements in cardiovascular anatomy and physiology may not become apparent for hours to days after birth, when the ductus arteriosus closes and the pulmonary vascular resistance begins to drop. When faced with a sick infant or child, the clinician must carefully evaluate the patient's overall status. Is this infant in distress, well or poorly perfused, cyanotic or fully saturated? Remember that congenital cardiac lesions are the single most common cause of sudden death in young children ( 1). The initial assessment should include complete vital signs with pulse and respiratory rate and temperature and blood pressure determinations in the right arm and a lower extremity. The presence of a murmur may indicate cardiac pathology, although significant heart disease may be present unassociated with a murmur. Murmurs may occur in systole or diastole, or be continuous ( Table 130–1.1). Hepatomegaly and rales may be noted in the child with congestive heart failure. Careful attention should be paid to the quality of distal pulses. Diminished pulse amplitude may be noted in patients with left heart obstructive lesions, and bounding pulses are often found in patients with lesions manifested by diastolic runoff (such as patent ductus arteriosus or aortic insufficiency).

Table 130–1.1. Classification of Cardiac Murmurs

Laboratory studies include chest radiograph (preferably in the upright position), electrocardiogram (ECG) (for normal values, see Table 130–1.2), and oxygen saturation in cases with respiratory distress or cyanosis. The chest radiograph of the neonate may show a falsely elevated cardiothoracic ratio when the radiograph is obtained in the recumbent position. Additionally, the thymic shadow may obscure the cardiac silhouette. The pulmonary vasculature may be increased, decreased, or even normal in patients with congenital heart disease. Echocardiography, when performed by an examiner experienced with children with heart disease, is usually sufficient to diagnose most cardiovascular disease in pediatric patients.

Table 130–1.2. Electrocardiographic Criteria in Children

CYANOTIC HEART DISEASE When asked to evaluate an infant for possible cyanotic congenital heart disease, first determine that systemic arterial desaturation is present. Acrocyanosis, or cyanosis of the extremities, may be present in normal neonates, and is caused by vasomotor instability in response to cold stress, with an increase in oxygen extraction from that extremity (1A). The arterial oxygen saturation is normal. True central cyanosis is characterized by cyanosis of the mucous membranes in addition to cyanosis of the extremities, and is the result of a reduced arterial oxygen saturation from either intracardiac right to left shunting or pulmonary disease. Pulmonary venous saturation is usually normal in patients with intracardiac right-to-left shunts, whereas pulmonary venous saturation is reduced in patients with lung disease. The administration of oxygen is helpful in differentiating these patients because oxygen saturation does not rise in infants with an obligatory intracardiac right-to-left shunt, and rises in patients with lung disease ( 2). Congenital cardiovascular lesions that produce cyanosis in infancy include those characterized by reduced pulmonary blood flow, parallel pulmonary and systemic circulations, admixture lesions, and defects whose manifestations include acute pulmonary edema. Emergency Use of Prostaglandin E1 (Dilates Ductus Arteriosus) When a reduced systemic arterial oxygen saturation is documented, an arterial blood gas should be obtained. Many infants with extreme hypoxemia (Pa O 2 1 L/kg), and is distributed in the body fat, it is not readily available for diuresis, dialysis, hemoperfusion, or exchange transfusion. 6. Half-Life T1/2 is the time required to reduce the blood concentration in half. It is the fraction or percentage of the total amount of drug in the body removed per unit of time and is a function of clearance and volume of distribution. 7. Elimination routes of detoxification allow the physician to make therapeutic decisions such as using ethanol to interfere with the metabolism of ethylene glycol into its toxic metabolites. 8. Urine identification is usually qualitative and allows only the identification of an agent. 9. Gastrointestinal decontamination includes gastric emptying (emesis-induction with syrup of ipecac, gastric lavage), activated charcoal, cathartics, and whole bowel irrigation. If modality is not mentioned in the text it indicates it is not recommended. 10. Disposition: All intentional overdose patients require suicide precautions in the hospital and psychiatric evaluation for competence before they can be discharged.

COMMON ABBREVIATIONS AC = activated charcoal ABG = arterial blood gases AIDS = acquired immunodeficiency syndrome ALT = serum alanine aminotransferase AMA = against medical advise AST = serum aspartate aminotransferase AV = atrioventricular BUN = blood urea nitrogen CDC = Centers for Disease Control and Prevention cAMP = cyclic 3¢5¢ adenosine monophosphate CHF = congestive heart failure CNS = central nervous system CPK = creatinine phosphokinase CPR = cardiopulmonary resuscitation CV = cardiovascular CVP = central venous pressure DNA = desoxyribonucleic acid ECG = electrocardiogram EEG = electroencephalograms ED = emergency department EPA = Environmental Protection Agency FDA = Food and Drug Administration g = gram GABA = gamma-amino butyric acid GI = gastrointestinal G-6-PD = glucose-6-phosphate dehydrogenase GU = genitourinary tract HIV = human immunodeficiency virus ICU = intensive care unit IDLH = immediately dangerous to life or health IM = intramuscular IV = intravenous kg = kilogram L = liter LFTS = liver function tests MAO = monoamine oxidase MDAC = multiple doses activated charcoal mcg or µg = microgram m2 = square meter mm3 cubic meter

NIOSH = National Institute for Occupational Safety and Health NAC = N-acetylcysteine OTC = over-the-counter OSHA = Occupational Safety Hazards Administration PEEP = positive end-expiratory pressure PaO2 = arterial oxygen partial pressure PaCO 2 = Arterial Carbon dioxide partial pressure pKa = dissociation constant where half is acid and half is alkaline ppb = parts per billion ppm = parts per million RNA = ribonucleic acid SA = sinoatrial SC = subcutaneous WBC = white blood cell WBI = whole bowel irrigation TLV-TWA = threshold limit value-time weighed allowance

INTRODUCTION AND EPIDEMIOLOGY An estimated 5 million potentially toxic exposures occur each year in the United States. Poisoning is responsible for almost 12,000 deaths (including carbon monoxide) and over 200,000 hospitalizations. Hospital visits and admissions. Poisoning accounts for up 2–5% of pediatric admissions, 10% of adult admissions, 5% of hospital admissions in the elderly (>65 years of age), and 5% of ambulance calls. In one urban hospital, drug related emergencies accounted for 38% of the emergency department (ED) visits. One evaluation of a medical intensive care unit and step-down unit over a 3-month period indicated poisonings were 19.7% of admissions. The largest number of fatalities resulting from poisoning are caused by carbon monoxide (CO). Most occur prior to arrival at the hospital. The mortality from CO poisoning has been decreasing from 600 deaths in 1989 to 500 in 1991. The other principle toxicologic fatalities in 1994 were due to gases and fumes, asthma therapies, automotive products, chemicals, hydrocarbons, antihistamines, and cleaning substances. Fewer than 1% of overdose cases reaching the hospitals result in fatality. However, patients presenting in deep coma to medical care facilities have a fatality rate of 13 to 35%. The largest single cause of coma of inapparent etiology is drug poisoning. Pharmaceutical preparations are involved in 40% of poisonings. The number one pharmaceutical toxic exposure is acetaminophen. The leading pharmaceuticals causing fatalities in 1994 were the analgesics, antidepressants, sedative/hypnotics/psychotics, stimulant and street drugs, cardiovascular and alcohols. The severity of the manifestations of acute poisoning exposures varies greatly with the intent of the victim. Nonintentional (accidental poisoning) exposures make up 60 to 65% of all poisoning exposures. The majority are acute, occur in children under 5 years, in the home and result in no or minor toxicity. Many are actually ingestions of relatively nontoxic substances that require minimal medical care. Intentional (suicide poisonings) constitute 10 to 15% of exposures, and may require the highest standards of medical and nursing care and the use of sophisticated equipment for recovery. Intentional ingestions are often of multiple substances and frequently include ethanol, acetaminophen, and aspirin. Suicides make up 60 to 90% of the reported fatalities. About 25% of suicides are attempted with drugs. Sixty percent of patients who take a drug overdose use their own medication and 15% use drugs prescribed for close relatives. The majority of the drug-related suicide attempts involve a central nervous system (CNS) depressant, and “coma management” is vital to the treatment.

ASSESSMENT AND MAINTENANCE OF THE VITAL FUNCTIONS The initial assessment of all medical emergencies follows the principles of basic and advanced cardiac life support ( Fig. 144.1). Determining the adequacy of the patient's airway, degree of ventilation and circulatory status. Establishing and maintaining the vital functions. Vital signs should be measured frequently and should include body core temperature. Evaluation of vital functions are not only of rate numbers but should indicate effective function (e.g., respiratory rate, depth and air exchange) (Table 144.1).

Figure 144.1. Exposure to potential toxins. ABG, arterial blood gases; CPR, cardiorespiratory resuscitation; ECG, electrocardiogram; LOC, level of consciousness; ET endotracheal tube; AVPU, alert-responds to verbal stimuli, responds to painful stimuli, unconscious.

Table 144.1. Important Measurements and Vital Signs

Assess level of consciousness by immediate alert, responds to verbal stimuli, responds to painful stimuli and unconscious (AVPU). If unconscious assess the severity

by the Reed (Table 144.2) or Glasgow coma scales (Table 144.3).

Table 144.2. Reed Classification of the Level of Consciousness

Table 144.3. Glasgow Coma Scale

If comatose: administer 100% oxygen, establish vascular access, obtain blood for pertinent laboratory studies and administer glucose, thiamine, and naloxone and consider intubation to protect the airway. Pertinent laboratory studies include arterial blood gases (ABG), ECG, glucose, electrolytes, renal and liver tests, and acetaminophen plasma concentration on all intentional ingestions. Consider radiograph of chest and abdomen. The severity of a stimulant's effects can also be assessed ( Table 144.4). The assessment should be documented to follow the trend.

Table 144.4. Classification of the Severity of Stimulant Manifestations

Completely expose the patient by removing clothes and other items that interfere with a full evaluation. Look for clues to etiology in the clothes and include the hat and shoes.

PREVENTION OF ABSORPTION AND REDUCTION OF LOCAL DAMAGE Poisoning Exposure Routes include ingestion (80%), dermal (7%), ophthalmologic (5%), inhalation (5%), insect bites and stings (3%), and parenteral injections (0.3%). The effect of the toxin may be local, systemic, or both. Local effects (skin, eyes, mucosa of respiratory or gastrointestinal tract [GI]) occur where contact is made with the poisonous substance. Local effects are nonspecific chemical reactions that depend on the chemical properties (e.g., pH), the concentration, contact time, and type of exposed surface. Systemic effects occur when the poison is absorbed into the body and depends on the dose, the distribution and the functional reserve of the organ systems. Complications from poisons such as shock, hypoxia, chronic exposure, and existing illness may also influence systemic toxicity. Delayed Toxic Action Most pharmaceuticals are absorbed within 90 minutes. However, the patient with exposure to a potential toxin may be asymptomatic at this time for several reasons: the substance may be nontoxic, an insufficient amount of the toxin has been involved, a sufficient amount has yet not been absorbed or metabolized to produce toxicity at the time the patient presented. Absorption may be significantly delayed by: (a) drug(s) with anticholinergic or sympathomimetic properties (e.g., antihistamines, belladonna alkaloids, diphenoxylate with atropine (Lomotil), phenothiazines, amphetamine-type drugs, and cyclic antidepressants; (b) sustained release and enteric coated preparations have delayed and prolonged absorption; (c) concretions may form (e.g., salicylates, iron, glutethimide and meprobamate) that can delay absorption and prolong the action; (d) amount of food in stomach. Substances must be metabolized into a toxic metabolite or time is required to produce a toxic effect on organ system (e.g., acetaminophen, Amanita phalloides type mushrooms, acetonitrile, carbon tetrachloride, colchicine, digoxin, ethylene glycol, heavy metals, methanol, methylene chloride, monoamine oxidase inhibitors, oral hypoglycemic agents, parathion, and paraquat).

Decontamination The asymptomatic patient who has been exposed to a toxic substance should have decontamination procedures considered if the patient has been exposed to potentially toxic substances in toxic amounts. Ocular exposure should be immediately treated with water or saline irrigation for 15 to 20 minutes with eyelids fully retracted. Do not use neutralizing chemicals. All caustic and corrosive injuries should be evaluated with fluorescein dye and by an ophthalmologist. Dermal exposure is treated immediately with copious irrigation for 30 minutes, not a forceful flushing. Hair shampoo, cleansing of fingernails and navel, perineum, and irrigation of the eyes are necessary in an extensive exposure. The clothes should be specially bagged and may have to be discarded. Leather goods can become irreversibly contaminated and must be abandoned. Caustic (alkali) exposures can require hours of irrigation. Dermal absorption can occur with pesticides, hydrocarbons, and cyanide. Envenomation and Injections of toxic substances. Injected exposures to drugs and toxins can be introduced by envenomation. Cold packs and tourniquets should not be used and incision is generally not recommended. Venom extractors may be used within minutes of envenomation and proximal lymphatic constricting bands or elastic wraps may be utilized to delay lymphatic flow and immobilize the extremity. Inhalation exposure to toxic substances is managed by immediately removing the victim from the contaminated environment by protected rescuers if necessary. Gastrointestinal exposure is the most common route of poisoning. Gastrointestinal (GI) decontamination may be done by gastric emptying (the induction of emesis, gastric lavage) and/or adsorption by administrating single and/or multiple doses of activated charcoal, or whole bowel irrigation. No procedure is routine but should be individualized on the basis of the age, properties of substance ingested and the time that elapsed since the ingestion. If no attempt is made to decontaminate the patient, the reason should be clearly documented on the medical record (e.g., time elapsed, past peak of action, ineffectiveness or risk of procedure). Gastric Emptying Procedures The procedure used is influenced by the age and effectiveness (in a small child the size of the orogastric tube for adequate lavage may not be large enough for iron tablets), the time of ingestion (gastric emptying is usually less effective after 1 to 2 hours postingestion, although there are exceptions, particularly when the toxic drug delays gastric emptying), clinical status (asymptomatic time of peak effect has elapsed or patient is too unstable), the formulation of substance ingested (regular release, sustained release, enteric coated), the amount ingested, caustic action and rapidity of onset of CNS depression or stimulation (convulsions). Most studies show only 30% (19 to 62%) of the ingested toxins is removed by gastric emptying under optimum conditions. A mnemonic for gathering information is SATS (S-substance, A-amount and age, T-time of ingestion, S-symptoms). Attempt to obtain AMPLE information about the patient (A = age and allergies, M = available medications, P = past medical history including if pregnant or psychiatric illnesses, substance abuse or intentional ingestions, L = time of last meal which may influence absorption and the onset and peak action and E = events leading to present condition). The intent should be determined. Consult the regional poison control center for the exact ingredients and the latest management. The first aid information on the labels of products are notoriously inaccurate and product ingredients change. Syrup of ipecac-induced emesis is most useful in young children with a recent witnessed ingestion of known agents. To be effective vomiting should be induced immediately at the site (in the home). The poison control center should be called before inducing emesis. Contraindications or inappropriate induction include: Caustic ingestions Loss of airway protective reflexes. Substances that can produce rapid onset of CNS depression (e.g., ethanol, short-acting [SA] benzodiazepines, SA barbiturates, SA nonbarbiturate sedative-hypnotics, SA opioids, tricyclic antidepressants) or convulsions (e.g., beta blockers, camphor, calcium channel blockers, chloroquine, codeine, isoniazid, mefenamic acid, nicotine, propoxyphene, phencyclidine, organophosphate insecticides, strychnine, and cyclic antidepressants). High viscosity petroleum distillates (e.g., gasoline, lighter fluid, kerosene) Significant vomiting prior to presentation or hematemesis age under 6 months (no established dose, safety or efficacy) Foreign bodies (ineffective, may aspirate) Clinical conditions: pregnancy, neurologically impaired, hemodynamically unstable, increased intracranial pressure, and hypertensive Delay in presentation (over 1–2 hours postingestion) unless substance is likely to delay gastric emptying (anticholinergic or sympathomimetic) Interference with administration of activated charcoal or oral antidotes. Patient cannot tolerate oral intake for a mean of 2 to 3 hours following ipecac-induced emesis. The dose of syrup of ipecac (SI) in the 6 to 9-month-old infant is 5 mL; in the 9 to 12-month-old, 10 mL; and in the 1 to 12-year-old, 15 mL. In children over 12 years and in adults, the dose is 30 mL. The dose may be repeated once if the child does not vomit in 15 to 20 minutes. The vomitus should be inspected for remnants of pills or toxic substances, and the appearance and odor should be documented. When not available, 30 mL of mild dishwashing soap (not electric dishwasher detergent) may be used although it is less effective. Complications are rare but include aspiration, protracted vomiting, rarely cardiac toxicity with long-term abuse, pneumothorax, gastric rupture, diaphragmatic hernia, intracranial hemorrhage and Mallory-Weiss tears. Gastric aspiration and lavage (GL) contraindications are similar to those for ipecac-induced emesis but can be accomplished after the insertion of a endotracheal tube in CNS depression or controlled convulsions. The patient should be placed head down, lower than hips in left-lateral decubitus position, with confirmation of location of tube by radiograph if necessary and with suctioning available. Contraindications to gastric aspiration and lavage include: Caustic ingestions (risk of esophageal perforation) Uncontrolled convulsions because of the danger of aspiration and injury during the procedure High-viscosity petroleum distillate products CNS depression or absent protective airway reflexes, which require the insertion of an endotracheal tube to protect against aspiration. Significant cardiac dysrhythmias, which should be controlled

Significant emesis prior to presentation or hematemesis Delay in presentation (more than 1 hour postingestion) The best results with gastric aspiration and lavage are obtained with the largest possible orogastric tube that can be reasonably passed (nasogastric tubes are not large enough except in liquid ingestions). In adults, use a large-bore orogastric Lavacuator hose or a 42F Ewald tube; in children, use a 22–28F orogastric-type tube but it is usually ineffective with solid ingestions, e.g., iron tablets. The amount of fluid used varies with the patient's age and size. In general, aliquots of 50 to 100 mL per lavage are used in adults and 5 mL/kg up to 50 to 100 mL per lavage in children. Larger amounts of fluid may force the toxin past the pylorus. Many physicians add activated charcoal after the initial aspiration as a marker to determine “till clear” and many instill activated charcoal before removing the tube. Lavage fluid is 0.89% saline. Complications are rare and may include: respiratory depression, aspiration pneumonitis, cardiac dysrhythmias due to increased vagal tone (e.g., b-adrenergic blockers, calcium channel blockers, digoxin overdoses) esophageal-gastric tears and perforation, electrolyte imbalance in young children, laryngospasm, and mediastinitis. Activated charcoal (AC) adsorbs the toxin onto its surface prior to gastrointestinal (GI) absorption and interrupts enterogastric and enterohepatic circulation of toxic metabolites. AC is a stool marker, indicating that the toxin has passed through the GI tract. Activated charcoal does not effectively adsorb small molecules or molecules lacking carbon as listed in Table 144.5. AC adsorption may be diminished by concurrent ethanol, milk, cocoa, powder, and ice cream.

Table 144.5. Substances Poorly Adsorbed by Activated Charcoal

There are a few relative contraindications to the use of AC. It should not be given before, concomitantly with, or shortly after oral antidotes unless it has been proven not to interfere significantly with their effectiveness. It does not interfere with effectiveness of N-acetylcysteine (NAC) in acetaminophen overdose (although there is up to 39% reduction in NAC) and it may contribute to vomiting. AC does not effectively adsorb caustics and corrosives, may produce vomiting or cling to the mucosa and falsely appear as a burn on endoscopy. It should not be given if patient is comatose without securing the airway and if there are no bowel sounds (may form concretions or perforation). The dose of activated charcoal is 1 g/kg per dose orally, with a minimum of 15 grams. Optimum dosage has not been established. Ideal therapy allegedly requires a 10:1 ratio AC:toxin. The usual initial adult dose is 60 to 100 grams and children 15 to 30 grams. It is administered as a slurry mixed with water orally, or by nasogastric or orogastric tube. Be sure the tube is in the stomach, AC is usually administered initially with a cathartic in adults. Cathartics are not necessary in children. Repeated dosing with AC decreases the half-life and increases the clearance of phenobarbital, dapsone, salicylate, quinidine, theophylline, and carbamazepine. In multiple dose activated charcoal (MDAC) subsequent cathartics should be given every 24 hours, not with each dose. The MDAC varies from 0.25 to 0.50 gm/kg every 1 to 4 hours and continuous nasogastric tube infusion 0.25 to 0.5 g/kg per hour has been used to decrease vomiting. Gastrointestinal dialysis is the diffusion of the toxin from the higher concentration in the serum of the mesenteric vessels to the lower levels in the GI tract mucosal cell and subsequently into the GI lumen where the concentration has been lowered by intraluminal AC adsorption and adsorbed by the intraluminal AC. Complications of AC include many cases of unreported pulmonary aspirations and “charcoal lungs,” intestinal obstruction (3 cases reported), empyema following esophageal perforation and hypermagnesemia and hypernatremia, which have been associated with repeated concurrent doses of activated charcoal and saline cathartics. Catharsis is used to hasten the elimination of any remaining toxin in the gastrointestinal tract. There are no studies to demonstrate the effectiveness of a cathartic used alone. AC and cathartic was more effective than AC alone in managing SR theophylline overdose. However, a cathartic with AC was less effective than AC alone in salicylate poisoning. A study using AC alone and magnesium citrate indicated no benefit when the cathartic was administered. Cathartics are relatively contraindicated in the following circumstances: 1. 2. 3. 4. 5.

Ileus as indicated by absence of bowel sounds. Intestinal obstruction or evidence of intestinal perforation. Cases with a preexisting electrolyte disturbances. Magnesium salts are contraindicated in renal impairment. Sodium salts in heart failure or diseases requiring sodium restriction.

Magnesium sulfate or sodium sulfate is administered in doses of 250 mg/kg per dose as 20% solutions. The adult dose is 30 grams. Sorbitol is given at 2.8 mL/kg to a maximum of 200 mL of a 70% solution, in adults. Sorbitol should not be used in children. It is best to avoid cathartics in pediatric patients because hyponatremia, hypocalcemia, hyperphosphatemia, and death have occurred. In whole-bowel irrigation (WBI) bowel-cleansing solutions of polyethylene glycol (PEG) with balanced electrolytes are used to avoid changes in body weight or electrolytes. WBI may be indicated although not FDA approved with ingestions of substances that are poorly adsorbed by activated charcoal, such as iron and other heavy metals, lithium, and sustained-release preparations. The procedure has been studied and used successfully in iron overdose when abdominal radiographs reveal incomplete emptying of excess iron. There are additional implications in other ingestions, e.g., body packing of illicit drugs (cocaine and heroin). The procedure is to administer, oral or by nasogastric tube, the solution (GoLytely or Colyte), 0.5 L/h in children younger than 5 years of age and 2 L/h in adolescents and adults for 5 hours. The end point is reached when the rectal effluent is clear or radiopaque materials can no longer be seen in the GI tract on abdominal radiograph. These measures should not be used if there is extensive hematemesis, ileus, or signs of bowel obstruction, perforation, or peritonitis. Animal experiments adding PEG to AC indicated AC-salicylates and AC-theophylline combinations showed decreased adsorption and desorption of salicylate and

theophylline and no therapeutic benefit over AC alone. Polyethylene solutions are bound by AC in vitro decreasing the efficacy of AC. Dilutional treatment is indicated for the immediate management of caustic and corrosive poisonings but is otherwise not useful. The administration of large quantities of diluting fluid, more than 30 mL in children and 250 mL in adults, may produce vomiting, re-exposing the vital tissues to the effects of local damage and possible aspiration. Neutralization has not been proved to be safe or effective. Surgery has been required in the management of body packers obstruction, intestinal ischemia produced by cocaine ingestion and iron local caustic action.

COMMON TOXICOLOGIC PRESENTATION Table 144.6 lists the common toxicologic presentations and their most frequent toxicologic and medical etiologies. A mnemonic for miosis is VCPOOP: Valproic acid, Clonidine, Phencyclidine, Organophosphates, Opioids, Phenothiazines. A mneumonic for mydriasis is SHAW: Sympathomometic, Hallucinogens, Anitcholineric, Withdrawal.

Table 144.6. Common Clinical Presentations and Etiologies

DIFFERENTIAL DIAGNOSIS OF POISONS ON THE BASIS OF CNS MANIFESTATIONS Neurologic parameters help to classify and assess the need for supportive treatment as well as provide diagnostic clues to the etiology ( Table 144.7, Table 144.8, Table 144.9 and Table 144.10). CNS depressants are cholinergics (C), opioids (O) and sedative-hypnotics (S-H), sympatholytic agents (Syly). The hallmarks are lethargy, sedation, stupor and coma. The CNS stimulants are anticholinergics (Ach), hallucinogens (H), sympathomimetics (Sy), and withdrawal (W). The hallmarks of CNS stimulants are convulsions and hyperactivity. There is considerable overlapping in the hallucinogen category, however, the major hallmark manifestation is hallucinations.

Table 144.7. Central Nervous System Depressants

Table 144.8. Central Nervous System Stimulants

Table 144.9. Hallucinogens

Table 144.10. Autonomic Nervous System

GUIDELINES FOR INHOSPITAL DISPOSITION Classification as “high-risk patients” depends on clinical judgement. Any patient with the need for cardiorespiratory support or persistent altered mental status for 3 hours or more should be considered for intensive care. Guidelines for admitting patients over 14 years of age to an intensive care unit, after 2 to 3 hours in ED, include the following: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Need for intubation Seizures Unresponsiveness to verbal stimuli Arterial carbon dioxide pressure more than 45 mmHg Cardiac conduction or rhythm disturbances (any rhythm except sinus arrhythmia) Close monitoring of vital signs during antidotal therapy or elimination procedures Need for continuous monitoring QRS more than 0.10 second, in tricyclic antidepressant poisoning Systolic blood pressure less than 80 mmHg Grade 3 or 4 stimulation or depression ( Table 144.2, Table 144.3, and Table 144.4) Hypoxia, hypercarbia, acid base, metabolic abnormalities Extremes of temperature Progressive deterioration or significant underlying medical disorders

USE OF ANTIDOTES Antidotes are available for only a relatively small number of poisons. An available antidote should be administered only after the vital functions have been established. Table 144.11A lists the toxins for which antidotes are available. Table 144.11B summarizes the commonly used antidotes, their indications, and methods of administration. (Consult the regional poison control center for additional information on these antidotes.)

Table 144.11A. Common Poisons and Their Recommended Antidote

Table 144.11B. Initial Doses of Antidotes for Common Poisonings

ENHANCEMENT OF ELIMINATION The medical methods for elimination of absorbed toxic substances are diuresis, dialysis, hemoperfusion, exchange transfusion, plasmapheresis, enzyme induction, and inhibition. Methods of increasing urinary excretion of toxic chemicals and drugs have been studied extensively, but the other modalities have not been well evaluated. In general, these methods are needed in only a minority of instances and should be reserved for life-threatening circumstances or when a definite benefit is anticipated. Diuresis Diuresis increases the renal clearance of compounds that are primarily eliminated by the renal route, are significantly reabsorbed in the renal tubules, have small volume distribution and low protein binding. The risks of diuresis are fluid overload, with cerebral and pulmonary edema, and disturbances in acid-base and electrolyte balance. Failure to produce a diuresis may imply renal failure. At present the only effective diuresis used in the management of the poisoned patient is alkaline diuresis. Diuretics have been administered to maintain the diuresis. Although acid diuresis may enhance the elimination of weak bases (e.g., amphetamines, fenfluramine [Pondimin], quinidine, phenyclidine, strychnine), it is not recommended because of adverse effects of metabolic acidosis with rhabdomyolysis (e.g., precipitation of myoglobin) cardiotoxicity, and lack of proven clinical

effectiveness. Alkalinization with or without diuresis with sodium bicarbonate (1 to 2 mEq/kg in 15 mL/kg of 5% dextrose may be used in the therapy of weak acids intoxications such as salicylates (severe salicylate poisoning can require hemodialysis which avoids complications of fluid overload), long-acting barbiturates (e.g., phenobarbital), 2,4 dichlorophenoxyacetic acid, chlorpropamide, methotrexate, and methanol. Additional boluses of 0.5 mEq/kg can be administered to maintain alkalinization but avoid blood pH values over 7.55. Many clinicians use the alkalinization without the diuresis because of the danger of fluid overload. The hemodynamic status, fluids, blood gases and electrolytes, glucose must be very closely monitored during these procedures ( Table 144.11B, sodium bicarbonate). Saline diuresis, but not forced diuresis, is used in lithium intoxications. Dialysis Dialysis is the extrarenal means of removing certain substances from the body and can substitute for the kidney when renal failure occurs. Dialysis is not the first measure instituted; however, it may be lifesaving later in the course of a severe intoxication. It is needed in only a minority of intoxicated patients. Peritoneal dialysis (PD) utilizes the peritoneum as the membrane for dialysis. It is only 1/20 as effective as hemodialysis. It is easier to use and less hazardous to the patient but also less effective in removing the toxin; therefore, it is seldom used except in small infants. Hemodialysis (HD) is the most effective means of dialysis but requires experience with sophisticated equipment. Blood is circulated past a semipermeable membrane by means of an extracorporeal method. Substances are removed by diffusion down a concentration gradient. Anticoagulation with heparin is necessary. The contraindications to HD (a) not dialyzable substance, (b) effective antidotes are available, (c) hemodynamic instability (e.g., shock), and (d) presence of coagulopathy because heparinization is required. The patient-related criteria for dialysis are (a) anticipated prolonged coma and the likelihood of complications, (b) renal compromise (toxin excreted or metabolized by kidneys and dialyzable chelating agents in heavy metal poisoning), (c) laboratory confirmation of lethal blood concentration, (d) lethal dose poisoning with an agent with delayed toxicity or known to be metabolized into a more toxic metabolite (e.g., ethylene glycol, methanol), (e) hepatic impairment when the agent is metabolized by the liver, and clinical deterioration despite optimum supportive medical management. Dialyzable substances are easily diffusible across dialysis membrane and have the following characteristics: (a) a small molecular weight less than 500 daltons preferably less than 350, (b) a volume of distribution (Vd) of less than 1 L/kg, (c) low-protein binding (PB) less than 50%, (d) are highly water soluble (low lipid solubility), (e) high plasma concentration and a toxicity that correlates reasonably with the plasma concentration ( Table 144.12 and Table 144.13).

Table 144.12. Dialysis and Hemoperfusion

Table 144.13. Plasma Concentrations Above Which Removal by Extracorporeal Measures May be Indicated

Hemodialysis also has a role in correcting disturbances that are not amendable to appropriate medical management. These are easily remembered by the “vowel” mnemonic: A—refractory acid-base disturbances, E—refractory electrolyte disturbances, I—intoxication with dialyzable substances, e.g., ethanol*, ethylene glycol*, isopropyl alcohol*, methanol*, lithium*, salicylates*, and theophylline. Dialysis is rarely indicated with aminoglycosides, carbamazepine, phenobarbital, and phenytoin. O—overhydration and U—uremia (renal failure). (*Toxins in which hemodialysis is preferred to hemoperfusion.) Complications are hemorrhage, thrombosis, air embolism, hypotension, infections, electrolyte imbalance, and thrombocytopenia removal of therapeutic medications. Hemoperfusion (HP) Hemoperfusion is the parenteral form of oral AC. Heparinization is necessary. The patient's blood is routed extracorporeal through an outflow arterial catheter through a filter adsorbing cartridge (charcoal or resin) and returned through a venous catheter. High flow rates (e.g., 300 mL/min) through the filter are utilized to maximize the most efficient use of the filter. Cartridges must be changed every 4 hours. The blood glucose, electrolytes, calcium, albumin, complete blood count (CBC) platelets and serum and urine osmolarity must be carefully monitored. This procedure has extended extracorporeal removal to a large range of substances that were formerly either poorly dialyzable or nondialyzable. It is not limited by molecular weight, water solubility, protein binding. However, HP is limited by Vd > 400 L, plasma concentration and rate of flow through filter. Activated charcoal cartridges are the primary type of hemoperfusion that is currently available in the United States. Analysis of studies with hemodialysis and hemoperfusion does not indicate that they reduce morbidity or mortality substantially except in certain cases (e.g., theophylline). Hemoperfusion may be recommended in combination with hemodialysis (e.g., paraquat, electrolyte disturbances). The contraindications are similar to those for hemodialysis. The patient-related criteria for HP are (a) anticipated prolonged coma and the likelihood of complications, (b) laboratory confirmation of lethal blood concentrations, (c) lethal dose poisoning with an agent with delayed toxicity or known to be metabolized into a more toxic metabolite, (d) hepatic impairment when an agent is metabolized by the liver, and clinical deterioration despite optimum supportive medical management. Limited data are available as to which toxins are best treated with hemoperfusion. However, HP has proved useful in glutethimide intoxication, barbiturate overdose even with short-acting barbiturates, carbamazepine, phenytoin, theophylline intoxication, and chlorophenothane (DDT) (see Table 144.12 and Table 144.13). Complications include hemorrhage, thrombocytopenia, hypotension, infection, leukopenia, depressed phagocytic activity of granulocytes, decreased immunoglobin

levels, hypoglycemia, hypothermia, hypocalcemia, pulmonary edema, air and charcoal embolism. Plasmapheresis consists of removal of a volume of blood. All the extracted components are returned to the blood except the plasma, which is replaced with a colloid protein solution. There is limited clinical data on guidelines and efficacy in toxicology. Centrifugal and membrane separators of cellular elements are used. It can be as effective as HD or HP for toxins with high-protein binding and may be useful in toxins not filtered by HD and HP. It has been used in certain diseases such as myeloma, idiopathic thrombocytopenia, systemic lupus erythematosus, rheumatoid arthritis, and myasthenia gravis. Plasmapheresis has been ancedotally used in the following intoxications (removed 10%), paraquat, propranolol (removed 30%), quinine, L-thyroxine (removed 30%), salicylate (removed 10%), and less than 10% of digoxin, phenobarbital, prednisolone, and tobramycin. Complications include infection, allergic reactions including anaphylaxis, hemorrhagic disorders, thrombocytopenia, embolus and thrombus, hyper and hypovolemia, dysrhythmias, syncope, tetany, paresthesia, pneumothorax, adult respiratory distress syndrome, and seizures.

SUPPORTIVE CARE, OBSERVATION, AND THERAPY OF COMPLICATIONS In the comatose or altered mental status patient (AMS), if airway protective reflexes are absent, endotracheal intubation is indicated, if ineffective respirations, ventilate with 100% oxygen. If a cyanotic patient fails to respond to oxygen consider methemoglobinemia. Perform a reagent strip test for blood glucose to detect hypoglycemia and send the specimen to the laboratory for confirmation. Administer glucose if the glucose reagent strip visually reads less than 150 mg/dL. Venous blood should be used rather than capillary for the reagent strip if the patient is in shock or hypotensive. Hypoglycemia accompanies many poisonings including ethanol (especially in children), clonidine, insulin, organophosphates, salicylates, sulfonylureas, and a Jamaican plant called akee. If hypoglycemia is present or suspected immediately administer glucose as a intravenous bolus. In a neonate: 10% glucose (5 mL/kg), child: 25% glucose 0.25 g/kg (2 mL/kg) and adults: 50% glucose 0.5 g/kg (1 mL/kg). Large amounts of glucose given rapidly to nondiabetic patients may cause a transient reactive hypoglycemia and hyperkalemia, and may accentuate damage in ischemic cerebrovascular and cardiac tissue. If focal neurological signs are present it may be prudent to withhold glucose since hypoglycemia rarely causes focal signs ( 10 mOsm/kg H2O suggests the presence of another osmotically active substance. Assessment of the osmolal gap can be used as a screening measure for the presence of certain selected solvents including alcohol. Treatment The therapeutic approach to the alcohol-intoxicated patient must begin with attention to the ABCs. Patients who are stuporous or comatose must have an assessment of the gag reflex. Any patient with a depressed gag reflex must be intubated to protect the airway. An intravenous line should be established with D5W NS. Enhanced Elimination Because the absorption of alcohol is rapid, evacuation more than 1 hour after ingestion usually offers little benefit unless the patient has ingested other toxic agents or gastric emptying is delayed by high concentration of alcohol, food, or drugs such as opiates or anticholinergics. While activated charcoal is of limited benefit in preventing the absorption of alcohols, other agents are often ingested with alcohol, and use of charcoal is recommended in severe cases. Fructose given intravenously to inebriated patients can increase the metabolism of alcohol by 25%. This increase, however, is outweighed by the serious side effects of fructose therapy: nausea and vomiting, abdominal pain, pruritus, lactic acidosis, and shock ( 92). Hemodialysis increases the clearance of alcohol by three- to four-fold and is appropriate in critically intoxicated patients. Hemodialysis has no place in the routine treatment of alcohol intoxication because most patients do well with good supportive care. Medical Treatment All fluid, glucose electrolyte, and acid-base abnormalities should be treated in the ED. All alcoholics should receive intravenous preparations of multivitamins in addition to thiamine 100 mg intravenously or intramuscularly. Clotting disorders should be corrected with vitamin K and fresh frozen plasma as needed. Patients who are malnourished, withdrawing from alcohol, or show signs of magnesium deficiency (e.g., tetany) should be given 2 g magnesium sulfate intravenously. Patients who are seizing and or withdrawing can be treated with intravenous diazepam or lorazepam. Patients who are encephalopathic from liver disease should be treated with cleansing enemas, and lactulose, 15 to 30 mL every hour or neomycin 0.5 to 1 g orally, as needed. If sepsis, meningitis, or peritonitis is suspected, the patient should be cultured and started on broad-spectrum antibiotics. Stimulants, including amphetamines and caffeine, do not reliably counteract the sedative effects of alcohol. Therefore, coffee is not an effective antidote to alcohol. In fact, coffee may antagonize the positive effect of small doses of alcohol on reaction time and coordination. Criteria for Admission Most uncomplicated patients intoxicated with alcohol can be successfully discharged from the ED after an evaluation and period of observation. No patient, however, should be discharged while still in an intoxicated state. Patients with altered mental status and a mixed overdose, those with severe trauma, those in moderate to severe alcohol withdrawal, and those with another disease state (e.g., pancreatitis, infection, gastrointestinal bleeding, encephalopathy, etc.) should all be admitted. The threshold for admission should be lower for alcoholics who are homeless, medically indigent, or otherwise disadvantaged. Alcoholics who are sober and desire alcohol detoxification can be admitted to special units for “drying out” and rehabilitation. Reports of short-term (6 months) improvement rates of 80% and long-term (abstinence for more than 1 year) improvement rates of up to 50% from “some facilities” are encouraging ( 93). The national average for improvement from treatment is much lower. Inpatient alcohol programs have an advantage over outpatient programs in that they enforce abstinence, provide more support and structure, and separate the patient from the social environment associated with drinking. Cost concerns and program availability have been major deterrents. Hospitalization should be considered in the following circumstances (58): 1. 2. 3. 4. 5. 6.

The patient has additional medical problems. Depression, confusion, or psychosis might interfere with outpatient care. The patient is in the midst of a severe life crisis. Outpatient treatment has been tried and failed. Unavailability of local outpatient treatment. Any suicidal risk.

No matter what type of rehabilitation is planned, an alcoholic patient can always be referred to Alcoholics Anonymous (AA). AA is a self-help group of recovering alcoholics that offers support and crisis intervention and is available in almost every community. Disulfiram (Antabuse) has been used with some success in the treatment of alcohol abuse ( 94,95). The drug inhibits aldehyde dehydrogenase leading to a build-up of acetaldehyde in the blood after the consumption of alcohol. Peak acetaldehyde levels usually occur approximately one-half hour after drinking, but this depends on the dose of alcohol ingested and the rate of intake. The disulfiram-alcohol reaction is manifested by: skin flushing, nausea, vomiting, diarrhea, palpitations, hypotension or hypertension, diaphoresis, vertigo, tremor, disorientation, headache, and chest and abdominal pains. Disulfiram should not be prescribed to patients with hypertension, diabetes, heart disease, or history of stroke. Alcoholics are often given 250 mg of disulfiram a day for 6 to 12 months at a time. Disulfiram is most

effective in highly motivated individuals. Studies have shown that the opiate antagonist naltrexone can decrease craving for alcohol and improve treatment outcomes in alcoholics ( 96,97). Serotonin uptake inhibitors and dopamine antagonists also show promise as anticraving agents ( 94,95,98).

ALCOHOL-DRUG INTERACTIONS Alcohol is responsible for various drug interactions with various agents ( 99) (Table 146–1.4). Depending on the agent involved and the duration of drinking, the results may be antagonistic, additive, or synergistic. Acute alcohol intoxication can transiently increase levels of certain drugs (e.g., phenytoin) because of competition for shared metabolic pathways. In contrast, chronic alcoholism can increase drug clearance and lower drug levels because of the enhancement of these same pathways.

Table 146–1.4. Drug Interactions with Alcohol

When increased microsomal oxidation occurs, there is a spill over stimulation to other microsomal-oxidizing systems. This leads to the accelerated metabolism of drugs sharing similar microsomal metabolic pathways. The half-lives of phenytoin, tolbutamide, and warfarin are 50% shorter in abstaining alcoholics than in nondrinkers (100). For a similar reason, the potential toxicity of acetaminophen can be enhanced by alcohol through the induction of hepatotoxic intermediates metabolized by way of the P450 system (101). Alcohol has additive effects when ingested with antihistamines, barbiturates, and other sedative-hyponotics, tricyclic antidepressants, glutethimide, phenothiazine, narcotics, and chloral hydrate (Mickey Finn). Alcohol can enhance the aspirin-induced increase in bleeding time. In addition to disulfiram, a large number of other drugs can cause a similar effect by inhibiting aldehyde dehydrogenase ( Table 146–1.4). Treatment is symptomatic and involves gut decontamination (if appropriate), charcoal, intravenous hydration, antiemetics, and monitoring for seizures and arrhythmias. References 1. Lieber CS: Medical disorders of alcoholism. N Engl J Med 1995;333:1058–1065. 2. Eighth Special Report to the U.S. Congress on Alcohol and Health Rockville, MD: U.S. Dept. of Health and Human Services, National Institute of Alcohol Abuse and Alcoholism, DHHS publication no. ADM-281-91-0003, 1993. 3. Shultz JM, Rice DP, Parker DL: Alcohol-related mortality and years of potential life lost—United States, 1987. MMWR 1990;39:173–178. 4. Heiien DM, Pittman DJ: The external costs of alcohol abuse. J Stud Alcohol 1993;54:302–307. 5. Grant BF, Harford TC, Dawson DA, et al: Prevalence of DSM-IV alcohol abuse and dependence. Alc Health Res World 1994;18:243–248. 6. Regier DA, Farmer ME, Rae DS, et al: Comorbidity of mental disorders with alcohol and other drug abuse. JAMA 1990;264:2511–2518. 7. Klatsky AL, Armstrong MA, Friedman GD: Alcohol and mortality Ann Intern Med 1992;117:646–654. 8. Lands WEM: Alcohol and energy intake. Am J Clin Nutr 1995;62(Suppl):1101S–110S. 9. Ellenhorn MJ, Barceloux DG: Alcohols and glycols In: Ellenhorn MJ, Barceloux DG, eds. Medical toxicology. New York: Elsevier, 1996:1127–1165. 10. Committee on Drugs, American Association of Pediatricians. Ethanol in liquid preparations intended for children. Pediatrics 1984;73:405–407. 11. Frezza M, Di Padova C, Pozzato G, et al: High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med 1990;322:95–99. 12. Ritchie JM: The aliphatic alcohols. In: Gilman AG, Goodman LS, Rall TW, et al: eds. The Pharmacological basis of therapeutics. New York: MacMillan, 1985:372–386. 13. Lieber CS: Metabolism and metbolic effects of alcohol. Med Clin North Am 1984;68:3–31. 14. Brennan DF, Betzelos S, Reed R, et al: Ethanol elimination rates in an ED population. Am J Emerg Med 1995;13:276–280. 15. Gershman H, Steeper J: Rate of clearance of ethanol from the blood of intoxicated patients in the emergency department. J Emerg Med 1991;9:307–311. 16. Porter TD, Coon MJ: Cytochrome P-450: multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. J Biol Chem 1991;266:13469–13472. 17. Takahashi T, Lasker JM, Rosman AS, et al: Induction of cytochrome P-4502E1 in the human liver by ethanol is caused by a corresponding increase in encoding messenger RNA. Hepatology 1993;17:236–245. 18. Lieber CS, Lasker JM, DeCarli LM, et al: Role of acetone, dietary fat and total energy intake in induction of hepatic microsomal ethanol oxidizing system. J Pharmacol Exp Ther 1988;247:791–795. 19. Hobbs WR, Rall TW, Verdoorn TA: Hypnotics and sedatives; ethanol. In: Hardman JG, Gilman AG, eds. The pharmacological basis of therapeutics. New York: McGraw-Hill, 1996:361–395. 20. Peoples RW, Li C, Weight FF: Lipid vs. protein theories of alcohol action in the nervous system. Annu Rev Pharmacol Toxicol 1996;36:185–201. 21. Wafford KA, Burnett DM, Leidenheimer NJ, et al: Ethanol sensitivity of the GABA A receptor expressed in Xenopus Oocytes requires 8 amino acids contained in the g2L subunit. Neuron 1991;7:27–33. 22. Whiting PJ, McKernan RM, Wafford KA: Structure and pharmacology of vertebrate GABA A receptors. Int Rev Neurobiol 1995;38:95–138. 23. Sieghart W: Structure and pharmacology of g-amino acid A receptor subtypes. Pharmacol Rev 1995;47:182–234. 24. Milhic SJ, Harris RA: Alcohol actions at the GABA A receptor/chloride channel complex. In: Deitrich RA, Erwin VG, eds. Pharmacological effects of ethanol on the nervous system. Boca Raton: CRC Press, 1996:51–72. 25. Lovinger DM, White G, Weight FF: Ethanol inhibits NMDA-activated ion current in hippocampal neurons Science (Washington, D.C.) 1989;243:1721–1724. 26. Tabakoff B, Hoffman PL: Ethanol and glutamate receptors. In: Deitrich RA, Erwin VG, eds. Pharmacological effects of ethanol on the nervous system. Boca Raton: CRC Press, 1996:73–93. 27. Collins AC: The nicotinic cholinergic receptor as a potential site of ethanol action. In: Deitrich RA, Erwin VG, eds. Pharmacological effects of ethanol on the nervous system. Boca Raton: CRC Press, 1996:95–115. 28. Lovinger DM, White G: Ethanol potentiation of 5-hydroxytryptamine 3 receptor-mediated ion current in neuroblastoma cells and isolated adult mammalian neurons. Mol Pharmacol 1991;40:263–270. 29. Mullikin-Kilpatrick D, Treistman SN: Voltage-gated calcium channels. In: Deitrich RA, Erwin VG, eds. Pharmacological effects of ethanol on the nervous system. Boca Raton: CRC Press, 1996:29–49. 30. Deitrich RA, Erwin VG, eds: Pharmacologic effects of ethanol on the nervous system. Boca Raton: CRC Press, 1996. 31. Alkana RL, Davies DL, Le AD: Ethanol's acute effects on thermoregulation: mechanisms and consequences. In: Deitrich RA, Erwin VG, eds. Pharmacological effects of ethanol on the nervous system. Boca Raton: CRC Press, 1996:291–328. 32. Brodie MS, Shefner SA, Dunwiddie TV: Ethanol increases the firing rate of dopamine neurons of the rat ventral tegmental area in vitro. Brain Res 1990;508:65–69. 33. Nestler EJ: Molecular mechanisms of drug addiction. J Neurosci 1992;12:2439–2450. 34. Koob GF: Drug addition: the yin and yang of hedonic homeostasis. Neuron 1996;16:893–896. 35. Hu X, Ticku MK: Chronic ethanol treatment upregulates the NMDA receptor function and binding in mammalian cortical neurons. Mol Brain Res 1995;30:347–356. 36. Trevisan L, Fitzgerald LW, Brose N, et al: Chronic ingestion of ethanol up-regulates NMDAR1 receptor subunit immunoreactivity in rat hippocampus. J Neurochem 1994;62:1635–1638. 37. Mhatre MC, Pena G, Sieghart W, et al: Antibodies specific for GABA A receptor a subunits reveal that chronic alcohol treatment down-regulates a-subunit expression in rat brain regions. J Neurochem 1993;61:1620–1625. 38. Tsai G, Gastfriend DR, Coyle JT: The glutamate basis of human alcoholism. Am J Psychiatry 1995;152:332–340. 39. Jernigan TL, Butters N, DiTraglia G, et al: Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging. Alcohol Clin Exp Res 1991;15:418–427. 40. Diana M, Pistis M, Carboni S, et al: Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: electrophysiological and biochemical evidence. Proc Natl Acad Sci 1993;90:7966–7969. 41. Lieber CS: Alcohol and the liver: 1994 update. Gastroenterology 1994;106:1085–1105. 42. Kumar V, Cotran RS, Robbins SL: Basic pathology. Philadelphia: WB Saunders, 1992. 43. Klassen LW, Tuma D, Sorrel MF: Immune mechanisms of alcohol-induced liver disease. Hepatology 1995;22:355–357. 44. Sherman DI, Williams R: Liver damage: mechanisms and management. Br Med Bull 1994;50:124–138. 45. Holstege A, Bedossa P, Poynard T, et al: Acetaldehyde-modified epitopes in liver biopsy specimens of alcoholic and nonalcoholic patients: Localization and association with progressive liver fibrosis. Hepatology 1994;19:367–374.

46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101.

Korsten MA, Matsuzaki S, Feinman L, et al: High blood acetaldehyde levels after ethanol administration. N Engl J Med 1975;292:386–389. Ward JB, Petersen OH, Jenkins SA, et al: Is an elavated concentration of acinar cytosolic free ionized calcium the trigger for acute pancreatitis? Lancet 1995;346:1016–1019. Nordback IH, MacGowan S, Potter JJ, et al: The role of acetaldedehyde in the pathogenesis of acute pancreatitis. Ann Surg 1991;214:671–678. Preedy VR, Richardson PJ: Ethanol induced cardiovascular disease. Br Med Bull 1994;50:152–163. Laposata EA, Louis LG: Presence of non-oxidative, ethanol metabolism in human organs commonly damaged by ethanol abuse. Science 1986;231:497–499. Modell JG: Behavioral, neurologic, and physiologic effects of acute ethanol ingestion. In: Fassler D, ed. The alcoholic patient: emergency medical intervention. New York: Gardner Press, 1990. Kalant H: Ethanol and the nervous system: experimental neurophysiological aspects. Int J Neurol 1974;9:111–124. Mellanby E: Alcohol: its absorption into and disappearance from the blood under different conditions. Medical Research Committee, Special Report Series (Lond) 1919;31:1–48. Tabakoff B, Cornell N, Hoffman PL: Alcohol tolerance. Ann Emerg Med 1986;15:1005–1012. Lindblad B, Olsson R: Unusually high levels of blood alcohol. JAMA 1976;236:1600–1602. Davis AR, Lipson AH: Central nervous system depression and high blood ethanol levels. Lancet 1986;1:566. Brust JCM: Alcoholism. In: Rowland LP, ed. Merrit's textbook of neurology. Baltimore: Williams and Wilkins, 1995:967–977. Schuckit MA: Alcohol and alcoholism. In: Fauci AS, Braunwald E, Isselebacher KJ, et al:, eds. Harrison's principles of internal medicine. New York: McGraw-Hill, 1998:2503–2508. Ettinger PO, Wu CF, De La Cruz C, et al: Arrhythmias and the “holiday heart”: alcohol-associated rhythm disorders. Am Heart J 1978;95:555–562. Greenspon AJ, Schaal SF: The “holiday heart”: electrophysiologic studies of alcohol effects in alcoholics. Ann Intern Med 1983;98:135–139. Engel TR, Luck JC: Effects of atrial vulnerability and “holiday heart.” J Am Coll Cardiol 1983;1:816–818. Konturek SJ, Stachura J, Konturek JW: Gastric cytoprotection and adaption to ethanol. In: Preedy VR, Watson RR, eds. Alcohol and the gastrointestinal tract. Boca Raton: CRC Press, 1996:123–141. Morse RM, Flavin DK: The definition of alcoholism. JAMA 1992;268:1012–1014. Mayfield D, McLeod G, Hall P: The CAGE questionaire: validation of a new alcoholism screening instrument. Am J Psychiatry 1974;131:1121–1123. Pokorny AD, Miller BA, Kaplan HB: A paper and pencil questionaire. Am J Psychiatry 1972;129:342–345. Helzer JE, Pryzbeck TR: The co-occurrence of alcoholism with other psychiatric disorders in the general population and its impact on treatment. J Stud Alcohol 1988;49:219–224. Klatsky AL, Armstrong MA: Alcohol use, other traits, and risk of unnatural death: a prospective study. Alc Clin Exp Res 1993;17:1156–1162. Cotton NS: The familial incidence of alcoholism: a review. J Stud Alcohol 1979;40:89–116. Ball DM, Murray RM: Genetics of alcohol abuse. Br Med Bull 1994;50:18–35. Heath AC: Genetic influences on alcoholism risk. Alc Health Res World 1995;19:166–171. McGue M: Genes, environment, and the etiology of alcoholism. In: Zucker R, Boyd G, Howard J, eds. The development of alcohol problems: exploring the biopsychosocial matrix of risk. Research Monograph No 26. Rockville, MD: NIAAA, 1994:1–40. Chao HM: Alcohol and the mystique of flushing. Alc Clin Exp Res 1995;19:104–109. Blum K, Noble EP, Sheridan PJ, et al: Allelic association of human dopamine receptor gene in alcoholism. JAMA 1990;263:2055–2060. Mendelson JH, Miller KD, Mello NK: Hospital treatment of alcoholism: a profile of middle income Americans. Alc Clin Exp Res 1982;6:377–383. Walsh DC, Hingson RW, Merrigan DM, et al: The impact of a physician's warning on recovery after alcohol treatment. JAMA 1992;267:663–667. Bradley KA: The primary care practitioner's role in the prevention and management of alcohol problems. Alc Health Res World 1994;18:97–104. Klatsky AL, Friedman GD, Sieglaub AB: Alcohol and mortality. Ann Intern Med 1981;95:139–145. Ishak KG, Zimmerman HJ, Ray MB: Alcoholic liver disease: pathologic, pathogenic and clinical aspects. Alc Clin Exp Res 1991;15:45–66. Conn HO, Fessel JM: Spontaneous bacterial peritonitis in cirrhosis: variations on a theme. Medicine 1971;50:161–197. Langlais PJ: Alcohol-related thiamine deficiency. Alc Health Res World 1995;19:113–121. Garro AJ, Lieber CS: Alcohol and cancer. Annu Rev Pharmacol Toxicol 1990;30:219–249. Klatsky AL: Alcohol, coronary artery disease, and hypertension. Annu Rev Med 1996;47:149–160. Renaud S, DeLorgeril M: Wine, alcohol, platlets, and the French paradox for coronary heart disease. Lancet 1992;339:1523–1526. Rimm EB, Klatsky A, Grobbee D, et al: Review of moderate alcohol consumption and reduced risk of coronary heart disease. BMJ 1996;312:731–736. Gaziano JM, Buring JE, Breslow JL, et al: Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. N Engl J Med 1993;329:1829–1834. Ridker PM, Vaughan DE, Stampfer MJ, et al: Association of moderate alcohol consumption and plasma concentration of endogenous tissue-type plasminogen activator. JAMA 1994;272:929–933. Freedland ES, McMicken DB, D'Onofrio G: Alcohol and trauma. Emerg Med Clin North Am 1993;11:225–239. Soderstrom CA: Detecting alcohol-related problems in trauma center patients. Alc Health Res World 1994;18:127–130. Moniz C: Alcohol and bone. Br Med Bull. 1994;50:67–75. Menzano E, Carlen PL: Zinc deficiency and corticosteroids in the pathogenesis of alcoholic brain dysfunction—a review. Alc Clin Exp Res 1994;18:895–901. Jones AW: Variability of the blood: breath alcohol ratio in vivo. J Stud Alcohol 1978;39:1931–1939. Lovejoy FH: Ethanol intoxication. Clin Toxicol Rev 1981;4:1. West LJ, Maxwell DS, Noble EP, et al: Alcoholism Ann Intern Med 1984;100:405–416. Miller NS: Pharmacotherapy in alcoholism. J Addict Dis 1995;14:23–46. Gorelick DA: Overview of pharmacologic treatment approaches for alcohol and other drug addictions. Psychiatr Clin North Am 1993;16:141–156. O'Malley SS, Jaffe AJ, Chang G, et al: Naltrexone and copng skills therapy for alcohol dependence. Arch Gen Psychiatry 1992;49:881–887. Volpicelli JR, Alterman AI, Hayashida M, et al: Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 1992;49:876–880. Anton RF: Medications for treating alcoholism. Alc Health Res World 1994;18:265–278. Abramowicz M: Interactions of drugs with alcohol. Med Lett 1981;23:17–28. Kater RMH, Zeive P, Tobon F, et al: Accelerated metabolism of drugs in alcoholics. Gastroenterology 1969;56:412. Whitcomb DC, Block GD: Association of acetominophen hepatotoxicity with fasting and ethanol use. JAMA 1994;272:1845–1850.

Chapter 146.2 Alcohol Substitutes: Treatment of Poisonings by Methanol, Ethylene Glycol, and Isopropyl Alcohol Principles and Practice of Emergency Medicine

CHAPTER 146 ALCOHOL

2 Alcohol Substitutes: Treatment of Poisonings by Methanol, Ethylene Glycol, and Isopropyl Alcohol Harold Osborn Methanol Characteristics Pharmacokinetics Pathophysiology Clinical Effects Laboratory Tests Treatment Ethylene Glycol Characteristics Pharmacokinetics Pathophysiology Clinical Effects Laboratory Tests Treatment Isopropyl Alcohol Characteristics Pharmacokinetics Pathophysiology Clinical Effects Laboratory Tests Treatment

METHANOL Methanol (wood alcohol, CH 3OH) is an alcohol made from the destructive distillation of wood pulp. It is used commercially as a solvent, antifreeze (especially in windshield-washer solution), and paint remover. It is present in varying concentrations in these different forms: antifreeze (95%), windshield fluid (35 to 95%), and Sterno canned heat (4%). Methanol is found in shellacs, paints, duplicating fluid, gas additives, and nail polish removers, and it is used to adulterate ethyl alcohol prepared for industrial purposes.

CHARACTERISTICS Methanol is a colorless, volatile liquid with a distinctive odor. It is fully miscible in water and has a molecular weight of 32 d. It penetrates body tissues easily and has a volume of distribution similar to that of ethanol, 0.6 to 0.7 L/kg. Methanol is intoxicating, and epidemics of methanol toxicity have resulted from the consumption of contaminated whiskey.

PHARMACOKINETICS Methanol is well absorbed from the gastrointestinal (GI) tract, with peak levels occurring within 30 to 90 minutes ( 1). Absorption may occur from the skin and through the lungs and occasionally has been significant enough to result in toxicity. After absorption, methanol is distributed widely throughout the body. Concentrations are highest in the kidney, liver, GI tract, vitreous humor, and optic nerve. Methanol is found in brain, muscle, and fat. A small amount of methanol is found in the expired breath of normal subjects, possibly because of endogenous production (2,3). In humans, the liver is responsible for most of the metabolism of methanol, resulting in the potentiation of other hepatotoxins (e.g., carbon tetrachloride) if taken concurrently (4). If persons have been poisoned, however, a significant amount of methanol is excreted in the breath. The kidneys excrete from 2 to 5% of unchanged methanol in the urine. In the liver, methanol is metabolized to formaldehyde in a reaction catalyzed by alcohol dehydrogenase, the enzyme common to the metabolism of ethanol (Fig. 146–2.1). Formaldehyde is metabolized quickly to formic acid by aldehyde dehydrogenase, and formate is oxidized to carbon dioxide in a reaction in which folate serves as a cofactor (5). Folate deficiency in exposed persons facilitates acidosis and may increase methanol toxicity. The variable rates of this folate-dependent pathway account for the variation in toxicity among species. Ethanol has 10 to 20 times greater affinity for alcohol dehydrogenase than methanol, thus, ethanol is metabolized preferentially if both are present. This fact explains the efficacy of ethanol in the prevention of methanol toxicity.

Figure 146–2.1. Principal pathways of methanol metabolism.

The elimination of methanol from the blood is slow compared to that of ethanol. Study of the kinetics of methanol has been hampered by the fact that the elimination of methanol in human intoxication usually is altered by hemodialysis or by the administration of ethanol. The median half-life was 43.1 hours, emphasizing the need for concomitant hemodialysis in treatment (6). At low doses (0.08 g/kg) in three human volunteers, methanol was metabolized after first-order kinetics with a half-life of 3 hours (7). Animal studies suggest that the elimination kinetics are “zero order” (saturation kinetics) at blood concentrations in the range encountered in many reported cases (i.e., 100 to 200 mg/100 mL) (8,9). Data obtained before treatment indicate that methanol is metabolized at 8 to 9 mg/100 mL per hour in an overdose ( 10).

PATHOPHYSIOLOGY Methanol, like ethanol, is a central nervous system (CNS) depressant but is not harmful by itself. Rather, it is the accumulation of its two main metabolites, formaldehyde and formic acid, that accounts for its toxicity. Formaldehyde is metabolized quickly to formic acid by various enzyme systems: aldehyde dehydrogenase, xanthine oxidase, glyceraldehyde-3-phosphate hydrogenase, catalase, perioxidases, aldehyde oxidase, and a glutathione-dependent formaldehyde dehydrogenase. The formation of formic acid accounts for the bulk of the anion gap metabolic acidosis that appears in methanol poisoning. Lactate may be generated secondary to a formate-induced inhibition of mitochondrial respiration and tissue hypoxia ( 11). Clinical toxicity correlates better with formic acid levels than with methanol levels, which is why the latter, are not totally reliable. Formate can disturb axoplasm flow by the inhibition of cytochrome oxidase ( 12). The local production of formaldehyde in the retina accounts for the optic papillitis and retinal edema seen with methanol poisoning. In addition, methanol can be oxidized in the kidney.

CLINICAL EFFECTS

Patients appearing early with methanol intoxication appear inebriated but lack the euphoria seen with ethanol. Once the CNS-sedating effect of methanol has dissipated, there may be a latent period of 1 to 72 hours. Presumably, this is the period during which methanol is metabolized and acidosis develops. The fatal dose of methanol is somewhere between 60 and 240 mL, but as little as 10 mL has proved toxic (13). Symptoms of methanol toxicity include vertigo, nausea and vomiting, diarrhea, abdominal pain, dyspnea, agitation, blurred vision, photophobia (often described as flashes or a snowstorm), and decreased visual acuity. Extremely ill patients may have bradycardia, blindness, seizures, or coma. Physical examination sometimes, but not invariably, reveals constricted visual fields, fixed and dilated pupils, retinal edema, or hyperemia of the disk. Methanol, rarely, can cause pancreatitis or low-grade hepatitis. Respiratory apnea, opisthotonos, and seizures develop in patients dying of methanol intoxication ( 14).

LABORATORY TESTS A frequent finding in methanol poisoning is the presence of acidosis. Most patients with a serum bicarbonate level less than 18 mEg/L were reported to have methanol levels greater than 50 mg/100 mL (15). Mortality rates correlate best with the severity of acidosis. When formate levels exceed 20 mg/100 mL, ocular injury and acidosis are likely ( 16). Significant methanol ingestion creates an osmolar gap. For every increase of 3.2 mg/100 mL in the methanol level, the osmolar gap increases by 1 mOsm/kg H 2O. A lethal level of methanol (80 mg/100 mL) increases the serum osmolality by 27 mOsm/kg H 2O (Table 146–1.2). Time since ingestion is particularly relevant ( 17). Methanol can cause hematologic abnormalities. The mean corpuscular volume of red blood cells is elevated. Leukocytosis and anemia have been reported. If the liver or kidney is affected, hyperamylasemia may result or findings of liver function tests may be elevated. Methanol poisoning may cause hypophosphatemia and elevated creatine phosphokinase levels. Because of some endogenous production, normal serum methanol levels may be approximately 0.05 mg/100 mL. Levels less than 20 mg/100 mL are usually not associated with toxicity, but patients with levels greater than 20 mg/100 mL are usually symptomatic. Central nervous system symptoms correlate with levels greater than 20 mg/100 mL; ocular symptoms are seen with levels greater than 100 mg/100 mL. Levels greater than 50 mg/100 mL usually imply serious poisoning. The concomitant ingestion of ethanol has a protective effect on methanol toxicity. Laboratory evaluation of patients with suspected methanol intoxication should include the following: serum electrolytes, blood-urea-nitrogen, and creatinine; arterial blood gases; serum osmolality; blood levels of methanol, ethanol, ethylene glycol; liver function tests; amylase; and complete blood count.

TREATMENT Basic treatment should proceed as for ethanol intoxication. Airway, breathing, and circulation should be assessed and stabilized. Gastrointestinal evacuation, glucose, thiamine, and naloxone should be provided as indicated. Because charcoal does not adsorb alcohol well, it should be provided only if the coingestion of other substances is suspected. The aggressive treatment of acidosis is imperative. Sodium bicarbonate, 1 to 2 mEg/L, should be administered intravenously and a bicarbonate infusion begun whenever the arterial pH is less than 7.20. Before current treatment modalities were available, the treatment of methanol poisoning with bicarbonate alone occasionally improved visual acuity. Data from individual patients indicate that bicarbonate administration may enhance the elimination of formate ( 10). Swartz, reporting on a prison epidemic of methanol poisoning, suggested that bicarbonate and ethanol sufficed for patients who were moderately intoxicated ( 15). Thus, bicarbonate and ethanol administration should be started early in the treatment of suspected methanol poisoning. Ethanol provides an alternative substrate for alcohol dehydrogenase and has greater affinity for the enzyme than does methanol. Its use is based on the assumption that competition for a shared metabolic pathway prevents the conversion of methanol to its toxic intermediates and allows time for its elimination. Optimally, a blood ethanol level of 100 to 150 mg/100 mL should be attained, although in practice it is often difficult to titrate precisely. A loading dose of 0.8 g/kg of 5 to 10% ethanol intravenously (IV), followed by 130 mg/kg per hour, should be provided. Oral loading with 20 to 40% ethanol is an acceptable alternative if no intravenous preparation of ethanol is available. Additional adjustments should be based on serial ethanol levels. When hemodialysis is performed, maintenance doses of 250 to 350 mg/kg per hour are advised because ethanol is dialyzed with methanol. The following are indications for ethanol therapy ( 18): 1. 2. 3. 4. 5.

Methanol level >20 mg/100 mL Presence of symptoms, pending levels Ingestions of more than 0.4 mL/kg, pending levels Acidosis Need for hemodialysis

Because folate is a cofactor in the conversion of formic acid to carbon dioxide, the administration of folate may assist in the detoxification of methanol metabolites. Folic acid (30 mg) may be administered IV every 4 hours for several days ( 1). Leucovorin folinic acid, the active form of folate, may be administered instead of folate. A compound that can inhibit the activity of the enzyme alcohol dehydrogenase in animals and humans is 4-methyl pyrazole (4-MP) ( 19,20). In animal studies, it has been shown to reduce the toxic effects of ethylene glycol and methanol ( 10). Usually the administration of 20 mg/kg of 4-MP inhibits the formation of formic acid for 24 hours (21). Hemodialysis, but not hemoperfusion, is effective in removing methanol and its toxic metabolites. Indications for hemodialysis include ( 22): 1. 2. 3. 4. 5.

Methanol level >20 to 50 mg/100 mL Metabolic acidosis unresponsive to bicarbonate Formate levels >20 mg/100 mL Visual impairment Renal failure

Because rebound rises in methanol have been reported after dialysis, patients with methanol poisoning should undergo dialysis until the methanol levels approach 0 mg/100 mL and the metabolic acidosis clears.

ETHYLENE GLYCOL Ethylene glycol (1,2 ethanediol, (CH 2)2(OH)2) is structurally similar to ethanol but comprises two hydroxyl groups. It is a nonvolatile, water-soluble liquid developed as a substitute for glycerine. It is used commercially in paints, lacquers, pharmaceuticals, polishes, cosmetics, and as a de-icer and antifreeze. Its viscosity and sweet taste may have made it popular as a poor man's substitute for alcohol.

CHARACTERISTICS Ethylene glycol is a colorless, odorless liquid with a boiling point of 197°C. It is completely miscible in water and has a low freezing point. Its volume of distribution is 0.8 L/kg, and it has a molecular weight of 62 d. The minimum lethal dose is approximately 1 to 1.5 mL/kg or 100 mL in an adult of average size. Survival after the ingestion of 240 to 2000 mL, however, has been reported ( 23,24). Ethylene glycol is estimated to cause 40 to 60 deaths each year in the United States ( 25). Like methanol, it is not the parent compound but its metabolites that are toxic to the body.

PHARMACOKINETICS

Ethylene glycol is absorbed rapidly from the GI tract, with peak levels occurring within 1 to 4 hours after ingestion. Inhalation is not usually associated with toxicity, although chronic poisoning has been reported in factory workers exposed to its vapors ( 26). The kidneys filter and then passively reabsorb most of the ethylene glycol absorbed by the body. Approximately 20% of a dose of 1 mg/kg is excreted unchanged (22). Metabolism occurs principally in the liver, where ethylene glycol is oxidized to glycoaldehyde by alcohol dehydrogenase ( Fig. 146–2.2). Glycoaldehyde is oxidized to glycolate and then to glyoxylate. Glyoxylate, in turn, can be metabolized in several ways: as a reversible transamination to glycine, as an irreversible oxidation to oxalate, and in conjugation with oxalomalate, a-hydroxy-a b ketodipate and g-hydroxy a ketoglutarate. Ethylene glycol metabolism increases the NADH–NAD ratio and produces lactic acid. The plasma half-life of ethylene glycol is approximately 3 hours.

Figure 146–2.2. Principal pathways of ethylene glycol metabolism.

PATHOPHYSIOLOGY Like ethanol, ethylene glycol is a CNS depressant, and, as with methanol, its metabolites, not the parent compound itself, are toxic. Of the metabolites, glyoxylate is more toxic than glycoaldehyde (27). Glycolate and glyoxylate interfere with the Krebs cycle and mitochondrial metabolism. Aldehyde production inhibits oxidative phosphorylation, respiration, and glucose metabolism. Aldehydes also interfere with protein synthesis, DNA replication, and ribosomal RNA synthesis ( 28,29). They react with enzymes requiring sulfydryl groups for activity, collagen, and amino groups on proteins. The prominent CNS symptoms that occur after the ingestion of ethylene glycol coincide with the greatest amounts of aldehyde production ( 25). Glycoaldehyde, glycolic acid, and glyoxylic acid all contribute to CNS depression. The metabolic acidosis that follows significant poisoning with ethylene glycol is caused by the accumulation of glycolic acid and, to a lesser extent, lactic acid ( 30). Oxalate accumulation in ethylene glycol poisoning can lead to extensive renal damage and myocardial depression. Hypocalcemia may result from the complexing of calcium with oxalate.

CLINICAL EFFECTS Ethylene glycol poisoning was first described by Pons and Custer ( 31) as occurring in three stages. In the first stage (1 to 12 hours after ingestion), CNS depression can occur. Patients may appear inebriated without the odor of alcohol or acetone and may have hallucinations, stupor, coma, meningismus, and focal or generalized seizures (32,33). Ocular findings include decreased visual acuity, papilledema, optic atrophy, opthalmoplegia, and nystagmus. The second stage of poisoning (12 to 24 hours after ingestion) is characterized by cardiovascular changes including congestive heart failure, hypertension, tachycardia, and arrhythmias. In the third stage (24 to 72 hours after ingestion), acute renal failure may be seen. Renal failure may be accompanied by oliguria and flank pain and is caused principally by proximal renal tubular damage. The deposition of oxalate crystals and the direct toxic effects of the metabolites of ethylene glycol contribute to CNS and renal damage.

LABORATORY TESTS Because oxalate is a product of the metabolism of ethylene glycol, calcium oxalate crystals may be identified in the urine, although not invariably. Hypocalcemia may occur and may be manifested by tetany and prolongation of the QT interval on the electrocardiogram. Creatine phosphokinase levels may be elevated, and frequently there is an anion gap metabolic acidosis. With severe ingestion, there may be an anion gap. Because the molecular weight is greater than that of ethanol and methanol, however, a significant osmolal gap may not appear. Serum osmolality may be measured by the vapor pressure method with ethylene glycol because it has such a high boiling point. A rise in the blood level of ethylene glycol by 6 mg/100 mL raises the serum osmolality 1 mOsm/kg of H 2O. The diagnosis of ethylene glycol poisoning should be suspected in an inebriated patient, with or without an odor of alcohol, whose urine contains calcium oxalate crystals. The diagnosis may be confirmed by ethylene glycol in the blood, but treatment is dependent on clinical findings or patient history (levels probably will not be available rapidly because few laboratories are able to measure ethylene glycol). Levels of 50 mg/100 mL or more are associated with serious toxicity and suggest the need for emergency dialysis. The highest level recorded in a patient who survived was 888/mg/100 mL (34A). If there is significant ingestion, peritoneal dialysis can be started immediately in the emergency department. As with methanol, because metabolites are the toxic elements, blood levels of ethylene glycol, even if readily available, are not a precise way to assess toxicity. Glycolic acid and bicarbonate levels correlate better with the clinical picture.

TREATMENT Basic treatment should be performed as it is for ethanol intoxication. Supportive care, including airway stabilization, GI evacuation, glucose, thiamine, naloxone, and charcoal, should be provided as needed. Acidosis should be treated with an infusion of bicarbonate when the pH is less than 7.2. Early dialysis (hemodialysis) and peritoneal dialysis (combined in severe cases) more rapidly correct acidosis and will improve renal function ( 34). Rapid absorption limits use of GI evacuation methods (34A). As in methanol poisoning, ethanol is an alternate substrate for alcohol dehydrogenase. It has an affinity for the enzyme 100 times that of ethylene glycol and can prevent the metabolism of the latter. A loading dose of 0.8 g/kg of a 5 to 10% IV ethanol solution should be followed by 130 mg/kg per hour to maintain the serum ethanol level at 100 to 150 mg/100 mL. As in methanol poisoning treated with hemodialysis, maintenance doses of 250 to 350 mg/kg per hour may be necessary once the patient is on hemodialysis. Indications for ethanol therapy are: 1. 2. 3. 4. 5.

Ethylene glycol level >20 mg/100 mL Presence of symptoms, pending levels Ingestions of more than 0.5 mL/kg, pending levels Acidosis Need for hemodialysis

Pyridoxine and thiamine are cofactors for the metabolism of ethylene glycol and should be given as follows: pyridoxine 50 mg intramuscularly every 4 hours for 2 days and thiamine 100 mg intramuscularly every 4 hours for 2 days. Magnesium is also a cofactor and should be provided, especially in alcoholic patients. As mentioned previously, 4-methyl pyrazole can inhibit the activity of alcohol dehydrogenase ( 19,20). Recently, it has proven to be successful in the treatment of a patient with a serious ethylene glycol ingestion ( 35). Hemodialysis, coupled with peritoneal dialysis (PD) or PD alone if hemodialysis is not readily available, remains the treatment of choice for ethylene glycol poisoning (34). Dialysis enhances the elimination of the metabolites of ethylene glycol as well as the parent compound itself. Indications for hemodialysis include: 1. Ethylene glycol level >20 to 50 mg/100 mL

2. 3. 4. 5.

Metabolic acidosis unresponsive to bicarbonate Crystalluria Renal failure Deteriorating vital signs

The end point of dialysis should be an ethylene glycol level approaching 0 mg/100 mL and clearance of the metabolic acidosis. While hemodialysis is performed, maintenance doses of ethanol should be raised to 250 to 350 mg/kg per hour or 95% ethanol should be added to the dialysate. The use of 4-methylpyrazole (4MP) should be undertaken if there is any delay in dialysis.

ISOPROPYL ALCOHOL Isopropyl alcohol (2-propanol, isopropanol, CH3CH0HCH3) is an aliphatic alcohol used as a solvent and disinfectant. It is used widely in rubbing alcohol, skin lotion, hair tonic, after-shave lotion, and window-cleaning fluid. Like ethanol, isopropyl alcohol is a CNS depressant though it lacks many of the toxic and metabolic effects of ethanol. Isopropanol is second to ethanol as the most commonly ingested alcohol ( 36).

CHARACTERISTICS Isopropanol is a clear, volatile hydrocarbon with a bitter taste and an aromatic odor. As a CNS depressant, it has twice the potency of ethanol. The toxic dose is estimated to be 1 mL/kg of a 70% isopropanol solution, although as little as 0.5 mL/kg can cause symptoms. The lethal dose in an adult is said to range from 2 to 4 mL/kg or roughly 200 mL or more (22). Adults, however, have survived ingestions of many times this amount.

PHARMACOKINETICS Isopropanol is absorbed rapidly and efficiently from the GI tract. Eighty percent of an ingested dose is absorbed within 30 minutes, and absorption is usually complete within 2 hours (8). Although ingestion is the major route of poisoning, toxicity can occur secondary to inhalation during sponge bathing of febrile patients ( 37). Dermal absorption after prolonged contact may contribute to the toxicity as well. Isopropanol, like ethanol and methanol, is distributed in body water and has a volume of distribution of 0.6 to 0.7 L/kg. The kidney excretes 20 to 50% of an absorbed dose in its unchanged form. Isopropyl alcohol is metabolized to acetone by alcohol dehydrogenase, and acetone is, in turn, eliminated by the lungs and kidneys. Acetone, however, can be metabolized to acetate, formate, and carbon dioxide. In the metabolism of isopropanol to acetone, few related ketoacids are formed, thus, in contrast to methanol and ethanol ingestions, acidosis rarely is seen. Isopropanol metabolism has first-order (concentration-dependent) ( 38) kinetics. The metabolic half-life is estimated to be 2.5 to 3.2 hours ( 39). By contrast, the elimination of isopropanol's metabolite, acetone, is more prolonged. Therefore, clinical effects last longer than do those seen in ethanol intoxication.

PATHOPHYSIOLOGY Isopropanol is a powerful CNS depressant, and it also depresses the cardiovascular system. Although acids are generated in the metabolism of isopropanol, in practice acidosis is rarely a significant clinical problem. The first step in its metabolism is catalyzed by alcohol dehydrogenase and requires NAD as a cofactor. As a consequence, the ratio NAD–NADH is shifted to the reduced form and, as seen with ethanol intoxication, gluconeogenesis can be blocked and hypoglycemia can occur.

CLINICAL EFFECTS Isopropanol intoxication typically occurs within 30 to 60 minutes of ingestion, though the euphoria induced by ethanol is lacking. Often it is accompanied by the sweet, pungent odor of acetone on the breath. The duration of CNS depression is more prolonged than it is with ethanol because of the biologic activity of isopropanol metabolites. Significant ingestion can result in coma, hypotension, and respiratory arrest. Nausea, vomiting, and dehydration may develop in patients. Hematemesis from hemorrhagic gastritis has been described. Hemorrhagic tracheobronchitis also may occur. Hypotension, when it occurs, is secondary to peripheral vasodilation but can be exacerbated by fluid and blood loss. Among the CNS effects are dizziness, headache, confusion, and coma. Depressive effects can last up to 24 hours. Pupillary myosis and nystagmus may be present ( 22). Acute tubular necrosis, hepatocellular damage, myoglobinuria, and hemolytic anemia have been described ( 40).

LABORATORY TESTS In the absence of dehydration, routine blood study findings are within normal limits. Unless there is a concomitant ingestion of ethanol, the alcohol level is not elevated. Occasionally, GI bleeding or hemolytic anemia results in a low hematocrit. Acetone levels are elevated and should be quantitated with dilutions to assess the amount of acetone in the blood. Hypoglycemia can occur and should be ruled out initially with a fingerstick assessment. Because it is an alcohol, isopropanol can contribute to the osmolal gap. With a molecular weight of 6 d, a rise in the isopropanol blood level of 6 mg/100 mL raises the serum osmolality by 1 mOsm/kg H2O and contributes to the generation of an osmolal gap. A toxic level of 50 mg/100 mL produces an elevation in serum osmolality of 8 to 9 mOsm/kg H2O, and a lethal level of 200 mg/100 mL produces a change of 34 mOsm/kg of H 2O. Acetone itself can elevate serum osmolality, and this must be considered when attempting to correlate serum osmolality with isopropanol levels. Thus, serious isopropanol ingestion should be diagnosable by assessing the osmolal gap. As with all alcohols, the serum osmolality must be measured by freezing point depression and not by vapor pressure. The hallmark of isopropanol ingestion is inebriation, a negative or low alcohol level, an elevated osmolar gap, and ketosis without acidosis. A given isopropanol level (which must be determined by gas chromatography) is roughly twice as toxic as a similar ethanol level. Blood levels of 50 mg/100 mL are associated with intoxication in nontolerant patients, whereas blood levels of 150 mg/100 mL should produce coma. Levels of 200 to 400 mg/100 mL and more are considered lethal, but they may be tempered by treatment. Survival with dialysis has been reported with isopropanol levels as high as 560 mg/100 mL ( 41).

TREATMENT The basis of treatment of isopropanol overdose is good supportive care. Like ethanol and methanol, isopropanol is well absorbed from the GI tract, and gut evacuation has little to offer more than 2 hours after ingestion unless gastric emptying is delayed or coingestion has occurred. Children who ingest more than 0.5 mL/kg of a 70% solution should undergo GI evacuation. Because CNS depression occurs within 30 minutes of ingestion, ipecac should not be used for evacuation. As with the other alcohols, isopropanol is not well absorbed by charcoal, although charcoal should be given for suspected polydrug ingestion. Severe isopropanol overdoses have been treated successfully with peritoneal dialysis and hemodialysis ( 42,43). Indications for dialysis include: 1. 2. 3. 4. 5. 6.

Ingestion of more than 3 to 4 mL/kg of a 70% solution Blood levels greater than 400 mg/100 mL Hypotension unresponsive to fluids and pressors Prolonged coma Complicating underlying diseases Renal failure ( 22)

References 1. Becker CE: Methanol poisoning. J Emerg Med 1983;51–58. 2. Eriksen SP, Kulkarni AB: Methanol in normal human breath. Science 1963;141:639.

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34.

Axelrod J, Daly J: Pituitary gland: enzymatic formation of methanol from 5-methyl adenosine. Science 1965;150:892. Simmons JE, McDonald A, Seely JC, et al: Potentiation of carbon tetrachloride hepatotoxicity by inhaled methanol: time course of injury and recovery. J Toxicol Environ Health 1995;46:203. Medinsky MA, Dorman PC: Recent developments in methanol toxicity. Toxicol Lett 1995;82:707. Palatnick W, Redman LW, Sitar DS, et al: Methanol half-life during ethanol administration. Ann Emerg Med 1995;26:202–207. Leaf G, Zatman LJ: A study of the conditions under which methanol may exert a toxic hazard in industry. Br J Ind Med 1952;9:19. Clay KL, Murphy RC, Watkins DW: Experimental methanol toxicity in the primate: analysis of metabolic acidosis. Toxicol Appl Pharmacol 1975;34:49. McMartin KE, Makao AB, Martin–Amat G, et al: Methanol poisoning: I. the role of formic acid in the development of metabolic acidosis in the monkey and the reversal by 4-methylpryrazole. Biochem Med 1975;13:319. Jacobsen D, Webb R, Collins TD, et al: Methanol and formate kinetics in late diagnosed methanol intoxication. Med Toxicol 1988;3:418. Jacobson D, McMartin KE: Methanol and ethylene glycol poisonings: mechanisms of toxicity, clinical course, diagnosis, and treatment. Med Toxicol 1986;1:309. National Institutes of Health. Use of folate analogue in treatment of methyl alcohol toxic reactions is studied. JAMA 1979;242:1961. Winchester JF: Methanol, isopropyl alcohol, higher alcohols. In: Hadded LM, Winchester JF, ed. Clinical management of poisoning and drug overdose. Philadelphia: WB Saunders: 1983:393–407. Bennet IL, Cary FH, Mitchell GL, et al: Acute methyl alcohol poisoning: a review based on experiences in an outbreak of 323 cases. Medicine 1953;32:431. Swartz RD, Millman RP, Billi JE, et al: Epidemic methanol poisoning: clinical and biochemical analysis of a recent episode. Medicine 1981;60:373. Osterloh JD, Rond SM, Grady S, et al: Serum formate concentrations in methanol intoxication as a criterion for hemodialysis. Ann Intern Med 1986;104:200. Glaser DS: Utility of the serum osmol gap in the diagnosis of methanol or ethylene glycol ingestion. Ann Emerg Med 1996;27:343. Ekins BR, Rollins DE, Duffy DP, et al: Standardized treatment of severe methanol poisoning with ethanol and hemodialysis. West J Med 1985;142:337. Li TK, Theorell H: Human liver alcohol dehydrogenase: inhibition by pyrazole and pyrazole analogs. Acta Chem Scand 1969;23:892. Pietrusko R: Human liver alcohol dehydrogenase—inhibition of methanol activity by pyrazole, 4-methylpyrazole. Biochem Pharmacol 1975;24:1603. McMartin KE, Hedstrom KG, Tolly BR, et al: Studies on the metabolic interactions between 4-methylpyrazole and methanol using the monkey as an animal model. Arch Biochem Biophys 1980;199:606. Ellenhorn MJ, Barceloux DG: Alcohols and glycols. In: Ellenhorn MJ, Barceloux DG, eds. Medical toxicology. New York: Williams & Wilkins, 1996. Sculy R, Galdabini J, McNealy B: Case records of the Massachusetts General Hospital. Case 38-1979. N Engl J Med 1979;301:650. Stokes JB, Averon F: Prevention of organ damage in massive ethylene glycol ingestion. JAMA 1980;243:2065. Parry MF, Wallach R: Ethylene glycol poisoning. Am J Med 1974;57:143. Troisifn FM: Chronic intoxication with ethylene glycol vapor. Br J Ind Med 1950;1:65. Beasley VR, Buch WB: Acute ethylene glycol toxicoses: a review. Vet Hum Toxicol 1980;22:255. Kun E: A study on the metabolism of glyoxal in vitro. J Biol Chem 1952;194:603. Klamerth OL: Influence of glycoxal on cell function. Biochim Biophys Acta 1968;155:271. Clay KL, Murphy RC: On the metabolic acidosis of ethylene glycol intoxication. Toxicol Appl Pharmacol 1977;39:39. Pons CA, Custer RP: Acute ethylene glycol poisoning. Am J Med Sci 1946;211:544. Brown CG, Trumbull D, Klein–Schwartz W, et al: Ethylene glycol poisoning. Ann Emerg Med 1983;12:501. DaRoza R, Henning RJ, Sunshine I, et al: Acute ethylene glycol poisoning. Crit Care Med 1984;12:1003. Sabeel AI, Kurkus J, Lindholm T: Intensified dialysis treatment of ethylene glycol intoxication. Scand J Urol Nephrol 1995;29:125.

34A. Davis DP, Bramwell KJ, Hamilton RS, et al: Ethylene glycol poisoning case report of a record high level and a review. J Emerg Med 1997;15:653–667. 35. 36. 37. 38. 39. 40. 41. 42. 43.

Galliot M, Astier A, Bien DV, et al: Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. N Engl J Med 1988;319:97. Litovitz TL, Normann SA, Veltri JC: 1985 annual report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med 1986;4:427. Spyker D, Sullivan JB: Oxygenated compounds: alcohols, glycols, ketones and esters. In: Hazardous material toxicology. Williams & Wilkins, 1992:1105. Lacouture PG: Isopropyl alcohol. Clin Toxicol Rev 1980;3:3. Daniel DR, McAnally BH, Garriott JC: Isopropyl alcohol metabolism after acute intoxication in humans. J Anal Toxicol 1981;5:110. Chguin MA: Isopropyl alcohol poisoning with acute renal insufficiency. J Maine Med Assoc 1949;40:288. Alexander CB, McBay AS, Hudson RP: Isopropanol and isopropanol deaths—ten years experience. J Forensic Sci 1982;27:541. Depner TA, Mecikalski MB: Peritoneal dialysis for isopropanol poisoning. West J Med 1981;137:322. Freireich AW, Unique TJ, Xanthaky G, et al: Hemodialysis for isopropanol poisoning. N Engl J Med 1967;277:699.

Chapter 146.3 Alcohol Withdrawal: Differential Diagnosis and Emergency Treatment Principles and Practice of Emergency Medicine

CHAPTER 146 ALCOHOL

3 Alcohol Withdrawal: Differential Diagnosis and Emergency Treatment David B. McMicken Capsule Pathophysiology Differential Diagnosis in the Emergency Unit Clinical Presentation of Withdrawal Prehospital Care and Assessment Emergency Department Care and Initial Physical Examination Management of Alcohol Withdrawal Syndrome Nonpharmacologic Intervention Pharmacologic Intervention Benzodiazepines Butyrophenones: Haloperidol and Droperidol b-Blockers a-Agonists Trial Use of Medications in the ED Adjunct Therapy Radiographs and Laboratory Testing Admission Guidelines and Disposition Acute Intoxication Alcohol Withdrawal (Delirium Tremens [DTs]) Seizures Psychiatric Hospital Admission Rehabilitation

CAPSULE Management problems in the emergency department (ED) usually involve assessment of the seriousness of the alcohol-related state, initiation of a suitable treatment for intoxication or withdrawal, and a decision regarding hospital admission. One study determined that 40% of all patients entering the ED in the evening had been drinking, and 32% had blood alcohol levels greater than 80 mg/dL (0.08%) ( 1). Alcohol use accounts for more than 15% of health care costs ( 1A,1B)

PATHOPHYSIOLOGY The neuropharmacology of alcohol withdrawal is complex. Chronic alcohol consumption has a depressant effect on the central nervous system (CNS). The hallmark of alcohol withdrawal is the sudden exhibition of CNS excitation with increased cerebrospinal fluid (CSF), plasma, and urinary catecholamine levels ( 2,3).

DIFFERENTIAL DIAGNOSIS IN THE EMERGENCY UNIT Alcohol withdrawal syndrome can be confused with acute schizophrenia, encephalitis, drug-induced psychosis, thyrotoxicosis, anticholinergic poisoning, withdrawal from other sedative–hypnotic drugs, and hypoglycemia. Acute schizophrenia usually has its onset in adolescence or early adulthood. Manifestations include multiple bizarre delusions and a flat affect; the patient is otherwise oriented. The patient in alcohol withdrawal is usually older (20s or 30s), hyperactive, and possibly disoriented. Encephalitis can produce headache, confusion, fever, and seizures. Thyrotoxicosis is more common in women, and its features include irritability, insomnia, tremor, weight loss (despite a good appetite), palpitations, and frequent stools. Physical examination may reveal lid lag, tachycardia, and a bruit over the thyroid. There is no relationship between the onset of encephalitis or thyrotoxicosis and alcohol consumption. Anticholinergic poisoning can occur with many different drugs or with plant ingestion. The classic clinical picture is a patient with dry mouth, dry eyes, dry skin, hypoactive bowel sounds, urinary retention, and delirium. Amphetamine and cocaine intoxication produce anorexia, insomnia, and physical signs of CNS sympathetic overactivity. In opioid withdrawal, the mental status is usually normal, the patient is afebrile, and seizures are uncommon except with meperidine. In contrast, patients with alcohol withdrawal usually are disoriented and febrile and may have seizures ( 4). Time of Alcohol Withdrawal Signs of alcohol withdrawal usually begin 6 to 24 hours after a decrease or cessation in the patient's usual intake of alcohol. It is rare for a patient to manifest withdrawal 3 or more days after his or her last drink. The barbiturate and benzodiazepine withdrawal syndromes usually progress more slowly and have a higher frequency of seizures, which appear later (7 days instead of 2 days), and status epilepticus is more common than from alcohol withdrawal ( 4,5). Alcohol Withdrawal vs. Alcohol-induced Hypoglycemia It may be difficult to differentiate immediately between alcohol withdrawal and alcohol-induced hypoglycemia. Glucose (25 g dextrose intravenously [IV]) produces a dramatic response in patients with hypoglycemia. Unlike hypoglycemia from other causes, alcohol-induced hypoglycemia is unresponsive to glucagon because of depleted liver glycogen stores ( 6). Thiamine (50 mg IV followed by 50 mg intramuscularly [IM]) should be administered to prevent the precipitation of Wernicke encephalopathy because of the dextrose solution depleting the last of the patient's thiamine stores. Although Wernicke encephalopathy is a medical emergency, alcohol-induced hypoglycemia is more common and results in serious and permanent morbidity if left untreated. Thiamine and glucose therapy should never be delayed (7).

CLINICAL PRESENTATION OF WITHDRAWAL Isbell's classic study in 1955 ( 8) confirmed the relationship between alcohol and the withdrawal syndrome. He documented that the severity of signs and symptoms depend on the dose and the duration of ethanol consumption. The withdrawal syndrome may occur any time after the blood alcohol level starts to fall. Therefore, only a reduction, and not the abrupt cessation of ethanol intake may precipitate withdrawal ( 8,9). The withdrawal syndrome develops 6 to 48 hours after the reduction of ethanol intake and lasts from 2 to 7 days. The alcohol withdrawal state constitutes a wide spectrum, ranging from mild withdrawal with insomnia and irritability to major withdrawal with diaphoresis, fever, disorientation, and hallucinations. The syndrome also includes anxiety, insomnia, irritability, tremor, anorexia, tachycardia, hyperreflexia, hypertension, fever, decreased seizure threshold, auditory and visual hallucinations, and finally delirium ( 10). Minor alcohol withdrawal occurs as soon as 6 hours, and usually peaks at 24 to 36 hours, after the cessation or significant decrease in alcohol intake. It is characterized by mild autonomic hyperactivity: nausea, anorexia, tremor, tachycardia, hypertension, hyperreflexia, insomnia, and anxiety. Major alcohol withdrawal occurs more than 24 hours, and usually peaks at 50 hours but may peak up to 5 days, after the decline or termination of drinking. Major

withdrawal is characterized by more pronounced hyperactivity and by disorientation, hallucinations, diaphoresis, and fever ( 11). Delirium tremens, seldom appearing before the third postabstinence day, is the extreme end of the spectrum and consists of gross tremor, profound confusion, fever, incontinence, frightening visual hallucinations, and mydriasis. It develops in only 5% of patients admitted to the hospital for alcohol withdrawal ( 12,13 and 14). True delirium tremens is rare ( 15). Alcohol withdrawal and delirium tremens are not synonymous. The mortality rate for delirium tremens is frequently quoted at 15 to 20% based on a 1953 study by Victor (15). Today, patients managed aggressively in the intensive care unit have mortality rates lower than 15% ( 14,16 and 17A). Historically the alcohol withdrawal syndrome was divided into stages. However, with so much individual variation and overlap of the signs, symptoms, temporal sequence, and duration of the syndrome, staging is not clinically useful. In addition, seizures can occur in minor and major withdrawal.

PREHOSPITAL CARE AND ASSESSMENT The alcohol-dependent patient may have withdrawal, a mixed alcohol-drug ingestion, occult head trauma, or cervical spine injury. Patients who are unable to sit without assistance or who have an altered mental status require an intravenous line. Naloxone (0.8 mg) and glucose (dextrose 25 g) with thiamine (100 mg) are given by IV push. Rapid blood glucose testing is preferable. The airway must be maintained and respiration supported. Emergency medical service personnel should monitor the patient's vital signs and neurologic status. The cervical spine should be immobilized if trauma is suspected. It is usually best to withhold treatment with benzodiazepines until the patient can be evaluated in the ED. The emergency medical technician should be alert for other medical disorders that accompany alcoholism, such as pneumonia, sepsis, gastrointestinal bleeding, hepatic failure, heart failure, and intracranial hemorrhage.

EMERGENCY DEPARTMENT CARE AND INITIAL PHYSICAL EXAMINATION Family, friends, bystanders, or paramedics may give more reliable historical data than the patient. Accurate vital signs are essential and should include rectal or core temperature. Hyperthermia, hypothermia, tachypnea, or tachycardia may indicate serious disorders that frequently accompany the alcohol-dependent patient ( Table 146–3.1). Rapid, thorough examination should be performed with attention to the level of consciousness, signs of hepatic failure, renal failure, or coagulopathy. It is important to be alert for signs of trauma, such as subcutaneous emphysema, ecchymosis, subconjunctival hemorrhage, Battle sign, or fractures. The neurologic examination should search for focal findings: central facial palsy, hemiparesis, asymmetry of reflexes, upgoing toes, or asymmetry of pupillary response. When errors occur in the management of the inebriated patient, it is usually because trauma is unrecognized.

Table 146–3.1. Disorders Associated with Abnormal Vital Signs in the Alcohol Dependent Patient

MANAGEMENT OF ALCOHOL WITHDRAWAL SYNDROME The alcohol withdrawal syndrome should be recognized and treated promptly. Treatment is necessary to provide relief from anxiety and hallucinations, halt progression to major withdrawal, allow detection of a treatable primary psychiatric illness, prepare the patient for long-term alcohol abstinence with minimal risk of new drug dependence, and prevent withdrawal seizures. Treatment is also necessary to calm the patient and allow adequate examination to detect medical illnesses frequently accompanied or precipitated by alcoholism, such as pancreatitis, pneumonia, and hepatitis. Restraints may be necessary. Theoretical liability for detention by reasonable restraint is inconsequential compared with potential injury the patient may inflict on himself or herself or on the hospital staff. Management includes nonpharmacologic and pharmacologic care, usually with benzodiazepines.

NONPHARMACOLOGIC INTERVENTION A growing body of data indicates that supportive care (reassurance, reality orientation, personal attention, and general nursing care) can be effective in patients with mild alcohol withdrawal. This requires frequent monitoring of signs and symptoms. Supportive care does not appear to prevent hallucinations, seizures, or arrhythmias. Therefore, patients in moderate to severe withdrawal should receive pharmacologic intervention in addition to supportive care ( 18,19 and 20A).

PHARMACOLOGIC INTERVENTION Many drugs have been suggested for the treatment of alcohol withdrawal. Such treatment regimens have included alcohol, a-adrenergic agonists, antihistamines, barbiturates, benzodiazepines, b-blockers, butyrophenones, calcium-channel blocking agents, clonidine, atenolol, carbamazepine, chloral hydrate, clomethiazole, dopamine agonists, lithium carbonate, magnesium sulfate, meprobamate, phenothiazines, paraldehyde, and valproic acid. However, benzodiazepines have consistently proven safest and effective ( 20B).

BENZODIAZEPINES It is important that the emergency physician become comfortable with a particular treatment regimen and be aware of side effects, dosage ranges, and risks. Benzodiazepines are the mainstay of treatment. Their efficacy is equal or superior to that of other agents, as is their anticonvulsant activity. Respiratory and cardiac depression are minimal compared with other CNS depressants, and they can be given parenterally in the uncooperative patient ( 19,20B,21). 20B Numerous benzodiazepines, including alprazolam (Xanax), chlordiazepoxide (Librium), chlorazepate (Tranxene), diazepam (Valium), flurazepam (Dalmane), halazepam (Paxipam), lorazepam (Ativan), midazolam (Versed), and oxazepam (Serax) have been studied. There is no evidence of the clear superiority of any particular benzodiazepine (14,19,22,23,24,25,26 and 27). Longer-acting agents may offer more inpatient benefits. The ideal benzodiazepine would have rapid and complete absorption from an intramuscular injection site; an intermediate elimination half-life; an elimination process unaffected by liver disease, renal insufficiency, or aging; and no active metabolite. Although no one benzodiazepine has all these characteristics, lorazepam (Ativan) comes close for usefulness in the ED setting. Lorazepam has good bioavailability with oral, intramuscular, and intravenous routes. It is absorbed rapidly and completely from intramuscular sites in agitated patients with no intravenous access. Lorazepam's half-life is intermediate (14 ± 7 hours) and reaches a steady state in 36 to 48 hours without extensive accumulation ( 28). It is metabolized (conjugated) in the liver, yielding inactive products ( 29). Although lorazepam's half-life increases in patients who have cirrhosis and liver failure, it is less than the increase with chlordiazepoxide. Its elimination is altered only minimally in renal failure and in the elderly. In contrast, chlordiazepoxide has these

disadvantages: Its half-life is significantly prolonged in liver failure and renal failure; parenteral chlordiazepoxide has to be refrigerated and reconstituted, and it is poorly absorbed from intramuscular injections ( 21,22,30,31 and 32). Lorazepam may be given intravenously in a dose of 0.5 mg to 4.0 mg, depending on the severity of the withdrawal. Dosing can be repeated at 15- to 30-minute intervals for patients in severe withdrawal. An intramuscular dose of 0.07 mg/kg can be used ( 33). The oral dosage schedule for moderate withdrawal is 6 to 7 mg/day in three divided doses, with the amount tapered 20 to 28%/day over 4 days ( 34,35). If lorazepam is unavailable, diazepam (Valium) can be given (5 mg IV every 5 minutes) until the patient is calm ( 36). For the critically ill patient in the intensive care unit, the short-acting midazolam may be more appropriate. The onset of action is rapid (minutes). Infusions of up to 20 to 75 mg/hour of midazolam have been reported with major alcohol withdrawal ( 22,23). The dosage of benzodiazepines required for alcohol withdrawal is highly variable. The dose should always be titrated to the patient's agitation. Massive doses have been required in patients with delirium tremens: 2335 mg diazepam in 48 hours, 2640 mg diazepam and 35 mg haloperidol over 48 hours, 75 mg midazolam in 1 hour, and 2850 mg midazolam over 5 days have all been reported ( 22,23,37,38). Such large dosages require admission to the intensive care unit for close monitoring, and if patients begin treatment in the ED ongoing monitoring including pulse oximetry is required.

BUTYROPHENONES: HALOPERIDOL AND DROPERIDOL Haloperidol, a dopamine blocker, can be considered in patients with major withdrawal or delirium tremens who do not respond to intravenous benzodiazepines. Haloperidol is more potent than chlorpromazine, has lower anticholinergic properties, and has less propensity to cause cardiovascular side effects or to lower the seizure threshold. Haloperidol has little effect on myocardial function or respiratory drive ( 14,39). Droperidol, another butyrophenone, offers several potential advantages over haloperidol in the acute management of agitation. When given in equal IM doses (5 mg), droperidol has a more rapid onset of action and a shorter half-life without any increase in undesirable side effects. Like haloperidol, droperidol alone has no anticonvulsant properties ( 40). The safety and efficacy of haloperidol by the IV, IM, or oral route in the ED have been reported ( 39). Haloperidol and lorazepam in combination are safe and may be synergistic. Safe use in extremely high doses in patients with serious underlying medical illness has been documented in several studies: 240 mg haloperidol and 480 mg lorazepam given over 24 hours in a patient and 485 mg haloperidol over 8 hours in another patient without significant adverse effects ( 14,41). Adams et al. (42) have advocated an aggressive protocol with escalating doses of the combination of haloperidol and lorazepam ( Table 146–3.2). Such high dosages must be accompanied by extremely careful monitoring because of respiratory impairment, seizures with aspiration, and cardiac changes. Pulse oximetry and cardiac monitoring is advised when large doses are used.

Table 146–3.2. Escalating Dosage Protocol for Combination Haloperidol Lorazepam Treatment of Psychotic Patients with Serious Underlying Medical Illness

a

b-BLOCKERS Propranolol and atenolol have been studied in alcohol withdrawal. b-blockers should be considered as an adjunct by the emergency physician for mild to moderate alcohol withdrawal. Contraindications include insulin-dependent diabetes, hypotension, lung disease that may lead to bronchospasm, and congestive heart failure (43).

a-AGONISTS The adrenergic agonist clonidine has proved effective in opiate withdrawal. Clonidine is not a controlled substance and has little or no addictive or abuse potential. Studies have found clonidine to be at least as effective as chlordiazepoxide at improving the vital signs and the subjective complaints of alcohol withdrawal ( 44,45). Theoretically, clonidine avoids the potential for oversedation and the dependency of benzodiazepines, and it treats mixed alcohol and opiate withdrawal ( 46). Clonidine is ineffective in preventing seizures ( 47). It may be a promising treatment agent for patients with mild alcohol withdrawal and no history of alcohol-related seizures who are candidates for an outpatient program and for patients with coincidental opiate addiction ( 48). Outpatient medical detoxification for selected patients with mild alcohol withdrawal can be effective and safe. The cost savings of outpatient detoxification can be substantial. Clonidine may be considered in this setting (49).

TRIAL USE OF MEDICATIONS IN THE ED In mild cases, an initial test dose of 1 to 2 mg lorazepam, 5 mg to 10 mg diazepam, or 50 to 100 mg chlordiazepoxide can be given orally to the patient in the ED. The patient is observed for 2 to 4 hours, which guides the emergency physician as to doses required for subsequent treatment ( 50,51). Outpatient treatment consists of 25 to 100 mg chlordiazepoxide three times a day, 5 mg to 10 mg diazepam three times a day, or 1 to 2 mg lorazepam three times a day in a tapering dose for 3 to 6 days, depending on the severity of symptoms. Patients should be observed until it is clear that withdrawal will not progress and necessitate hospital admission. Adequate diet, abstinence, and participation in a rehabilitation program in the community are optimal but difficult to obtain. Moderate to severe cases or patients with underlying medical problems need inpatient treatment. Approximate equivalent doses relative to 100 mg chlordiazepoxide are 20 mg diazepam, 120 mg oxazepam, and 5 mg lorazepam (19). Haloperidol or droperidol can be considered for patients in major withdrawal who not respond adequately to benzodiazepines. In stable, admitted patients, b blockers can be considered as an adjunct to benzodiazepine therapy if there are no contraindications. Combination therapy makes pharmacologic sense in alcohol withdrawal; benefits include the reduction of the risks associated with prolonged and heavy sedation, faster symptom resolution, and quicker recovery ( 21).

ADJUNCT THERAPY Patients treated for alcohol withdrawal should be administered thiamine (100 mg IV), glucose (dextrose, 25 g IV), and magnesium (2 g IV). Multivitamin preparations usually are added to the patient's IV fluid because of chronic malnutrition. Two preparations are available—MVI (5 mL), which contains vitamins A through E, and MVI-12, which adds folic acid, vitamin B 12, and biotin. If the patient has significant anemia, serum folate and cobalamin (vitamin B 12) levels should be drawn before 5 mL or one ampule of MVI-12 is used. Serum folate levels, however, are of limited usefulness in alcoholics because low levels are common in the absence of morphologic changes of folate deficiency, and normal levels are not infrequent in the presence of megaloblastic change ( 52). Volume depletion can be corrected with normal saline. Reversal of electrolyte and metabolic disorders (hypomagnesemia, hypophosphatemia, hypokalemia, and

acidosis) are goals of intravenous therapy. However, the treatment of electrolyte disorders and acidosis may do little to abate the withdrawal syndrome. Paraldehyde, ethyl alcohol, and phenothiazines no longer have a routine place in the treatment of alcohol withdrawal ( 12,36). Phenothiazines are undesirable because they can, in the dosages required to calm patients in alcohol withdrawal, produce hypotension, lower seizure threshold, disturb central temperature regulation, and cause extrapyramidal effects ( 34,36,50,53).

RADIOGRAPHS AND LABORATORY TESTING Blood samples should be taken to determine electrolytes, blood urea nitrogen, complete blood count, creatinine, glucose, prothrombin time–international normalized ratio, calcium, phosphate, magnesium, and serum levels of any anticonvulsants the patient may be taking. Arterial blood gases should be considered if there is a suspicion of acidosis or pulmonary compromise. Chest radiography and pulse oximetry should be routine in patients with temperature elevation, tachypnea, or abnormal findings on physical examination of the chest. A pregnancy test should be performed in women of childbearing age. The benefit of skull radiography is the determination of occult head trauma not appreciated previously. There is little relationship between significant intracranial sequelae and the presence of a skull fracture ( 58). Patients with focal findings on neurologic examination or those with signs of head trauma and seizures should be considered for urgent CT (Table 146–3.3).

Table 146–3.3. Indications for Urgent CT Scan in the Alcohol Dependent Patient

Fever with Alcohol Withdrawal It is well known that alcohol withdrawal itself is capable of producing fever ( 3). More than half of febrile patients in withdrawal, however, have an infectious cause (usually pneumonia) of fever ( 54). Therefore, fever in an alcoholic should be considered to have resulted from an infectious cause until proven otherwise. Although fever may indicate meningitis, it also may occur with intracranial hemorrhage, brain abscess, alcohol withdrawal, toxic ingestion, and infections outside the CNS. If meningitis is suspected but increased intracranial pressure is possible, blood cultures should be taken and the patient should be started empirically on antibiotics. Because of the dangers of lumbar puncture in a subarachnoid hemorrhage or brain abscess, this may be delayed until an intracerebral lesion can be ruled out with computed tomography (CT) or magnetic resonance imaging (MRI) ( 55,56 and 57).

ADMISSION GUIDELINES AND DISPOSITION Because of the alcoholic's inability to care for himself or herself, satisfactory outpatient treatment is difficult. Optimal outpatient therapy includes a concerned family member or friend to ensure that the patient takes medications properly, appears at follow-up appointments, abstains from alcohol, and maintains an adequate diet. Alcoholic patients who undergo outpatient treatment need close supervision. The problem of when and on what service to admit the alcoholic is a constant dilemma for the emergency physician. Most alcoholic patients have medical, psychiatric, and social problems. Hospital admission is frequently necessary to diagnose and treat these multiple problems. Moreover hospital admission is often dictated if the alcoholic is no longer able to care for himself or herself. The following are suggested guidelines for admission for detoxification of alcohol-dependent patients. In choosing medical or psychiatric admission, medical illness always takes priority.

ACUTE INTOXICATION Acute intoxication alone seldom requires admission. Combined alcohol–drug overdose or associated medical, psychiatric, or social problems may necessitate admission. Acute intoxication is a diagnosis of exclusion. Hypoglycemia, hypoxia, carbon dioxide narcosis, carbon monoxide poisoning, mixed alcohol–drug overdose, ethylene glycol and methanol poisoning, hepatic encephalopathy, psychosis, severe vertigo, and psychomotor seizures can manifest in a manner similar to that of ethanol intoxication. Blood alcohol level or breath alcohol determination can help to support this diagnosis. Beware of the person who has a relatively low blood alcohol level (e.g., 100 mg/100 mL or less) but has substantial mental changes. These patients should be observed and should undergo additional evaluation. Alcohol levels that may be tolerated by an adult can be lethal in children. It is prudent to admit children with significant acute intoxication unless close psychosocial follow-up can be assured. Children with hypoglycemia or medical complications should be admitted. Child abuse or neglect should be considered.

ALCOHOL WITHDRAWAL (Delirium Tremens [DTs]) Patients with signs of major withdrawal (fever, hallucinations, confusion, extreme agitation) require admission. Patients with mild alcohol withdrawal can be observed in the ED. After 3 to 6 hours of observation, the alert, oriented patient whose vital signs, physical examination, suggested laboratory analysis, and chest radiograph are within normal limits may be released from the ED. Nevertheless, the patient requires treatment for the underlying alcoholism and should be advised or referred accordingly. Benzodiazepines can be used to treat alcohol withdrawal safely and effectively in an outpatient setting if the patient has mild or moderate symptoms without comorbid illness or a history of alcohol-related seizures. Individualized benzodiazepine administration can result in significantly less benzodiazepine than fixed-dosage regimens (49,59,60).

SEIZURES Patients are usually admitted for their first alcohol-related seizure. This allows the initiation of drug therapy, diagnostic evaluation, and continuous monitoring of patient status. However, the alcoholic with a first-time alcohol-related seizure occasionally may be discharged to a suitable social situation under the following circumstances: if the patient's alcohol withdrawal is mild and easily controlled either by supportive care or with low-dose benzodiazepines; if the diagnostic work-up, including a head CT scan, is unremarkable; if the patient has had fewer than three seizures; and if the patient has been observed to be alert and oriented, to have normal vital signs and normal findings on physical examination and laboratory studies during the 6 hours since the last seizure, and appropriate outpatient follow-up and close observation can be assured. Patients with a documented history of alcohol-related seizures need observation. If they have had no more than two alcohol-related seizures over a 6-hour period,

have a lucid interval between seizures, they are observed to be seizure free and at baseline mental and physical status for at least 6 hours after the last alcohol-related seizure, and blood chemistries are normal, they can be considered for discharge to a treatment facility. Three to six brief, self-limited seizures are not uncommon with alcohol withdrawal seizures. Nevertheless, admission is usually mandatory for patients with three or more seizures because of the potential for deterioration to status epilepticus. This is especially appropriate in the malnourished, immunocompromised, homeless, or noncompliant alcoholic. Patients with partial seizures or focal neurologic findings on physical examination require admission unless these findings have been documented previously. Patients with seizures associated with head trauma or with mixed alcohol–drug withdrawal seizures are admitted. Status epilepticus or recurrent seizures during observation in the ED indicate a lack of seizure control, which also requires hospitalization ( 61,62 and 63). There have been many prospective, randomized, placebo-controlled, double-blind studies addressing the efficacy of phenytoin in the management of alcohol withdrawal seizures. These studies demonstrated no significant benefit of phenytoin over placebo in preventing the recurrence of alcohol withdrawal seizures. Considering the risks and the lack of demonstrated benefit in these situations, phenytoin is not indicated for the treatment of alcohol withdrawal seizures ( 61,62,64). However, when there is a possibility of seizures independent of alcohol withdrawal, phenytoin (or fosphenytoin) should not be withheld.

PSYCHIATRIC HOSPITAL ADMISSION Alcoholic patients requiring admission for acute intoxication, withdrawal, seizures, or medical–surgical disorders are best managed on acute care floors and initially should not be admitted to a general psychiatric service. Many hospitals today have chemical dependency units that combine the advantage of the acute care floor and a secure psychiatric unit. Some psychiatric and social conditions in the alcoholic still can be handled better on a general psychiatric unit. These include psychosis, exacerbation of schizophrenia, depression with suicidal tendencies, and any patient who is a danger to self or others or any patient with alcoholic hallucinosis with an otherwise clear sensorium. Any patient who is no longer able to care for himself or herself also requires admission. Although this patient's ultimate destination is a rehabilitation center or a board-and-care program, hospital admission may be necessary to rule out medical or psychiatric illness and to treat impending withdrawal symptoms. Patients who want to stop drinking are often admitted to a hospital or a detoxification unit to treat impending withdrawal ( 65,66 and 67). In the new managed care era, this may prove more difficult in some cases. Be aware of depression and a suicide risk in all alcoholics.

REHABILITATION Most communities have either an Alcoholics Anonymous chapter or a treatment center for anyone who desires help with alcohol. The ED should have lists of such facilities available. In small communities, clergy or social workers can usually arrange rehabilitation. Whatever medical, psychologic, or social problem brings the alcoholic to the ED, the underlying problem is alcoholism. The ultimate goal is abstinence. Abstinence can be attained, even in the most difficult patient. This disease will surely progress if we do not first recognize alcoholism and then make sure that the patient has the opportunity to participate in a rehabilitation program (65,67,68,69 and 70). References 1. Holt S, Stewart IC, Dixon JM, et al: Alcohol and the emergency service patient. Br Med J 1980;281:638–640. 1A. O Connor PG, Schottenfeld RS: Medical progress: patients with alcohol problems. N Engl J Med 1998;338:592–603. 1B. HHS report to the US Congress on alcohol and health. NIH Pub 97:4017. Washington, DC, 1997. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

Hawley RJ, Major LF, Schulman EA, et al: Cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol and norepinephrine levels in alcohol withdrawal. Arch Gen Psychiatry 1985;42:1056. Linnoila M, Mefford I, Nutt D, et al: Alcohol withdrawal and noradrenergic function. Ann Intern Med 1987;107:875. Goldfrank LR: Alcohol withdrawal. Emerg Med 1986;10:24. Sellers EM: Alcohol, barbiturate and benzodiazepine withdrawal syndromes: clinical management. Can Med Assoc J 1988;139:113. Freinkle N, et al: Alcohol hypoglycemia: I. carbohydrate metabolism in patients with clinical alcohol hypoglycemia and the experimental reproduction of the syndrome with pure ethanol. J Clin Invest 1963;42:1112. Marx JA: The varied faces of Wernicke's encephalopathy. J Emerg Med 1985;3:411. Isbell H, Franser HR, Wikles A, et al: An experimental study of the etiology of ‘rum fits' and delirium tremens. Q J Study Alcohol 1955;16:1. Brown CC: The alcohol withdrawal syndrome. Ann Emerg Med 1982;11:276. Victor M, Adams RD: The effect of alcohol on the nervous system. Res Publ Assoc Nerv Ment Dis 1953;32:526. Berk WA, Todd K: Relationship of abstinence to the presentation and peak intensity of signs and alcohol withdrawal. Ann Emerg Med 1993;22:339. Jacob MS, Sellers EM: Emergency management of alcohol withdrawal. Drug Ther 1977;24:28. Nordstrom G, Berglund M: Delirium tremens: a prospective long-term follow up study. J Stud Alcohol 1988;49:178. Sellers EM, Kalant H: Alcohol intoxication and withdrawal. N Engl J Med 1976;294:757. Victor M: Treatment of alcoholic intoxication and the withdrawal syndrome: a critical analysis of the use of drugs and other forms of therapy. Psychosomatics 1966;28:636. Adinoff B, Bone GH, Linnoila M: Acute ethanol poisoning and the ethanol withdrawal syndrome. Med Toxicol 1988;3:172. Olbrich R: Alcohol withdrawal states and the need for treatment. Br J Psychiatry 1979;134:466.

17A. Lieber CS: Medical disorders of alcoholism. N Engl J Med 1995;333:1058–1065. 18. Naranjo CA, Sellers EM, Chater K, et al: Nonpharmacologic intervention in acute alcohol withdrawal. Clin Pharmacol Ther 1983;34:214. 19. Sellers EM, Naranjo CA: New strategies for the treatment of alcohol withdrawal. Psychol Pharmacol Bull 1986;22:88. 20. Whitfield CL, Thompson G, Lamb A, et al: Detoxification of 1,024 alcoholic patients without psychoactive drugs. JAMA 1978;239:409. 20A. Practice guidelines for the treatment of patients with substance use disorders: alcohol, cocaine, opiods. Am J Psych 1995;152(Suppl.):1–80. 20B. Mayo-Smith MF, and the American Society of Addiction Medicine Working Group: Pharmacologic management of alcohol withdrawal—a meta-analysis and evidence-based practice guideline. JAMA 1997;278:144–151. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49.

Rosenbloom AJ: Optimizing drug treatment of alcohol withdrawal. Am J Med 1986;81:901. Rosenbloom AJ: Emerging treatment options in the alcohol withdrawal syndrome. J Clin Psychiatry 1988;49:12. Lineaweaven WC, Anderson K, Hing DN: Massive doses of midazolam infusion for delirium tremens without respiratory depression. Crit Care Med 1988;16:294. Linnoila M: Benzodiazepines and alcoholism. In: Trimble MR, ed. Benzodiazepines divided. New York: John Wiley, 1983:291. Erstad B, Cotugno C: Management of alcohol withdrawal. Am J Health Syst Pharm 1995;52:697–709. Bird RD, Makela EH: Alcohol withdrawal: what is the benzodiazepine of choice? Ann Pharmacother 1994;28:67–71. Mendels J, Wasserman TW, Michaels TJ, et al: Halazepam in the management of acute alcohol withdrawal syndrome. J Clin Psychiatry 1985;46:172. Hollister LE, Greenblatt DJ, Rickels K, et al: Benzodiazepines 1980: current update. Psychosomatics 1980;21:1. Kyriakopoulous AA, Greenblatt DJ, Shade RI: Clinical pharmacokinetics of lorazepam: a review. J Clin Psychiatry 1978;39:16. Kraus JW, Desmond DV, Marshall JP, et al: Effects of aging and liver disease on disposition of lorazepam. Clin Pharmacol Ther 1978;24:411. Perry PJ, Wilding DC, Fowler RC, et al: Absorption of oral and intramuscular chlordiazepoxide by alcoholics. Clin Pharmacol Ther 1978;23:535–541. Verbeeck R, Tjandramaga TB, Berberckmoes R, et al: Biotransformation and excretion of lorazepam in patients with chronic renal failure. Br J Clin Pharmacol 1976;3:1033. Hosein IN, DeFreitas R, Beaubrun MH: Intramuscular and oral lorazepam in acute alcohol withdrawal and incipient delirium tremens. Curr Med Res Opin 1978;5:632. Miller WC, McCurdy L: A double-blind comparison of the efficacy and safety of lorazepam and diazepam in the treatment of the acute alcohol withdrawal syndrome. Clin Ther 1984;6:364. Solomon J, Rouck LA, Keopke HH: Double-blind comparison of lorazepam and chlordiazepoxide in the treatment of the acute alcohol abstinence syndrome. Clin Ther 1983;6:52. Thompson WL, Johnson AD, Maddrey WL: Diazepam and paraldehyde for treatment of severe delirium tremens: a controlled trial. Ann Intern Med 1974;82:175. Nolop KB, Natow A: Unprecedented sedative requirements during delirium tremens. Crit Care Med 1985;13:246. Woo E, Greenblatt DJ: Massive benzodiazepine requirements during acute alcohol withdrawal. Am J Psychiatry 1979;36:821. Clinton JE, Sterner S, Stelmachers Z, et al: Haloperidol for sedation of disruptive emergency patients. Ann Emerg Med 1987;16:319. Thomas HJ, Schwartz E, Petrilli R: Droperidol versus haloperidol for chemical restraint of agitated and combative patients. Ann Emerg Med 1992;21:407–413. Teaser GE, Murray GB, Cassem NH: Use of high-dose intravenous haloperidol in the treatment of agitated cardiac patients. J Clin Psychopharmacol 1985;5:344. Adams F, Fernandez F, Anderson BS: Emergency pharmacotherapy of delirium in the critically ill cancer patient. Psychosomatics 1986;27:33. Kraus ML, Gottlieb LD, Horwitz RI, et al: Randomized clinical trial of atenonol in patients with alcohol withdrawal. N Engl J Med 1985;313:905–909. Baumgartner GR: Clonidine vs. chlordiazepoxide in acute alcohol withdrawal: a preliminary report. South Med J 1988;81:56. Baumgartner GR, Rowen RC: Clonidine vs. chlordiazepoxide in the management of acute alcohol withdrawal syndrome. Arch Intern Med 1987;147:1223. Wilkins AJ, Jenkins WJ, Steiner JA: Efficacy of clonidine in treatment of alcohol withdrawal state. Psychopharmacology 1983;81:78. Robinson B, Robinson G, Maling T, et al: Is clonidine useful in the treatment of alcohol withdrawal? Alcohol Clin Exp Res 1989;13:95–98. Castanedo R, Cushman P: Alcohol withdrawal: a review of clinical management. J Clin Psychiatry 1989;50:278. Hayashida M, Alterman AI, McLellen AT, et al: Comparative effectiveness and costs of inpatient and outpatient detoxification of patients with mild-to-moderate alcohol withdrawal syndrome. Engl J Med 1989;320:358–365.

N

50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70.

Golbert TM, Sanz CJ, Rose HD, et al: Comparative evaluation of treatments of alcohol withdrawal syndromes. JAMA 1967;201:99–102. Lewis J:. Washington report. J Stud Alcohol 1979;40:539. Savage D, Lindenbaum J: Anemia in alcoholics. Medicine 1986;65:322. Sellers EM, Kalant H: Alcohol withdrawal and delirium tremens. In: Pattison and Kaufman, eds. The encyclopedic handbook of alcoholism. New York: Gardner Press, 1982:147–166. Rose HD, Golbert TM, Sanz CJ, et al: Fever during acute alcohol withdrawal. Am J Med Sci 1970;2650:112–121. Duffy GP: Lumbar puncture in spontaneous subarachnoid hemorrhage. Br Med J 1982;285:1163. Pettito F, Plum F: The lumbar puncture. N Engl J Med 1974;290:225. Talan DA: Role of empiric parenteral antibiotics prior to lumbar puncture in suspected bacterial meningitis: state of the art. Rev Infect Dis 1988;10:365. Masters SJ: Evaluation of head trauma: efficacy of skull films. J Roentgenogr 1980;135:539. Saitz R, Mayo–Smith MF, Roberts MS, et al: Individualized treatment for alcohol withdrawal: a randomized double-blind controlled trial. JAMA 1994;272:519–523. Fuller RK, Gordis E: Refining the treatment of alcohol withdrawal. JAMA 1994;272:557–558. Chance JF: Emergency department treatment of alcohol-withdrawal seizures with phenytoin. Ann Emerg Med 1991;20:520. Aldredge BK, Lowenstein DH, Simon RP: Placebo-controlled trial of intravenous diphenylhydantoin for short-term treatment of alcohol withdrawal seizures. Am J Med 1989;87:645–648. McMicken DB, Freeland ES: Alcohol-related seizures. Emerg Clin North Am 1994;12:1057–1079. Rathlev NK, D'Onofrio G, Fish SS, et al: The lack of efficacy of phenytoin in the prevention of recurrent alcohol-related seizures. Ann Emerg Med 1994;23:513–518. McGrady BS, Langenbuchen JW: Alcohol treatment and health care reform. Arch Gen Psych 1996;53:737–746. Leery CM: When to hospitalize the patient with cirrhosis. Hosp Pract 1968;3:40. Langenbucher J: Rx for health care costs: resolving addictions in the general medical setting. Alcohol Clin Exp Res 1994;18:1033–1036. Lewis DC, Femino J: Management of alcohol withdrawal. Rational Drug Ther 1982;16:1. Kane GP: Helping the alcoholic into treatment. Hosp Physician 1979;15:55. Smith JW: Rehabilitation for alcoholics. Postgrad Med 1978;64:143.

Chapter 146.4 Alcohol-Related Diseases: Emergency Department Management Principles and Practice of Emergency Medicine

CHAPTER 146 ALCOHOL

4 Alcohol-Related Diseases: Emergency Department Management John I. Ellis, Michael Whiting, Martha Roper Capsule Metabolic Disorders Neurologic Disorders Other Gastrointestinal Disorders Cardiac Disorders Alcohol-Related Pulmonary Diseases and Infections Acute Abdomen (Spontaneous Bacterial Peritonitis) Fetal Alcohol Syndrome Medicolegal Pearls

CAPSULE The acute and chronic diseases associated with the use of alcohol are myriad. They range from trauma to dementia to malnutrition and to the effects on the developing fetus of a pregnant woman. All organ systems may be affected through either direct toxic effects or the nutritional deficiencies that often accompany alcohol use.

METABOLIC DISORDERS Alcoholic Ketoacidosis In 1940, Dillon et al (1) described five patients with severe ketoacidosis and normal or only slightly elevated blood glucose levels. All five either admitted to alcoholism or had presumptive evidence of chronic alcohol abuse. Since then, the distinct syndrome of alcoholic ketoacidosis (AKA) has been described and is well documented (2,3 and 4). Most patients with the disorder are chronic alcoholics; classically, there is an increase in their baseline consumption in the weeks before presentation. Because of gastrointestinal problems such as gastritis or pancreatitis, vomiting, or the exclusive consumption of alcohol, a decrease in food intake occurs in the days preceding presentation. It appears that cessation of carbohydrate consumption and depletion of body carbohydrate stores are a prerequisite to the onset of the syndrome. When this happens, fatty acids are increasingly used leading to ketone production. This disorder recurs in patients who are predisposed and is not directly related to the amount of alcohol ingested. Patients commonly have complaints related to gastrointestinal distress or shortness of breath. Alteration of mental status, either with or without signs of withdrawal, is common. Physical examination uniformly demonstrates Kussmaul respirations. Other findings, such as ketotic breath, tachycardia, or specific abdominal findings, are variable. Often an infection such as pneumonia has developed. Laboratory findings are typical. A high anion gap metabolic acidosis with low, normal, or only slightly elevated serum glucose is pathognomonic with alcohol abuse. The pH may be normal because of metabolic alkalosis from protracted vomiting. Specifically measured serum ketones are markedly elevated, with a markedly elevated b-hydroxybutyrate-acetoacetate ratio. Because of this, results of urinary or serum colorimetric tests, which measure only acetoacetate, may be misleadingly negative or only trace positive. Serum lactate levels are usually only modestly elevated. Insulin levels are typically low normal, whereas cortisol, growth hormone, and glucagon all tend to be elevated. Serum electrolytes, especially phosphate and magnesium, may be diminished. The arterial pH is usually in the range of 7.10 to 7.30, although profound acidemia may occur. The differential diagnosis of AKA includes diabetic ketoacidosis (DKA), alcoholic gastritis with starvation, peptic ulcer disease, and pancreatitis. The differential diagnosis of an anion gap acidosis in an alcoholic includes AKA; DKA; uremia; lactic acidosis from hypoxia, hypertension, or sepsis; and ingestion of salicylates, isonicotinoylhydrazine, iron, methanol, or ethylene glycol. The treatment of this syndrome, when recognized, is fairly straightforward. Replacement of fluids and carbohydrate stores usually reverses the abnormalities within 24 to 36 hours. Large amounts of intravenous (IV) 5% dextrose in saline, along with oral nutrition when this becomes possible, are necessary. Without adequate replenishment of carbohydrates, ketosis may recur. Any electrolyte abnormalities—with special emphasis on magnesium, potassium, and phosphate—should be corrected (5). There is no place for insulin in the treatment of alcoholic ketoacidosis. Sodium bicarbonate may be considered in patients with severely depressed pH (less than 7.0), but, considering the prompt response usually seen to fluid and dextrose replacement, this is usually unnecessary and should be done cautiously. In uncomplicated cases and with proper therapy, prognosis is excellent. Deaths do occur, usually in patients with severe volume depletion or other concurrent illness. Alcoholic Hypoglycemia This syndrome is seen exclusively in chronic, severe alcoholism. Several factors must exist before it can occur. First, hepatic glycogen stores must be depleted, primarily through the consumption of a diet severely deficient in carbohydrates for a prolonged period. Additionally, alcohol inhibits glycogenesis by numerous pathways, causing fat instead of glycogen to be deposited in hepatocytes ( 6). With continued alcohol consumption, the liver becomes less and less able to engage in gluconeogenesis, leading to a gradual decline in serum glucose levels ( 2). Profound hypoglycemia may result, with complications of coma, seizures, and death. Unlike other forms of hypoglycemia, the alcoholic type is unresponsive to glucagon. The typical patient is a chronic “street alcoholic,” usually found unresponsive. Physical examination may reveal the signs of hypoglycemia with diaphoresis, tachycardia, and tremulousness. In patients with alcoholic neuropathy or infection, these signs may be absent. Neurologic examination usually reveals a depressed level of consciousness and nonfocal neurologic motor examination, although transient focal neurologic findings in hypoglycemia occasionally are seen. The patient may have seizures. If not treated promptly, hypoglycemia can lead to permanent brain injury. For this reason, all patients with altered levels of consciousness, even those with a strong odor of ethanol on the breath, either should undergo serum glucose evaluation with a rapid bedside test strip or be administered IV dextrose immediately on presentation. Thiamine, 100 mg IV intramuscularly (IM) should be administered with the glucose because of the possibility of precipitating acute Wernicke encephalopathy with the administration of glucose alone ( 5,6). Serum glucose before dextrose administration should be measured immediately, preferably with one of the bedside glucose tests, and serum should be sent to the laboratory for confirmation. Repeated IV boluses of 50% dextrose may be necessary. Because all patients with alcoholic hypoglycemia are in a state of starvation, treatment is not complete even after the initial glucose is given and the level of consciousness is normalized. These patients should be continued on IV 10% dextrose until they can ingest adequate amounts of carbohydrates by mouth to create at least a partial glycogen buffer in the liver. Water and Electrolyte Disorders in Alcoholics The effects of alcohol on body water and electrolyte balance are complex. Any generalization, such as “all alcoholics are dehydrated” is obviously false because the habits and nutritional patterns of alcoholics vary as widely as socioeconomic status or choice of beverage. Although most disorders of water and electrolytes in the alcoholic patient are variable and unpredictable, a few consistent observations have emerged ( Table 146–4.1).

Table 146–4.1. Serum Electrolyte Findings in Chronic Alcoholism

Alcohol ingestion produces an immediate increase in urine volume and fall in urine osmolarity, caused by the suppression of alcohol dehydrogenase ( 7). Alcohol administered by way of the carotid artery in animals produces the same response without a rise in blood alcohol level ( 8). This prompt but limited diuresis is reversed in the withdrawal phase by increased levels of ADH and antidiuresis yielding no net change in water balance in the well-hydrated drinker ( 7). The water balance seen in any particular patient, therefore, depends more on factors other than on the effects of ethanol itself. Many chronic alcoholics have a poor diet and poor intake of nonalcoholic fluids. The consumption of distilled spirits, which contain relatively little water compared to beer and wine, contributes to volume contraction. This, along with the effects of withdrawal, vomiting, diarrhea, and possible infection, can cause severe intravascular and total body water depletion, at times manifesting as hypovolemic shock. On the other hand, severe chronic alcohol abuse can lead to water intoxication and hyponatremia. Patients with vomiting or diarrhea who replace the volume lost with hypotonic beer or wine, or those who drink massive quantities of beer, which is low in sodium, are prone to this. Water intoxication may cause seizures and altered sensorium, and has been implicated in the syndrome of central pontine myelinolysis ( 9). Alcohol use is associated strongly with hypomagnesemia and total body magnesium depletion ( 7,10). Poor dietary intake is a major factor in its development. Additionally, alcohol causes decreased gastrointestinal absorption and a direct renal leak of magnesium even on the first day of consumption ( 7). Magnesium levels in alcoholics have been found to be diminished in serum, brain, cerebrospinal fluid (CSF), and muscle. Hypomagnesemia has been implicated in cardiac arrhythmias, seizures, tremors, and central nervous system irritability. Hypophosphatemia is a common and significant derangement found in alcoholics. In addition, serum phosphate commonly drops significantly after carbohydrate feeding, probably as a result of a shift of phosphate to hepatocytes ( 7). Severe hypophosphatemia is associated with rhabdomyolysis, cardiovascular collapse, and hematologic abnormalities. Although unpredictable, electrolyte and water abnormalities are common in alcoholics. An IV line with dextrose, sodium chloride, multivitamins, 100 mg thiamine, 1 mg folate, and 1 to 2 g magnesium sulfate should be administered to alcoholic patients with evidence of chronic use. Additionally, serum sodium, potassium, chloride, bicarbonate, calcium, phosphorus, and magnesium should be measured. Special attention should be paid to serial measurements of the serum phosphate levels in alcoholic patients admitted to the hospital to detect the sometimes severe drop in their serum phosphate levels often seen with the resumption of adequate nutrition. Other Metabolic and Endocrine Disorders Alcohol may be a factor in the cause of many endocrine disorders likely to be treated in the ED ( 10A). Although many are chronic or multifactorial, ethanol abuse should be considered in the differential diagnosis of these conditions. Table 146–4.2 lists some of these.

Table 146–4.2. Other Metabolic and Endocrine Effects of Alcoholism

NEUROLOGIC DISORDERS Wernicke–Korsakoff Syndrome Well known as one of the disorders most closely associated with chronic alcoholism, Wernicke encephalopathy remains underdiagnosed in a large percentage of patients (5,11,12 and 13). Its prevalence in autopsy studies is between 0.8 and 3% of the general population, depending on the geographic region involved (11,12,13,14,15 and 16). Among alcoholics, the prevalence is as high as 12.5% ( 14). Approximately 20% of patients cases are diagnosed before death. This underdiagnosis is unfortunate because Wernicke encephalopathy is a major reversible cause of dementia and, if untreated, has a 10 to 20% mortality rate ( 5,11,14). Additionally, approximately 80% of patients who survive Wernicke encephalopathy evidence some degree of Korsakoff psychosis ( 11,12). Increased awareness and treatment of this disorder are vital. At its root, Wernicke encephalopathy is a nutritional disorder caused by a deficiency of thiamine, (vitamin B 1). Thiamine as thiamine pyrophosphate is a coenzyme necessary for the metabolism of glucose in the Krebs cycle and oxidative phosphorylation. Because the brain depends on glucose for its metabolism, it is particularly susceptible to the deranged glucose metabolism caused by thiamine deficiency. Important in the alcoholic patient is the fact that magnesium is necessary in the utilization of thiamine ( 12). Although the only prerequisite to the development of Wernicke encephalopathy is a diet deficient in thiamine, it has been observed that the disease does not develop in all thiamine-deficient alcoholics. This is perhaps caused by an inherited difference of activity of thiamine-dependent transketolase ( 12,17). Wernicke encephalopathy is associated with necrosis of neurons and myelinated structures in a symmetric pattern involving the mammillary bodies, cerebellar vermis, hypothalamus, third- and sixth-cranial nerve nuclei, and areas of the tegmentum ( 6,11,12,13,14,15 and 16). Petechial and occasionally gross hemorrhage are seen in these areas on gross pathologic examination. Computed tomography and magnetic resonance imaging (MRI) occasionally demonstrate characteristic changes in the diencephalon in patients with Wernicke encephalopathy ( 12,13,18). Because laboratory and radiographic findings are nonspecific or only occasionally present, Wernicke encephalopathy remains a clinical diagnosis. The abrupt onset of the triad of oculomotor abnormalities (nystagmus, gaze paresis, pupillary abnormalities, or ptosis), ataxia, and mental confusion comprise the classic description of Wernicke syndrome. Ocular changes and ataxia may precede the confusional state by a few days ( 13). The nystagmus typically seen is bilateral horizontal and upgaze-evoked nystagmus. Ataxia is cerebellar in nature and characterized by broad-based gait and truncal ataxia, with lower extremity involvement predominating over upper extremity ataxia. Disorientation, apathy, inattention, and drowsiness, described as a “generalized confusional state,” constitute the classic mental status

changes observed. The classic presentation notwithstanding, many variants of the syndrome exist, contributing to underdiagnosis. The classic triad may be incompletely present. Importantly, coma or stupor may be the sole presentation. Hypothermia and hypotension from hypothalamic involvement frequently are seen ( 5,6,11,12,13,14,15 and 16,19). The often extremely protean presentation of the disease mandates that Wernicke encephalopathy be considered in the differential diagnosis of all alcoholic patients with mental status changes. Wernicke encephalopathy must be treated as a true medical emergency because delay or failure to treat it may result in long-term disability or death. Essentially, all alcoholic patients with abnormal mental status should receive at least 100 mg thiamine IM or IV. Those in whom the diagnosis is suspected strongly or is confirmed by examination should be admitted and receive at least 100 mg thiamine IV for 5 days or more. Ocular findings can be expected to resolve within hours to days with adequate therapy (11,12 and 13,20). Indeed, it has been suggested that reversal of ocular findings be used as a criterion for “titrating” initial thiamine therapy, with up to 1000 mg necessary in the first 12 hours ( 13). Ataxia and confusion may be slower to resolve, gradually disappearing over weeks to months even with adequate therapy. Variable amounts of permanent disability may remain. Resistance to thiamine therapy may be seen in patients with hypomagnesemia because magnesium is a necessary cofactor in thiamine utilization ( 5,9,13,21). The many nutritional deficiencies seen in alcoholics argue strongly for the use of a standard IV solution in alcoholic patients seen in the ED to avoid inadvertently omitting any part of therapy. In our institution, a standing protocol exists for the administration to alcoholic patients of an IV solution consisting of 1 L D 5 0.45 N saline with 1 amp of a commercially prepared multivitamin solution, 100 mg thiamine, 1 mg folate, and 2 g MgSO 4. The solution should be adjusted to correct other metabolic disorders as identified. Korsakoff psychosis, originally thought to be a distinct disorder, is now recognized as the chronic phase of the Wernicke–Korsakoff syndrome. It is characterized by various degrees of retrograde and anterograde amnesia, with often fanciful confabulation appearing in early stages to cover for the patient's lapses in memory ( 22). Later in the disease, the adaptive confabulation often disappears, and patients become severely disabled. Institutionalization may be the only recourse. Wernicke and Korsakoff syndromes may blend imperceptibly into each other. Treatment with thiamine early in the course of Korsakoff syndrome may reverse or arrest some aspects of the disease, but in more than half the patients recovery is incomplete ( 13). Alcoholic Cerebellar Degeneration This syndrome, characterized pathologically by degeneration of Purkinje cells in the anterior and superior cerebellar vermis and adjacent hemispheric areas, is encountered in the brains of as many as 27% of alcoholic patients at autopsy ( 13,14). Men are affected more frequently than women. Clinically, patients with this disorder evidence a wide-based stance with varying degrees of gait and truncal ataxia. As in Wernicke syndrome, the lower extremities are affected more than the upper extremities. Nystagmus, dysarthria, and tremor may be observed almost exclusively during acute episodes of intoxication, metabolic derangement, or withdrawal; with resolution of these acute states, nystagmus, dysarthria, or tremor disappears ( 12). Disorders of consciousness are absent in the pure syndrome of cerebellar degeneration. CT or MRI may demonstrate atrophy of the midline cerebellar cortex. The differential diagnosis of ataxia in an alcoholic includes phenytoin or barbiturate toxicity, heavy metal poisoning, subdural hematoma, cerebrovascular accident, hepatic encephalopathy, tumor, cerebellar hematoma, neuropathy, and carcinomatous cerebellar degeneration. The cause of alcoholic cerebellar degeneration remains largely unknown. Although it is seen almost exclusively in chronic alcoholics who have consumed excessively for at least 10 years, there is little evidence that alcohol itself causes the lesions. The similarity of the cerebellar lesions to those of Wernicke syndrome suggest a nutritional component. Other experiments suggest that electrolyte abnormalities may play a role ( 23). The only treatment of this disorder involves alcohol abstention and adequate nutrition. With therapy, the symptoms may be arrested or even reversed. In emergencies, it is critical to identify potentially treatable conditions in alcoholics. Central Pontine Myelinolysis Central pontine myelinolysis (CPM) is a rare disorder that most commonly affects alcoholics but is also seen in patients with other diseases complicated by electrolyte abnormalities or malnutrition, such as burns, cancer, diabetes, or Addison disease. The pathologic lesion is an area of pallorous demyelination in the base of the pons. Approximately 10% of patients also have symmetric extrapontine lesions in the striatum, thalamus, cerebellum, or cerebral white matter ( 12). These lesions often may be seen on high-resolution CT or MRI. The cause of this syndrome is unknown. It is encountered almost exclusively in patients with hyponatremia. The first reports coincided with the beginning of the widespread use of intravenous fluids for the correction of electrolyte abnormalities, leading to the hypothesis that this is an iatrogenic disorder caused by too-rapid correction of severe hyponatremia resulting in water shifts within the brain ( 12,13,24). Others have proposed that it is the brain edema caused by hyponatremia itself that is the root of the problem (25). Clinical experience and recent investigations suggest that though both factors play a role, higher rates of correction of hyponatremia definitely are associated with higher incidences of CPM ( 26). The signs and symptoms of CPM may be subclinical or obscured by other problems, such as alcohol withdrawal. It may appear in a vague, protean fashion. Classically, during treatment of hyponatremia, manifestations are the subacute onset of progressive quadriparesis, pseudobulbar palsies such as dysarthria or difficulty in swallowing, and paresis of horizontal eye movements. With more severe involvement, pupillary paresis, decerebrate posturing, respiratory failure, and stupor or coma may become prominent. The “locked-in” state can result. Although rare cases of partial or complete recovery have been reported, CPM is often fatal in 2 to 3 weeks. The cornerstone of treatment is prevention. In light of increasing evidence that excessively rapid correction of hyponatremia plays a major role in the development of the syndrome, the careful, slow correction of hyponatremia to levels of not more than 120 to 130 mOsm/L seems the only prudent course. A rate of correction of less than 12 mOsm/L per day through the use of free-water restriction or isotonic saline infusion is probably safest ( 27,28). Once the syndrome has developed, the only treatment is general supportive care ensuring adequate nutrition and maintenance of normal serum electrolytes. Chronic Dementia And Cerebral Atrophy Studies have indicated that, matched for age, alcoholic persons have significantly increased incidences of cortical atrophy, low brain weight and volume, dilation of the lateral ventricles, widening of the cerebral sulci, and impaired performance on neuropsychologic tests over control, nonalcoholic patients ( 1,11,12,13 and 14,29). With abstinence from alcohol, some of these changes may be reversible ( 30). The acute or subacute onset of dementia in an alcoholic patient, as in any other patient, may signal metabolic encephalopathy, infection, or posttraumatic lesion such as subdural hematoma. All patients with new-onset dementia deserve a thorough workup to identify potentially reversible causes of dementia. Alcoholic Peripheral Neuropathies Alcoholic polyneuropathy seen commonly in the chronic alcoholic patient probably is caused by nutritional deficiencies. Symptoms usually are related to burning, painful paresthesias or numbness in a “stocking-glove” distribution. Physical examination usually reveals deficits in light touch and vibratory sensation. Deep tendon reflexes, especially the Achilles reflex, often are diminished or absent. In severe cases, motor weakness, muscle atrophy, muscle changes, and loss of proprioception leading to ataxia are seen. Autonomic dysfunction causing impotence, orthostatic hypotension, bladder and bowel control problems, or Argyll–Robertson pupils occasionally is encountered ( 13). Treatment again involves nutritional support and abstention from alcohol. Mononeuropathies, such as the well-known “Saturday night palsy,” are usually the result of pressure damage to superficially located individual nerves. The usual scenario is that of an intoxicated person lying in the same position without moving for a number of hours, then awakening with a wrist or ankle drop. Commonly involved are the radial, ulnar, and common peroneal nerves. A dense deficit of sensory and motor modalities in the distribution of the nerve in question is the rule on physical examination. Recovery of function depends on the amount of damage suffered by the nerve and the general metabolic and nutritional status of the patient. Treatment involves splinting of the extremity in a position of function to avoid contracture and additional damage to the often insensate limb, range-of-motion exercises, and referral to a neurologist for long-term care. Occasionally swelling around the nerve may be severe, with vascular compromise, requiring surgical

decompression. The presence of fasciitis is an emergency that requires rapid decompression to save the function of the extremity. Alcohol-Related Myopathies The muscles are affected by alcohol abuse to a larger extent than has been appreciated, through direct toxic effects and the nutritional and metabolic derangements discussed previously. Two fairly distinct syndromes, the acute and chronic alcoholic myopathies, have been described. Acute Alcoholic Myopathy This is a syndrome of acute muscle necrosis that occurs largely in binge drinkers. It may range in severity from an asymptomatic state or a mild muscle achiness with transient, small rises in serum creatine kinase to frank rhabdomyolysis. Alcoholism is the most common cause of rhabdomyolysis ( 31,32). Numerous factors contribute to the pathogenesis of acute alcoholic myopathy. Alcohol itself has a direct toxic effect on skeletal muscle; the administration of ethanol to well-nourished volunteers causes muscle damage (12,33). Additionally, the hypophosphatemia common in alcoholics is well known to cause rhabdomyolysis. Ischemic muscle damage may result when a drunken person “passes out” and lies immobile on an extremity for a number of hours. Finally, the increased muscle activity associated with alcohol withdrawal may contribute to this condition. The patient with acute alcoholic myopathy has muscle pain with or without swelling, usually after a heavy bout of drinking lasting a day or more. It becomes apparent on awakening after the heavy binge and often is accompanied by symptoms of alcohol withdrawal (34). Involvement in the lower extremities often predominates especially in the calves. Involved muscle groups are usually tender and may be tense. Compartment syndromes may occur. Laboratory examination always shows elevated serum levels of creatine kinase (CK) activity usually greater than 10 to 20 times normal values. Myoglobinemia may be detectable, although this is often transient because of rapid renal clearance ( 32). Serum potassium levels may be increased. In severe rhabdomyolysis, the main complication is the development of acute renal tubular necrosis. Elevated blood urea nitrogen (BUN) and creatinine and an active urine sediment are seen in these patients. The urine may be brown to red if myoglobin is excreted. Urine ortholidine testing, the commonest test found on urinary dipsticks, does not distinguish between the heme in hemoglobin and myoglobin; therefore, urine dipstick show positive blood during myoglobinuria. An acellular urine sediment with positive dipstick for blood is highly suggestive of myoglobinuria. Hemolysis, however, must be ruled out to diagnose myoglobinuria positively. The most sensitive and specific laboratory test remains elevated CK MM isoenzyme levels; when markedly elevated, this test is virtually pathognomonic for skeletal muscle injury. As mentioned, the major risk for morbidity in patients with acute alcoholic myopathy is the development of acute renal tubular necrosis. Obviously, any alcoholic patients with complaints of acute muscle pain should be investigated with measurement of serum CK, BUN, creatinine, and urinalysis. Additionally, alcoholic myopathy should be considered in any binge-drinking alcoholic or patient in alcohol withdrawal. Patients with significantly elevated CK, BUN, or creatinine, or with evidence of myoglobinuria should be considered for admission for observation and intravenous hydration to avoid renal damage. Specific details of the management of rhabdomyolysis and acute renal tubular necrosis may be found in the appropriate sections of this text. Chronic Alcoholic Myopathy In contrast to the acute syndrome, chronic alcoholic myopathy usually is seen in the chronic, daily alcohol abuser. Notably absent are such acute markers of muscle injury as pain, swelling, and elevated CK or serum and urinary myoglobin. These patients often have other chronic complications of ethanol abuse such as neuropathy, Wernicke syndrome, or cirrhosis, and they usually are seen for symptoms and problems unrelated to their muscular disease. The cause of the chronic syndrome is thought primarily to be nutritional deprivation ( 34). The usual muscular-related complaint in these patients is a progressive, gradual muscle weakness, most prominent in the hips and shoulder girdle. Physical examination often reveals atrophy. Histologic studies have shown that this disorder selectively affects type I (“fast twitch”) fibers, relatively sparing the type II myocytes (35). These patients usually have no history of episodes of acute myopathy. Treatment of this chronic syndrome, as with most other chronic alcoholic problems, consists of abstinence from alcohol and adequate nutrition. Alcohol-Associated Gastrointestinal Disorders The effects of ethanol on the gastrointestinal (GI) tract are diverse. Many of the common and life-threatening complaints encountered in the alcoholic patient in the ED are related to the effects of alcohol on various parts of the gastrointestinal system. A brief discussion of some of the most prominent problems is presented; the reader is referred to the more in-depth discussions of each specific problem elsewhere in the text for details of diagnosis and management. Alcoholic Liver Disease One of the major sources of morbidity and mortality in alcoholics, liver disease in alcoholism consists of three classic syndromes: fatty liver, alcoholic hepatitis, and cirrhosis. As many as 30,000 deaths per year occur from the complications of alcoholic liver disease ( 1). Fatty Liver A common clinical and biopsy finding in alcoholic patients, excessive fat deposition in hepatocytes, may occur in persons who consume even the relatively moderate amount of 20 to 40 g alcohol per day (36). Usually asymptomatic and merely an incidental finding on physical examination, the hepatic enlargement caused by hepatic steatosis may cause mild jaundice or upper abdominal pain from capsular stretching. No specific treatment is necessary or available beyond abstinence from alcohol and adequate nutrition. Alcoholic fatty liver does not predispose to cirrhosis, and it resolves in 4 to 6 weeks in the absence of alcohol consumption ( 36,37). Alcoholic Hepatitis This is often the most difficult of alcoholic liver diseases to diagnose because of its variable, often vague manifestations, which may range from totally asymptomatic to fulminant hepatic failure. Classically characterized by the insidious, slow onset of anorexia, vomiting, jaundice, low-grade fever, and abdominal pain, it may be impossible to distinguish from other causes of hepatitis. Extrahepatic manifestations such as GI bleeding may predominate. Emergency management is similar to that of other forms of hepatitis. Physical examination should concentrate on estimating the severity of hepatitis and on recognizing any potentially life-threatening complications. Laboratory evaluation should include complete blood count, liver enzymes to estimate the severity of ongoing hepatic necrosis, and a prothrombin time. Viral serology should be considered to rule out other causes of hepatitis. Treatment depends on the severity of the disease. Only patients with mild disease should be considered for discharge from the ED, but there should be prompt follow-up with a gastroenterologist or internist. Indications for admission include intractable vomiting, significantly abnormal vital signs, any sign of encephalopathy, GI bleeding, renal insufficiency, deep jaundice, or prolonged prothrombin time. Alcoholic Cirrhosis Cirrhosis, the irreversible stage of alcoholic liver disease, develops in only 10 to 20% of chronic alcoholics, suggesting that other factors besides alcoholism contribute to its development ( 39). Approximately 120 to 180 g alcohol per day for 15 years appears to be a critical “total dose” necessary for the development of cirrhosis (38). Usually seen in the ED only when complications intervene, the patient with cirrhosis may be asymptomatic or have vague chronic complaints relating to weight loss, fatigue, or abdominal discomfort. Advanced cirrhosis yields a fragile patient at high risk for GI bleeding from esophageal varices or other sites, infection, encephalopathy, or frank liver failure. Emergency management of the patient with cirrhosis should concentrate on the identification and treatment of complications. Gastrointestinal bleeding should be treated gently, because overhydration can increase bleeding rates from esophageal varices ( 36). Abdominal pain or increased ascites may signal the development of spontaneous bacterial peritonitis, even with no fever, and it mandates paracentesis for Gram stain and culture. Coagulopathies predispose to intracranial and GI bleeding; signs of these should be sought actively. Any relatively minor infection, GI bleeding, or use of alcohol or other sedative

drugs may tip the patient into encephalopathy. Additionally, patients with alcoholic cirrhosis are at significantly higher risk for hepatocellular carcinoma. Cirrhosis is a chronic, end-stage disease characterized by a slow, gradual loss of function. Any acute or subacute change in the patient, therefore, probably signals a new problem or complication and mandates an intensive effort to identify and treat any of the multitude of complications that may accompany this disorder. Most patients with complications of cirrhosis should be admitted for inpatient care. Alcoholic Pancreatitis Although the exact pathogenesis of this disease is unclear, alcohol abuse definitely is associated with pancreatitis, both acute and chronic ( 39A). The most common symptoms are related to epigastric abdominal pain radiating to the back and vomiting. History usually reveals an alcoholic binge immediately before the onset of pain and vomiting. The patient usually lies still in bed, often curled on his or her side. Abdominal findings may vary from benign to board-like rigidity. A mass representing an inflamed, phlegmonous pancreas or a pseudocyst may be found. Bowel sounds usually are preserved ( 39). Laboratory findings are nonspecific. Elevated serum amylase and lipase often are found, but their degree of elevation does not correlate with the severity of the attack. Normal levels may be encountered in chronic pancreatitis; alternatively, an amylase may be elevated because of vomiting. Radiographic findings are variable: occasional calcifications in the area of the pancreas are seen, and a “sentinel loop” of localized ileus may be helpful. CT may be necessary to identify the severely edematous, hemorrhagic pancreas or pseudocyst. Hypotension, tachycardia, and skin signs of shock are ominous findings, as are acidosis, decreased hematocrit, and diminished serum calcium levels. Prognosis in acute pancreatitis is inversely proportional to the patient's age. Complications include shock, pseudocysts, abscess formation and sepsis, coagulopathies, diabetes mellitus, and malabsorption. Management consists of the fluid resuscitation of patients, control of vomiting, and pain control. Signs of infection and hemorrhage should be actively sought and treated. Only patients with relatively minor episodes who are able to tolerate oral nutrition and hydration and in whom outpatient pain control is possible should be considered for discharge. All others require admission. Close follow-up is essential even in cases that seem mild.

OTHER GASTROINTESTINAL DISORDERS Excessive ethanol consumption is a well-known cause of esophageal reflux, hemorrhagic gastritis, esophageal and gastric carcinoma, and chronic diarrhea. The newly developed bacterium Heliobacter pylori (first cultured in 1982) may be involved in alcoholic gastritis and ulcer, offering the possibility of more treatment options (e.g., bismuth and metronidazole with tetracycline or ampicillin) ( 40). Gastrointestinal bleeding from Mallory–Weiss tears, esophageal varices, or gastric or duodenal bleeding is common and often life threatening. See Table 146–4.3 for a list of alcohol-related GI problems. Hematemesis, melena, marked anemia from bleeding, or any unstable vital signs mandate admission to the hospital.

Table 146–4.3. Gastrointestinal Disorders Associated with Alcoholism

Hematologic Disorders Alcohol affects all elements of the blood in complex ways. Many of these may have an impact on a patient's presentation to the ED ( Table 146–4.4). Anemia of varying degrees is common among patients with severe alcoholism. Although ethanol itself has a myelosuppressive effect and causes vacuolization of erythrocyte precursors, most alcohol-related anemias appear to be caused primarily by malnutrition ( 41). The most characteristic finding is macrocytosis, often with mean cell volumes greater than 100 m3. This is caused by folate deficiency in most cases. Disorders of iron metabolism are common among alcoholics, giving rise to microcytic, hypochromic anemias and sideroblastic anemia. With cessation of alcohol abuse and adequate nutritional support, these anemias usually resolve. Chronic GI bleeding also may cause hypochromic, microcytic anemia in the alcoholic. Alcoholics with liver disease are often predisposed to hemolytic anemia. The peripheral blood may show many bizarre erythrocyte forms. These anemias carry a poorer prognosis for resolution. Patients with profound or symptomatic anemia should be admitted. Other patients with anemia should be referred for appropriate evaluation and treatment.

Table 146–4.4. Hematologic Disorders Associated with Alcoholism

Leukocyte cell lines are affected by alcohol also. Leukopenia may become profound if the alcoholic patient with nutritional deficiencies is stressed by infection ( 42). Additionally, leukocyte function is depressed by alcoholism and may be responsible for the reduced resistance to infection seen in alcoholics. Coagulopathies are common in alcoholics because of platelet and humoral defects. Platelet number and function are depressed by alcoholism. Contributing to this are nutritional deficiencies, especially of folate, splenic sequestration caused by portal hypertension, and a direct toxic effect of alcohol ( 41). Additionally, patients with liver disease may have humoral coagulation deficiencies, usually decreased activity of the vitamin K-dependent clotting factors II, VII, IX, and X. Patients with prolonged prothrombin times should be given parenteral vitamin K. This may be expected to effect a variable decrease in prothrombin time, depending on the amount of hepatic dysfunction and the patient's nutritional status.

CARDIAC DISORDERS Alcohol and alcohol abuse have diverse effects on cardiac structure and function. Although effects of lifestyle and other habits have been difficult to separate from the actual effects of alcohol, certain definite associations have been observed. Additionally, alcohol may exacerbate or uncover preclinical cardiac disease from other causes.

Acute Effects of Alcohol on the Heart Acute alcohol consumption has a variable effect on cardiac function. Although it has been shown to have a direct negative inotropic effect, it has a vasodilatory effect, often yielding no change or even a slight improvement in cardiac index ( 1,43,44). Patients on b-blockers or other drugs that interfere with adrenergic tone may show a more pronounced decrease in cardiac function when acutely intoxicated ( 43,45). Patients with already compromised left ventricular function may have exacerbations of their congestive heart failure caused by alcohol intoxication. Arrhythmias, both supraventricular and ventricular, are well known to be a complication of alcohol abuse. Dubbed the “holiday heart syndrome” because it was observed originally in alcoholics who increased their consumption at the holiday season, this syndrome occurs in alcoholics during or immediately after a heavier-than-normal drinking binge ( 46). Atrial fibrillation is by far the most commonly observed arrhythmia, but premature atrial contractions, atrial flutter, paroxysmal atrial tachycardia, premature ventricular contractions, and ventricular tachycardia also are seen ( 43,44,46,47). A positive correlation between blood alcohol concentration and mean rate of ventricular premature contractions has been observed ( 47). Organic heart disease, even subclinical, increases the risk for holiday heart many times (43,44). Many epidemiologic studies have shown a positive correlation between alcohol abuse and sudden cardiac death ( 43,44,48,49 and 50). Electrocardiographic and electrophysiologic changes that have been observed during acute alcohol intoxication include P-R, QRS, and Q-T prolongation, varying degrees of heart block including third degree, bundle branch blocks, and prolonged H-V intervals ( 43,44,47). It is not possible to make any generalization, however, because the effects of chronic alcoholism, electrolyte and nutritional abnormalities, and underlying heart disease are difficult to discriminate. Chronic Effects of Alcohol on the Heart Chronic alcohol consumption may lead to progressive cardiac dysfunction and eventual development of congestive heart failure with all its complications. Studies in which the various effects of the metabolic, nutritional, and lifestyle problems to which alcoholics are prone have been controlled and have demonstrated clearly that alcohol consumption itself can cause progressive myocardial damage leading ultimately to dilated cardiomyopathy ( 43,44). It has been suggested that alcohol abuse is a contributing factor in as many as 50% of patients with congestive cardiomyopathy ( 51). Alcoholic cardiomyopathy is impossible to distinguish clinically from dilated cardiomyopathy of any other cause; it is diagnosed in a patient with dilated cardiomyopathy because of a history of alcohol abuse and the exclusion of other possible etiologic factors. It is typically seen in men aged 30 to 55 years with alcohol consumption comprising 30 to 50% of daily calories over a 10- to 15-year period ( 44). Onset is usually insidious, with progressive symptoms of dyspnea, fatigue, and palpitations. Overt CHF with orthopnea, paroxysmal nocturnal dyspnea, peripheral and pulmonary edema, and ascites often follows. The treatment of alcoholic cardiomyopathy is essentially the same as the treatment of dilated cardiomyopathy of any cause. Additionally, however, abstinence from alcohol is vital because it may arrest or slow the disease. Many investigators have reported improved cardiac function after the cessation of alcohol consumption, a process that requires as long as a year ( 52,53,54 and 55). Attention to nutrition, thiamine, and other B vitamins is also important.

ALCOHOL-RELATED PULMONARY DISEASES AND INFECTIONS Alcoholics are prone to infections because of a lifestyle of neglect, poor nutrition, decreased serum bactericidal activity, impaired phagocytosis, decreased cell-mediated immunity, and abnormalities in migration and function of polymorphonuclear leukocytes. Although alcohol is known to be toxic to pulmonary mucosa and cilia, there is no compelling evidence that it causes any predictable effect on the lungs in most patients ( 56). In some patients of Asian or native American descent, in whom alcohol also causes facial flushing, alcohol consumption is associated with bronchoconstriction and wheezing ( 56). The mechanism for this is unclear, although some feel that an allergic response to ingredients in alcoholic beverages may be responsible. The major impact of ethanol on the respiratory system is through the loss of airway protective reflexes which acute alcohol intoxication causes, including impaired cough reflex, decreased lung clearance, increased intolerance of smoking, and recurrent aspirations (secondary to intoxications and seizures). Alcoholics have significantly higher incidences of pneumonia caused by various organisms, most notably Klebsiella and pneumococcus ( 56). Pneumonia in alcoholics tends to be more severe and has a poorer prognosis, probably because of associated nutritional factors. Persons acutely intoxicated by ethanol have periodic aspiration of oral flora, leading to aspiration pneumonias and pulmonary abscesses. Alcohol appeared to be the major cause of primary lung abscesses in several series ( 56,57 and 58). Tuberculosis is also significantly more common in alcoholics ( 59).

ACUTE ABDOMEN (SPONTANEOUS BACTERIAL PERITONITIS) Alcoholic patients have an increased incidence of spontaneous bacterial peritonitis, unassociated with perforation within the intestinal tract. Possibly, microscopic perforation occurs and, with decreased immunologic response, overgrowth occurs. The condition is more common in alcoholics with cirrhosis and ascites. Diagnostic paracentesis can confirm the diagnosis and enable culture. Fluid resuscitation and intravenous broad-spectrum antibiotic therapy (for aerobic and anaerobic organisms) is necessary until culture reports are returned. The possibility of a perforated viscus causing peritonitis must be evaluated. Gastric perforation, too, is increased in alcoholics.

FETAL ALCOHOL SYNDROME Although the fetal alcohol syndrome is not an emergency problem, the physician should caution all women of childbearing age on the possible effects of alcohol on a developing fetus. These include retardation, congenital abnormalities in appearance, and cardiac abnormalities. The ED can provide this information to patients who otherwise may not receive it.

MEDICOLEGAL PEARLS Never assume that a diminished level of consciousness is caused only by alcohol intoxication. Thorough evaluation of any patient with an altered level of consciousness is mandatory. All comatose patients should be administered 2 mg naloxone IV and 100 mg thiamine IV and either undergo a rapid bedside glucose strip test or be administered 25 g dextrose IV empirically. Indications for CT include evidence of trauma, focal neurologic findings, a discrepancy between measured blood alcohol concentration and clinical status, or lack of improvement in response to graded stimuli over time. In any patient withdrawing from alcohol, exclude trauma or medical catastrophe as the inciting event. Administer dilantin to patients in status epilepticus or with proven seizure foci. Guard against aspiration. Wernicke encephalopathy may be accompanied by the classic signs of oculomotor dysfunction, ataxia, and clouding of consciousness. Alternatively, coma, hypotension, or hypothermia may be the only presenting signs. Central pontine myelinolysis is associated with the rapid correction of hyponatremia. Serum sodium should be corrected slowly over days in the absence of life-threatening symptoms of hyponatremia. Any acute or subacute deterioration of function in the patient with chronic dementia may signal a new metabolic encephalopathy, infection, infarction, or subdural hematoma. These patients require thorough workup, including CT and LP. Acute alcoholic myopathy is underdiagnosed and causes death from acute renal tubular necrosis. Evidence of rhabdomyolysis should be sought in the binge drinker with muscle pain, the patient in withdrawal, and in the drinker “found down.” Alcohol use causes erosive gastritis, but no association with peptic ulcer disease has been shown. Gastrointestinal bleeding in alcoholics is common and may be immediately life threatening. Do not overlook treatable causes of dementia in the chronic alcoholic who is not acutely intoxicated. Pancreatitis can be lethal in an alcoholic. Hospital admission and intensive treatment are indicated in all but the mildest cases. Signs of an acute abdomen may signal spontaneous bacterial peritonitis, which requires rapid diagnosis and initiation of treatment. Seizure-prone patients should be observed. In prison, patients who have had seizures with aspiration have died, and lawsuits have resulted. References 1. 2. 3. 4. 5. 6.

Dillon ES, Dyer WW, Smelo LS: Ketone acidosis of nondiabetic adults. Med Clin North Am 1940;24:1813. Williams HE: Alcoholic hypoglycemia and ketoacidosis. Med Clin North Am 1984;68. Levy LJ, Duga J, Girgis M, Gordon EE: Ketoacidosis associated with alcoholism in nondiabetic subjects. Ann Intern Med 1973;78. Jenkins DW, Eckel RE, Craig JW: Alcoholic ketoacidosis. JAMA 1971;217. Lindberg MC, Oyler RA: Wernicke's encephalopathy. Am Fam Physician 1990;41. Watson AJ, Walker JF, Tomkin GH, et al: Acute Wernicke's encephalopathy precipitated by glucose loading. Ir J Med Sci 1981;150.

7. 8. 9. 10.

VanDyke HB, Ames RG: Alcohol diuresis. Acta Endocrinol 1951;7. Eisenhofer G, Johnson RH: Effect of ethanol ingestion on plasma vasopressin and water balance in humans. Am J Physiol 1982;242. Burcar PJ, Norenburg MD, Yarnell PR: Hyponatremia and central pontine myelinolysis. Neurology 1977;27. Flink EB: Magnesium deficiency in alcoholism. Alcohol Clin Exp Res 1986;10.

10A. Noth RH, Walter RM, Jr: The effects of alcohol on the endocrine system. Med Clin North Am 1984;68. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39.

Reuler JB, Girard DE, Cooney TG: Wernicke's encephalopathy. N Engl J Med 1985;312. Charness ME, Simon RP, Greenberg DA: Ethanol and the nervous system. N Engl J Med 1989;321. Nakada T, Knight RT: Alcohol and the central nervous system. Med Clin North Am 1984;68. Torvik A, Lindboe CF, Rogde S: Brain lesions in alcoholics: a neuropathological study with clinical correlations. J Neurol Sci 1982;56. Craviato H, Korein J, Silberman J: Wernicke's encephalopathy: a clinical and pathological study of 28 autopsied cases. Arch Neurol 1961;4. Harper C: The incidence of Wernicke's encephalopathy in Australia—a neuropathological study of 131 cases. J Neurol Neurosurg Psychol 1983;46:46. Mukherjee AB, Svoronos S, Ghazanfari A: Transketolase abnormality in cultured fibroblasts from familial chronic alcoholic men and their male offspring. J Clin Invest 1987;79. Roche SW, Lane RJ, Wade JP: Thalamic hemorrhages in Wernicke–Korsakoff syndrome demonstrated by computed tomography. Ann Neurol 1988;23. Letter. Ackerman WJ: Stupor, bradycardia, hypotension, and hypothermia—a presentation of Wernicke's encephalopathy with rapid response to thiamine. West J Med 1974;121. Cole M, Turner A, Frank O, et al: Extraocular palsy and thiamine therapy in Wernicke's encephalopathy. Am J Clin Nutr 1969;22. Traviesa DC: Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke–Korsakoff encephalopathy. J Neurol Neurosurg Psychol 1974;37. Sacks O: The lost mariner. In: The man who mistook his wife for a hat. New York: Harper Row, 1987. Kleinschmidt–DeMasters BK, Norenberg MD: Cerebellar degeneration in the rat following rapid correction of hyponatremia. Ann Neurol 1981;10. Kleinschmidt–DeMasters BK, Norenberg MD: Rapid correction of hyponatremia causes demyelination: relation to central pontine myelinolysis. Science 1981;211. Messert B, Orrison WW, Hawkins MI, et al: Central pontine myelinolysis. Neurology 1979;29. Brunner JE, Redmond JM, Haggar AM, et al: Central pontine myelinolysis and pontine lesions after rapid correction of hyponatremia: a prospective magnetic resonance imaging study. Ann Neurol 1990;27. Sterns RH: Severe symptomatic hyponatremia: treatment and outcome: a study of 64 cases. Ann Intern Med 1987;107. Laureno R, Karp BI: Pontine and extrapontine myelinolysis following rapid correction of hyponatremia. Lancet 1988, 1. Harper CG, Kril JJ, Holloway RL: Brain shrinkage in chronic alcoholics: a pathological study. Br Med J 1985;290. Carlen PL, Wilkinson DA, Wortzman G, Holgate R: Partially reversible cerebral atrophy and functional improvement in recently abstinent alcoholics, measured by MRI. Neuroradiology 1988;30. Wrenn KD, Slovis CM: Sorting through rhabdomyolysis: an enigma made manageable. Emerg Med Rep 1987;8. Gabow PA, Kaehny WD, Kelleher SP: The spectrum of rhabdomyloysis. Medicine 1982;61. Song SK, Rubin E: Ethanol produces muscle damage in human volunteers. Science 1972;175. Haller RG, Knochel JP: Skeletal muscle disorders in alcoholism. Med Clin North Am 1984;68. Hanid A, Slavin G, Mair W, et al: Fiber type changes in striated muscles of alcoholics. J Clin Pathol 1981;34. Pimstone NR, French SW: Alcoholic liver disease. Med Clin North Am 1984;68. Leevy CM: Fatty liver: a study of 270 patients with biopsy proven fatty liver and a review of the literature. Medicine 1962;41. Pequignot G, Tuyns AJ, Berta JL: Ascitic cirrhosis in relation to alcohol consumption. Int J Epidermiol 1978;7. Horwitz RI, Gottlieb LD, Kraus ML: The efficacy of atenolol in the outpatient management of the alcohol withdrawal syndrome. Arch Intern Med 1989;149:1089.

39A. Geokas MC: Ethanol and the pancreas. Med Clin North Am 1984;68. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59.

Peterson WL: Heliobacter pylori and peptic ulcer disease. N Engl J Med 1991;324:1043–1048. Eichner ER: The hematologic disorders of alcoholism. Am J Med 1973;54. Larkin EC, Watson–Williams EJ: Alcohol and the blood. Med Clin North Am 1984;68. Davidson DM: Cardiovascular effects of alcohol. West J Med 1989;151. Segel LD, Klausner SC, Gnadt JT, Amsterdam EA: Alcohol and the heart. Med Clin North Am 1984;68. Child JS, Kovick RB, Levisman JA, et al: Cardiac effects of acute ethanol ingestion unmasked by autonomic blockade. Circulation 1979;59. Ettinger PO, Wu CF, De la Cruz C, et al: Arrythmias and the ‘holiday heart': alcohol associated cardiac rhythm disorders. Am Heart J 1978;95. Buckingham TA, Kennedy HL, Goenjian AK, et al: Cardiac arrhythmias in a population admitted to an acute alcoholic detoxification center. Am Heart J 1985;110. Rosengren A, Wilhelmsen L: Separate and combined effects of smoking and alcohol abuse in middle aged men. Acta Med Scand 1988;223. Suhonen O, Aromaa A, Reunanen A: Alcohol consumption and sudden coronary death in middle-aged Finnish men. Acta Med Scand 1987;221. Gordon T, Kannel WB: Drinking habits and cardiovascular disease: the Framingham study. Am Heart J 1983;105. Brigden W, Robinson J: Alcoholic heart disease. Br Med J 1964;2. Schwartz L, Sample KA, Wigle DE: Severe alcoholic cardiomyopathy reversed with abstention from alcohol. Am J Cardiol 1975;36. Kupari M: Reversibility of alcoholic cardiomyopathy. Postgrad Med J 1984;60. Agatston AS, Snow ME, Samet P: Regression of severe alcoholic cardiomyopathy after abstinence of 10 weeks. Alcoholism 1986;10. Baudet M, Rigoud M, Rocha P, et al: Reversibility of alcoholic cardiomyopathy with abstention from alcohol. Cardiology 1979;64. Krumpe PE, Cumminskey JM, Lillington GA: Alcohol and the respiratory tract. Med Clin North Am 1984;68. Bernhard WF, Malcolm JA, and Wylie RH: Lung abscess: a study of 148 cases due to aspiration. Dis Chest 1974;43. Estrera AS, Platt MR, Mills LJ, et al: Primary lung abscess. J Thorac Cardiovasc Surg 1980;79. Smith FE, Palmer DL: Alcoholism, infection, and altered host defenses: a review of clinical and experimental observations. J Chron Dis 1976;29.

Suggested Readings Browning RG, Olson DW, Stueven HA, Mateer JR. 50% dextrose: antidote or toxin? Ann Emerg Med 1990;19. Brust JCM: Alcoholism. In Rowland LP, ed. Merrit's textbook of neurology. Williams & Wilkins: Baltimore; 1995;967–977. Carroll P, Maher VF: Legal issues in the care of neurologically impaired patients. Adv Clin Care 1989;4:10. Earnest MP, Feldman H, Marx JA, et al: Intracranial lesions shown by CT scans in 259 cases of first alcohol-related seizures. Neurology 1988;38:1561. Fink EB: Magnesium deficiency in alcoholism. Alcohol Clin Exp Res 1986;10:683. Fluckiger A, Hartmann D, Leishman B, Ziegler WH: Lack of effect of the benzodiazepine antagonist flumazenil (Ro 15-1788) on the performance of healthy subjects during experimentally induced ethanol intoxication. Eur J Clin Pharmacol 1988;34:273. Hatch RC, Jernigan AD: Effect of intravenously administered putatative and potential antagonists of ethanol on sleep time in ethanol-narcotized rats: Life Sci 1988;42:11. Lieber CS: Medical disorders of alcoholism. N Engl J Med 1995;333:1058. Meyer RE: Prospects for a rational pharmacotherapy of alcoholism. J Clin Psychiatry 1989;50:403. Minocha A, Herold DA, Barth JT, et al: Activated charcoal in oral ethanol absorption: lack of effect in humans. J Toxicol Clin Toxicol 1986;24:225–234. O'Connor PG, Schottenfeld RS: Medical progress. Patients with alcohol problems. N Engl J Med 1998;338:592–603. O'Sullivan GF, Wade DN: Flumazenil in the management of acute drug overdosage with benzodiazepines and other agents. Clin Pharmacol Ther 1987;42:254. Peterson WL: Heliobacter pylori and peptic ulcer disease. N Engl J Med 1991;324:104–1048. Prischl F, Donner A, Grimm G, et al: Value of flumazenil in benzodiazepine self-poisoning. Med Toxicol Adverse Drug Exp 1988;3:334. Turner RC, Lichstein PR, Peden, JG, et al: Alcohol withdrawal syndromes: a review of pathophysiology, clinical presentation, and treatment. J Gen Intern Med 1989;4:432. Young GP: The agitated patient in the emergency department. Emerg Med Clin North Am 1987;5:4.

CHAPTER 147 OCCUPATIONAL EXPOSURES AND ART HAZARDS Principles and Practice of Emergency Medicine

CHAPTER 147 OCCUPATIONAL EXPOSURES AND ART HAZARDS Steven H. Lesser and Steven J. Weiss Neurotoxins Respiratory Tract Irritants Ocular Hazards

Recent trends to combine occupational medicine with emergency medicine requires awareness of the toxic chemicals used in industry and the arts.

NEUROTOXINS Generalized neurotoxins include mercury, manganese, carbon disulfate, and organophosphate plasticizers ( Table 147.1). Plasticizers are substances used to improve the working properties of resins in fiberglass sculpture. Isolated peripheral neuropathies are produced by methylberyl ketone, aerosols, polyester resins, and lead. Central nervous system (CNS) problems are caused by organic solvent intoxication (e.g., toluene and xylol). Printmakers and silk screen printers volatilize these solvents as sprays, potentiating their toxicity. Neurotrauma from the use of hammers and chisels can cause vibration syndrome and carpal tunnel syndrome.

Table 147.1. Neurotoxin Sites

RESPIRATORY TRACT IRRITANTS Respiratory tract irritants affect different sites based on their particle size and solubility ( Table 147.2). Highly lipid-soluble dusts and fumes usually cause systemic injury, and minimally lipid-soluble substances usually produce local effects. Those substances that are more water-soluble remain in the upper tract and the skin, whereas the less water-soluble substances affect the lower respiratory tract. Among the direct irritants are nitrogen dioxide (welding gas, carbon arc, etching, and enameling), chromium gas (from etching acid), hydrogen chromide (heating, plastics, and polyvinyl chloride), caustic dusts (lime, dichromate, soda ash, and potassium), and antiskinning agents (eugenol and clove oil). Certain substances have been associated with specific respiratory diseases. Pneumoconiosis is caused by iron oxides, aluminum and barium, and sulfate. Pulmonary fibrosis is caused by silica, coal, talc, scrap stone, and asbestos. Asthma is exacerbated by wood and bone dust, fibers, reactive dyes, formaldehyde, turpentine, polyurethane, isocyanate, and freshly formed aluminum oxide (pot-room asthma). Hypersensitivity pneumonitis is caused by wood dusts and heavy metals. Anthracosis is caused by smoke elaborated when coke is combusted.

Table 147.2. Occupational Exposures

OCULAR HAZARDS The eyes are subjected to trauma and toxicity from almost all art procedures. Chips of flying materials used by sculptors and blacksmiths can penetrate the globe and even enter the cranial vault. Ultraviolet light and heat exposure can cause cataracts, retinal damage, and a superficial punctate keratopathy (welder's conjunctivitis). Cardiotoxins Cardiotoxic heavy metals may be contained in paints. Barium cobalt and many of the organic solvents (toluol, methyl chloroform, and methylene chloride) are direct cardiac toxins. Methylene chloride may induce myocardial infarction. Liver function impairment can result, as can renal impairment ( Table 147.3).

Table 147.3. Specific Sites

Severe dermatitis is caused by various compounds. The grinding of fiberglass-reinforced sculptures produces microscopic fibrous particles that can cause an intensely pruritic rash. Plaster and cement contain lime, which can produce severe dermatitis. Other causes of dermatitis include photographic developers, exotic woods, soaps, drying agents, and solvents. Numerous hematologic effects can be seen. Cyanosis is caused by hydroxylamine (a color developer), polyvinyl chloride, nitrates, cobalt, and other photography developing agents. Lead, cadmium, benzene, and naphthalene can cause hemolytic anemia. Other forms of hemaglobinopathic disease include carboxyhemoglobinemia, methemoglobinemia, sulfhemoglobinemia, and cyanohemoglobinemia. Teratogens and carcinogens include chromium, zinc, and arsenic ( Table 147.4). Chromium, a documented carcinogen, may be inhaled when mental sculptors grind through or weld scraps of chromium-plated steel (used in car manufacturing). Cadmium, a chronic renal toxin is also a carcinogen.

Table 147.4. Specific Sites

Metal Sculpture Metal sculpture is a constructive sculptural technique that includes foundry casting, metal fabrication, and blacksmithing. Metal Fabrication and Welding This is a type of constructive sculpture. Pieces of metal are joined together using techniques such as arc welding, metal inert gas (MIG) welding, oxyacetylene welding, or tungsten inert gas (TIG) welding. Steel is the most commonly used metal because it is economical and easy to use. After the materials are welded, surface preparations such as grinding, polishing, and finishing are performed. An arc welder uses a high-voltage electrical arc to produce heat that melts a metal rod, fusing two pieces of metal together. The metal rods are coated with a flux that, when combusted, stabilizes the weld. Fluxes used in the steel welding rods include cadmium, manganese, chromates, phosphorus, zinc, and hydrofluoric acid. The toxic fumes produced when the flux burns may cause upper and lower respiratory tract irritation, and metal fume fever ( Table 147.5).

Table 147.5. Metal Sculpture: Occupational Hazards

Oxyacetylene welding is the combustion of a mixture of oxygen and acetylene producing heat to melt metal rods without flux. Oxygen is stored in steel bottles at less than 2,000 pounds of pressure. If the oxygen tank is tipped over and the regulator is knocked off, the tank can become a missile that can penetrate walls. Acetylene is stored in steel bottles at 200 pounds of pressure. To prevent the acetylene from exploding under pressure, it is stabilized by an equilibrium reaction with acetone (contained in an inner ceramic core of the tank). If the acetylene in the tubes to the welding torch develops pressure greater than 35 psi, it can explode spontaneously. Oxyacetylene, MIG and arc welding processes all may produce airborne molten metal droplets ( Table 147.6). Welders seen in the emergency department (ED) often have innumerable holes in their clothing caused by these bits of metal or “bees.” If the clothing is penetrated, third-degree burns may be sustained from the bees trapped within the clothing.

Table 147.6. Metal Sculpture

The release of toxic flux fumes is avoided by the use of a MIG welder because this type of welding uses inert gases to create a stable environment for the arc and avoids the need for fluxes such as those coating the welding rods used in arc welding. A MIG welder supplies the welding material as a wire spool rather than a

flux-coated rod. MIG and arc welders emit ozone (O 3) because of the high-voltage arc that is produced. Ozone produced by welder has a pungent odor, is water soluble, and is primarily an upper respiratory tract irritant. Low-grade exposures to this strong irritant cause burning of the eyes and throat, nonproductive cough, substernal pain, and bronchial irritation. Symptoms of the more serious syndrome of acute ozonism are respiratory distress, dyspnea, cyanosis, and pulmonary edema. Chest radiograph may demonstrate increased interstitial markings. Other symptoms and laboratory findings include alteration of visual responses, increased red blood cell fragility, an increase in glucose–phosphate dehydrogenase and lactic dehydrogenase, and a decrease in red blood cell acetylcholinesterase. Symptoms usually resolve in 1 or 2 weeks, although there may be long-lasting, persistent headache, fatigue, and dyspnea. All of the welding processes emit ultraviolet radiation from the arc heated. The best welding process for stainless steel and nonferrous metals is TIG welding. In addition to producing flux fumes and ozone, as do arc and MIG welding processes, TIG produces the most intense ultraviolet radiation. The light may produce firstand second-degree burns on unprotected areas of the artist's skin and a punctate keratopathy on the cornea known as welder's burn. Because the torch (approximate temperature, 6300°F) produces intense visible, ultraviolet, and infrared light TIG welding is the most likely process to cause damage to the retina. Welding masks come in dark shades of green glass to protect the eyes from the intense ultraviolet invisible light produced by welding. Artists must know which of the shades (3 through 12) is appropriate for a particular kind of work. Different eye colors and welding processes require different shades. Surface preparation is the next stage in metal fabrication. After metals are welded they are ground, polished, and finished. Grinding is done with 3- to 4-horsepower handheld grinders, weighing 20 to 30 pounds each, with abrasive wheels spinning as high as 9000 rpm. Fiberglass and polymer resin are combined as a matrix for support of the abrasive silicon dioxide and carborundum in the grinding wheels. The sculpture is polished using a wire wheel composed of hundreds of stiff wires formed into a cup or disk, also rotating as speeds as high as 9000 rpm. Finishing includes surface preparation with acids and cleansers or anodizing (electromagnetic pigment binding), galvanizing (electromagnetically binding a layer of zinc to the surface), or painting with a variety of paints, polymers, or resins. The grinding and polishing wheels can fatigue and shatter, producing shrapnel that flies at speeds sufficient to go through clothes, skin, and eyes. As grinding wheels wear down, they produce fiberglass and resin dusts that are respiratory irritants. Although masks will protect an artist from chips and dust produced by the wire wheels, they will not always protect the artist from a wire thrown from a polishing wheel spinning enough to propel an unfortunately directed wire around or through the mask to become an intraocular foreign body. Blacksmithing This is another form of metal sculpture. Iron heated in a forge is given form by being struck by a hammer on an anvil. The forge generates heat by using a forced stream of air to maintain the combustion of coke. The hammer and anvil both are made of hot iron that is frozen into shape (forged). This process creates brittle tools that, when struck together, may shatter and produce shrapnel-like shards of iron. Blacksmiths are exposed to fumes from the forge that contain carbon monoxide, carbon dioxide, various cyanogenic compounds, and lead ( Table 147.7). Burns and respiratory irritation (chronic or acute) are sources of morbidity to blacksmithing artists.

Table 147.7. Blacksmithing

FOUNDRY CASTING This is the art of producing constructive sculpture with cast iron, bronze, and brass. The process of cast sculpture begins with melting scraps of metal. Iron requires the highest temperature and is melted between layers of coke, a specially prepared form of coal, in a large pot called a cupola. To produce the heat necessary to burn the coke and melt the iron, the cupola gas-fired and fanned by an electric blower. After the iron melts, a clay plug on the bottom of the cupola is removed, allowing the liquid iron to pour into the crucible, a ceramic pot made to withstand temperatures of 5000°F. Molten iron from the crucible is poured into molds. Molds are either hollow or they have a combustible solid core that is destroyed by the molten metal. When cool, the mold is fractured with hammers and pried from the metal. The surface of the newly created sculpture is cleaned or “chased” using grinders, chisels, and files. The sculpture is then treated with chemicals to form a patina, the coloration on the surface producing the characteristic aged look of the sculpture. Among the specific hazards of cast-iron sculpture are those associated with the lack of appropriate protective equipment, the metal itself, and impurities in the materials. Additionally, the physical fatigue associated with working in high ambient temperatures with heavy materials in often primitive foundries increases the likelihood of accidents ( Table 147.8). Artists wear face shields constructed from metal window screens to prevent droplets of splashed molten iron from hitting their faces. Ideally, Kevlar gloves, aprons, and foot covers are worn to protect the torso and extremities from the intense radiant heat. This equipment is expensive and is not always used, so that the risk for serious burns exists. Respirators intended to protect the airways from contaminants, such as the sooty black smoke diffused by the blowers, are only effective if the correct cartridges specific for dust, fumes, or solvents are used. The metal itself is extremely dangerous. If there is any fatigue in the crucible or the mold, or if either is dropped, it will fracture and release molten iron hot enough to shatter concrete floors, producing shards of concrete shrapnel. Contact of the hot metal with oxyacetylene tanks near an accidental spill can cause the tanks to explode, producing metal shrapnel. Protective equipment that is designed for radiant heat reflection is minimally effective against flying debris. There are impurities in both hollow and solid core molds. Hollow molds may contain residual impurities (i.e., lime dust and soda ash) that are released into the atmosphere when the hot metal is poured. Solid core molds contain wax, plastics (such as Styrofoam), or other organic materials that release toxic fumes when they are burnt out (the term used for the destruction of the core material by the molten metal). Burnt out Styrofoam, for example, produces cyanide gas. Other respiratory toxins include ammonia, benzene, carbon monoxide, hydrogen sulfide, and sulfur oxide.

Table 147.8. Metal Sculpture: Occupational Hazards

Unlike iron casting, brass and bronze casting does not require a cupola because of lower freezing points (2000°F to 3000°F). At these temperatures, gas heat is required but coke is not. Lead, copper, or glass may be added to the brass or bronze as a flux to make it more workable and less brittle. Fumes produced in this

process may cause metal fume fever or plumbism (lead poisoning), which would not necessarily occur in cast-iron foundries ( Table 147.9). Metal fume fever is also known as foundry auge, zinc shakes, Monday morning fever, welder's fever, and solderer's fever. It is called Monday morning fever because workers develop a tolerance to the effects of the fumes during repeated exposures. They lose their tolerance over the weekend and get sick on Monday night after a full day back at work. The manifestation is as a flulike illness with a 4- to 6-hour onset of symptoms, generally appearing the evening after exposure to noxious fumes. The patient has fever, chills, fatigue, myalgia, cough, dyspnea, thirst, a metallic taste in the mouth, salivation, rhinitis, and conjunctivitis. The chest radiograph may show nondescript increased interstitial markings, and there may be nonspecific leukocytosis. Resolution occurs within 36 hours of cessation of exposure. The substances associated with metal fume fever are copper, magnesium, aluminum, antimony, iron, manganese, nickel, and zinc ( Table 147.10).

Table 147.9. Metal Sculpture

Table 147.10. Metal Sculpture

STONECARVING This type of subtractive sculpture is formed by chipping, slicing, grinding, and polishing. Two major problems encountered by stone sculptors are dust inhalation and vibration-induced peripheral neuropathy. Dust exposure occurs each time a sculptor strikes a stone with a chisel, grinder, or polishing device. White marble is relatively pure calcium carbonate: however, common stones such as field stone may contain harmful or irritating minerals, including asbestos. Exposure to dust can cause or exacerbate sinus, bronchus, and small airway diseases. Stone dust-related pneumoconiosis (including silicosis and silicotuberculosis) based on characteristic gross pathologic changes has been noted in the lungs of stoneworking artisans for centuries. Vibration syndrome is a neuropathy in the hands after prolonged exposure to vibration. Vibration-induced peripheral neuropathy is produced by pneumatic or electromotive hammers or grinders frequently used to form the stone. Stonecutters may have bilateral parasthesias in their upper extremities. Occupational stone cutters in Italy, who worked with pneumatic tools throughout their lifetimes, eventually had edematous claw-like hands. Foam may be placed around the tools or specialized gloves may be worn to decrease vibrational exposure. WOODCARVING Respiratory and dermatologic irritants result from wood associated with wood sculpture. The dusts produced by sanding can cause bronchial irritation (exacerbating asthma), hypersensitivity pneumonitis, or pneumoconiosis. Certain exotic woods (e.g., western red cedar) contain caustic oils that may cause contact dermatitis and are particularly irritating to the respiratory tract. Exposure to glues (including epoxies) and solvents (e.g., toluene) can potentiate the irritative respiratory effects of wood dusts. Rhus sensitivity (poison ivy, poison oak) has been described as cross-sensitizing some persons to the dermatologic effects of substances in exotic trees and their derivatives (lacquers, varnishes, and oils). FIBERGLASS Reinforced fiberglass is used to form hollow sculptures. The production of fiberglass sculptures requires a fiberglass fiber mesh or fibers, a liquid resin, and a catalyst. The fiberglass fiber is used to reinforce the resin. The liquid synthetic resin is poured, sprayed, or painted onto the reinforcing fiberglass mesh or fibers. The catalyst used to harden the liquid resin is a concentrated peroxide. The hardened resin, reinforced by the fibers, becomes a strong structural material. Silica gel, a finely divided silica dust, is sometimes added to the liquid resin as additional reinforcement. The elements are occasionally combined using a chop gun, a pneumatic device that chops long ribbons of fiberglass into small slivers. The chop gun combines the fiberglass silvers with a resin catalyst and sprays them on the surface of a mold to build up the reinforced fiberglass mass. When finished, reinforced fiberglass is ground or sanded to produce the final product. Fibers from the mat can produce a localized pruritic dermatitis caused by fibrils entering the skin. The resin contains organic solvents that are irritating to the skin and mucous membranes and that are hepatotoxic and neurotoxic. The catalyst can be intensely irritating to the skin. During sanding or grinding, fragments are released into the air. These fragments can cause pruritic dermatitis or pneumoconiosis. The aerosolized solvents, fibers, resins, and catalysts are respiratory irritants. Pneumatic chop guns are notorious for producing particularly large amounts of noxious fumes. Printmaking Printmaking processes have in common the application of liquid or semiliquid pigment-bearding media to a prepared surface, which is then transferred to paper in a pressing device. ETCHING (INTAGLIO) This very old form of printmaking uses the surfaces of either copper, aluminum, or zinc plates, which are etched by exposure to inorganic acids. Ink—a complex medium consisting of pigment, oil, and modifiers in an organic solvent—is applied to the plates and then rubbed into the recesses formed in the etching process. The excess ink is removed, and the prepared plate is passed through a printing press where the image is produced by transferring the remaining ink to paper. The intaglio press is a machine consisting of a roller and a flat bed. The paper is run between the roller and the bed at enormous pressures, typically 24,000 pounds per linear foot. Excess ink is cleaned from the plate with organic solvents. Because these machines frequently lack guards, fingers may be entrapped between the roller and the press bed. ENGRAVING

Engraving involves direct mechanical incision of the metal plate face. The incisions hold ink and are printed as are etchings. LITHOGRAPHY This is a related process using a fine-grained limestone instead of metal plates. The first step in lithography is applying the image to the surface of a clean flat limestone using an oily crayon called tuche, which produces hydrophobic areas. A negative image is then bitten into the stone using organic acids that dissolve a tiny layer of the stone face not protected by the tuche. Finally, ink, a hydrophobic oily substance, is applied to the face of the stone, adhering specifically to the areas that were covered with tuche and now are slightly raised. The ink is rolled on, and the image is transferred to paper by scraping the back surface of the paper with a bar. The lithography press is mechanically related to the intaglio press and has similar hazards. PHOTOETCHING In this process, a copper or a zinc plate is coated with light-sensitive emulsion, and a photographic transparency is placed on top of it. The plate is exposed with a carbon arc lamp, a source of intense ultraviolet light, which hardens the areas exposed to the ultraviolet light as it passes through the transparency. These hardened areas create an acid resistance. The plate is bitten with acid after an organic solvent (e.g., toluene) is used to remove the nonhardened sections. Prolonged contact with toluene (similar to sniffing glue) causes dermatitis, sinusitis, hepatitis, and other kinds of damage. The lamp emissions can cause retinal and corneal damage. Printmakers of all types may be exposed to organic solvents, inorganic etching acids, or alkali. These agents are chiefly upper respiratory and mucous membrane irritants as acids release water and heat on contact with mucous membranes. The printing inks, in addition to containing pigment and oil, are complex mixtures of stabilizers, surface agents, various organic solvents, antiskinning agents, reducers, thinners, tack reducers, stiffeners, and dryers. As an example, eugenol, an ingredient of the antiskinning agent, is a strong upper respiratory and dermatologic irritant. Some of the dryers contain lead or magnesium. Central nervous system toxicity caused by organic solvent exposure is important in lithography and photoengraving, particularly when the solvents are volatilized in sprays. Toxicity may not be suspected until the physician determines the composition of the ink. Olfactory fatigue or nonrecognition of toxic fumes may limit the artist's awareness of toxic exposure. Painting The cutaneous exposures of painters to their paints dates back to the Cro-Magnon man, as evidenced by the handprints found on the walls of the cave of Lascaux in France. Modern painters may be exposed to heavy metal pigments if mixing their own paints. There is a long list of toxic exposures associated with painting, most of which are from the solvents and the pigment agents that constitute the paints. The powdered pigments are added to an organic medium, such a linseed oil, to make paint, then thinned with solvents, such as acetone, benzene, turpentine, methanol, or methylene chloride. Acrylic paints are water based instead of oil based, but they have similar pigments and release ammonia fumes as they dry. Mucous membrane absorption can occur from pointing the brush (the process of sharpening the tip of a paintbrush by placing it between the pursed lips of the painter) or from other fomites such as food or cups used in the studio. HEAVY METALS Used as coloring agents in paints, heavy metals have a wide range of site-specific toxicities. These include metals used to produce white (barium, magnesium, titanium, and lead), ultramarine blue (cobalt), blue, purple, and green (manganese), and red and yellow (zinc and cadmium). Barium and cobalt, for example, are direct cardiac toxins, which can result in a cardiomyopathy. Other specific sites of disease caused by pigments and solvents include the renal bed, the central nervous system, and the reproductive system. Cadmium, the coloring agent in some vivid yellow, red, and orange paints, provides a typical example of pigment-related heavy metal poisoning. The clinical problems associated with exposure illustrate the complexity of the disease processes encountered with the heavy metals. Normally, in the nonexposed person, the total life body burden of cadmium is 30 ng. The elimination half-life of the element is between 16 and 33 years. Distinct acute and chronic exposure syndromes exist for cadmium toxicity. Acute exposure is rare, but massive ingestions have been described in industrial settings and are associated with a 15% mortality rate. Symptoms can be respiratory, dermatologic, or gastrointestinal. In small quantities, inhalation exposures are more toxic than ingestions. Acute respiratory exposure begins with a metal-fume feverlike flu syndrome additionally characterized by a decreased sense of smell, edema of the face and larynx, discoloration of the teeth (yellow rings), cough, and dyspnea developing 12 hours after the exposure. Acute ingestion was described in a painter who had severe stomatitis. Acute massive ingestions are described with acute pulmonary edema developing in 1 to 4 days and persisting for months. Systems involved in chronic cases include the following: respiratory (bronchitis, emphysema, pneumonitis), gastrointestinal (nausea, vomiting, diarrhea); genitourinary (decreased spermatid and spermatocyte counts, testicular necrosis, calciuria resulting in renal stone formation, b 2-microglobulin proteinuria); hematologic (hypochromic anemia); musculoskeletal (osteoporosis associated with calcium loss); and neurologic (vertigo, headache, shivering). Acute ingestion causes an increased risk for lung and prostate cancer. “Itai itai” (“ouch ouch”) disease has been described in middle-aged Japanese women with low calcium intake who are exposed to cadmium. Lumbar pain, lower extremity myalgias, and osteomalacia develop. Treatment, as with any other metal exposure, is cessation of contact and chelation therapy. The most important component of management is the high index of suspicion that leads to the diagnosis. Manganism Manganism is a disease that has respiratory, hepatic, psychiatric, and neurologic symptoms. The most prominent manifestations are psychiatric and neurologic. “Locura mangania” or “manganese madness” is an insidious onset of psychiatric symptoms, among them apathy, insomnia, confusion, bizarre behavior, visual hallucinations, emotional lability, decreased libido, and anxiety. Neurologic manifestations include nystagmus, disequilibrium, paresthesia, memory impairment, a vocal pattern described as “whispering speech,” problems with fine motor movement, lumbosacral pain, impotence, urgency, and incontinence. The neurologic syndrome is similar to that of Parkinson disease—tremor, ataxia, loss of memory, flat affect, muscle rigidity, and gait disturbances. Unlike Parkinson, however, pathologic lesions are found in the globus pallidus and the striatum rather than the globus pallidus and the substantia nigra. The most common respiratory symptom is dyspnea. Because of its low solubility in water, airborne manganese does not cause oral or dermal problems. Instead, it penetrates the lower respiratory tract and leads to manifestations of bronchitis, pneumonitis, and pneumonia. This pattern is characteristic of low-solubility airborne toxins in general. Pathologic hepatic changes (increased Golgi bodies and dilated biliary canaliculi), but rarely clinical hepatitis, develop in patients with manganism. The diagnosis of manganism relies heavily on the history and physical examination. Urine and serum manganese levels, assays of head hairs, or better slower-growing chest hairs, and elevated serum calcium levels can suggest the diagnosis. Standard heavy metal screens only detect mercury, arsenic, bismuth, and antimony. If the physician suspects another heavy metal a specific assay must be specifically requested. Response to calcium edetic acid (EDTA) chelation therapy helps to confirm the diagnosis. Treatment is withdrawal from exposure, which is the treatment for most nonsevere heavy metal exposures. There is a good response to L-dopa in doses of 3.5 g daily and, interestingly, these patients can tolerate greater doses of L-dopa than can unaffected patients. The antiparkinsonian drug trihexyphenidyl (Artane; Lederle Laboratories, American Cyanamid Co., Pearl River, NY) may ameliorate the psychiatric manifestations but does not improve neurologic symptoms. The differential diagnosis for locura manganica includes Wilson disease, Parkinson disease, myxedema, psychiatric disease, and other heavy metal exposures. Photography Industrial and amateur photographers use three sequential chemical baths to produce prints: a developer, a stop bath, and a fixer. Photography developing agents are the most toxic chemicals used in the process, especially after accidental ingestion. Nervous system (tinnitus, headache, vertigo, diploplia, weakness), respiratory (asthma), gastrointestinal (nausea, vomiting, splenic and liver disease), and dermatologic symptoms (allergic reactions) are encountered secondary to these complex hydrocarbons. Stop baths are usually weak solutions of acetic acid, and fixing baths contain sodium thiosulfate, acetic acid, and preservatives, none of which produce

serious disease from short-term, small-dose contact. Unlike industrial and amateur photography, fine arts photography encompasses a wider range of printmaking processes and uses exotic pigmenting and developing systems with unique hazards. A good example of this is salt printing, a primitive process adopted by civil war photographers (e.g., Matthew Brady) using salt and silver nitrate to produce a yellowish image. The photograph is then given a rich brown hue by the addition of potassium bichromate. Today, many photographers continue to use the subtle gradations of tone that can be achieved by this process. Bichromate, a powder that must be mixed with water, causes severe upper respiratory diseases, including nasal septa perforations, allergies, and annoying skin irritation. Glassworking Glassworking includes hot glass (blown and casted), neon art (manipulation of glass tubes evacuated and filled with neon), and stained glass (cutting and joining of pigmented glass). Hot glass art is produced from bags of pure silica in a fine powdered form known as batch. Gas fire tanks are charged (filled) with batch, which is heated until it is molten. Minerals may be added to the hot glass as colorants. The white-hot glass has a honey-like consistency. It is removed from the tank either on the end of a blowpipe (to be blown) or with a steel ladle (to be poured into a mold). After the glass is formed by either technique, it is placed in an annealing oven to cool slowly, which relieves internal stresses in the hardening glass so that it doesn't crack. Diseases related to heat exposure, silica, and the minerals used as colorants can develop in hot glass sculptors. Prolonged thermal exposure of the lenses of the eyes can result in cataracts. The potential for physical trauma from hot materials, the hot working environment, and the stress of working the glass quickly before it cools is high. Pieces of hot glass that are rejected are not placed in an annealing oven and may shatter spontaneously as they cool in the working environment. Silica exposure occurs during the charging process or from the production of silica dust when the cooled glass is cut or ground. Cobalt, a mineral used as a coloring agent in glass, causes cardiac disease. Neon art is a form of glassworking that begins with the manipulation of a glass tube to a desired shape or form. The hot tubes are washed by introducing a small amount of liquid mercury into the tube and then running current through it to burn out the particulate contaminants. The warm glass tube is sealed by heating one end and applying oral suction on a rubber tube connected to the other end of the glass tube, causing the soft, treated glass walls to collapse into a point. The tube is completely evacuated using a vacuum pump and is filled from flasks containing noble gases (helium, neon, argon, and krypton). The contents finally are purged of impurities by the application of 24,000 volts across the tube. Toxicity can be caused by the inhalation of mercury vapors or electrical arc-produced ozone, thermal trauma can be caused by hot glass, and electrical injuries can be caused by high-voltage transformers. Elemental mercury, although poorly absorbed through the gastrointestinal tract, may become volatilized when passed over hot glass and subsequently may be inhaled. Symptoms of mercury poisoning (erethism) include the insidious onset of behavioral changes (the “mad hatters” of England), anorexia, peripheral neuritis, tremor known as “hatter's shakes,” weakness, and renal impairment. The arc associated with tremendous voltages may cause ozone release leading to ozonism (as discussed previously in relation to welding). Stained glass is produced by cutting pieces of colored glass and joining them with lead strips called caming. Ingestion of the lead from fomites leads to plumbism (saturnine gout). Ceramics Ceramic art is produced by forming and baking (bisque-firing) selected clays into sculptures and pottery. Pigment agents are applied to the surface to produce textures and colors (glazes), then the ceramic is fired again at higher temperatures to fuse the glazes to the clay. Exposures are from the glazes and sulfur dioxide produced in firing. Although lead is no longer used in pottery glazes in the United States, pottery in developing countries still commonly contains lead glazes. Oral absorption can occur when drinking or eating acidic foods (e.g., grapefruit juice), which solubilize the lead from the glaze. Heavy metals used in glazes in the United States include arsenic, antimony, and cadmium. Sulfur dioxide, emitted during the initial firing of clay, can produce pulmonary disease and may act synergistically with particulate matter. Children and Art Supplies Children are particularly at risk for the effects of toxic exposure. They have a faster metabolic rate, higher surface area, developing brain and nervous system, and faster intestinal absorption, and (particularly in those younger than 5 years) they tend to put solid objects and fingers in their mouths. “Nontoxic” on children's products refers to a definition in the Federal Hazardous Substance Act that only relates to immediate toxicity, not long-term poisoning. The Crayon, Watercolor and Craft Institute puts a CP or an AP on the product, meaning “certified product” or “approved product.” These are tested by toxicologists for immediate toxicity but not for long-term toxicity. There is a common misconception that all water-soluble children's products are safe. This is not true because they contain preservatives. For example, water-soluble paints may be preserved with ammonia or formaldehyde. Fluorescent paints are toxic. Felt-tip markers have aromatic hydrocarbons. Modeling clay may contain toxic preservatives. Papier mache is just flour and water, but if fresh newspaper is used, the color-illustrated sections may have toxic materials in the inks. There are several types of glue. Water-based glues have polyvinyl acetate emulsions. Many organic glues have solvents. Super glues have cyanoacrylate, which can cause adhesions of the conjunctiva to the cornea if it gets in the eyes. Governmental Protection Most artist's work in private studios not covered by occupational laws governing toxic exposure. The risk for disease is variable and relates to each artist's awareness of the toxicity of their materials and the level of avoidance that they are aware of or can afford. The National Institute of Occupational Safety and Health, a research arm of the Occupational Safety and Health Administration and a branch of the Department of Health, makes recommendations for industrial hygiene and product usage. The Consumer Product Safety Agency requires labeling but cannot regulate how a product is used. It only intervenes if “there is a reasonable risk of injury,” such as in 1978 when it banned benzene in paint remover because it was linked to leukemia. The Toxic Substance Control Act of 1976 allows the Environmental Protection Agency to test products before they are released rather than waiting for illnesses to manifest themselves. The Federal Hazardous Substances Act requires safe and adequate labels. The rules do not apply if the product is repackaged. For example, the label on a 55-gallon drum of bulk-reactive dye would read, “Dust may cause allergic respiratory reactions. Avoid breathing dust. Keep container closed. Use forced ventilation. Use respirators or dust masks approved by the Bureau of Mines.” The same item sold in a jar, however, may read, “ecologically safe.” Glazes often are labeled poorly, or toxic ingredients may be trade secrets and not included on the list of ingredients. Arts, Crafts and Theater Safety, an organization established to act as a national clearinghouse provides information, education, and a newsletter to interested parties (1-212-777-0062). Suggested Readings Armstrong DG, Kazantzis G: The mortality of cadmium workers. Lancet 1983;1:1425–1427. Barach AL: Treatment of sulfur dioxide poisoning. JAMA 1971;215:485.

Brooks SM: The evaluation of occupational airways disease in the laboratory and workplace. J Allergy Clin Immunol 1982;70:56–66. Chandra SV, Shukla GS, Srvastava RS, et al: An exploratory study of manganese exposure to welders. Clin Toxicol 1981;18:407–416. Cook DG, Fahn S, Brait KA: Chronic manganese intoxication. Arch Neurol 1974;30:59–64. Davies TAL: Manganese pneumonitis. Br J Ind Med 1946;3:111–135. De Silva PE, Donnan MB: Chronic cadmium poisoning in a pigment manufacturing plant. Br J Ind Med 1981;38:76–86. Driscoll RJ, Mulligan WJ, Schultz D, et al: Malignant mesothelioma: a cluster in a native American pueblo. N Engl J Med 1988;318:1437–1438. Dula D: Metal fume fever. J Am Coll Emerg Physicians 1978;7:448–450. Elinder CG, Edling C, Lindberg E, et al: B2-microglobulinemia among workers previously exposed to cadmium: Follow-up and dose response analyses. Am J Ind Med 1985;8:553–564. Ellenhorn MJ, Barceloux DG: Medical toxicology—diagnosis and treatment of human poisoning. New York: Elsevier, 1988. Elofsson SA, Gamberale F, Hindmarsh T, et al: Exposure to organic solvents: A cross-sectional epidemiologic investigation on occupationally exposed and industrial spray painters with special reference to the nervous system. Scand J Work Environ Health 1980;6:239–273. Emmerson BT: ‘Ouch-ouch' disease: the osteomalacia of cadmium nephropathy. Ann Intern Med 1970;844–854. Fischbein A, Wallace J, Sassa S, et al: Lead poisoning from art restoration and pottery work: unusual exposure source and household risk. J Environ Pathol Toxicol Oncol 1992;11:7–11. Fisher AA: ‘Blackjack diseases' and other chromate puzzles. Cutis 1976;18:21–36. Hanninen H, Eskelinen L, Husman K, et al: Behavioral effects of long term exposure to a mixture of organic solvents. Scand J Work Environ Health 1976;2:240–255. Hine CH, Pasi A: Manganese intoxication. West J Med 1975;123:101–107. Jaffe KM, Shurtleff DB, Robertson WO: Survival after acute mercury vapor poisoning: role of supportive care. Am J Dis Child 1983;137:749–751. Hallee TJ: Diffuse lung disease caused by inhalation of mercury vapors. Am Rev Resp Dis 1969;99:430–436. Joselow MM, Louria DB, Browder AA: Mercuralism: environmental and occupational aspects. Ann Intern Med 1972;76:119–130. Kennedy A, Dornan JD, King R: Fatal myocardial disease associated with industrial exposure to cobalt. Lancet 1981;1:412–414. Lahaye D, Demedts M, Vanden Oever R, et al: Lung diseases among diamond polishers due to cobalt? Lancet 1981;1:156–157. Landrigan PJ: Occupational and community exposures to toxic metals: lead, cadmium, mercury and arsenic. West J Med 1982;137:531–539. Langard S, Vigander T: Occurrence of lung cancer in workers producing chromium pigments. Br J Ind Med 1983;40:71–74. Lesser S, Weiss S: Art hazards. Am J Emerg Med 1995;13:4, 451–458. Lindstrom K: Psychological performances of workers exposed to various solvents. Work Environ Health 1973;10:151–155. Lucas PA, Jariwalla AG, Jones JH, et al: Fatal cadmium fume inhalation. Lancet 1980;2:205. Maizlish NA, Langolf GD, Whitehead LW, et al: Behavioral evaluation of workers exposed to mixtures of organic solvents. Br J Ind Med 1985;42:579–590. McCann MF: Artist beware. New York: Lyons and Burford Publishers, 1992. Mueller EJ, Seger DC: Metal fume fever: a review. J Emerg Med 1985;2:271–274. Nasr ANH: Ozone poisoning in man: clinical manifestations and differential diagnosis: a review. Clin Toxicol 1971;4:461–466. Roberts CJC, Marshall FPF: Recovery after ‘lethal' quantity of paint remover. Br Med J 1976;1:20–21. Roels H, Djubgang J, Buchet JP, et al: Evolution of cadmium-induced renal dysfunction in workers removed from exposure. Scand J Work Health Environ 1982;8:191–200. Speight FY, Campbell HC: Fumes and gases in the welding environment. Miami: American Welding Society, 1979. Stewart RD, Hake CC: Paint remover hazard. JAMA 1976;235:398–401. Waldren HA: Did the mad hatter have mercury poisoning? Br Med J 1983;287:1961. Walsh EN: Chromate hazards in industry. JAMA 1953;153:1305–1308.

CHAPTER 148 FOOD POISONING Principles and Practice of Emergency Medicine

CHAPTER 148 FOOD POISONING George R. Schwartz Capsule Part 1: Food Poisoning Caused by Botulism Part 2: Food Poisoning Caused by Microorganisms

CAPSULE Food poisoning may be caused by bacterial toxins that are ingested preformed or are elaborated in the intestine by bacteria contaminating the particular food. For example, the ingestion of food (such as salads, ham and other cold meat products, and cream-filled desserts) contaminated with enterotoxin is responsible for staphylococcal food poisoning. Botulism, staphylococcal food poisoning, cholera ( Vibrio cholerae), and food poisoning from Clostridium perfringens and Bacillus cereus are considered true intoxications, because clinical illness is produced in each case by a toxin. Food poisoning also may be caused by a direct infection or “invasion” of the intestine by bacteria, as classically occurs in salmonella food poisoning after the ingestion of contaminated food—particularly poultry, dairy products, and egg products. Other causes of food poisoning by direct bacterial infection include shigellosis (bacillary dysentery), Campylobacter fetus (enteritis), Streptococcus faecalis, and Yersinia enterocolitica. Escherichia coli produces gastroenteritis both by elaboration of an enterotoxin, as the cause of E. coli “traveler's diarrhea,” and by direct bacterial invasion. In addition in certain bacterial infections, it is unclear whether the acute gastrointestinal symptoms are caused by toxin or by direct infection, such as with Vibrio parahemolyticus. Food poisoning may be caused by viruses (an example is rotavirus in children) and protozoa, such as Entamoeba histolytica, the etiologic agent in amebiasis, and Giardia lamblia. Food poisoning produced by marine organisms, plants, and mushrooms is discussed later in this chapter. Food poisoning may be caused by toxic contaminants (polychlorinated biphenyls, aluminum, heavy metals, radioactivity) or from natural toxic substances (e.g., akee fruit).

PART 1: FOOD POISONING CAUSED BY BOTULISM Botulism is caused by the toxin elaborated by the spore-forming anaerobic bacillus Clostridium botulinum. The toxin generally is conceded to be the most poisonous substance yet discovered. As an example of its toxicity, as few as 950 molecules of toxin can be lethal for white mice, and the amount that can cause human death has been estimated to be between 0.1 and 1 mg. The toxins are good antigens, but natural immunity in humans rarely occurs because the lethal dose is less than that needed to elicit antibody production. Botulism is a rare disease, and outbreaks must be reported to the Centers for Disease Control (CDC) in Atlanta, Georgia. From 1899 to 1977, 766 outbreaks involving 1961 persons were reported in the United States. There were 99 deaths. The Canadian experience from 1919 through 1973 was reported by Dolman (1). He found 62 authenticated outbreaks involving 181 persons, with 83 deaths. The incidence of fatality has been reduced substantially over the past two decades from greater than 60% to less than 20%. This reduction is primarily because of the better respiratory care of victims, although it is possible that milder cases are being recognized. Prompt administration of antitoxin is probably also a factor. There is good reason to suspect that botulism is more common than generally realized and that it is underdiagnosed. For example, between 1976 and 1995 there were 1418 infant botulism cases reported after the first report in 1976 (1A). The diagnosis is difficult to make, particularly in isolated cases. One analysis of eight patients with botulism caused by contaminated smoked fish showed that each attending physician initially failed to reach the diagnosis. An outbreak of botulism occurred in New Mexico in 1978, and more than half the patients were not correctly diagnosed initially in the emergency department (ED). Because death may occur rapidly from respiratory paralysis, cases unassociated with a large outbreak are likely to be unrecognized. Conversely, because there is a range of disease—from mild to lethal (mild cases are associated with only slight headache and perhaps some malaise and nausea)—mild botulism may never come to medical attention. Mode of Toxin Action The enzymatic action of the toxin prevents the release of the neurotransmitter acetylcholine at the neuromuscular and other cholinergic junctions ( 1B). The botulinum toxin has a protein nature, and there are at least seven immunologically distinct types ( 2). In humans, almost all disease results from the types identified as A, B, and E, although there have been recent reports of type F. It is impossible to determine, in the acute situation, the type of toxin involved in a case of botulism. As a result, the initial treatment requires use of a trivalent (A, B, and E) anti-serum. Geographic Considerations Of the outbreaks reported in the United States, approximately 40% were tested for type of toxin; 26% were type A, 7.8% were type B, and 4.2% were type E. Although outbreaks were reported from 44 states, 5 states (California, Oregon, Washington, Colorado, and New Mexico) accounted for more than half the cases. In Europe, type B is more commonly identified (3). Temperature makes a substantial difference when it comes to killing spores of C. botulinum in foods. Type A and type B spores can be destroyed totally by boiling for 6.5 hours at 100° C. At 95° C, the time required for killing spores is doubled (13 hours). Using a pressure cooker can make a substantial difference. Heating to 120° C (248° F) results in spore death within 3 minutes. Although spores are resistant to heat, toxin is readily inactivated by heat. Boiling for 5 minutes, even at high altitude, ensures destruction of the toxin through protein denaturation. More than 90% of reported botulism outbreaks caused by type A occurred west of the Mississippi River. Two thirds of the reported type B outbreaks occurred in eastern states. Most of the type E outbreaks in the United States occurred in Alaska or in the Great Lakes region. No type A or type B has been reported from Alaska. Although global in scope, few cases have been documented in Australia and New Zealand ( 4). One CDC study (5), demonstrated a more severe illness with type A and a shorter time to disease onset with type E. Types of Food Implicated Botulism is more likely to result from home-processed foods—particularly those that are smoked, pickled, or canned—than from commercially processed foods. Despite the widely publicized outbreaks that have resulted from commercially prepared foods, of 766 outbreaks in the United States over a 78-year period, only 66 could be traced to commercial foods. Home-canned vegetables (e.g., tomatoes, beans) frequently have been implicated. If the pH of the food is lower than 4.5, toxin formation is unlikely, although there have been some reports of toxin production from pickled herring kept at a pH of 4 to 4.2. Cases have been reported from smoked fish and from ham and other meats. In France, of 108 cases, 83% came from home-cured ham (6). The word botulism actually arises from the Latin botulus, which means sausage. In Alaska, an outbreak involved stored beaver tail and beaver flippers. The incidence of botulism appears to be higher among Eskimos because of their storage and ingestion of uncooked meat. Spoilage of food may be obvious, but relying on gross signs is inadequate because of the lethality of very small amounts of the toxin. Although toxin-containing foods are the principal cause of the clinical syndrome of botulism, it has been demonstrated that infants who ingest spores may develop botulism through the formation of toxin within the gut (1A). Although uncommon, wound botulism has been reported in association with soil-contaminated deep wounds suitable for growth of the anaerobic C. botulinum. All age groups may be affected by botulism. The observation has been made that, in an outbreak, children fare better than adults. This is thought to be related to lesser food intake by children. Infant Botulism Infant botulism was first recognized in 1976, and 58 cases were reported in 1976 and 1977. By 1980, there were 139 laboratory-confirmed cases, 815 by 1988, and more than 1000 by 1992. Approximately one third of all reported cases of infant botulism in 1976 were associated with the ingestion of honey containing C. botulinum spores. In an analysis of 90 different jars of honey, nine (10%) were contaminated by C. botulinum spores. Most incidences were in infants younger than 6 months old.

Because of these findings, honey is not recommended for children younger than 1 year of age. One recent case in Italy was linked to honey ( 7). Still unexpained is an association with breast feeding. Symptoms in children are more insidious and may be chronic. Children with botulism are lethargic and flaccid. They have a poor cry and problems with eating. Constipation is the most common symptom. Loss of head control is particularly striking and eye muscle paralysis is common. Weakness may progress to respiratory paralysis. However, symptoms can be confusing. One report of two neonates with botulism demonstrated a history of diarrhea, apnea, and suspected sepsis ( 8). Usually there are prolonged intubation times (16 days), but tracheotomy rarely is needed ( 9). Botulism may be one cause of the sudden infant death syndrome (SIDS). This hypothesis was questioned in 1992 ( 10), when fecal samples from 248 cases of SIDS were cultured without a single positive result in the series. Diagnosis rests on the identification of C. botulinum or botulinum toxin in the child's feces. Of 58 cases reported, 90% had botulinum toxin in the feces. Differential diagnosis includes sepsis, myasthenia, heavy metal poisoning, muscular dystrophy, hypothyroidism, poliomyelitis, diseases of metabolism, and nonspecific syndromes. The only other clinical test that showed an alteration in infant botulism was the electromyogram, which demonstrated a peculiar pattern of brief duration, small amplitude, and overly frequent motor unit action potential. However, investigations ( 11) have demonstrated that electrodiagnosis is not consistently reliable. Guitterez et al. (12) came to the conclusion that low action potential and tetanic facilitation without exhaustion can support the diagnosis. Polymerase chain reaction can be reliable ( 13,14) but takes considerable time, so it is not yet useful in the first days of illness. Wound Botulism The syndrome of botulism resulting from the infection of a wound by C. botulinum was first reported in 1943. Neurologic signs and symptoms develop within 1 to 2 weeks after a wound has been contaminated with C. botulinum. The wound is usually one that has significant tissue injury, such as an open fracture, crush injury, or amputation. Wounds infected with C. botulinum may appear innocuous and without induration, crepitus, or lymphadenopathy, and prophylactic antibiotics may not prevent the colonization of clostridium in the wound. The neurologic picture is indistinguishable from that resulting from ingestion of the toxin, and treatment with antitoxin is advised as soon as this rare syndrome is suspected. Unlike cases of food-borne botulism in which a certain amount of toxin is ingested, wound botulism results in the ongoing production of toxin. Delays in diagnosis may make a substantial difference in the clinical course. Either the incidence is increasing or diagnostic accuracy is increasing. For example from January to November 1995, 19 laboratory-confirmed cases of wound botulism were reported in California. Almost all involved the intravenous or subcutaneous injection of illegal drugs, particularly black tar heroin. However, botulism may be found after traumatic wounds and may even result from sinusitis and tooth abscess ( 15). One review (16) demonstrated a fatality rate of 10%. Clinical Signs of Botulism 1. In many outbreaks, initial cases are incorrectly diagnosed as flu, viral syndrome, or strok4. 2. Symptoms usually appear within the first 24 hours but may be delayed. My experience with the New Mexico outbreak (34 cases) exhibited a range of 8 to 80 hours for initial symptoms to develop. 3. Earliest symptoms are vague malaise, headache, weakness, dizziness, blurred vision, and dry mouth. In the largest series of patients with botulism from a single outbreak (Michigan, 1977), dry mouth was found in all those affected, and 86% had difficulty with focusing or diplopia. This botulism was type B. 4. Progression is variable, but commonly there are initial symptoms. In severe cases, progression over the subsequent 6 to 8 hours leads to respiratory paralysis after increasing problems with vision, slurred speech, dryness of mouth, diffuse weakness, difficulty in swallowing, and difficulty in walking. Of 34 patients studied in New Mexico, 11 required mechanical ventilation. Botulism can also be mild; symptoms rarely progress beyond nausea and mild visual problems, or perhaps fatigue. Mild cases usually clear in 1 week. 5. Neurologically, the sensorium and intellectual functioning remain intact, and memory is not usually impaired. Neurologic symptoms are usually bilateral, symmetric, and motor, not sensory. The cerebrospinal fluid is normal. 6. Nausea and vomiting may occur in 30 to 40% of patients. In contrast, visual difficulty was reported in more than 90% of patients. Constipation and urinary disturbance was found in fewer than half the patients. 7. More severe cases show early third cranial nerve involvement. Pupils may become fixed and dilated. 8. As a general rule, the earlier the onset, the more severe the case. Clinical Differentiation in Adults Early cases are difficult to diagnose, as are mild cases that do not progress. No laboratory test can be used readily to diagnose botulism in the ED, although EMG is suggestive. Common conditions that figure in the differential diagnosis include Guillain–Barré syndrome, cerebrovascular accident or transient ischemic attack, tick paralysis, heavy metal poisoning (particularly lead), psychiatric conditions, drug abuse, alcohol intoxication, untoward reaction to anticholinergic medication, myasthenia gravis, dilantin toxicity, atropine poisoning, encephalitis, carbon monoxide poisoning, electrolyte abnormalities, and amyotrophic lateral sclerosis. Diagnosis in adults rests on clinical grounds. Confirmation comes from observing botulism in a mouse (sensitive to 900 molecules) that has been injected with toxin from the patient's serum or with the suspected food. It is worthwhile to test for toxin even weeks after the onset of clinical illness because of the high sensitivity of the mouse to the toxin and because of reports of circulating toxin even 2 weeks after onset. C. botulinum and toxin also may be identified in the patient's feces. Put all specimens in leak-proof containers. Neutralize any spill with a strong alkaline solution, if available. Suitable specimens may include serum, stool, vomitus, food samples, food containers, or wound material. The specimens should be refrigerated. Label carefully! Include in particular any drugs the patient is taking. A CDC analysis (5) of 309 cases demonstrated positive results in only 40 to 44% of stool tests within 3 days of illness. Medical Treatment IMMEDIATE CARE Immediate attention must be given to airway and respiratory function. When deaths occur early, they almost always result from respiratory paralysis. If the ingestion of food was relatively recent (less than 4 hours earlier, emesis or lavage followed by charcoal administration can be attempted. If the patient has difficulty breathing and arterial blood gases and vital capacity deteriorate or show hypoxia, hypercapnia, or a vital capacity of less than 1000 mL, a trial of ventilatory assistance and endotracheal intubation can be instituted before any surgical procedure. In the large 1977 Michigan outbreak of type B botulism, the presence of ptosis, dilated and sluggishly reacting pupils, and paresis of the medial recti were associated with the need for eventual artificial ventilatory support in 8 of 11 patients. These aspects of third-nerve dysfunction became apparent after approximately 12 hours. If tracheostomy is needed, it is best performed under ideal conditions in the operating room because a ventilator may be necessary for months. ANTITOXIN THERAPY Trivalent antitoxin is available from the CDC and should be administered to all patients with suspected botulism. Each vial of equine antiserum contains 7500 IU of type A, 5500 IU of type B, and 8500 IU of type E antitoxins. One to two vials are administered intravenously and again in 4 hours. One vial of antiserum may be given intramuscularly in 24 hours; repeated injections may be necessary depending on the clinical condition. Desensitization may be necessary because the antitoxin is a derivative of horse serum. In cases of known reactions to horse serum, 100 mg hydrocortisone can be injected before antiserum is used. Allergic reactions can be treated with antihistamines, steroids, or both. Antitoxin of human origin (from people who received muscle injections for dystonia) has been used in infant botulism with some reported success (17) but must be administered early (called human-derived botulism immune globulin). PENICILLIN Penicillin is indicated in the management of infant botulism and in patients with wound botulism because these two forms of botulism are caused by active infection with C. botulinum. Because botulinum food poisoning is caused by toxin and not by the organism, penicillin serves no role in the management of these patients. The question of worsening the condition due to bacterial lysis has been raised, but there is little confirmation. GUANIDINE HYDROCHLORIDE Guanidine hydrochloride has been used experimentally to compete chemically with the toxin. No dramatic results have been observed with guanidine, and its use is

no longer routinely recommended in the United States. Continued use is reported in Europe. RESPIRATORY FUNCTION Continued meticulous maintenance of respiratory function is a most important aspect of treatment. A patient's improvement is best followed by the periodic assessment of vital capacity and arterial blood gases apart from ventilatory support, with ongoing pulse oximetry. HOSPITALIZATION In severe cases, patients may be kept in the hospital for as long as 3 to 6 months. Weaning from the ventilator may be difficult. With long-term hospitalization, release must follow a graded rehabilitation program. Muscle wasting, lack of conditioning, orthostatic hypotension, and syncope frequently result from prolonged bed rest and muscle inactivity. There may be some minor dysphagia or malaise 6 to 12 months after the onset of illness. MORTALITY The use of antitoxin and supportive therapy can reduce the mortality rate from a range of 50 to 70% in untreated patients to a range of 10 to 25%.

PART 2: FOOD POISONING CAUSED BY MICROORGANISMS Shigella (Shigellosis) The Shigella species are aerobic, Gram-negative, nonmotile bacteria. There are four main species, all of which can cause human disease. Asymptomatic carriers are common. Differentiation of type is determined serologically with type-specific antisera. The invading organisms usually produce Shiga toxin when the cause is Shigella dysenteriae. When bacillary dysentery occurs, the cause can be the ingestion of as few as 200 organisms. If a “suboptimal” number of bacteria are ingested, or if there is some immunity, a person can have a subclinical infection or be in a nonsymptomatic carrier state. The range of clinical illness is broad. Children between the ages of 1 and 10 years are more susceptible to severe illness, as are the elderly. Although the condition is found more often in the tropics, it is endemic throughout the world. Epidemics have been traced to a variety of foods contaminated by feces, but milk, eggs, and dairy products are especially implicated. The incubation period is usually approximately 48 hours, but it may be as short as 8 hours, or symptoms can be postponed for a week. There is some colonization in the small intestine, but the large intestine is the preferred area. Bacterial growth depends on factors of immunity, existing flora, and the number of shigella organisms. Usually, within 1 week of recovery, the organism is no longer found in the feces. Occasionally, sequelae including neuropathy, arthritis, and skin eruptions are reported. Sepsis in the acute stage is rare but serious. Symptoms and Signs The following are features of Shigella poisoning: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Diarrhea, mucus, bloody stool Abdominal colic and tenderness Tenesmus Fever to 40° C (104° F) (bacteremia in 5 to 10% of patients) Pain often relieved by defecation Bowel sounds active and high pitched Possible syncope and hypotension with S. dysenteriae; if this species is responsible for the illness, it is usually more severe Outpouring of polymorphonuclear leukocytes into the intestines and stool; sometimes sheets of white blood cells can be seen on microscopic examination Rising white blood cell count, with left shift Possible convulsions, particularly in younger children with higher peak temperature and a family history of seizures; serum sodium may be low (alcohol dehydrogenase secretion occasionally stimulated) 11. Hypotension and shock (more common in the elderly) Diagnosis Table 148.1 shows a differential diagnosis of shigellosis with a comparison of amoebic dysentery. These are helpful in the diagnosis: stool culture; a rise in serum agglutinin titer in half the patients, though this is not useful in diagnosis or treatment because of the delay; white blood cell count usually greater than 10,000 with a left shift.

Table 148.1. Acute Differentiation of Shigellosis from Amoebic Dysentery in Elderly Patients a

Treatment For the management of shigellosis, give supportive treatment by preventing dehydration and maintaining electrolytes, particularly sodium. The diarrheal condition is usually self-limited. Shock with dehydration and acidosis may occur, however, particularly in infants and the elderly. Convulsions respond to titrated diazepam or lorazepam. Antibiotics are useful in moderate to severe cases for shortening the clinical course. The widespread resistance of the organism has rendered ampicillin of secondary use. Third-generation cephalosporins are now preferred (e.g., 1 g ceftriaxone every 12 hours or 50 mg/kg per day in children. In the United States and Europe, fluoroquinolone antimicrobials have gained use in this condition, such as norfloxacin or ciprofloxacin given early in the course (500 mg twice a day for adults). Antidiarrheal agents (e.g., diphenoxylate hydrochloride and atropine [Lomotil], paregoric, or opiates) must be used cautiously because they may prolong the clinical course. Nonproductive tenesmus is the best indication for using such agents. For amoebic colitis, antimicrobial therapy is needed—usually metronidazole followed in 1 week by diiodohydroxyquin (to eradicate cysts) ( Table 148.1). Hospital admission and intensive treatment may be needed in infants and in elderly patients.

Salmonella Food Poisoning The salmonellae, named for Dr. Salmon who described them in 1885, are Gram-negative motile bacteria. The most common form of salmonella-induced human disease is the syndrome of Salmonella gastroenteritis. The range of gastroenteritis can be mild to severe; the severe form is associated with abdominal pain, colitis, and signs of a systemic inflammation (fever, elevated white blood cell count, malaise). Identification of the phage type of salmonella has allowed the tracking of epidemics. One type (Salmonellae enteritis phage type 4) has been increasing (1). Typhoid fever is caused by Salmonella typhosa and differs from the common gastroenteritis primarily by its severity, prolonged course, and hematogenous dissemination of the bacillus with accompanying diffuse manifestations. A persistent carrier state can result. The primary reservoir is the vertebrate intestine, and the passage is from person to person by fecal contamination of foodstuffs. Most commonly, meat, poultry, dairy, egg and seafood products have been implicated. One recent enormous outbreak (estimated at 224,000 persons) occurred from a nationally distributed ice cream ( 2), probably because of cross-contamination from eggs. Sterilization of contaminated foods is not always achieved by cooking, especially in large stuffed turkeys and in cooked eggs. Disease may come by way of pets because salmonellae can cause disease in animals, usually dogs, cats, birds, and turtles. To produce clinical disease in humans, at least 100,000 to 1 million bacteria of the nontyphoid salmonellae usually are required. To achieve these levels, a growth medium (i.e., food and eggs in particular) is necessary because simple contamination does not involve the transfer of so many organisms. Subsequently, intestinal multiplication occurs. The need for a “minimum dose” makes direct fecal–oral transmission uncommon except with infants and children. In the United States, waterborne transmission is uncommon because of overall water sanitation. The clinical disease results from an infection without the production of toxin. Thus, prevention must focus on overall sanitation and identification of asymptomatic carriers. Because Salmonella bacteria are killed at a pH level of 2, antacid use may increase susceptibility, as do conditions of reduced stomach acidity (including subtotal gastrectomy, vagotomy, and gastroenterostomy). Salmonella gastroenteritis is a reportable infectious disease. Estimates have been made that the incidence reported by the CDC (10 cases per 100,000 population) represents one tenth to one hundredth of the actual incidence. The incidence is highest in the summer, and although all age groups may be affected, children younger than 5 years have the highest rate of infection. Increased intercountry tourism, as well as intracountry and intercountry trade involving foods, has resulted in increased risks for acquiring Salmonella gastroenteritis. Large companies with wide food distributions can be responsible for thousands of cases. For example, from one large dairy, contaminated low-fat milk was the vehicle for the transmission of Salmonella typhimurium to 14,000 persons. In 1987, the New York State Department of Health investigated a hospital outbreak traced to raw eggs and involving almost 1000 patients. This led to attempts by some states to regulate the cooking of eggs. At least nine deaths occurred from this outbreak. The median age of 77.5 years among those who died emphasizes the increased severity of illness in the elderly and the immunocompromised. Symptoms and Course of Illness The general incubation period is 8 to 48 hours. General malaise, headache, mild abdominal pain, and fever of 37.78° C to 38.33° C (100° to 101° F) are common initially. Despite some nausea and vomiting, major symptoms are cramps and diarrhea; tenesmus is common. Bloody diarrhea is rare; shigellosis and amobic dysentery are more often associated with bloody stools. Occasionally, abdominal symptoms are so severe that they may suggest appendicitis or some other acute intra-abdominal process. Although most acute symptoms subside within 2 to 5 days, occasionally a prolonged course may last weeks. Death from Salmonella gastroenteritis is uncommon and occurs primarily in infants, the elderly, and persons with severe underlying disease. Although arbitrary divisions have been made between a gastroenteritis and the systemic disease Typhoid fever, the division may not be clinically clear-cut. Salmonella bacteria other than S. typhosa (the cause of typhoid fever) may produce gastrointestinal symptoms, sustained fever, and even positive blood cultures. In addition, it is possible to be infected by Salmonella bacteria and to have few gastrointestinal signs and symptoms but to have chills, fever, anorexia, and even some hepatosplenomegaly or respiratory symptoms. Spiking fever, headache, abdominal cramps, and rose spots on the torso can help in the diagnosis. The presence of bacteremia may result in a localized internal abscess as well as endocarditis, septic arthritis, or osteomyelitis, particularly in those with sickle-cell anemia. Meningitis may develop in newborns and infants. Such severe infections usually show striking signs and marked leukocytosis, though in typhoid fever leukopenia is characteristic after the first week. Diagnosis Diagnosis and differentiation from shigellosis, enterotoxic E. coli, and amoebic dysentery may be difficult. Other less common causes of acute diarrheal disease, such as that produced by Vibrio parahaemolyticus or viral agents, can be difficult to diagnose. Definitive diagnosis clinically rests on isolation of the organism from the stool. If the contaminated food is available, it can be cultured. Excretions from pets can be tested if they appear to be possible sources. A fecal smear may show inflammatory leukocytes, but usually less than with shigellosis and amoebic dysentery. Bloody diarrhea is uncommon in Salmonella enterocolitis. If there are systemic signs, blood cultures may show bacteremia. Although immunologic tests of various titers may show increases, and polymerase chain reaction analysis can lead to definite identification, the time delays usually render such tests of limited value. Treatment The cornerstone of treatment is prompt correction of dehydration and of fluid and electrolyte imbalances. Intravenous fluids may be necessary, depending on the clinical symptoms. Antimotility agents (e.g., Lomotil and similar agents) that inhibit the activity of the bowel substantially may increase the severity of the disease and must be used cautiously. If the patient shows high fever, chills, or other evidence of severe systemic infection, or if the patient is immunocompromised, antibiotics are indicated. Because of widespread resistance to chloramphenicol, ampicillin and trimethoprin–sulfamethoxozole ( 2A), ciprofloxin and ceftriaxone have become the agents of choice for initial treatment (ciprofloxin 500 mg twice a day for 10 to 14 days). In pregnant women or in children, ceftriaxone is the initial choice (1 g twice a day). After sensitivities are returned, one can switch to ampicillin or amoxicillin if the organism is sensitive ( 3). The trend is to use these antibiotics early to shorten the clinical course and to decrease carrier states. The course of antibiotics ranges from 10 days to 2 weeks. If there is evidence of an abscess, endocarditis, osteomyelitis, or other evidence of persistent internal infection, antibiotics may have to be continued for 4 to 6 weeks, and surgical drainage may be needed. Carrier states may require 4 weeks of treatment, and success of eradication is diminished if there is gallbladder disease. Antibiotic Resistance Probably the biggest dilemma facing physicians in the treatment of acute infectious diarrhea is antimicrobial resistance. Early treatments will improve patient outcome, but at the cost of increased resistance of micro-organisms, particularly in “third world” countries where sanitation and food storage remain daily problems, and antibiotics are used freely ( 2B). For example, the formerly widespread use of doxycycline is now limited by resistance of up to 50% for shigellosis. For salmonella, ampicillin, chloramphenicol, and co-trimoxazole are approaching the 40% resistance level ( 2B). Ciprofloxacin and ceftriaxone have little resistance, but there is an expectation of changing resistance patterns for these antibiotics. The long-term answer involves prevention and vaccination, but this is not practical at this time. Enteropathic Escherichia Coli (Traveler's Diarrhea) METHOD OF ACQUISITION Dairy and meat products and contaminated water are common vehicles for infection. There is some suggestive evidence that bismuth salicylate may be an effective

prophylactic therapy against traveler's diarrhea (30 to 60 mL every 4 hours). Other prepared foods (salads, sauces) may harbor bacteria from fecal contamination. A general rule is to eat cooked foods shortly after preparation and to wash and peel raw fruits and vegetables thoroughly. SYMPTOMS AND COURSE OF ILLNESS Acute diarrhea may begin 8 to 12 hours after the ingestion of contaminated food or water, but onset may be delayed for several days. Common symptoms include abdominal cramps, tenesmus, and profuse watery diarrhea, though there is a wide range of clinical illness. Two types of E coli are associated with food poisoning. One type does not produce a toxin, and symptoms result from intestinal infection. The other type is associated more commonly with the epidemic traveler diarrhea. This type does produce an enterotoxin, and symptoms result from infection and from the effect of one of the toxins on the colon. In general, E. coli produces a clinical disease that is usually milder than Salmonella disease or shigellosis, but in severe cases it may be indistinguishable from them. One strain of E coli can cause severe hemorrhagic colitis (type 0157:H7) ( 4) and produce a toxin similar to the one produced by S dysenteriae. E coli hemorrhagic colitis can be particularly severe in institutional settings. In one situation, 55 of 169 residents of a nursing home were affected. Of the residents, older age and previous gastrectomy increased the risk for acquiring the infection. Of the 55 affected residents, 19 (35%) died from the following causes: hemolytic–uremic syndrome (12 patients), acute colitis ( 1), cardiorespiratory failure ( 1), and nonspecific causes (5). This study also highlights the increased susceptibility in the elderly—55 of 169 residents versus 18 of 137 staff members—and the much higher morbidity and mortality rates. Of the total, 35% of the residents died of the infection, whereas none of the staff died. The use of antibiotics in this colitis syndrome are not well established because toxin is involved. However, infection should be treated. E coli diarrheal disease is of particular concern in infants and young children and in the elderly, who have limited tolerance for electrolyte imbalance because of overall condition, underlying illness, or medications that can affect electrolytes (e.g., diuretics). DIAGNOSIS Diagnosis may be possible by isolation of the organism in food or water and by stool culture. Serologic diagnosis can be determined through testing for rises in titer against E coli, but such tests are not readily available. Stool smear is important. Polymorphonuclear leukocytes may be present, usually in smaller numbers than with shigellosis, and bloody diarrhea is less common. TREATMENT The trend in moderate to severe cases is to begin antibiotics early in the course to reduce the duration and severity along with intravenous fluids as needed. In its acute form, the disease generally lasts for only 2 or 3 days. Nonspecific symptoms and malaise, however, usually continue for at least 1 week when untreated. In the mild case, however, the disease is treated effectively with clear liquids. Although antibiotic treatment can reduce the clinical course of traveler's diarrhea, the growing problem of antimicrobial resistance must be emphasized. In Operation Desert Shield (1990–1991), numerous outbreaks of diarrhea occurred among U.S. forces. Stool cultures were positive in almost half the 400 cases analyzed. Of 125 E coli infections, 39% were resistant to trimethoprim–sulfamethoxazole (Bactrim), 63% to tetracycline, and 48% to ampicillin. Of 113 Shigella infections, 85% were resistant to Bactrim, 68% to tetracycline, and 21% to ampicillin. Importantly, all bacterial isolates were sensitive to ciprofloxacin and norfloxacin, newer antibiotics to which significant resistance had not yet developed ( 5). OTHER CAUSES OF TRAVELER'S DIARRHEA Although E coli is the most common cause, traveler's diarrhea may be caused by other microorganisms including Rotavirus (up to 10% of cases), Salmonella or Shigella (15 to 20%), and parasites (2 to 5%). Rotavirus infection is generally self-limiting. Infants who are breast-feeding have some resistance. A woman traveling to an endemic area with an infant should breast-feed if possible, because infants can become dehydrated rapidly from diarrhea. Immunization against rotavirus has been successful in endemic areas. Giardia lamblia infection generally occurs days to weeks after the exposure and is characterized by foul-smelling, watery stools. A stool smear and culture will help in diagnosing this parasite. This condition is usually not severe, but it often requires treatment with metronidazole (250 mg three times daily for 5 days). Quinacrine formerly was used but is no longer distributed in the United States, and tinidazole is not available in this country ( 6). Pregnant women generally should not be treated because the drugs are dangerous to the fetus. In severe cases, the aminoglycoside antibiotic paromomycin has been given orally after the first trimester. Its absorption from the gastrointestinal tract is poor, and it has high fecal concentrations. Entamoeba histolytica is a parasite that invades the mucous membranes of the intestines, causing ulcerations, hemorrhage, and diarrhea. In severe cases, the parasite may cause perforation of the intestines or may invade other organs, particularly the liver or lung. Diagnosis rests on physical and stool examinations and possibly on liver function tests and liver scan. Treatment of confirmed cases is mandatory and should include metronidazole and iodoquinol. Cyclosporiasis cayetanensis is a parasite that causes gastroenteritis. Usually rare in the United States, there have been outbreaks due to infected raspberries from Guatemala (1,000+ cases in 1996). Symptoms are those of gastroenteritis, treatment with trimethopren-sulfamethoxazide is effective. Clostridium Perfringens Conditions Clostridium perfringens is a nonmotile, Gram-positive, spore-forming rod. Disease is caused by the growth of bacteria and toxin formation. It is now considered one of the most common types of food poisoning. METHOD OF ACQUISITION Meat and poultry products commonly are implicated, as are gravies and creamy (dairy or mayonnaise-containing) foods. SYMPTOMS AND COURSE OF ILLNESS Because large numbers of organisms (usually greater than 10 6 organisms per gram) are generally necessary to cause significant disease, most food poisoning resulting from C. perfringens is relatively mild. The incubation period is more than 8 hours and usually less than 24 hours. The disease is associated with cramps and diarrhea. Diarrhea is generally not as profuse as that found with Shigella, Salmonella, or E coli; characteristically, it is not bloody. There may be mild nausea, but vomiting is uncommon. Clostridium difficile occurs after antibiotic use and usually resolves with no specific treatment, although a course of metronidazole or vancomycin occasionally is needed. DIAGNOSIS Diagnosis is made by detection of the organism in food and stool. TREATMENT Symptomatic therapy is all that is required. Bacillus Cereus Conditions Bacillus cereus is a slightly curved, Gram-positive rod found singly and in chains. It is motile. Disease arises from infection and some toxin production. Of the toxins

produced, the emeter toxin has been associated with liver failure and death. METHOD OF ACQUISITION Food, particularly meat, dairy, and poultry products, becomes contaminated with this organism. Dried foods (e.g., mixes, potatoes) may be contaminated (growth occurs after hydration). Fried rice or cooked rice left unrefrigerated for prolonged periods has been the source of some outbreaks. SYMPTOMS AND COURSE OF ILLNESS Average incubation period is 8 to 12 hours. Average duration of illness is approximately 24 hours. Symptoms, in order of magnitude, are diarrhea, abdominal cramps, nausea, and vomiting. Fever is generally absent or is below 37.78° C (100° F). The clinical course may resemble that of staphylococcal food poisoning, with vomiting as the dominant symptom. TREATMENT Supportive therapy with intravenous fluids is usually sufficient even for relatively severe cases. Antinauseants may be given. There is no evidence that antibiotics are of value. Severe cases require intensive care and rarely fulminant liver failure may require transplantation. Cholera Cholera is caused by V cholerae, a curved, motile, Gram-negative rod. It is rare in the United States. During worldwide cholera pandemics, there have been many cases in the United States (150,000 deaths in 1832 and 1849 and 50,000 deaths in 1866). In the United States, cholera is still endemic along the Gulf Coast, especially in Texas and Louisiana, where association with contaminated water and seafood has been found. The organism produces a proteinaceous toxin that can be inactivated by heat and acids. METHOD OF ACQUISITION In the epidemic form, the vibrio are water borne or come from seafood. Person-to-person transmission is usual in the nonepidemic form. Occasionally, it may originate from a restaurant in which a worker is infected. The food can become contaminated, particularly when “night soil” (human excrement) is used as a fertilizer. SYMPTOMS AND COURSE OF ILLNESS Usually, the illness develops within 8 to 48 hours of ingestion. Severe enteritis is associated with the passage of copious amounts of non-foul-smelling diarrhea usually containing mucus and occasionally blood. The disease arises in association with an exotoxin that causes a severe disorder of the intestinal tract and results in marked intestinal secretions. Frequently, the first stool contains more than 1000 mL with a characteristic appearance of “rice water.” The symptoms arise directly from the gastrointestinal fluid and electrolyte losses. Prostration and a shock-like state may occur rapidly. The patient may die within 12 to 24 hours if intravenous fluids or oral electrolytes are not provided. The illness characteristically lasts 1 to 7 days. With adequate fluid and electrolyte repletion, recovery is rapid. Hypokalemia is a particular problem in children. DIAGNOSIS Clinical suspicion of cholera is important, particularly in endemic or epidemic areas. Persons with decreased stomach acidity (because of surgical operations and antacids) are at higher risk. In addition, those with type O blood are at higher risk for unknown reasons. The organism may be identified by culture, and one may look for the organisms on a Gram-stain slide. At medical centers familiar with cholera, a fluorescent antibody technique may identify the organism positively within 1 hour. TREATMENT The patient in shock must be treated with intravenous fluids. Oral fluids may be used when intravenous fluids are unavailable. A glucose-containing electrolyte solution may be given orally. Generally acidosis, severe potassium losses, and dehydration occur. Those experienced in treating cholera use weight as a measure of dehydration and consider the case to be severe if body weight loss is greater than 10% and mild if it is less than 5%. In severely ill patients, the use of tetracycline has caused a highly significant reduction in total stool volume and duration of diarrhea and has resulted in more rapid disappearance of the organism from the stool. The dose administered should be approximately 1 g tetracycline by mouth initially, then at least 500 mg every 6 hours for a total of 3 days. The usual stool composition per liter in adults is sodium (135 mEq), potassium (15 mEq), bicarbonate (45 mEq), and chloride (100 mEq); in children, it is sodium (105 mEq), potassium (25 mEq), chloride (90 mEq), and bicarbonate (30 mEq). In children and pregnant women, treatment with furazolone (Furoxone) has been used successfully and averts the risks of tetracycline. Cholera may be prevented by cooking all foods thoroughly, boiling water, and proper immunization, which offers as much as 75% protection for up to 18 months. Even when clinical disease develops, cholera appears to be less severe in the vaccinated patient. Other vibrio organisms can cause septicemia or infections in immunocompromised. Early antibiotic therapy is indicated because of the high mortality rate from septicemia. Campylobacter Enteritis METHOD OF ACQUISITION Raw milk most frequently has been implicated in the transmission of Campylobacter enteritis. DIAGNOSIS Diagnosis rests on isolating the organism from a fecal specimen. The common symptoms include diarrhea (in more than 90%) and abdominal pain (in more than 80%), frequently with fever, headache, nausea, or vomiting. Bloody diarrhea is less common, but blood in the stool is present in about one fourth of patients. Those with acquired immune deficiency syndrome have a much higher incidence of this infection ( 7). TREATMENT Treatment is supportive but must include identification of and avoiding the offending food. For severe illness (particularly in the elderly or young children), trimethoprim-sulfa or erythromycin can be used, as can ciprofloxacin, which has been shown to shorten the clinical course. When Campylobacter fetus is the infectious agent, a treatment of choice is gentamicin or imipenem ( 7A). Still unexplained is a relationship between campylobacter infection and subsequent Guillain–Barre syndrome (8). Listerosis Caused by the Gram-positive bacillus Listeria monocytogenes, listerosis can result in septicemia, meningitis, and focal infectious symptoms. Milk and cheese products have been increasingly involved in its spread. One recent large outbreak (45 persons) resulted from contaminated chocolate milk. Diarrhea and fever were the most frequent symptoms (9). In this series, the median incubation period was 20 hours (range, 9 to 32), and four persons were hospitalized. In another outbreak of 57 persons (10), 21% had bacteremia and 40% had meningitis. The cause was identified as cheese, and the mortality rate was 32%. There is an increased susceptibility in immunocompromised patients and pregnant women leading to a high (20%) fetal death rate. Ampicillin is usually the antibiotic of choice.

Staphylococcal Food Poisoning Enterotoxic staphylococci are found widely on the skin and mucous membranes of many persons. Most staphylococci (a Gram-positive, clustered coccus) cannot elaborate this particular toxin. When foodstuffs are contaminated, lack of refrigeration and warm environment are ideal for bacterial growth and toxin elaboration. Foods usually implicated are those with a high fat content, such as creamy cakes, custards, creamed soups, mayonnaise, and so on. Cases, however, have been reported from meat products as well. Milk rarely has been implicated. The ideal culture medium is pancake batter, which has a pH close to 7, a high moisture content, and frequently is left unrefrigerated for hours. Turkey stuffing and a cooked, dressed turkey too large to fit into a refrigerator and handled by many persons during its preparation is another source. One recent outbreak resulted from canned mushrooms from China ( 11). The toxin is pre-formed and is remarkably heat stable. Therefore, even if food subsequently is cooked, a period of hours is necessary for toxin destruction. SYMPTOMS AND COURSE OF ILLNESS Symptoms usually begin within half an hour to 6 hours of ingestion and may begin slowly or violently. Severe nausea and vomiting are common. The affected person vomits repeatedly, then has dry heaves and may vomit blood. A vomiting-induced Mallory–Weiss syndrome is possible. After vomiting, abdominal cramps may become severe and diarrhea may develop. The diarrhea, however, is usually relatively mild. Patients appear markedly “gray” and severely ill. Severe dehydration can occur, and intravenous therapy should be started. Although the acute stage usually lasts less than 12 hours, many patients have severe nausea and malaise for 1 to 2 days. Milder cases do occur and may not be diagnosed as staphylococcal food poisoning unless a careful history is taken. Initial studies were conducted with paid volunteers. Despite increased pay, few, if any, said they would volunteer again. Toxin is not formed in appreciable amounts below 12.78°C (55°F) or above 48.89°C (120°F). If the food is acidic, toxin is produced slowly, depending on temperature and acidity. If contaminated food has a pH of 7 or a moisture content greater than 30%, appreciable amounts of toxin are produced in 4.5 hours at 32.22°C (90°F). With the same food but a different temperature, the same amount of toxin was produced in 10 hours at 18.33°C (65°F) and in 9 hours at 46.11°C (115°F). Thus, the conclusion is that to prevent staphylococcal food poisoning, “keep it hot, keep it cold, or eat it within 2 hours.” Simple diagnosis can be made by a Gram stain of the suspected food, which shows abundant staphylococci if contaminated (although this, of course, is not a test for the toxin). A culture can verify type, but the time necessary for culturing renders the findings primarily of scholarly interest. TREATMENT To manage staphylococcal food poisoning, give intravenous fluids. To prevent vomiting, prochlorperazine or promethazine can be given parenterally. In addition, H blockers can be given intravenously. Monitor electrolytes and urine output.

2

Fatalities have been reported in young children owing to mineral imbalance and dehydration. In the elderly, severe retching may worsen any existing heart disease, and myocardial infarction has been reported, as has a Mallory–Weiss esophageal tear. Supportive treatment results in a satisfactory outcome in most patients. Because the disease is caused by a preformed toxin, antibiotics are of no value. No suitable antitoxin is available for routine use. Physicians should document their findings carefully; many restaurant outbreaks result in legal action. Although the acute stage usually is over within 2 days, weakness and malaise can continue for 2 weeks in some patients. Trichinosis The worm Trichinella spiralis enters the body through pork or other meat that has been cooked inadequately. For many reasons, the United States does not routinely inspect for trichinosis, although an enzyme assay under development will allow such testing in the future—a necessity for exporting pork to many countries. Trichinosis in humans causes weakness, swelling, and muscle pain along with general malaise and low-grade fever. The duration of the acute illness is usually 3 weeks, although chronic indolent cases have been reported as have rapidly developing cases that lead to death. Thiabendazole and albendazole have been successful experimentally to treat this condition. Few cases are actually diagnosed. Symptoms are usually ascribed to flu. The condition is rarely progressive. More often, the worms become encapsulated and do not cause later clinical disease. This is in contrast to Echinococcal disease caused by ingestion of larvae from infected animals. Severe hytadid cysts may occur throughout the body (mostly in the liver). Drainage of cysts and albendazole therapy are needed for treatment ( 11A). Food Additives More than a thousand food additives generally recognized as safe (GRAS); most of them are benign. Certain substances may trigger reactions in sensitive people. For example, sulfites are added to fruit and vegetable salads and to potatoes to prevent darkening. Acute attacks of asthma have been triggered by such substances. Because of their dangers, sulfites have been removed from the GRAS list for use in restaurants and salad bars. Another substance widely used is monosodium glutamate (MSG), which acts as a flavor enhancer. Depending on the dosage, it may cause tingling, flushing, diaphoresis, nausea, vomiting, balance difficulties, diarrhea, headache, or neurologic disturbances. The subject of additives is generally beyond the scope of emergency medicine unless reactions occur that bring people to emergency facilities (e.g., migraine headache caused by MSG). Other food poisonings are shown in Table 148.2.

Table 148.2. Other Food Poisonings and Their Treatments a

Eosinophilia–Myalgia Syndrome This strange syndrome deserves mention as an ongoing mystery caused by either tryptophan ingestion or a contaminant. The major symptoms are myalgia, arthralgia, weakness, rash, and scleroderma-like skin changes. Inquiry should be made of tryptophan use and if EMS is suspected, refer to the CDC for evaluation ( 12). Mushroom Poisoning Poisoning from ingestion of Psilocybin mushrooms can induce severe vomiting, abdominal cramps, and marked hallucinations, but the poisoning is relatively benign because of the body's large tolerance to psilocybin. The mushroom Amanita muscaria has been eaten for its hallucinatory effects, and the Vikings were said to have consumed them before going into battle because of the rage-like reaction induced. With overdose, muscarine causes parasympathomimetic symptoms that occur usually within half an hour of ingestion and cause profuse salivation, lacrimation, bradycardia, and other cholinergic responses. Treatment involves atropine, which can be given at a dose of 0.5 to 1 mg intramuscularly or intravenously (when symptoms warrant). This dose can be repeated every 30 minutes. However, most

reported cases are caused by Amanita phalloides (90%) (13), which require aggressive and life-saving treatment. Important questions in the assessment of mushroom poisoning are: 1. When were the mushrooms eaten, and when did symptoms appear (time course)? Rationale: Symptoms that begin immediately or within the first hour usually herald a relatively minor poisoning. Emesis, charcoal, and a cathartic should be used. Delayed symptoms are characteristic of the amatoxin-containing mushrooms. The nature of the symptoms may indicate the seriousness of the ingestion (e.g., hallucinations, muscarinic effects, sweating, delirium). 2. How many mushrooms were eaten, and what types were they? Rationale: If different types were ingested, it is difficult to arrive at identification by symptoms. In addition, of course, there is a dose-related effect. 3. Did anyone who ate the mushrooms not get sick? Rationale: People often blame mushrooms because of the widespread awareness of their toxicity, whereas another food poisoning or virus might be the cause of symptoms. 4. Did the patient consume alcoholic beverages? Rationale: Some mushrooms have a disulfiram-type effect with added alcohol. As with Antabuse, there can be extreme nausea, vomiting, and headache. The most severe mushroom poisoning comes from those containing peptide toxins (phallotoxins or amatoxins). They can be deadly at low doses, and even one mushroom can kill. These mushrooms look appetizing and do not have an offensive taste to warn of danger. Symptoms may be delayed several hours to as long as 24 hours after ingestion. Patients have severe abdominal pain, diarrhea, and vomiting. Amatoxins cause liver, brain, and renal tubule cell injury, which may lead to death. Early treatment consists of the following: 1. Emesis, gastric lavage and activated charcoal. 2. Supportive treatment, with monitoring of vital signs and urine output. Renal failure may occur. Liver failure requiring emergency transplant has been reported. Urine output must remain high. Early diuresis may be necessary. 3. Large doses of steroids have been used empirically. 4. Hemodialysis or peritoneal dialysis should be used early because of the small molecular size of the peptide toxins. 5. Intravenous penicillin, chloramphenicol, and sulfamethoxazole have been used in animals to decrease binding of the toxin to albumin. This is of unproven value. Thioctic acid (50 to 150 mg every 6 hours) has been used in Europe but is not well tested. If severe poisoning has occurred, all these measures should be instituted as early as possible, along with activated charcoal and catharsis. The characteristic course has been divided into three stages: acute symptoms (first 24 hours); some remission (24 to 36 hours); and severe stage (with clinical liver damage, renal failure, and seizures), which can lead to death in more than 1 to 2 weeks. A specimen of the ingested mushroom can prove valuable in identification. For quick ED testing, rub some of the mushroom cap over newsprint and allow it to dry. Apply a drop of concentrated hydrochloric acid to the paper. A bluish-green color indicates amatoxins. The mushroom should then be sent for chemical analysis. A negative “newsprint” test does not mean that amatoxins may not be present. Only a positive test is useful. Miscellaneous Food Poisons Table 148.2 summarizes some other food poisonings and their treatment. Other Food Toxins (Toxidromes) TYPES OF FOOD TOXINS There are several ways in which food toxins find their way into the foods we eat. They may be produced by organisms found in the food, such as microorganisms (e.g., botulism, staphylococcal food poisoning, or scombroid); algae (e.g., neurotoxic mussel poisoning); or dinoflagellates (e.g., ciguatera). They may be natural chemical constituents of substances not safe to ingest, such as poisonous mushrooms or unripe fruits and vegetables (e.g., the unripe Jamaican akee fruit contains a substance that causes hypoglycemia; the green potato contains toxic solanine alkaloids). They may even be the result of the inadvertent inclusion of animal glands during the preparation of a food product. For example, a large outbreak of thyrotoxicosis occurred after neck trimmings that contained a large amount of bovine thyroid hormone were inadvertently included during the preparation of ground beef. Some cases of illness from food toxins occur as the result of the ingestion of excessive amounts of a substance that is tolerated in smaller doses. For example, the ingestion of large amounts of nutmeg can cause toxicity from the sympathomimetic effects of myristin, a natural constituent of the spice. “Fugu,” a culinary delicacy highly prized by the Japanese, is a fish that contains tetrodotoxin, a cholinergic neurotoxin, which can cause respiratory paralysis and rapid death if ingested in excessive amounts. Specially licensed chefs learn how to prepare the fugu with an apparently “desirable” small amount of the tetrodotoxin, which is tolerated by fugu devotees. Overdose causes respiratory paralysis. Alcohol is yet another example of a foodstuff that is well tolerated in small amounts but can cause serious illness, and even death, if consumed in excess. Some food “toxins” cause illness as a result of interactions with medications. Tyramine, present in aged cheese, pickled herring, chianti wine, and some other aged foods, can cause headaches and hypertension in patients taking monamine oxidase inhibitors for the treatment of depression. Similarly, the “broad bean” can cause illness through the formation of derivatives of dihydroxyphenalaline and dopamine. Some patients with genetic deficiencies of enzymes may have illness precipitated by the ingestion of foods not toxic to others (e.g., severe hemolysis may develop in some patients with a variety of glucose-6-phosphate dehydrogenase deficiency after they ingest fava beans). Examples of some of these types of toxic food ingestion will be covered in depth; others are summarized in Table 148.2. Diagnosis of food toxin-related illness is difficult, especially in the ED. The clinical history is often confusing, and toxin identification is difficult. An important clue from the history is the determination of whether the case is isolated or one of a large group. Epidemiologic assessment may be difficult, however, if the outbreak is small or if a possible multitude of foods is involved. Although some food toxins have highly characteristic complexes of symptoms and are, therefore, relatively easy to diagnose (e.g., staphylococcal, MSG, ciguatera poisonings), others, such as botulism, are notoriously difficult to diagnose. Scombroid Food Poisoning As in botulism and staphylococcal food poisoning, scombroid is the result of the ingestion of a toxin produced by bacterial contaminants of the foodstuff—in scombroid, it is fish contaminated by Proteus morgani. These bacteria cause a breakdown of histadine in the fish with chemical decarboxylation and the production of a histamine-like toxin. Among the fish associated with this poisoning are tuna, albacore, mackerel, and skipjack. Contaminated fish may smell foul (ammonia-like) and have an unpleasant metallic taste. Most laboratories cannot test for histamine. The normal histamine level of fish flesh is less than 6 mg/100 g. More than 10 mg signifies likely bacterial contamination (usually with proteus or achromobacter). Severe illness generally requires a level greater than 100 mg/100 g. CLINICAL SIGNS AND SYMPTOMS The symptoms begin within 10 minutes to 1 hour of ingestion of the contaminated fish and resemble those of a histamine reaction (flushing and pruritus). Other symptoms include nausea, headache, thirst, chest pain, diarrhea, skin blotches, and sometimes mouth blisters. Symptoms can be severe. Treatment consists of intravenous antihistamines, such as diphenhydramine hydrachloride or chlorpheniramine. Cimetidine and other H-2 blockers have been successful for scombroid. Production of the toxin is prevented by the proper refrigeration of fresh-caught fish. Ciguatera Fish Poisoning Ciguatera poisoning results primarily from the ingestion of contaminated barracuda, snapper, and fish from warm waters, such as the Caribbean, the Gulf of Mexico, and near Hawaii. Larger fish tend to be more implicated because they ingest smaller fish with toxin. A dinoflagellate (the green algae Lyngbia majuscula) becomes concentrated in the organs of these fish and elaborates an unpleasant neurotoxin that is not readily inactivated by heat or cold. This toxin causes paresthesias

(especially of the lips, tongue, and throat), pruritus, a feeling of hot–cold reversal, and a variety of gastrointestinal symptoms, including nausea, vomiting, and diarrhea. Encephalopathy and respiratory failure, as well as shock, may occur. Symptoms usually begin within 12 hours of fish ingestion, but they may be delayed as long as 30 hours. Gastrointestinal symptoms, often delayed up to 30 hours, are usually the cause for patients to seek treatment, and the neurologic symptoms may be insidious. Treatment is supportive, and there is no specific antidote. Severe cases may benefit from the use of intravenous mannitol. Intravenous fluids, oxygen, and pain relief are all important. Intravenous calcium has reportedly been of some benefit. Laboratory test results are usually normal. An immunoassay is available to confirm the presence of this toxin, and a sample of the possibly contaminated fish can be sent for assay. The time delay for confirmation, however, requires that the diagnosis and treatment of ciguatera poisoning be based on clinical grounds. Toxic Encephalopathy from Mussel Poisoning Intoxication associated with the ingestion of shellfish include paralytic shellfish poisoning, neurotoxic shellfish poisoning, and a recently described toxic encephalopathy associated with the ingestion of mussels contaminated by the neuroexcitatory amino acid, domoic acid. Only the latter is discussed here. One outbreak of more than 250 cases of mussel-associated poisoning occurred in Canada. Reported symptoms included vomiting (75%), abdominal cramps (50%), diarrhea (42%), headache (43%), and short-term memory impairment (25%). Encephalopathy, coma, mutism, seizures, and purposeless chewing and grimacing also occurred. The more severe neurologic symptoms occurred primarily in older patients and in patients with coexistent medical problems. Treatment was supportive and included intubation for airway protection, management of unstable blood pressure, cardiac arrhythmias, and seizures. Cognitive deficits that had not resolved more than 2 years after the ingestion were described. The illness was associated with the production of domoic acid, a neuroexcitatory amino acid similar to glutamic acid, which is thought to be produced by an algae (Nitzschia pungens) that lodges in the digestive glands of mussels. Plant Poisoning The number of plants that can exert toxic actions is vast. For emergency treatment, it is useful to identify the major type of chemical actions caused by the poisoning. Table 148.3 identifies common plants and their chemical actions. Table 148.4 offers symptoms and signs associated with plant intoxications, and Table 148.5 was prepared by the Food and Drug Administration to alert health professionals and consumers to some herbal remedies that can be dangerous.

Table 148.3. Poisonous Plants and their Chemical Actions in the Body

Table 148.4. Signs and Symptoms of Common and/or Serious Plant Intoxications*

Table 148.5. Common Dangerous Herbal Remedies

References, Part 1 Food Poisoning Caused by Botulism 1. Dolman CE: Human botulism in Canada (1919–1973). Can Med Assoc J 1974;110:191. 1A. Arnon SS: Infant botulism. In: Feigin RD, Cherry RD, ed. Textbook of pediatric infectious disease. Philadelphia: WB Saunders Co., 1997;1570–1577. 1B. Montecocco C, Schiavo G: Tetanus and botulism neurotoxins—A new group of zinc proteases. Trends Biochem Sci 1993;18:324–327. 2. 3. 4. 5. 6.

Hambleton P: Clostridium botulinum toxins: a general review of involvement in disease, structure, mode of action and preparation for clinical use. J Neurol 1992;239:16–20. Simcock PR, Kelleher S, Dunne JA: Neuro-ophthalmic findings in botulism type B. Eye 1994;8 (part 6):646–648. Williams G: A recent reminder of botulism. Aust Crit Care 1992;5:8–11. Woodruff BA, Griffin PM, McCroskey LM, et al: Clinical and laboratory comparison of botulism from toxin types A, B, and E in the United States, 1975–1988. J Infect Dis 1992;166:1281–1286. Roblot P, Roblot F, Fauchere JL, et al: Retrospective study of 108 cases of botulism in Poitiers, France. J Med Microbiol 1994;40:379–384.

7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

Fenicia L, Ferrini AM, Aureli P, et al: A case of infant botulism associated with honey feeding in Italy. Eur J Epidemiol 1993;9:671–673. Hurst DL, Marsh WW: Early severe infantile botulism [see comments]. J Pediatr 1993;122:909–911. Wohl DL, Tucker JA: Infant botulism: considerations for airway management. Laryngoscope 1992;102:1251–1254. Byard RW, Moore L, Bourne AJ, et al: Clostridium botulinum and sudden infant death syndrome: a 10 year prospective study. J Pediatr Child Health 1992;28:156–157. Graf WD, Hays RM, Astley SJ, Mendelman PM: Electrodiagnosis reliability in the diagnosis of infant botulism [see comments]. J Pediatr 1992;120:747–749. Gutierrez AR, Bodensteiner J, Gutmann L: Electrodiagnosis of infantile botulism. J Child Neurol 1994;9:362–365. Fach P, Hauser D, Guillou JP, et al: Polymerase chain reaction for the rapid identification of Clostridium botulinum type A strains and detection in food samples. J Appl Bacteriol 1993;75:234–239. Szabo EA, Pemberton JM, Gibson AM, et al: Polymerase chain reaction for detection of Clostridium botulinum types A, B and E in food, soil and infant faeces. J Appl Bacteriol 1994;76:539–545. Weber JT, Goodpasture HC, Alexander H, et al: Wound botulism in a patient with a tooth abscess: case report and review. Clin Infect Dis 1993;16:635–639. Mechem CC, Walter FG: Wound botulism. Vet Hum Toxicol 1994;36:233–237. Hatheway CF: Clostridium botulinum. In: Gorbach SL, et al, eds. Infectious disease. Philadelphia: WB Saunders, 1992.

Suggested Readings, Part 1 Food Poisoning Caused by Botulism Anonymous: Foodborne botulism—Oklahoma, 1994. MMWR 1995;44:200–202. Anonymous: Outbreak of type E botulism associated with an uneviscerated, salt-cured fish product—New Jersey, 1992. MMWR 1992;41:521–522. Anonymous: Wound botulism—California, 1995. MMWR 1995;44:889–892. Anonymous: Type B botulism associated with roasted eggplant in oil—Italy, 1993. MMWR 1995;44:33–36. Arnon SS: Infant botulism. Ann Rev Med 1980;31:57. Arnon SS, Midural TF, Damus K, et al: Honey and other environmental risk factors for infant botulism. J Pediatr 1979;94:331. Botulism from wounds. Br Med J 1974;214. Editorial. Burningham MD, Walter FG, Mechem C, et al: Wound botulism. Ann Emerg Med 1994;24:1184–1187. Centers for Disease Control. Botulism in the United States, 1899–1977: handbook for epidemiologists, clinicians, and laboratory workers. Atlanta: Author, May 1979. Cherington M, Ginsberg S: Type B botulism: neurophysiologic studies. Neurology 1971;21:43. Cherington M. Botulism: ten-year experience. Arch Neurol 1974;30:432. de Jesus V, Slater R, et al: Neuromuscular physiology of wound botulism. Arch Neurol 1973;29:425. Field M, Rao MC, Chang EB: Intestinal electrolyte transport and diarrheal disease. N Engl J Med 1989;321:879–883. Fujinaga Y, Takeshi K, Inoue K, et al: Type A and B neurotoxin genes in a Clostridium botulinum type AB strain. Biochem Biophys Res Commun 1995;213:737–745. Fullerton P, Gogna NK, Stoddart R: Wound botulism. Med J Aust 1980;28:662. Haaland KY, Davis LE: Botulism and memory. Arch Neurol 1980;37:657. Hatheway CL: Botulism: the present status of the disease. Curr Top Microbiol Immunol 1995;195:55–75. Hauschild AH: Clostridium botulinum in food-borne pathogens. New York: Dekker, 1989. Hill OW, Chesney J: Botulism—an ever-present menace: a report of three simultaneous cases due to type E. Review of the pediatric aspects and treatment. Clin Pediatr 1966;5:554. Infant botulism in 1931. discovery of a misclassified case. Am J Dis Child 1979;133:580. Jankovic J, Brin MF: Therapeutic uses of botulinum toxin. N Engl J Med 1991;324:1187. Jensen LB: Poisoning misadventures. Springfield, IL: Charles C Thomas, 1970:65. Johnson RO, Clay SA, Arnon SS: Diagnosis and management of infant botulism. Am J Dis Child 1979;133:586. Jurwitz S, Jacobs MR, Lichter J, et al: Botulism: a case report. S Afr Med J 1980;47:1003. Koenig MG, Drutz DJ, Mushlin AJ, et al: Type B botulism in man. Am J Med 1967;42:208. Kothare SV, Kassner EG: Infant botulism: a rare cause of colonic ileus. Pediatr Radiol 1995;25:24–26 (discussion 27). Lagos JC, Hagwood KW: Flaccid paralysis of acute onset in children. South Med J 1970;63:451. Lecour H, Ramos H, Almeida B, et al: Food borne botulism: a review of 13 outbreaks. Arch Intern Med 1988;148:578. Linial M: Bacterial neurotoxins—a thousand years later. Isr J Med Sci 1995;31:591–595. Mayer RF: The neuromuscular defect in human botulism. Electroencephalogr Clin Neurophysiol 1968;25:397. Merson MH, Hughes JM, Dowell VR, et al: Current trends in botulism in the United States. JAMA 1974;229:1305. Midura TF, Snowden S, Wood RM, et al: Isolation of Clostridium botulinum from honey. J Clin Microbiol 1979;9:282. Mygrant BI, Renaud MT: Infant botulism. Heart Lung 1994;23:164–168. Neff TA: Total management of botulism. N Engl J Med 1970;282:816. Nelson KE: The clinical recognition of botulism. JAMA 1979;241:503. Editorial. Oh SJ: Botulism: electrophysiologic studies. Ann Neurol 1977;1:481. Polin RA, Brown LW: Infant botulism. Pediatr Clin North Am 1979;26:345. Ryan DW, Cherington M: Human type A botulism. JAMA 1971;216:513. Schantz EJ, Sugiyama H: Toxic proteins produced by Clostridium botulinum. J Agr Food Chem 1974;22:26. Schmidt RD, Schmidt TW: Infant botulism: a case series and review of the literature. J Emerg Med 1992;10:713–718. Schuck PH: Botulism and nitrites. Science 1973;180:1322. Seals JE, Snyder JD, Edell TA, et al: Restaurant-associated type A botulism: transmission by potato salad. Am J Epidemiol 1981;113:436. Sonnabend D, Sonnabend W, Heinzle R, et al: Isolation of Clostridium botulinum type G and identification of type G botulinal toxin in humans: report of five sudden unexpected deaths. St. Gallen, Switzerland: Department of Pathology, Institute of Medical Microbiology, Kantans Hospital, 1980.

Stuart PF, Wiebe JD, McElroy R, et al: Botulism among Cape Dorset Eskimos and suspected botulism at Frobisher Bay and Wakeham Bay. Can J Public Health 1970;61:509. Terranova W, Breman JG, Locey RP, et al: Botulism type B: epidemiologic aspects of an extensive outbreak. Am J Epidemiol 1978;108:150. Terranova W, Palumbo JN, Breman JG: Ocular findings in botulism type B. JAMA 1979;241:475. Thomas DG: Infant botulism: a review in South Australia (1980–89). J Paediatr Child Health 1993;29:24–26. Tsunenari S, Uchimura Y, Kanada M: Puffer poisoning in Japan—a case report. J Forensic Sci 1980;25:240. Wand M, Mather JA: Diphenylhydantoin intoxication mimicking botulism. N Engl J Med 1972;286:88. Wise EJ: Preventing complications in infant botulism. Dimens Crit Care Nurs 1995;14:86–91. Wound botulism—Texas, California, Washington. MMWR 1980.

References, Part 2 Food Poisoning Caused by Microorganisms 1. Passaro DJ, Reporter R, Mascola L, et al: Epidemic Salmonella enteritidis infection in Los Angeles County, California—the predominance of phage type 4. West J Med 1996;165:126–130. 2. Hennessy TW, Hedberg CW, Slutsker L, et al: A national outbreak of Salmonella enteritidis infections from ice cream: The Investigation Team. N Engl J Med 1996;334:1281–1286. (See comments.) 2A. Glynn KM, Bopp C, Dewitt W: Emergence of multi-drug resistant salmonella enterica serotype (typhimurium DT104) infections in the U.S. N Engl J Med 1998;338:1333–1338. 2B. Sack RR, Rahman M, Yunus M, et al: Anti-microbial resistance in organisms causing diarrheal disease. Clin Infect Dis 1997;24(suppl 1):102–105. 3. 4. 5. 6. 7.

Ribner BS: Salmonella. In: Schlossberg D, ed. Current therapy of infections disease. St. Louis: CV Mosby, 1996. Bender JB, Hedberg CW, Besser JM: Surveillance for E Coli 0157:H7 infections. N Engl J Med 1997;337:388–394. Hyams KC, Bourgeois AL, Merrell BR, et al: Diarrheal disease during Operation Desert Shield. N Engl J Med 1991;325:1423–1428. Liu LX, Weller PF: Drug therapy: antiparasitic drugs. N Engl J Med 1996;334:1178. Sorvillo FJ, Leif LE, Waterman H: Incidence of campylobacteriosis among patients with AIDS in Los Angeles County. J Acquir Immune Defic Syndr 1991;4:598–602.

7A. Medical letter. The choice of antibacterial drugs. Med Letter 1996;38:25–34. 8. 9. 10. 11.

Allos BM, Blaser MJ: Campylobacter jejuni and the expanding spectrum of related infections. Clin Infect Dis 1995;20:1092–1101. Dalton CB, Austin CC, Sobel J, et al: An outbreak of gastroenteritis and fever due to Listeria monocytogenes in milk. N Engl J Med 1997;336:100–105. Bula CJ, Bille J, Glauser MP: An epidemic of food-borne listeriosis in western Switzerland: description of 57 cases involving adults. Clin Infect Dis 1995;20:66–72. Levine WC, Bennett RW, Choi Y, et al: Staphylococcal food poisoning caused by imported canned mushrooms. J Infect Dis 1996;173:1263–1267.

11A. Khuroo MS, Wani NA, Javid G, et al: Percutaneous drainage compared with surgery for hepatic hytatid cysts. N Engl J Med 1997;337:881–887. 12. Sullivan EA, Kamb ML, Jones JL, et al: The natural history of eosinophilia–myalgia syndrome in a tryptophan-exposed cohort in South Carolina. Arch Intern Med 1996;156:973–979. 13. Jacobs J, Behren JV, Kreutzer R: Serious mushroom poisonings in California requiring hospital admission, 1990 through 1994. West J Med 1996;165:283.

Suggested Readings, Part 2 Food Poisoning Caused by Microorganisms and Toxins Altekruse SF, Swerdlow DL: The changing epidemiology of foodborne diseases. Am J Med Sci 1996;311:23–29. Anonymous: Tetrodotoxin poisoning associated with eating puffer fish transported from Japan—California, 1996. MMWR 1996;45:389–391. Auerbach PS: Marine envenomations. N Engl J Med 1991;325:486. Balandrin MF, Klocke JA, Wurtele ES, et al: Natural plant chemicals: sources of industrial and medicinal materials. Science 1985;228:1154–1160. Barbato MP: Poisoning from accidental ingestion of mushrooms. Med J Aust 1993;158:842–848. Battle EH, Elliott SO: Three cases of hemorrhagic colitis in West Virginia due to Escherichia coli 0157:H7. WV Med J 1995;91:320–321. Bean NS, Goulding JS, Cao C, et al: Food borne disease outbreaks in USA 1998–1992. MMWR 1996;45:1–66. Bishop NJ, Morley R, Day JP, et al: Aluminum Neurotoxicity in pre-term infants receiving intravenous feeding solutions. N Engl J Med 1997;336:1557–1562. Blaser MJ: How safe is our food? lessons from an outbreak of salmonellosis. N Engl J Med 1996;334:1324. Carter AO, Borczyk AA, Carlson JA, et al: A severe outbreak of Escherichia coli 0157:H7: associated hemorrhage colitis in a nursing home. N Engl J Med 1987;317:1496–1500. Chia JK, Clark JB, Ryan CA, et al: Botulism in an adult associated with food borne intestinal infection with Clostridium botulinum. N Engl J Med 1986;315:239. Drusco GM, Serrao E: Healthy carriers of positive staphylococcal coagulase and the prevention of food poisoning in aircraft catering. Minerva Med 1980;14:1991. DuPont HL, Sullivan P, Evans DG, et al: Prevention of travelers diarrhea (emporiatric enteritis). JAMA 1980;243:237. Eastaugh J, Shepherd S: Infection and toxic syndromes from fish and shellfish consumption. Arch Intern Med 1989;149:1735. Evans MR, Hutchings PG, Ribeiro CD, et al: A hospital outbreak of salmonella food poisoning due to inadequate deep-fat frying. Epidemiol Infect 1996;116:155–160. Evans MR, Tromans JP, Dexter EL, et al: Consecutive salmonella outbreaks traced to the same bakery. Epidemiol Infect 1996;116:161–167. Fleming DW, Cochi SL, MacDonald KL, et al: Pasteurized milk as a vehicle of infection in an outbreak of listerosis. N Engl J Med 1985;312:404–407. Goruzzo E, et al: Use of norfloxacin to treat chronic typhoid carriers. J Infect Dis 1988;157:1221. Gross RL, Newberne PM: Naturally occurring toxic substances in foods. Clin Pharmacol Ther 1978;22:680. Hedberg CW, David MJ, White KE, et al: Role of egg consumption in sporadic Salmonella enteritidis and Salmonella typhimurium infections in Minnesota. J Infect Dis 1993;167:107–111. Hedberg CW, White KE, Johnson JA, et al: An outbreak of Salmonella enteritidis infection at a fastfood restaurant: implications for foodhandler-associated transmission. J Infect Dis 1992;164:1135–1140. Hedberg CW, Fishbein DB, Janssen RS, et al: An outbreak of thyrotoxicosis caused by the consumption of bovine thyroid gland in ground beef. N Engl J Med 1987;316:993. Herwaldt BL, Ackers ML, Cyclospora Working Group. An outbreak of cyclosporiadid in 1996 associated with imported raspberries. N Engl J Med 1997;336:1548–1556. Holmberg SD: Cholera and related illnesses caused by Vibrio species. In: Gorbach SL, et al., eds. Infectious diseases. Philadelphia: WB Saunders, 1992. Hooper DC, Wolfson JS: Fluoroquinolone antimicrobial agents. N Engl J Med 1991;324:385.

Hughes JM, Potter ME: Scombroid-fish poisoning—from pathogenesis to prevention. N Engl J Med 1991;324:766. Kolata G: Testing for trichinosis. Science 1985;227:621. Koppel C: Clinical symptomatology and management of mushroom poisoning. Toxicon 1993;31:1513–1540. Lee C: Fish poisoning with particular reference to ciguateria. J Trop Med Hyg 1980;83:93. Mahler H, Pasi A, Kramer JM, et al: Fulminant liver failure in association with the emetic toxin of bacillus virus. N Engl J Med 1997;336:1142–1148. McClain JL, Hause DW, Clark MA: Amanita phalloides mushroom poisoning: a cluster of four fatalities. J Forensic Sci 1989;34:83–87. McMillan M, Thompson JG: An outbreak of suspected solanine poisonining in schoolboys. Quart J Med 1979;48:227. Mishu B, Koehler J, Lee LA, et al: Outbreaks of Salmonella enteritidis infections in the United States, 1985–1991. J Infect Dis 1994;169:547–552. Morris JG, Black RE: Cholera and other vibrioses in the United States. N Engl J Med 1985;312:343. Morrow JD, Margolies GR, Rowland J, et al: Evidence that histamine is the causative toxin of scombroid-fish poisoning. N Engl J Med 1991;324:716–720. Munro LC: Naturally occurring toxicants in foods and their significance. Clin Toxicol 1976;9:647. Olesen LL: Amatoxin intoxication. Scand J Urol Nephrol 1990;24:231–234. Olson KR, Pond SM, Seward J, et al: Amanita phalloides-type mushroom poisoning. West J Med 1982;137:282–289. Paydas S, Kocak R, Erturk F, et al: Poisoning due to amatoxin-containing Lepiota species. Br J Clin Pract 1990;44:450–453. Perl TM, Bedard L, Kosatsky T, et al: An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. N Engl J Med 1990;322:1775. Pinson CW, Daya MR, Benner KG, et al: Liver transplantation for severe Amanita phalloides mushroom poisoning. Am J Surg 1990;159:493–499. Pinson CW, Bradley AL: A primer for clinicians on mushroom poisoning in the west. West J Med 1996;165:318. Riedo FX, Pinner RW, Tosca ML, et al: A point-source foodborne listeriosis outbreak: documented incubation period and possible mild illness. J Infect Dis 1994;170:693–696. Rodrigue DC, Tzuxe RV, Rowe B: International increase in Salmonella enteritidis: a new pandemic? Epidemiol Infect 1990;105:21–27. Salmonella surveillance: annual tabulation summary, 1993–4. Atlanta: Centers for Disease Control and Prevention, 1995. Schlech WF III: Listeria gastroenteritis—old syndrome, new pathogen. N Engl J Med 1997;336:130. Schwartz GR: In bad taste: the MSG syndrome. Santa Fe: Health Press, 1988. Su C, Brandt LJ: Escherichia coli 0157:H7 infection in humans. Ann Intern Med 1995;123:698–714. Sundaram MB, Swaminathan R: Body potassium depletion and myopathy due to chronic licorice ingestion. Postgrad Med J 1981;55:48. Tappero JW, Schuchat A, Deaver KA, et al: Reduction in the incidence of human listeriosis in the United States: effectiveness of prevention efforts? The Listeriosis Study Group. 1995;273:1118–1122.

JAMA

Taylor DN, Porter BW, Williams CA, et al: Campylobacter enteritis: a large outbreak traced to commercial raw milk. West J Med 1982;137:365. Teitelbaum JS, Zatorre RJ, Carpenter S, et al: Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. N Engl J Med 1990;322:1781. Telzak EE, Bodnick LD, Greenberg MS, et al: A nosocomial outbreak of Salmonella enteritidis due to the consumption of raw eggs. N Engl J Med 1990;323:395–397. Trestrail JH: Mushroom poisoning in the United States—an analysis of 1989 United States Poison Center Data. J Toxicol Clin Toxicol 1991;29:459–465. Ward LR, de Sa JD, Rowe B: A phyage-typing scheme for Salmonella enteritidis. Epidemiol Infect 1987;99:291–294. Wistrom J, Jertborn M, Hedstrom SA, et al: Short-term self-treatment of traveler's diarrhoea with norfloxacin: a placebo-controlled study. J Antimicrob Chemother 1989;23:905–913. Wittman RJ, Flick GJ: Microbial contamination of shellfish: prevalence, risk to human health, and control strategies. Ann Rev Public Health 1995;16:123–140. Yolken RH, Losonsky GA, Vonderfecht S, et al: Antibody to human rotavirus in cow's milk. N Engl J Med 1985;312:605–610. Books148Ovid Copyright © 1999, Williams and Wilkins GR Schwartz, et al, Principles and Practice of Emergency Medicine, 4th edition

CHAPTER 149 EMS SYSTEMS DEVELOPMENT IN THE UNITED STATES Principles and Practice of Emergency Medicine

CHAPTER 149 EMS SYSTEMS DEVELOPMENT IN THE UNITED STATES Alexander Kuehl Capsule Introduction Medical Oversight Indirect Medical Control Direct Medical Control Personnel and Education Communications Operations EMS: Moving into the Twenty-First Century National Contacts

CAPSULE The influence of experienced physicians on the development of prehospital care has ebbed and flowed over the years. Because emergency medical services (EMS) has entered a period of consolidation and change, it is critical that physicians, especially emergency physicians, interact at every level of EMS systems.

INTRODUCTION Throughout the world, during the century before 1950, physicians were involved both conceptually and operationally in the provision of ambulance services; however, during World War II, physician involvement began to wane. After the war, rapid changes in the structure and delivery of health care—reflecting differences in the philosophy of basic health care and in the integration of new clinical methodologies—accentuated international differences in the approach to prehospital care ( 1). In the United States, two major patterns of ambulance services evolved. In the larger cities, uncoordinated hospital-based ambulances gradually coalesced into centrally coordinated city-wide programs, usually administered by the municipal hospitals or by the fire departments. In rural areas, the traditional funeral home “ambulances” gave way to volunteer fire department or rescue squad models. In most locales, a few for-profit providers continued to deliver transport services, occasionally contracting with government to provide emergency prehospital and transport services. Before the mid-1960s, there was neither coordination among the various providers nor integration of prehospital services with medical facilities; there existed little legislation or regulation applicable to ambulance services, limited formal training, and minimal physician involvement. Several factors converged in the late 1960s to create a revolution in prehospital care. One of these factors grew out of a mandate of the 1966 National Highway Act for the individual states to develop programs addressing highway trauma (2). Another was the report by the National Academy of Science/National Research Council, “Accidental Death and Disability: The Neglected Disease of Modern Society,” which identified accidental death and disability as a serious and unrecognized medical epidemic; it focused attention specifically on problems with the delivery of prehospital care ( 3). In 1971, partly as a result of that report, the Nixon Administration funded EMS demonstration projects. Hence, the Department of Health, Education, and Welfare (DHEW) underwrote several EMS demonstration projects, and the Department of Transportation (DOT) began to develop national standards for training and for ambulances (4). The following year, the Robert Wood Johnson Foundation created a grant program for the establishment of regional EMS systems (EMSS) ( 5). Ultimately, in 1973, the Emergency Medical Service System Act (P.L. 93-154), largely based on the experience of the demonstration projects and grant programs, was adopted (6). The thrust of P.L. 93-154 was to encourage the development of nationwide multicounty comprehensive EMS systems. The 15 “essential” components mentioned in the legislation were a usable template for initial EMS system design efforts. Although medical oversight was not formally addressed as one of the essential elements, the medical director of the DHEW program recognized the need for and encouraged the development of local physician leadership ( 7). To create the individual multicounty regions necessary to secure federal funding, state EMS legislation was necessary. The resultant state laws varied tremendously, especially in regard to the issues of responsible medical oversight, operational authority, and financing. In some states, physician input was required; in others, medical oversight was simply not addressed. Usually the responsibility for coordinating the regional activities was assigned to a regional council composed of physicians, prehospital providers, and consumers; unfortunately, medical input was often limited to physicians removed from the emergency medicine mainstream. Even now, although most states have EMS directors, only a handful have physicians in that position. Because the Federal regulations regarding P.L. 93-154 were relatively flexible, an earlier series of innovations in medicine beginning in the 1960s influenced the initial designs of the regional programs ( 8,9). Cardiopulmonary resuscitation was shown to be effective. Physician-directed prehospital cardiac response programs and the Vietnam War experience with organized trauma care were publicized and emulated ( 10). Quickly, it was recognized that prehospital care could be delivered by nonphysician personnel, such as those educated as emergency medical technicians (EMTs). Although the various EMT curricula did not require physician input, the paramedics who evolved directly from the original prehospital cardiac response programs were essentially extensions of physicians ( 11). These two diverse groups of providers developed more or less independently; the DOT EMT curriculum became a nationally EMT standard level, whereas paramedic curriculum continued to differ significantly by locality. The practice of the EMT commonly was called basic life support (BLS), and the practice of the paramedic was labeled advanced life support (ALS). The latter required medical oversight, whereas the former did not. Because of the relatively great differences in initial training requirements between those two levels, many jurisdictions introduced intermediate level providers, immediately and forever blurring the distinctions between ALS and BLS. By 1980, prehospital care providers existed at virtually every possible level of education between 70 and 3,000 hours; the degree of required medical oversight was almost as variable (9). The decade of the 1970s was a period of rapid EMS innovation; some concepts grew and others faded from the scene. Unfortunately, subsequent amendments to the EMSS Act of 1973 never addressed the absence of required medical oversight in the original legislation.

MEDICAL OVERSIGHT Although some state EMS legislation mandated medical oversight, most neglected to address the issue. In 1978, the National Academy of Science released a report finding “EMS in the United States in midpassage is urgently in need of midcourse corrections but uncertain as to the best direction and degree.” The Academy then recommended “research and evaluation directed both to questions of immediate importance to EMS system development and to long range questions.” Without adequate investment in both types of research, EMS in the United States will be in the same position of uncertainty a generation hence as it is today” ( 9). Nevertheless, throughout the 1980s, federal involvement in funding regional EMS was gradually phased out ( 1). As states attempted to update EMS legislation and as physicians took a greater interest in prehospital care, medical oversight began to trickle down from the paramedic level through the intermediate levels and ultimately to the BLS level (12). Transiently, in the early 1980s, it appeared that independent licensure for paramedic providers would emerge; however, this trend peaked and then diminished as the medical community began to exert influence to the contrary. Currently, medical oversight is a standard nationwide conceptual requirement for intermediate and advanced providers, whereas medical oversight for EMTs and first responders is growing ( 13). Unfortunately, in most jurisdictions, the vagueness of the enabling legislation has created a confused situation regarding actual medical oversight authority. Although many EMS regions have either a formally designated regional medical director or a physician advisory committee, the authority varies from absolute to nil. In the latter case, the individual ambulance service medical directors retain authority and accountability. More enlightened and often newly developing or reorganizing EMS regions have established a relatively powerful medical director selected by a medical advisory committee. Obviously, system medical directors must delegate significant responsibility to the service medical advisors. State law, however, remains the determining factor as to actual medical oversight. In many states, the law remains unclear or even contradictory, effectively preventing the local assumption of medical oversight ( 14). In some parts of the country, medical oversight is contracted from a local medical school or teaching hospital by the ambulance agency. Medical oversight is the medical, legal, and moral responsibility for the delivery of prehospital medical care. The two traditional elements of medical oversight are direct (on-line) and indirect (off-line) medical control. Because systems of EMS medical oversight are not uniform, a universal terminology remains elusive ( 1). As early as 1978, direct medical control was defined as “the direction of patient care by a physician ... remote from the ambulance attendant and his patient. Some degree of direct medical control through the use of treatment protocols that are in effect such as standing orders is commonly practiced. It is not certain what degree of authority or responsibility is appropriate to delegate” ( 8).

Today, direct medical control normally refers to either the electronic direction or the actual on-scene presence of a physician or a designated surrogate. Indirect medical control is provided prospectively, concurrently, and retrospectively to the actual patient care. Prospectively, it includes the medical design of the EMS system, the creation of clinical protocols, and the education and certification of the providers; concurrently, it consists of the observational monitoring of prehospital patient care; and retrospectively, it includes the provision of quality assurance, risk management, continuing education, and remediation activities. Before the widespread use of the military antishock trousers (MAST) as a BLS adjunct, neither first responders nor EMTs had significant medical input in their education, operation, or quality processes. The formal introduction of MAST (now rarely used) into the national EMT curriculum brought most EMTs into the sphere of medical oversight. If EMTs were upgraded to the intermediate levels through education in traditional ALS interventions, such as advanced airway control and intravenous (IV) cannulation, they almost always came under the auspices of some degree of medical oversight ( 13). The original national EMT-A curriculum and the subsequent state regulations regarding BLS care essentially created practitioners independent of medical oversight, the simultaneous development of paramedic programs created physician extenders. The first paramedic programs began with intense direct medical control, which often ebbed due to many factors identified in reference 1.

INDIRECT MEDICAL CONTROL Most EMS systems developed with a significant degree of prospective medical input and the need for telemetry transmission. Medical direction was sought concerning the choices of system configurations and provider levels, the development of training programs and protocols, the expansion of emergency medical dispatch, and disaster medicine preparedness. Depending on the specific clinical interests and expertise of the involved physicians, the foci of the programs were defined. For example, in Maryland and Illinois, leadership by surgeons led to the development of renowned trauma systems, whereas in Seattle, internists created a program focused on the area of cardiac emergencies ( 8). Usually, several physicians became prominent members of the local EMS governing body or regional council; often, a single physician became the project medical director ( 8). In recent years, a growing public demand for better and more accountable prehospital emergency care encouraged local political leaders to recruit and appoint physicians to paid, occasionally full-time, regional medical director roles. One of the first prospective medical requirements that must be addressed is the assessment of the emergency medical requirements of the community. These need determinations, along with an analysis of all existing medical resources, effectively define the initial system design. Other than medical need, the major influence on provider level decisions is the economic ability of the jurisdiction to educate and to maintain the skills of the field providers. State laws usually limit the choice of provider level to that defined by the state EMS regulations; however, there is often significant flexibility for local variation and innovation, especially in the area of ALS protocols ( 1). The development of treatment protocols for intermediate-level providers and paramedics originally was the sole domain of either the service medical director or the local medical advisory committee. Gradually, other involved medical providers requested and usually were granted the opportunity to participate in the development of the local medical protocols. Some states, however, developed universal protocols that mandated statewide treatment options ( 14). The structure and operation of call receiving, patient questioning, and call priority determination are the areas in which medical oversight most rapidly is expanding. Along with the initial conceptualization of a comprehensive EMS system, the tasks of optimally prioritizing and responding to patient requests are “mission critical” in providing optimal or even satisfactory patient care ( 1). Local medical directors daily face the dilemma of getting the right unit to the right patient at the right time, all in the face of sometimes overwhelming demand. Clawson (15) developed a philosophy that combined and refined many of the evolving dispatch concepts. When modified for local differences, the resultant emergency medical dispatch (EMD) algorithms can be used effectively in most EMS systems. As physicians became more knowledgeable and sophisticated about EMS systems, they began to realize the medical importance of operational issues such as ambulance placement strategies, work schedules, and staffing patterns. In most jurisdictions, long and complex political and economic histories influence these decisions. Physicians, however, should not be reticent about suggesting or even mandating medically appropriate changes. Originally, the education of prehospital care providers, especially at the intermediate and advanced levels, was service specific; however, as the various states adopted standardized statewide training curricula, the differences within states disappeared. Marked differences still exist among the states because of the lack of a universally accepted national curriculum above the EMT-B level. The adoption of a standardized paramedic curriculum in 1997 encouraged some states to adopt a common national paramedic level. Because most EMS provider curricula have been developed to establish minimal levels, local physician input remains critical to the refinement and expansion of standard state education requirements. Some states, however, do not allow providers to practice skills beyond those taught in the standardized statewide programs ( 14). Obviously, the development of treatment and transport protocols should reflect the existing provider levels, the philosophies of the responsible physicians, and the results of the few solid clinical studies. Treatment protocols are divided between standing orders, which may be performed without concurrent physician input, and direct medical control options, which require concurrent direct physician control. Among EMS systems, there is a continuum, ranging from all standing orders to no standing orders; in the latter, direct medical control is required for every clinical action. The exact point chosen on the continuum depends on local operational factors, physician preferences, and state law. Most clinical protocols are initiated after identification by the prehospital care provider of either a presumptive diagnosis or a specific constellation of symptoms. Logically, more highly educated and more experienced prehospital care providers operate with more standing orders; however, other factors influence these decisions. In urban environments with short transport times, the medical need for time-consuming direct medical control options is less than it is rural environments. In reality, the attitude of the responsible physicians is the single most influential factor in the determination of the degree of clinical independence allowed the prehospital care providers. Indirect medical control, performed concurrently with patient care, generally is limited to process-oriented quality assurance, such as the observation of prehospital care or EMD operations by either physicians or physician surrogates who may be senior-level providers or nurses. Despite the 1978 prediction of the Committee on EMS of the National Academy of Science, concurrent quality assurance remains popular ( 13). Concurrent process-oriented quality assurance has many theoretical advantages over retrospective run review, but it is obviously much more expensive and difficult, especially in larger systems. Today, the majority of retrospective, indirect medical control is focused on call review, documentation-related quality assurance, remedial education, and risk management. A confusing aspect of retrospective medical control is the imprecise division between prehospital quality assurance and employee discipline ( 14).

DIRECT MEDICAL CONTROL Direct medical control traditionally describes the concurrent interaction between care providers at the scene and a physician ( 14). The extent of direct medical control reflects the degree to which the physician-director wants to maintain hands-on authority over the actions of the providers. Clearly, there is a dearth of research about how much direct medical control is appropriate; in fact, the best answer probably varies with the prehospital provider, with the protocols, and with the physician ( 8). As long as the “physician extender” model is applied to paramedics, there is likely to be a trend toward less direct medical control. Whenever less-educated providers undertake more sophisticated interventions, a greater degree of direct and indirect medical control is required; however, the increased availability of devices such as the automated external defibrillator (AED) allows providers with less education to deliver sophisticated interventions traditionally reserved for paramedics. The provision of direct medical control by radio, with or without the transmission of medical telemetry, has been the usual exposure of most physicians to prehospital care; however, direct medical control originally was provided at the scene by physicians responding with the providers ( 13). After the initiation of the original prehospital programs, telemetry sent from the field and direct communication with a physician were thought essential for the appropriate operation of a paramedic system. The usefulness and necessity of the transmission of telemetry are increasingly questioned ( 14). Chapter 16 highlights the increasing controversies regarding which intervention actually helps. The challenge of the twenty-first century will be to find the balance that best serves research-proven medical needs and the budget of the public. Obviously, each jurisdiction will make its own decision, but more clinical and educational research is required. Currently, myriad configurations are used for the provision of direct medical control, ranging from systems in which a single physician educates the provider, has direct medical control, and actually treats the patient, to systems in which the physician occasionally gives orders over the radio but never sees either the patient or the provider ( 14). The direct medical control facility (sometimes imprecisely called a base station) is the site designated by an EMS system to provide such medical control. Although some large, mature systems have removed direct medical control from hospitals, most direct medical control still emanates from emergency departments. These sites may be staffed by physicians, by specially trained nurses, or by paramedics acting as physician surrogates. If the direct medical control facility is staffed by physician surrogates, a physician should be available for consultation. Physician preparation for direct medical control should include ride-alongs, exposure to the medicolegal aspects of prehospital care, curriculum preparation, management problems, and a supervised probationary period. Major problems facing regional EMS systems as they evolve into the new millennium are codifying and clarifying medical oversight. As the significant players of the

recent past leave the arena, many new physicians are beginning to lead. Because mechanisms for choosing the medical directors are often not defined, optimal constructs have not been universally accepted. High legal and social visibility makes the risks significant, and smooth transitions may be difficult. No matter who provides medical oversight in the future, we are on the verge of technologic revolutions that will alter the way in which medical oversight physicians view clinical, educational, and supervisory problems. The efficient and economical solutions of the future may place the medical community in direct conflict both with strongly established provider groups and with demanding consumers. The design of the medical oversight construct for a specific crew, a service, a region, or a state must be crafted while taking into account the existing medical, economic and political environments. Authority for the various aspects of medical oversight must be established so that the medical community, care providers, and society understand who is medically responsible. The direct and indirect facets of medical control must be fitted carefully together, with neither overlaps nor gaps. Legal liability will further define responsibility.

PERSONNEL AND EDUCATION There are five general levels of training for prehospital providers. Although the borders among them are vague, there are now national curricula for each of the levels: 1. 2. 3. 4. 5.

Citizen cardiopulmonary resuscitation (CPR) and first aid (initial responder) First responder Basic emergency medical technician (EMT-Basic) Intermediate emergency medical technician (EMT-intermediate) Advanced emergency medical technician (EMT-Paramedic).

First responder was originally the generic name for police officers or firemen trained in CPR and first aid ( 9). Many jurisdictions have expanded the role of first responders to include many of the activities traditionally taught to EMT-Basics, and, in a growing number of jurisdictions, the use of the AED. The specific term First Responder (FR) is now used to describe persons trained to the DOT national standard. The descriptive term “initial responder” is used for emergency personnel who are not educated to a formal FR level. The EMT-Basic curriculum was originally standardized in 1970 as EMT-A, which gradually expanded to more than 100 hours and soon included training in the use of the MAST garment. In 1994, the EMT-Basic level was reframed as EMT-B to allow for advanced airway and AED. Obviously the need and requirement for medical oversight, although not necessarily direct medical control, expands as the prehospital provider activities become more medically sophisticated ( 16,17). The first intermediate providers were EMT-Basics with added training modules in advanced airway management, intravenous cannulation, drug use, arrhythmia recognition, and/or defibrillation. Initially, the intermediate EMTs were thought to be starting on a progressive career ladder to paramedic. However, it became obvious that progress up the ladder to paramedic from an intermediate level was difficult and perhaps unnecessary ( 9). Consequently, today it is possible for intermediate EMTs with less than 200 hours of training to duplicate effectively the clinical interventions performed by paramedics with 500 or more hours of training. This paradox developed because the initial paramedic programs put a heavy emphasis on teaching the scientific basis of prehospital care, whereas more recently developed intermediate programs have deemphasized the fundamental science requirements and focused on actions. The significant financial cost of training and of refreshing traditional paramedics is pushing local programs and medical directors away from the paramedic level and toward the intermediate levels. Only recently have researchers started to compare rigorously the clinical success of various types of interventions, providers, and system models (9,18,19). No matter which level of provider is chosen for a given system, physicians must be involved in the choice of the provider level, the education, and the operations ( 13,20). Unless expanded health care roles can be developed for the more highly educated paramedics, many regions likely will revert to intermediate levels as more cost-effective and medically acceptable prehospital care providers become available ( 21). In the more rural areas of the United States and in developing countries, the focus of prehospital education remains at the basic and intermediate levels. Although there has been a quest for an expanded role for paramedics, at this point it is still unclear whether a paramedic role can be developed that can economically and safely fill a primary care niche in certain medically underserved areas. In countries in which there is a surplus of physicians or nurses, those providers are effectively used as the main element of the evolving EMS systems. (See Chapter 154.)

COMMUNICATIONS Most ambulance services in the United States are accessed by dialing 911, although some areas still use a seven-digit telephone number. Universal use of 911 and ultimately “enhanced” 911 must be encouraged across the country ( 9). Newer satellite technology will play a larger role in the future. As EMS systems developed, the organization and function of dispatching ambulances was usually left as the responsibility of non-EMS administrators. The awareness of the medical need to prioritize responses on something other than a “first in–first out” basis gradually became obvious. Although organization structure and ambulance distribution remain, for the most part, outside the direct domain of medical oversight, the caller-questioning sequences for determination of medical priority and the algorithmic determinations of which unit is dispatched to a given call increasingly have been scrutinized by those responsible for medical oversight. In the early 1980s, many medically developed prioritization–dispatching systems independently evolved. By the 1990s, a small number of EMD paradigms rapidly created a standard for all aspects of medical dispatch. Such programs make it much easier for local medical directors to develop successful EMD programs for their localities (15,22). Generally, ultrahigh frequencies (UHF) are used for direct medical control and for the transmission of medical information, and very high frequencies (VHF) are used for dispatch. Increasingly, telephone lines and cellular telephone networks are used in EMS communications. There is a danger that in disaster situations, these modes will be inoperative. Already, managed care information systems are being merged with EMS dispatch activities.

OPERATIONS If one uses Stout's definition that “an EMS system is a network of organizations generating a comprehensive, coordinated response to a patient's need for on-scene medical care, medical transportation, and enroute support,” the system can be created in dozens of ways ( 7). Urban systems are increasingly multitiered with first responder, EMT-B and paramedic components. Rural systems tend to use a variety of levels, often with an intermediate EMT level as the most sophisticated; however, a growing number of rural and suburban systems have a formal nurse or physician response built in as the highest level component. Unsolved operational issues for EMS include whether nontransport response vehicles should be used, the optimal response time target, which type of transport vehicle design is safest and most efficient, and how aeromedical responses should be integrated into the system ( 7,23,24). Generally, the combination of a smoothly functioning EMS system and a plan to augment and expand its function is the underpinning of medical disaster preparedness for all but the most extensive disasters. Because the first 12 hours are critical for medical disaster response, medical resources from distant areas must arrive within that relatively short time frame to be meaningful. The National Disaster Medical System has been developed with the dual purposes of bringing medical resources to victims of disaster and of transporting patients to distant hospital facilities within an acceptable time frame ( 25,26).

EMS: MOVING INTO THE TWENTY-FIRST CENTURY When paramedic providers first began to deliver medical care in the field, the physician community expressed strong concerns as to how well care would be provided and the impact on the practice of medicine. Consequently, extensive direct medical control was required in most early paramedic programs ( 1). As it became apparent that prehospital care was relatively safe and unthreatening to the day-to-day practice of medicine, the requirements for direct medical control by physicians waned. In some areas, physician surrogates, such as nurses, actually replaced the physicians; in others, the providers operated under expanded standing orders ( 9,27). Originally, cardiac telemetry was transmitted regularly from prehospital scenes to direct medical control physicians. The aggressive retrospective call review that marked the early days of paramedics has become more routine and perfunctory. Only recently has the need for more thorough concurrent and retrospective quality assurance of prehospital care reappeared as a critical task for medical oversight ( 13,27,28). Arguably, the most significant modern advance in prehospital care has been the gradual development of comprehensive organized EMS systems. Because the initial impetus for the regional organization of EMS systems was the EMSS Act of 1973, many of the resultant systems were organized around the trauma center concept ( 6,8,29,30). Although the organization of EMS systems varies significantly, several future trends can be identified. First, EMS is in transition from a relatively unimportant cottage industry to a significant force in health care delivery. Initially perceived as a relatively inexpensive and insignificant facet of health care, EMS is now a medically, politically, and economically influential partner. As the health care industry recognizes that EMS systems have a profound impact on many aspects of health care delivery, no longer are a few persons allowed to direct, within a vacuum, the provision of prehospital care. The citizens and leaders of most jurisdictions have come to view EMS with the same attitudes and expectations they do police and fire protection. In some areas, fire

services are aggressively developing or coopting EMS activities ( 31,32 and 33). Second, the cost of providing contemporary prehospital care has accelerated even faster than health care costs in general. With the universal diminution of volunteerism and the rapid growth in sophistication of prehospital medicine, those financially responsible are asking logical and penetrating questions concerning the efficiency and the quality of prehospital and disaster medicine ( 18,26). As costs and visibility grow, the public will demand fully integrated and efficient systems. In addition, clinically unproven medical interventions will be discontinued. Third, eventually those responsible for the development of regional EMS systems must cross the prehospital–hospital interface to influence health care system design, designation, and operation. Such new directions will capture the intense attention of the entire health care industry, especially regarding call-receiving triage. Fourth, sooner or later EMS provision in a jurisdiction becomes a politically charged topic. Because it has a high profile, EMS is a highly visible element of government. It is a service that is vulnerable to criticism because of the duality of the high frequency of its need and the high cost of its failure. It is increasingly common to observe EMS administrators and medical directors caught in the media spotlight, buffeted by political agendas, financial cutbacks and expanding needs. Fifth, the rapid growth in size and innovation that marked the adolescence of EMS has come to an end. In fact, the next expected evolutionary trend, that of more gradual growth and consolidation, has not universally occurred. EMS development is trapped in the status quo, a sort of equilibrium in which evolutionary change is either not acceptable or too expensive for the existing stakeholders. Although little doubt exists that appropriate medical organizations and technical advances applicable to the prehospital environment eventually will be integrated into our systems, the resistance to change may be great. When a developmental stalemate is reached, cataclysmic change is likely. The emergence of managed care may be that change. As greater efficiency and professionalism are demanded of EMS and as volunteerism and funding decline, it may be necessary to expand the scope of prehospital services to keep EMS as an affordable public service. Therefore, it is not surprising that many are choosing to view prehospital care more broadly as a public health activity rather than a public safety or even an emergency medical activity. Nor is it surprising that the privatization of prehospital care and the integration into managed care often are promoted as logical next steps.

NATIONAL CONTACTS American Academy of Emergency Medicine, 611 E. Wells Street, Milwaukee, WI 53202; 800-884-AAEM. American College of Emergency Physicians, PO Box 619911, Dallas, TX 75261; 800-798-1822. National Association of EMS Physicians, 230 McKee Place, Suite 500, Pittsburgh, PA 15213; 800-228-3677. National Academy of Emergency Medical Dispatch, 139 E. South Temple, Salt Lake City, UT 84111; 800-960-6236. National Disaster Medical System, 5600 Fishers Lane, Rockville, MD 20857. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33.

Kuehl AE: Prehospital systems and medical oversight. St. Louis: CV Mosby, 1994. Law of the 89th Congress, Highway Safety Act of 1966, Washington, DC, 1966. Accidental death and disability, the neglected disease of modern society. Washington, DC: Division Medical Sciences—National Academy of Sciences, 1966. Hanlan JJ: Emergency medical services: New program for old problem. Health Services Rep 1973;88:205. Special Report on Emergency Medical Service Systems. Princeton, NJ: Robert Wood Johnson Foundation, 1973. Law of the 93rd Congress, Emergency Medical Services System Act of 1973, Washington, DC, 1973. Stout JL: High performance EMS systems. Miami: The Fourth Party: 1989:8–12. Boyd DR, Edlich RF, Mialq SH: Systems approach to emergency medical care. Norwalk, CT: Appleton, Century–Crofts, 1983. Emergency Medical Services at Midpassage. National Research Council—National Academy of Sciences, Washington, DC, 1978. Pantridge JF, Geddes JF: A mobile intensive care unit in the management of myocardial infarction. Lancet 1967;2:271. Page JO: Paramedics. Morristown, NJ: Backdraft Publications, 1979. American College of Emergency Physicians. Position paper on emergency medical services. Dallas: 1986. Pepe PE, Stewart RD: Role of the physician in the prehospital setting. Ann Emerg Med 1986;15:1480. Braun O, McCallion R, Fazackerly J: Characteristics of midsized urban EMS systems. Ann Emerg Med 1986;16:490. Clawson JJ: Dispatch priority training strengthening the weak link. J Emerg Med 1981;6:32. Eisenberg M, Bergner L, Hallstrom A: Paramedic programs and out-of-hospital arrest: I. Factors associated with successful resuscitation. Am J Public Health 1979;69:30. Stults KR, Brown DD, Schug VL, et al: Prehospital defibrillation performed by emergency medical technicians in rural communities. N Engl J Med 1984;310:219. Hargarten KM, Stueven HA, Waite EM: Prehospital experience with defibrillation of coarse ventricular fibrillation: a ten-year review. Area Emerg Med 1990;19:157. Eisenberg M, Copses M, Hallstrom A, et al: Treatment of out-of-hospital cardiac arrests with rapid defibrillation by emergency medical technicians. N Engl J Med 1980;302:1379. Kuehl AE: Perspectives on international EMS system development. Emerg Med Services 1989;18:37. Eisenberg MS, Horwood BT, Cummins RO, et al: Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med 1990;19:179. Eisenberg MS, Carter W, Hallstrom A, et al: Identification of cardiac arrest by emergency dispatchers. Am J Emerg Med 1986;4:299. Baxt WG, Mordy P: The impact of rotocraft aeromedical emergency care service on trauma mortality. JAMA 1984;249:327. Brismar B, Alveryd A, Johnson O, et al: The ambulance helicopter is a prerequisite for centralized emergency care. Acta Chir Scand 1986;530(Suppl):89. Cowan M, Butman AM, Bosner LV: Mass casualty planning: model for in-hospital disaster response. JWAEDM 1986;2:83. Jacobs LM, Ramp JM, Breay MJ: An emergency medical system approach to disaster planning. J Trauma 1979;19:157. Holroyd BR, Knopp R, Kallgen G: Medical control quality assurance in prehospital care. JAMA 1986;256:1027. Medical control of emergency medical services. an overview for emergency physicians. Dallas: American College of Emergency Physicians, 1984. Cales RH, Helig RW: Trauma care systems. Rockville, MD: Aspen Publications, 1986. West JG, Trunkey DD, Lim RC: Systems of trauma care: a study of two counties. Arch Surg 1979;114:455. Paris P: Prehospital medicine. St. Louis: Mosby Lifeline, 1996. Swor RA: Quality management in prehospital care. St. Louis: CV Mosby, 1993. Delbridge TR: EMS: agenda for the future. Washington, DC: NHTSA, 1996.

Suggested Readings Cook RT Jr: The Institute of Medicine report on emergency medical services for children—emergency medical technicians, paramedics, and emergency physicians. Pediatrics 1995;96:199–206. Foltin GL: Critical issues in urban emergency medical services for children. Pediatrics 1995;96:174–179. Grossman DC, Hart LG: From roadside to bedside: the regionalization of trauma care in a remote rural county. J Trauma 1995;38:14–21. Neely KW: Analysis of hospital ability to provide trauma services—comparison between teaching and community hospitals. Prehosp Disaster Med 1991;6:455. Riner RM, Collins KM, Foulke GE, et al: Categorization of hospital emergency services—developing valid criteria. West J Med 1987;147:602. Spaite DW: Emergency medical service systems research: problems of the past, challenges of the future. Ann Emerg Med 1995;26:146–152.

CHAPTER 150 EMS SYSTEMS FACTORS AND SURVIVAL OF CARDIAC ARREST Principles and Practice of Emergency Medicine

CHAPTER 150 EMS SYSTEMS FACTORS AND SURVIVAL OF CARDIAC ARREST Mickey S. Eisenberg Capsule Pathophysiology of Sudden Cardiac Arrest Options to Improve Survival “In the industrially developed countries, sudden cardiac death is the leading cause of death. It was recognized at the dawn of recorded history and even depicted in Egyptian relief sculptures from the tomb of a noble of the sixth dynasty approximately 4,500 years ago. Sudden cardiac death has left no age untouched; sparing neither saint nor sinner, it has burdened man with a sense of uncertainty and fragility. The enormity of this problem demands attention. In the United States sudden cardiac death claims about 1,200 lives daily or approximately one victim every minute.” Bernard Lown (1)

CAPSULE Sudden cardiac death is defined as “death caused by underlying heart disease occurring without symptoms or with symptoms of less than an hour's duration ( 2). Almost all sudden cardiac deaths occur before the patient can reach hospital care. Sudden cardiac death is a major subset of the larger problem of coronary artery disease. Coronary artery disease is the leading cause of death among adults and, according to the National Center for Health Statistics, accounts for more than half a million deaths per year (3). More than half the deaths from coronary artery disease occur suddenly, with little or no warning, often in adults without known heart disease (4). The average age for sudden cardiac death is 64 years (in men 63, in women 68). It is three to four times more likely to occur in men than in women. Because sudden cardiac death is a prehospital emergency for which emergency medical service (EMS) systems and emergency departments (EDs) are the primary sources of care, it is important that emergency physicians understand the factors associated with successful resuscitation to help increase the likelihood that a patient can be resuscitated. Physicians should ask themselves, “What is the likelihood of resuscitation from sudden cardiac arrest in my community? How can this likelihood increase?”

PATHOPHYSIOLOGY OF SUDDEN CARDIAC ARREST Cause Although the causes of sudden cardiac death are many and include valvular heart disease, cardiomyopathy, myocarditis, coronary artery spasm, the most common cause, accounting for 80 to 90% of all sudden cardiac deaths, is coronary artery disease. Autopsy studies of patients with sudden cardiac death demonstrate that 80% have underlying coronary artery disease, usually involving major pathologic changes in two or more arteries ( 5,6). Risk Factors The risk factors for sudden cardiac death are identical to those associated with coronary artery disease, namely cigarette smoking, hypercholesterolemia, hypertension, and diabetes ( 7,8). Because men are more prone to coronary artery disease, they have a higher incidence of sudden cardiac death. Cobb and associates (9) have shown that a history of myocardial infarction, angina, congestive heart failure, or hypertension was present in three quarters of patients who were resuscitated from out-of-hospital cardiac arrest. For the remainder, cardiac arrest was the first manifestation of cardiovascular disease. Numerous clinical risk factors have been identified that place persons at higher risk for sudden cardiac death. These include ventricular ectopy, especially complex ventricular premature depolarizations in patients with underlying cardiovascular disease, electrocardiographic abnormalities such as prolonged QT intervals or repolarization abnormalities, extensive coronary artery narrowing, and abnormal left ventricular function (as manifested by a decreased ejection fraction) ( 10,11). These predictors have been determined from studies of selected populations at high risk. The sensitivity and specificity of these predictors throughout the general population are not well characterized; thus, their applicability to the general population is poorly defined. In addition, the invasiveness and cost of some of these studies limit widespread use. There is, regrettably, no unique or practical combination of risk factors, signs, symptoms, or studies that can identify accurately patients at immediate risk for sudden cardiac death. Although factors for high risk can be shown, there is no way to identify the imminent likelihood of a sudden cardiac arrest episode. Syndromes of Sudden Cardiac Arrest Numerous triggers for sudden cardiac death have been postulated. These include ischemia, electrolyte imbalances, platelet abnormalities, psychologic stress, and neurochemical transmitters. Unfortunately, the precise mechanism for sudden cardiac death is not well characterized. Data from Cobb and associates ( 9) demonstrate that approximately 20% of patients who were resuscitated and admitted to the hospital after an out-of-hospital episode of ventricular fibrillation had electrocardiographic (ECG) evidence of transmural myocardial infarction, a smaller percentage had a myocardial infarction of indeterminate age, almost half had ST-T wave changes, and approximately 25% had no ECG changes at all. The lack of consistent pathologic, electrocardiographic, or other findings among patients with sudden cardiac death suggests that several pathophysiologic syndromes may exist. Based on prodromal symptoms, pathologic findings, and prognosis, it is possible to suggest three syndromes ( Table 150.1). As causes are better understood, it may be possible to identify more syndromes. (See also Chapter 3-1.)

Table 150.1. Syndromes of Sudden Cardiac Death

Prevention Prevention is the only means to deal decisively with the problem of sudden cardiac death. Unfortunately, at this time, prevention is not realistically possible. Although the reduction of risk factors may reduce the incidence of coronary artery disease, and thus the incidence of sudden cardiac death, it is unlikely that there will be a dramatic communitywide lowering of risk factors. Furthermore, some risk factors cannot be lowered, such as male sex or the presence of diabetes. Although prevention remains an elusive dream, the only practical solution at present is the treatment of the acute event.

Factors Associated With Successful Resuscitation Every instance of cardiac arrest is associated with a unique set of circumstances related to the patient and the events surrounding the cardiac arrest. These factors can be grouped into fate and system factors. Fate factors include patient characteristics or chance events, such as medical condition of the patient, cardiac rhythm at the time of collapse, and whether the collapse was witnessed. System factors include EMS characteristics such as the type of service, whether a bystander initiates CPR, and the various time intervals from collapse to CPR and collapse to defibrillation and definitive care. System factors most predictive of outcome are the time from collapse to CPR and the time from collapse to defibrillation and definitive care ( 12,12A). Fate Factors Age, sex, and medical condition are the predominant fate factors associated with successful resuscitation from sudden cardiac death. For patients discharged alive after out-of-hospital arrest, the average age is 61 compared to 66 for nonsurvivors. There is no relationship of sex to admission or discharge. Patients with a history of congestive heart failure have a lower likelihood of survival. Another strong predictor of successful or unsuccessful resuscitation is whether the collapse was witnessed (12). If the collapse is seen or heard directly, the patient has a much higher likelihood of survival than if it is unwitnessed. Another important predictor is the cardiac rhythm associated with the arrest. Patients with ventricular fibrillation or ventricular tachycardia have the highest likelihood of admission and discharge after cardiac arrest. Patients with asystole, idioventricular, and other rhythms have a much poorer likelihood of resuscitation. Table 150.2 illustrates the survival rates for patients with various rhythms who were treated by paramedics in King County, Washington.

Table 150.2. Cardiac Rhythm and Outcome for Paramedic-Treated Cases

System Factors Characteristics of the system are associated strongly with the likelihood of survival. An important system factor, CPR initiated by bystanders, is associated with an increased likelihood of survival. In a review of articles reporting controlled studies of prehospital CPR, Cummins demonstrated that bystander CPR has a dramatic effect on the likelihood of resuscitation ( 13,14). Table 150.3 shows the results of 14 controlled studies comparing patients with early bystander CPR versus those with late CPR. In all the studies except one, the odds ratio for the probability of survival from an out-of-hospital cardiac arrest was significantly greater than 1.0.

Table 150.3. Controlled Studies of Survival (Discharged Alive) from Out-of-Hospital Cardiac Arrest: Bystander CPR Compared to Late CPR

A single study from Milwaukee did not demonstrate a beneficial effect of bystander CPR ( 15,16), probably because of an extremely rapid aid unit response time. In Milwaukee, the average response time for the first arriving emergency vehicle is 2.1 minutes. There is little discrepancy between the time from collapse to CPR by bystanders and the time from collapse to CPR by aid unit personnel. In King County, Washington, where the average aid unit response is approximately 5 minutes, and in other communities with response times longer than those in Milwaukee, there is a greater opportunity to perform bystander CPR and a longer duration of bystander CPR. In all these other cities, a beneficial effect of bystander CPR has been shown. Other important system factors include the time from collapse to provision of difibrillation and definitive care. The two critical system factors of time from collapse to CPR and time from collapse to defibrillation and definitive care appear to be intimately related. Previous studies suggest that the early initiation of CPR prolongs the duration of ventricular fibrillation (VF) and therefore prevents deterioration from coarse VF to fine VF and ultimately to asystole. This increases the likelihood that VF will last longer and that the response to defibrillation will be positive ( 17). When CPR is delayed or the time to defibrillation is greater than 10 to 12 minutes after the start of CPR, it is more likely the patient will be in fine VF, and a defibrillatory shock will convert the rhythm to asystole ( 18). Shown in Table 150.4 is the relationship between time from collapse to CPR and time from collapse to definitive care.

Table 150.4. Discharge Rates After Out-of-Hospital Cardiac Arrest Related to the Time Until Initiation of CPR and Definitive Care

The term definitive care encompasses all advanced life support (ALS) interventions, including defibrillation, intravenous medications, and endotracheal intubations.

Although some studies have demonstrated the independent benefit of defibrillation ( 19,20 and 21), no studies have quantified the individual benefit of medications or intubation. It would be difficult to conduct such studies because the combination of all these treatments define the standard of care for cardiac arrest. The probability of successful resuscitation is determined by the combination of fate and system factors associated with the cardiac arrest event. This relationship is shown in Figure 150.1. Only when there is a combination of “good” fate and system factors is there any reasonable likelihood of survival. For example, if the rhythm is ventricular fibrillation, the collapse is witnessed, bystander CPR occurs, and the paramedic response time is 2 to 6 minutes, there is a 50% probability of successful resuscitation and discharge from the hospital.

Figure 150.1. Chance of successful resuscitation (bars) from sudden cardiac death depends critically on the particular circumstances surrounding the cardiac arrest and on the speed with which definitive care can be provided by paramedics or physicians. The nature of the arrhythmia that results in the victim's loss of circulation and the presence of bystanders who witness the victim's ensuing collapse cannot be controlled. The response time of paramedic units and the likelihood that a bystander will be able to perform CPR can be improved by increasing the number of emergency cardiac care vehicles and personnel and educating the public in CPR. (Reproduced with permission from Eisenberg MS, Bergner L, Hallstrom AP, and Cummins RO. Sudden cardiac death. Sci Am 1986;254:40. Copyright © 1986 by Scientific American. All rights reserved.)

One review of 113 studies of CPR outcomes found an overall survival rate to hospital discharge of approximately 15% ( 22). However, when conditions are favorable (young adults with sudden cardiac arrest with rapid treatment) outcomes can be as high as 70% ( 23). Development of Prehospital EMS As recently as the early 1960s, prehospital EMS was inadequate and ineffective. Care was provided predominantly by private ambulance and mortuary companies, with the ambulance often doubling as a hearse. The vehicles were staffed by attendants with variable training in first aid. The National Highway Safety and Traffic Act, enacted in 1966, encouraged the development of EMS at the local level. Although the motive for the passage of this act was the desire to reduce the mortality rate from traffic accidents, it stimulated general improvements in emergency care. Furthermore, the act developed the standardized emergency medical technician (EMT) 81-hour training course, which subsequently has been increased to 110 hours. The course provides instruction for firefighters, ambulance personnel, and first responders in basic life support (BLS) techniques including patient assessment, cardiopulmonary resuscitation, control of external hemorrhage, management of airway problems, and immobilization of patients with musculoskeletal injuries. By the mid 1980s, there were more than 400,000 certified EMTs in the United States. The late 1960s and early 1970s saw the development of a more sophisticated form of emergency medical prehospital service. The first prehospital advanced unit was started in 1966 in Belfast, Ireland by Drs. Pantridge and Geddes. Their unit, known as a mobile intensive care unit (MICU), was staffed by a physician and a nurse and provided early treatment, primarily anti-arrhythmic drugs for suspected acute myocardial infarction ( 24). These early units were able to defibrillate successfully a small number of patients who went into cardiac arrest after arrival of the unit. The first MICUs in the United States, patterned after the Belfast model, were started in the late 1960s by Grace in New York City, Crampton in Charlottesville, Virginia and Warren in Columbus, Ohio. Shortly thereafter, Nagel in Miami, Cobb in Seattle, Criley in Los Angeles, and Warren in Columbus pioneered the concept of substituting paramedics for physicians. Initially, MICUs were concerned with delivering emergency coronary care, but soon they began to encompass all types of prehospital emergency care ( 25). Five Types of Systems Virtually all prehospital EMS systems in the United States, whether privately or publicly run, can be characterized as one of five types: 1. 2. 3. 4.

Basic EMT: Ambulance or aid response unit staffed with personnel trained in basic cardiac life support. EMT-D: Basic EMTs also trained in the use of defibrillators. Paramedic: Personnel trained in advanced cardiac life support and able to provide definitive care, defibrillation, medication, and endotracheal intubation. Basic EMT/Paramedic: A double-response system with the first responding unit staffed with basic EMTs and the second responding unit staffed with paramedics. 5. EMT-D/Paramedic: A double-response system with the first responding unit staffed with EMT-D trained personnel and the second responding unit staffed with paramedics. Several dozen communities represented by one of these five types of prehospital systems have published their survival experience for managing sudden cardiac arrest. The range of discharge rates within the five systems for all rhythms and ventricular fibrillation is shown in Figure 150.2. The respective adjusted discharge rates for VF for the five systems were 12%, 16%, 17%, 24%, and 29% (26).

Figure 150.2. Percent discharged from out-of-hospital cardiac arrest in all rhythms (top panel) and ventricular fibrillation (bottom panel) from five emergency medical service systems. The circles represent the percent discharged from individual communities, and the horizontal line represents the weighted mean discharge rate. (Reproduced with permission from Eisenberg MS, et al. Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med 1990;19:179–186.)

Basis for Outcomes from the Five Types of Systems The upward trend in survival among the five EMS systems suggests a strong correlation between the type of system and survival. There is a general improvement in survival as the type of EMS system increases in sophistication. The largest increase occurs between single-response and double-response systems. What is the explanation for this improvement in survival? The most obvious difference between the systems is in the times required to provide cardiopulmonary resuscitation,

defibrillation, intravenous medications, and endotracheal intubation. Conceptually, these therapeutic interventions can be considered to alter the survival curve after cardiac arrest. Physicians think of survival curves in months or years. The survival curve for cardiac arrest, however, is defined in minutes. It can be argued that the natural history of cardiac arrest without intervention is biologic death within minutes. If, however, various interventions can be brought to the scene of the cardiac arrest, the survival curve can be altered, and if definitive care can be provided, the survival curve can reach a plateau. The hypothetic cardiac arrest survival curves for the five EMS systems, which display the effects of various interventions on survival, are shown in Figure 150.3.

Figure 150.3. Survival from cardiac arrest for (a) EMT system with response time of 4 minutes; (b) EMT-D system with a response time of 4 minutes; (c) EMT-D system with a response time of 10 minutes; (d) paramedic system with a response time of 4 minutes; (e) paramedic system with a response time of 6 minutes; (f) EMT-paramedic system with response times of 4 and 9 minutes, respectively; (g) EMT-D-paramedic system with response times of 4 and 9 minutes, respectively; (h) King County with an MET-paramedic system with response times of 4 and 9 minutes, respectively, and 50% bystander CPR. (Reproduced with permission from Larsen MP, et al. Predicting survival from out-of-hospital cardiac arrest: a graphic model. Ann Emerg Med 1994;22:1652–1658.)

EMT System The survival curves, though hypothetic, correspond with the actual survival experience of these five types of systems. The curves propose that the ability to resuscitate a person is a function of time, type, and sequence of therapy. The curves display a series of interventions occurring at different times—CPR, defibrillation, intubation, and medication. In presenting these hypothetic curves, several assumptions are made. The first is that the probability of survival after cardiac arrest falls linearly with time and varies according to the therapeutic intervention. The slope of the survival curve is steepest without intervention; the probability of survival is zero after 10 minutes without CPR. In all systems, the survival curves start at 100% because at that moment there is a theoretic 100% chance of resuscitation. The slope of the curves improves after CPR and defibrillation and stabilizes after medication and intubation are provided. In the EMT system, the survival curve improves when EMTs arrive at the scene (assuming an average interval of 5 minutes). Survival continues to fall, but at a slower rate. The ultimate result, however, is still poor because of the long time required to reach the hospital, where definitive care can begin. The few lives that are saved are those for whom there is rapid response and close location to the hospital. Basic EMT systems are found in many rural parts of the country. EMT-D System The EMT-D system demonstrates the same initial fall in survival rate as that of the EMT system. In an EMT-D system, however, CPR and defibrillation are brought to the patient simultaneously. The survival curve is shifted with a flatter slope than it is with CPR alone. The slope continues downward because medications and intubation are unavailable until arrival at a hospital. In King County, Washington, EMT-D systems can save almost 20% of patients with out-of-hospital cardiac arrest (19). Paramedic System In most communities, paramedic systems have slower average response times than basic EMT systems. In single-response paramedic systems, the reported response times in the literature range from 6 to 8 minutes on the average. CPR is administered later, and defibrillation is delayed compared to EMT-D systems. Although theoretically this should decrease survival rates, with the paramedic system they are in fact often equal to or better than with EMT-D systems. This is probably because of the earlier medications and intubation provided by paramedics. The probability of survival initially falls lower than that of EMT and EMT-D systems because of the longer response time. Once paramedics arrive at the scene, however, definitive care is provided, and patient survival is stabilized. EMT–Paramedic System In this system, the EMTs start CPR early, and paramedics provide defibrillation and definitive care several minutes later. The EMTs provide CPR at approximately 5 minutes, thus altering the slope of survival, and paramedics arrive approximately 5 minutes later, providing definitive care and stabilizing survival. EMT-D–Paramedic System In an EMT-D–paramedic system, the best situation exists. EMTs arrive at the scene providing both CPR and defibrillation, again improving the slope of the survival curve. Paramedics arrive approximately 10 minutes after collapse and are able to stabilize the patient, achieving survival rates of up to 35%.

OPTIONS TO IMPROVE SURVIVAL Shortening the Time from Collapse to Cardiopulmonary Resuscitation It is clear that any measure that can allow CPR to occur sooner is likely to increase survival from out-of-hospital cardiac arrest. This assumes, however, that defibrillation and advanced care will also arrive in a reasonable time. CPR alone does not save patients who have sudden cardiac arrest. One way to shorten the time from collapse to CPR is to increase the number of emergency vehicles. There are, however, practical and financial limits to this approach. In many communities, the average response time of EMT vehicles is already extremely short. Additional improvements in response time may require substantial investments in equipment and personnel with little likelihood of gain. For example, King County, Washington currently has an average response time of 4 minutes, an achievement requiring the use of 100 fire department EMT vehicles scattered throughout 500 square miles. To lower the response time by 30 seconds would require an additional 31 new vehicles. Response time is proportional to the square root of the area in square miles divided by the number of vehicles. In other communities, geography and physical structures such as high-rise buildings may impose a practical limit on response times that may be difficult to improve. Another way to improve the time from collapse to CPR is to improve access to the emergency system. Emergency telephone numbers (911) have done much to speed the response to the person in cardiac arrest. Efforts to train the public in CPR have been successful and have contributed to increasing rates of bystander CPR. Citizen CPR programs were first initiated by Cobb and his colleagues in 1971 ( 27). Citizen CPR programs have become an important part of many EMS systems. Training is usually provided by local fire departments or public agencies, often free or for a small fee. The American Red Cross and the American Heart Association actively endorse and support the concept of citizen CPR training. Both organizations provide training programs ranging from 3 to 9 hours. In addition, these training courses afford the opportunity to teach students emergency telephone numbers, risk factors for coronary artery disease, and the warning signs of myocardial infarction. Efforts to target CPR training to persons more likely to perform it may offer an even more effective use of public education dollars. The mass media may play an important role in educating the public in CPR. Demonstrations have been shown during nationally televised baseball games, and several public service spots have been shown on evening news programs. Other potential instructional options include placing CPR instructions in telephone books and on shopping bags. Another approach to provide CPR quickly is for the emergency dispatcher to provide telephone instructions in CPR to the person reporting a cardiac arrest. In 1974, the Phoenix Fire Department implemented a telephone instruction program. Reports suggested that it was possible to give instructions over the telephone. Based on

the Phoenix experience, a CPR message was developed by Carter and colleagues ( 28,29) in King County, Washington. The telephone CPR message is presented in two parts. The bystander is instructed to perform ventilation and then to return to the telephone to receive the second part of the instructions on chest compressions. Since the program began in 1981, the rate of bystander CPR has increased from 32 to 54%. Shortening the Time from Collapse to Defibrillation Although defibrillation is only one component of definitive care, it is the most important. When provided rapidly, it may be all that is necessary to convert the heart to a self-perfusing rhythm. A way to provide defibrillation rapidly is to train EMTs or first responders, such as firefighters or police officers, to perform defibrillation. Programs involving EMT defibrillation have demonstrated the benefit of this procedure. Defibrillation can occur with manual or automatic defibrillators. The use of automatic defibrillators lowers the training time, and studies have demonstrated that its sensitivity and specificity is comparable to that of EMTs using manual defibrillators (30). Automatic external defibrillators have been placed in public places, and lay responders are trained to attach the device to persons in cardiac arrest. Studies have demonstrated the benefits and limitations of such strategies ( 31,32 and 33). Improving Survival from Cardiac Arrest: The Chain of Survival Effective prehospital emergency care for out-of-hospital cardiac arrest involves a sequence of steps that, if provided rapidly enough, can result in successful resuscitation. These steps are linked in a chain that has been termed the chain of survival. The four links are early access, early basic CPR, early defibrillation, and early advanced cardiac life support. For prehospital EMS programs to be successful, each link in the chain must receive special attention. An emergency service is literally only as good as its weakest link. Concentration on one link to the exclusion of the others results in programs that have little impact on improving cardiac arrest survival rates. Improvements in each of the links can shave valuable seconds and minutes in the management of cardiac arrest, particularly when drugs are involved (34). A keener understanding of the factors associated with successful resuscitation and the role prehospital EMS systems play in cardiac resuscitation has done much to improve survival from otherwise fatal events. Acknowledgments. The content of this chapter is based in part on research activities conducted by the Center for Evaluation of Emergency Medical Services, Division of Emergency Medical Services, Seattle–King County Department of Public Health, Seattle, Washington. Research by the Center for Evaluation of Emergency Medical Services is supported by grants from the National Heart Lung and Blood Institute, the Medic One Foundation, the Laerdal Medical Corporation, and the Physio-Control Corporation.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Lown B: Sudden cardiac death: the major challenge confronting contemporary cardiology. Am J Cardiol 1979;43:313. Cobb LA, Werner JA: Predictors and prevention of sudden cardiac death. Hurst W, ed. The heart. New York: McGraw–Hill, 1982. Advanced data from vital and health statistics of the National Center for Health Statistics. No. 172, August 24, 1989. Washington, DC: U.S. Department of Health and Social Services. Kuller LH: Sudden death: definition and epidemiologic considerations progress. Prog Cardiovasc Dis 1980;23:1. Reichenbach DD, Moss NS, Meyer E: Pathology of the heart in sudden cardiac death. Am J Cardiol 1977;39:865. Weaver WD, Lorch GS, Alvarez HA, et al: Angiographic findings and prognostic indicators for patients resuscitated from sudden cardiac death. Circulation 1976;54:895. Friedman GD, Klatsky AL, Siegelaub AB: Predictors of sudden cardiac death. Circulation 1975;52:164. Kuller LH, Perper J, Cooper M: Demographic characteristics and trends in arteriosclerotic heart disease mortality: sudden death and myocardial infarction. Circulation 1975;52:1. Cobb LA, Werner J, Trobough G: Sudden cardiac death: I. A decade's experience with out-of-hospital resuscitation. Mod Concepts Cardiovasc Dis 1980;49:31. Ruberman W, et al: Ventricular premature beats and mortality after myocardial infarction. Circulation 1981;64:297. Haynes RE, Hallstrom AP, Cobb LA: Repolarization abnormalities in survivors of out-of-hospital ventricular fibrillation. Circulation 1978;57:654. Eisenberg MS, Bergner L, Hallstrom A:Sudden cardiac death in the community. New York: Praeger, 1984:34.

12A. Shimauchi A, Toki Y, Ito T, et al: Characteristics of pre-hospital cardiac arrest patients in Japan and determinant factors. Am J Emerg Med 1998;16:209–213. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.

Cummins RO, Eisenberg MS: Prehospital cardiopulmonary resuscitation: is it effective? JAMA 1985;253:2408–2412. Cummins RO, Graves J: Clinical results of standard CPR: prehospital and inhospital. Cardiopulmonary resuscitation. In: Kaye W, Bircher NG, eds. New York: Churchill Livingstone, 1989. Stueven H, Troiano P, Thompson B, et al: Bystander first responder CPR: ten years experience in a paramedic system. Ann Emerg Med 1986;15:707–710. Thompson BM, Stueven H, Mateer JR, et al: Comparison of clinical CPR studies in Milwaukee and elsewhere in the United States. Ann Emerg Med 1985;4:750–754. Cummins RO, Eisenberg MS, Hallstrom AP, et al: Survival of out-of-hospital cardiac arrest with early initiation of cardiopulmonary resuscitation. Am J Emerg Med 1985;3:114–119. Weaver WD, Copass MK, Bufi D, et al: Improved neurologic recovery and survival after early defibrillation. Circulation 1984;69:943–948. Eisenberg MS, Copass MK, Hallstrom A, et al: Treatment of out-of-hospital cardiac arrest with rapid defibrillation by emergency medical technicians. N Engl J Med 1980;302:1379–1383. Stults KR, Brown DD, Schug VL, Bean JA: Prehospital defibrillation performed by emergency medical technicians in rural communities. N Engl J Med 1984;310:219. Cummins RO, Eisenberg MS, Litwin PE, et al: Automatic external defibrillators used by emergency medical technicians: a controlled clinical trial. JAMA 1987;257:1605–1610. Saklayen M, Liss H, et al: In-hospital cardiopulmonary resuscitation: survival in one hospital and literature review. Medicine 1995;74:163–175. Markert R: Cardiopulmonary resuscitation on TV. N Engl J Med 1996;335; 21:1605. Pantridge JF, Geddes JS: A mobile intensive care unit in the management of myocardial infarction. Lancet 1967;2:271. Cahill E: Prehospital systems and medical oversight. St. Louis: CV Mosby, 1994. Eisenberg MS, Horwood BT, Cummins RO, et al: Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med 1990;19:179–186. Cobb LA, Hallstrom AP: Community-based cardiopulmonary resuscitation: what have we learned? NY Acad Sci 1982;382:330. Carter WB, Eisenberg MS, Hallstrom AP, et al: Development and implementation of emergency CPR instruction by telephone. Ann Emerg Med 1984;13:695–700. Eisenberg M, Hallstrom A, Carter W, et al: Emergency CPR instruction via telephone. Am J Public Health 1985;75:47–50. Cummins RO, Eisenberg MS: Automatic external defibrillators: clinical issues for cardiology. Circulation 1986;73:381–385. Eisenberg MS, Moore J, Cummins RO, et al: Use of the automatic-external defibrillator in homes of survivors of out-of-hospital ventricular fibrillation. Am J Cardiol 1989;63:443–446. Cummins RO, Schubach JA, Litwin PE, Hearne TR: Training lay persons to use automatic external defibrillators: success of initial training and one year retention of skills. Am J Emerg Med 1989;7:143. 33. Weaver WD, Sutherland K, Wirkus M, Bachman R: Emergency medical care requirements for large public assemblies and a new strategy for managing cardiac arrest in this setting. Ann Emerg Med 1989;18:155. 34. Weiss LD, et al: Non-traumatic prehospital sudden death in young patients—an urban EMS experience. Prehosp Disaster Med 1991;6:315.

CHAPTER 151 THE EFFECT OF EMS SYSTEMS FACTORS ON TRAUMA SURVIVAL Principles and Practice of Emergency Medicine

CHAPTER 151 THE EFFECT OF EMS SYSTEMS FACTORS ON TRAUMA SURVIVAL George R. Schwartz Time Factors Response Time Scene Time Type of Injury Measurements and Quantification: Injury Severity Scales Advanced Life Support Helicopter Transport Level 1 Trauma Centers Versus Nearest Hospital Helicopter Transport in Rural Areas Total Prehospital Time Time in the Emergency Department Time from Injury to Operative Intervention Trauma Center Designation

This chapter reviews the effects of emergency medical service (EMS) factors on the process and outcomes of trauma patient care. Such a review is complicated because any given EMS system is complex and made up of many interrelated components. These include manpower, communications, equipment, systems procedures, and trauma center designation, as well as triage, treatment, and transfer protocols (See Chapter 153). Three major areas are addressed: 1. the effects of variation in time factors in the prehospital care of patients; 2. the effects of configurations of prehospital care (the role of physicians, of basic life support (BLS) versus advanced life support (ALS), and of procedures performed by ALS-trained paramedics); 3. the effects of hospital characteristics, such as trauma center designation, number of beds, and number of major trauma patient admissions. Issues of patient triage—decisions regarding the sorting of patients with respect to “disposition, destination, or priority”—cut across all three areas ( 1). The primary purpose for such a focus is to maintain prehospital interventions.

TIME FACTORS Factors related to time are grouped into six categories: time from injury to initial ambulance response (response time); time spent by the ambulance crew at the scene of the injury (scene time); time spent transporting the patient from the scene of the injury to the receiving hospital (transport time); total prehospital time (the sum of response time, scene time, and transport time); time spent in an emergency department (ED time), and time from injury to operative intervention (time to OR).

RESPONSE TIME Time from injury to initial ambulance response is most critical in ruralareas, where distances between patients and ambulances often are great and response times are often long.

SCENE TIME The time spent by EMS personnel at the scene varies according to the type of injury (penetrating or blunt), whether ALS procedures are used, and whether helicopter transport is used. A study of patients with severe trauma indicated that rapid transport by private means led to better outcomes that those transported by the EMS system (1). This finding deserves close analysis to identify the reasons for this apparent unexpected benefit ( 1). Certainly other studies have suggested the heightened value of the EMS system (2), but there are persistent and troubling findings, such as the benefits of delayed fluids in some patients with hypotension ( 9). The overall need is for careful study to ensure that costly EMS systems offer benefits and to identify which patients will benefit from “load and go.” Certainly the MAST suit or pneumatic antishock garment has failed to live up to its promise and most EMS systems no longer routinely use it ( 4). The prehospital (EMS) system must undergo the same rigorous scientific scrutiny as the ED and inhospital medicine to avoid costly and ineffective practices.

TYPE OF INJURY Times at the scene for penetrating injuries tend to be relatively brief. Most such injuries occur in urban environments, in which distances to hospitals, where definitive care is available, are short. The general triage decision rule for patients with penetrating injuries is to get them to hospitals as quickly as possible. On the other hand, times at the scene for patients with blunt injuries tend to be longer because extrication and axial splinting often are required. Reines found that extrication increased mean scene times from 20.5 to 31.1 minutes (5). The need for extrication has been accompanied frequently by the need for other procedures such as intravenous (IV) line insertions, endotracheal intubations, and MAST (no longer routinely recommended). Although there are no clear triage guidelines with respect to the optimal time frames for the care of patients in the field, on-line medical control is essential when scene times for blunt trauma are delayed by extrication or patient inaccessibility, particularly when newer studies show no benefit from advanced life support at the scene ( 6).

MEASUREMENTS AND QUANTIFICATION: INJURY SEVERITY SCALES Injury Trauma tracers were once the cornerstone of United States Public Health Service-inspired evaluation efforts. All funded regions tracked patients with head injury to determine whether they were taken to an appropriate hospital. Tracking specific injuries, however, is no longer considered the best option available to contend with case-mix variability. Evaluating trauma care systematically entails collecting injury data on a regional basis. Instead of using tracers, evaluative efforts now center on comparing outcomes of care given to a set of trauma patients with known norms for survival for similar patients. Severity indices are the hallmark of these evaluations. Indices are used for triage, epidemiology, clinical research, and systems evaluation. Injury indices have been developed primarily along two lines: anatomic and physiologic. The Abbreviated Injury Score (AIS) and the Injury Severity Score (ISS) derived from it are anatomic severity scores. The Revised Trauma Score is a physiologic severity score. The TRISS method, based on the Revised Trauma Score Injury Severity Score and age, has been used within institutions primarily to identify unexpected deaths for audit. These scores have limited ED usefulness due to case variability and time for analysis. The complexity of prospective guidance was seen when the American College of Surgeons attempted to provide field triage guidelines for use by prehospital personnel with poor results ( 7).

ADVANCED LIFE SUPPORT It has been argued that ALS procedures unnecessarily extend scene time. Aprahamian, however, showed that the combination of IV and endotracheal tube insertion resulted in scene times of no longer than 22 minutes ( 8). Cwinn (9) and Pons (10) found that mean scene times for patients requiring both IVs and MAST were no longer than were times for those patients requiring only IVs. However, the more compelling analysis suggests that “on scene” ALS offers no clear survival benefit ( 11).

HELICOPTER TRANSPORT

On average, helicopter transport requires crews to spend longer times at the scene because time is required for the helicopter to reach the injury site. In a series of studies, average scene times ranged from 18.5 minutes in San Diego ( 12) to 61.8 minutes for entrapped patients in a study in Danville, Pennsylvania ( 13). Seriously injured patients in rural areas far from trauma centers generally benefit most from helicopter transport. The triage decision to call for a helicopter is easiest if extrication is required because the already lengthy scene time gives the helicopter time to arrive. Flight time to scene is likely to be less important in short-term survival than other variables ( 14). Helicopter triage to a trau- ma center has been found to improve with physician medical control ( 23).

LEVEL 1 TRAUMA CENTERS VERSUS NEAREST HOSPITAL Some trauma center experts contend that the relatively small amount of time lost in urban areas in bypassing the nearest hospital is more than compensated for by the continuous readiness of a trauma center to care for severely injured patients ( 15,16 and 17). Lowe, for example, documented delays of 1 to 2 hours in the provision of definitive care at nontrauma centers ( 18). Difficulties have arisen due to economic factors and “prestige” issues, which make such designation political instead of medical.

HELICOPTER TRANSPORT IN RURAL AREAS Decreases in military evacuation times have been associated with improved survival rates. Studies of helicopter transport in civilian settings relate improved survival rates more closely to the presence of physicians on helicopters than to shorter transport times ( 19,20 and 21). Studying patients injured in motor vehicle crashes in rural San Diego County, Baxt (19a) compared the survival rates of patients transported by ambulances with those transported by helicopters. Although transport times were longer for patients transported by helicopters, the average survival rate was higher. Baxt concluded that survival was improved because physicians on the helicopters frequently performed advanced resuscitative procedures that could not be performed in ambulances staffed by paramedics. In rural settings, air transport is often desirable for hospital-to-hospital transfer and to avoid removing equipment and an ambulance from a rural area.

TOTAL PREHOSPITAL TIME Total prehospital time is considered the time from injury (or from call for ambulance dispatch) to arrival at the hospital. Prehospital times are generally longer in rural than in urban settings. The relationship between total prehospital time and survival has been studied ( Table 151.1). In general, the research supports the view that prehospital times of up to 50 minutes to trauma centers do not adversely affect mortality rates. For example, Pepe studied 498 consecutive patients with penetrating injuries who were hypotensive and brought to a regional trauma center rather than to local hospitals in Houston ( 22). Patient survival was not significantly related to total prehospital time in the first hour except for a slight trend toward decreased survival in patients when total prehospital time was longer than 40 minutes.

Table 151.1. Differential Diagnosis of Infectious Causes of Splenomegaly

TIME IN THE EMERGENCY DEPARTMENT Once a patient is in the ED, survival often depends on prompt and definitive treatment. For many patients, particularly those with penetrating injuries, this means rapid triage from the ED to the OR or rapid transfer to another hospital facility. It is in this area that a trauma center offers an advantage.

TIME FROM INJURY TO OPERATIVE INTERVENTION Although Cowley's data (23) and some military casualty data suggest that trauma patient survival rates vary inversely with the length of time between injury and definitive care, relatively few studies relate patient outcome to time elapsed between injury and surgical intervention. Not only is the actual time of injury often unknown, the relationship between survival and time to OR is made problematic by the intervention of events in the prehospital care and the ED care systems. Nevertheless, some neurosurgical conditions, by virtue of their pathophysiology, are expected to be more sensitive to lengthy times from injury to surgical intervention. For example, Sielig and Decker ( 24) found higher mortality rates and diminished functional recoveries among patients with subdural hematomas who were operated on more than 4 hours after their injuries. The presence of rapid deterioration prior to the 4-hour period is associated with poor outcome unless surgery occurs expeditiously (seeChapter 18). Endotracheal Intubation Successful endotracheal intubation by paramedics is a well-established ALS procedure considered by some to be the prehospital procedure with the greatest life-saving potential. Triage criteria for endotracheal intubation are standard in most ALS systems. Medications can then be administered by this route as well. Intravenous Fluids As with endotracheal intubation, triage criteria for IV insertions vary among EMS systems; thus, the proportion of patients in whom IV insertions are attempted and are successful vary widely. The issue of increasing bleeding through raising blood pressure has been a major concern.

TRAUMA CENTER DESIGNATION The American College of Surgeons Committee on Trauma (ACSCOT) has suggested three levels of hospital resource commitment for trauma care. Trauma center designations (level 1, level 2, and level 3) are related to resources committed. Level 1 trauma centers (the highest level) have the resources required to deal with the most severelyinjured trauma patients and the required ability for research. Research hasfocused on whether level 1 trauma center designation is related to improvedsurvival rates. The results of a series of studies support the conclusion that trauma centers improve chances for survival ( 12,25,26 and 27). West and Trunkey (27) compared Orange County, where MVA patients were brought to the nearest hospital, to San Francisco County, where the severely injured were brought to the level 1 trauma center at San Francisco General Hospital. They found significantly more preventable deaths among younger and less severely injured patients in Orange County. This study, however, compared only one trauma center with several community hospitals. Based on these studies, it has become accepted that optimal survival is based on the adequacy of the initial resuscitation and the early recognition of serious injuries (28). This usually requires ED skill at initial care and the timely availability of a trauma surgeon, a fully trained and equipped trauma team, an operating room, and intensive care capability. Whether level 1 trauma center designation additionally improves patient outcome is difficult to assess. Official designation probably has its greatest impact in upgrading hospital capabilities for trauma care. Although sometimes the designation of “trauma center” offers political and prestige advantages, the need for effective performance requires commitment and financial dedication.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

Demetriades D, Chan L, et al: Paramedic vs private transportation of trauma patients. Arch Surg 1996;131:133. McNicholl BP: The golden hour and pre-hospital trauma care. Injury 1994;95:251–254. Bickell WH, Wall MJ, et al: Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 1994;331:1105–1109. Chang FC, Harrison PB, Beech R, et al: PASG: does it help in the management of traumatic shock? J Trauma 1995;39:453–456. Reines HD, Bartlett RJ, Chudy NE, et al: Is advanced life support appropriate for victims of motor vehicle accidents: the South Carolina highway trauma project. J Trauma 1988;28:563. McSwain NE: Usefulness of physicians functioning as EMTs. J Trauma 1995;39:1027–1028. Norcross D, Ford DW, Cooper ME, et al: Application of ACS field triage guidelines by prehospital personnel. J Am Coll Surg 1995;181:539–544. Aprahamian C, Darin JC, Thompson BM, et al: Traumatic cardiac arrest: scope of paramedic services. Ann Emerg Med 1985;14:583. Cwinn AA, Pons PT, Moore EE, et al: Prehospital advanced trauma life support for critical blunt trauma victims. Ann Emerg Med 1987;16:399. Pons PT, Honigman B, Moore EE, et al: Prehospital advanced trauma life support for critical penetrating wounds to the thorax and abdomen. J Trauma 1985;25:828. Sampalis JS, Boukas S, Lavoie A, et al: Preventable death evaluation of the appropriateness of on-site trauma care provided by “urgences-sante” physicians. J Trauma 1995;39:1029–1035. Shackford SR, Mackersie RC, Hoyt DB, et al: Impact of a trauma system on outcome of severely injured patients. Arch Surg 1987;122. Anderson TE, Rose DW, Leicht MJ: Physician-staffed helicopter scene response from a rural trauma center. Ann Emerg Med 1987;16:58. Bonatti J, Goschl O, Larcher P, et al: Predictors of short-term survival after helicopter rescue. Resuscitation 1995;30:133–140. Border JR, Lewis FR, Aprahamian C, et al: Panel: prehospital trauma care—stabilize or scoop and run. J Trauma 1983;23:708. Cales RH: Trauma mortality in Orange County: the effect of implementation of a regional trauma system. Ann Emerg Med 1984;13:1. Certo TF, Rogers FB, Pilcher DB: Review of care of fatally injured patients in a rural state: five-year follow-up. J Trauma 1983;23:559. Lowe DK, Gately HL, Frey CL, et al: Patterns of death, complications and error in the management of motor vehicle accidents: implications for a regional system of trauma care. J Trauma 1983;23:503. 19. Hedges JR, Sacco WJ, Champion HR: An analysis of prehospital care of blunt trauma. J Trauma 1982;22:989. 19A. Baxt WG, Moody P: The impact of rotocraft air medical emergency service on trauma mortality. JAMA 1983;249:3047. 20. 21. 22. 23. 24. 25. 26. 27. 28.

Baxt WG, Moody P, Cleveland HC, et al: Hospital-based rotocraft aeromedical emergency care services and trauma mortality: a multicenter study. Ann Emerg Med 1985;14:859. Fischer RP, Flynn TC, Miller PW, Duke JH: Urban helicopter response to the scene of injury. J Trauma 1984;24:946. Pepe PE, Wyatt CH, Bickell WH, et al: The relationship between total prehospital time and outcome in hypotensive victims of penetrating injuries. Ann Emerg Med 1987;16:3. Cowley RA, Hudson F, Scanlan E, et al: An economical and proved helicopter program for transporting the emergency critically ill and injured patient in Maryland. J Trauma 1973;13:1029. Seelig JM, Becker DP, Miller D, et al: Traumatic acute subdural hematoma: major mortality reduction in comatose patients treated within four hours. N Engl J Med 1981;304:1511. Baker CC, DeGutis LC, De Santis, et al: Impact of atrauma service on trauma care in a university hospital. Am J Surg 1985;149:453. Clemmer TP, Orme JF, Thomas FO, Brooks KA: Outcome of critically injured patient treated at level I trauma centers versus fullservice community hospitals. Crit Care Med 1985;13:861. West JG, Trunkey DD, Lim RC: Systems of trauma care: a study of two counties. Arch Surg 1979;114:455. Roy P: The value of trauma centers: a methodologic review. Can J Surg 1987;30:17.

Suggested Readings Buckman RF, Badellino MM, Mauro LH, et al: Penetrating cardiac wound: prospective study of factors influencing initial resuscitation. J Trauma 1993;34:717–727. Cayten CG: Evaluation of emergency medical services. In: Kuehl A, ed. EMS medical directors handbook. St. Louis: CV Mosby, 1989:103–117. Cayten CG, Stahl WH, Murphy J, et al: Limitations of TRISS for interhospital comparison: a multihospital study. J Trauma 1990;30:916. Champion HR, Sacco WJ, Copes WS, et al: A revision of the trauma score. J Trauma 1989;29:623. Dagher M, Lloyd RJ: Developing EMS quality assessment indicators. Prehosp Disaster Med 1992;7:69. Eisenberg MS, Horwood BT, Cummins RO, et al: Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med 1990;19:2. Feero S, Hedges JR, Simmons E, et al: Does out-of-hospital EMS time affect trauma survival? Am J Emerg Med 1995;13:133–135. Herlitz J, Estrom L, Wennerblom B, et al: Survival among patients with out-of-hospital cardiac arrest found in electromechanical dissociation. Resuscitation 1995;29:97–106. Ma OJ, Atchley RB, Hutley T, et al: Intubation success rates improve for an air medical program after implementing the use of neuromuscular blocking agents. Am J Emerg Med 1998;16:125–128. McKenzie EJ: Injury severity scales: overview and directions for future research. Am J Emerg Med 1984;2:537. Rhodes M: Direct transport to the operating room for resuscitation of trauma patients. J Trauma 1988;28:1095. Sampalls JS, Lavoie A, Williams JL, et al: Impact of on-site care, pre-hospital training, and level of in-hospital care on survival in severly injured patients.

J Trauma 1993;34:252–261.

van der Hoeven JG, de Koning J, van der Weyden PK, et al: Improved outcome for patients with a cardiac arrest by supervision of the emergency medical services system. 1995;46:123–130.

Neth J Med

CHAPTER 152 GROUND AND AIR EMERGENCY TRANSPORT Principles and Practice of Emergency Medicine

CHAPTER 152 GROUND AND AIR EMERGENCY TRANSPORT Gregory W. Hendey Capsule Ground Transport Medical Direction Emergency Medical Technicians Unique Settings Field Interventions Prehospital Thrombolytics Air Transport Future Trends Conclusions

CAPSULE The idea of rapidly moving injured people from the site of injury to a hospital for emergency medical treatment has been used by the military for many years, but only since the late 1960s has it been applied to the civilian population in the United States. Today, emergency medical service (EMS) systems are designed to extend emergency medical care to the community and to transport patients rapidly to the hospital for additional evaluation and treatment. This chapter will detail how EMS systems use ground ambulances and air transport to achieve these goals. The EMS system must be well organized to offer a consistent level of response at any given time or place within the community. Medical direction, whether from a single medical director or from a committee, should develop clear policies and protocols to direct emergency medical technicians (EMTs). A good system for gathering information is critical for ensuring quality improvement. Recent questions have been raised about outcomes and even the need for training levels (e.g., EMT versus paramedic). Data are essential if the system is to examine itself. Bukata ( 1) has scrutinized key concepts and found logic and outcome studies lacking. There are various levels of training for EMTs. The scope of practice of the EMT is defined largely by local agencies, and it ranges the entire spectrum. At one end are basic life support and simple transport, and at the other extreme is the administration of neuromuscular blockers to facilitate endotracheal intubation and thrombolytics for patients with acute myocardial infarction (MI). Helicopters were used in the Korean and Vietnam conflicts to evacuate casualties from battlegrounds to medical areas, but civilian aeromedical programs were not developed until the 1970s. Air transport programs have become the “shining star” of many EMS systems, with an extended scope of practice and aggressive treatment protocols. The most common crew compositions are two nurses or a nurse and a paramedic, and most programs use two-engine helicopters specially equipped for patients care. Any EMS system that uses helicopters must have well-defined criteria for the use of these valuable but costly resources. Questions have been raised about whether we are overusing this “dramatic” intervention, particularly in cities in which overall transport time may not be greatly improved.

GROUND TRANSPORT Historical Overview One of the earliest descriptions of organized trauma care was recorded in The Iliad. Homer described soldiers wounded in the battle of Troy being carried off the battlefield and treated in nearby barracks and ships. By the first century AD, wounded Roman soldiers were taken to hospitals along the borders of the Roman empire. In the 19th century, Baron Dominque Jean Larrey, the chief surgeon in Napoleon's army, made two innovative changes in the care of wounded soldiers that have endured. First, he used horse-drawn ambulances to transport injured soldiers off the battlefield within hours of injury. Second, he concentrated the wounded soldiers in one area, close to the front lines, where he and other medical personnel initiated initial medical treatment ( 2,3). Military conflicts have continued to be a source of innovation and improvement in the development of patient care and transport systems. During World War I, there was a 12- to 18-hour average time lag between injury and definitive treatment. During World War II, this time lag was reduced to between 6 and 12 hours, and the mortality rate fell from 8.5% to 5.8%. It was during the Korean conflict that the United States Army used the mobile army surgical hospital (MASH). This reduced the time from injury to definitive surgical care to between 2 and 4 hours, and the overall mortality rate was reduced to 2.4%. This concept was improved even more during the Vietnam war, in which the average time required to remove an injured soldier from the field was 65 minutes and the mortality rate fell to 1.7% ( 4). Part of the decrease in mortality has been attributed to a systems approach to trauma patients and the realization that the sooner injured patients receive definitive care, the better they fare. During this same period, many other aspects of medical care saw great improvement, including surgical techniques, methods of anesthesia, antibiotics, knowledge of antisepsis, attention to nutrition, and critical care. These factors undoubtedly played a role in lowering overall mortality rates. The most important advance, however, was creating an organized response to the trauma patient and realizing that trauma is a time-related disorder ( 4). The more rapidly hemorrhage is controlled, the patient transported, and definitive care administered, the better the outcome. Before the development of EMS as we know it today, there were almost no standards for ambulance services regarding personnel training and services rendered. Transportation of patients to hospitals was performed by morticians in approximately half the ambulance services because hearses could hold stretchers ( 5). Patients were given minimal care en route to the hospital because the driver, often the only responder, may have had no training in first aid ( 6). As Belfast, Northern Ireland was establishing a revolutionary program in 1966 to send mobile coronary care units to care for patients with acute myocardial infarction, the United States was focusing more on trauma (5). The deficiencies in the emergency care of injured patients were brought to the attention of the public and of policy makers in a document entitled “Accidental Death and Disability: The Neglected Diseases of Modern Society” ( 6,7). This landmark publication by the National Academy of Sciences National Research Council outlined the magnitude of the problem in the United States and cited 30 recommendations to reduce the rates of death and disability from trauma. The report cited the need for a National Council on Accident Prevention. It cited deficiencies in ambulance services, including diverse or nonexistent standards for vehicles and equipment, inadequate training and certification standards for ambulance personnel, limited data on current services, and insufficient research toward improvement of existing ambulance services. The report recommended the institution of a Trauma Registry and Hospital Trauma Committee to establish standards of care, cardiopulmonary resuscitation (CPR) training, and evaluation of prehospital care. The National Highway Safety Act of 1966 authorized funding for the development of EMS systems, under the administration of the Department of Transportation—National Highway Traffic Safety Administration. It also funded the development of a standardized emergency medical technician curriculum ( 6). In 1973, passage of the EMS Systems Act, Public Law 93-154, was accomplished as part of the Public Health Services Act. The administration of the EMSS Act was the responsibility of the Department of Health, Education, and Welfare. These laws created authority for an organized framework at the national, state, regional, and local levels within which a sophisticated EMS system could be developed. Specifically, it divided the states into 300 geographic regions for the purpose of EMS planning and funding. The Robert Wood Johnson Foundation also funded many projects that greatly advanced EMS communications and 911 systems ( 5,6). Since the Budget Reconciliation Act of 1981 was signed, EMS activities have been covered under the Preventive Health Services Block Grant to the States (PL. 97-35). This shifted responsibility for EMS funding and administration from the federal to the state level. In the 1990s, the trend has been to incorporate EMS units as city or county services. EMS System Organization To ensure a consistent level of response to a need for emergency medical care at any place or time within a community, a sophisticated network of communications and cooperation among agencies must be established. Numerous features make it possible to send the right personnel quickly to a scene when a call for help is received: 911

First, it is critical that there be single-source, easy access into the system. The 911 system serves this purpose, and enhanced 911 adds the desirable feature of automatically detecting the location of the caller. This saves the dispatcher the time it would take to collect this information from every caller and, more important, identifies the location of the caller who is unable to verbalize it because of anxiety, age, or medical condition. DISPATCH A consistent system for emergency medical dispatch must be developed so that the most serious conditions draw the fastest paramedic response every time. Many dispatch centers use a system to prioritize calls according to the chief complaint and a few key questions. The most serious situations get a “lights and siren” paramedic response, whereas less urgent complaints, which are assigned a lower priority, may get a less urgent response ( 8). In general, the highest priority call should receive an ALS response within 9 minutes 90% of the time ( 9). Attempts should be made to make this process as objective and consistent as possible. Many dispatchers also give information and instructions to the caller while medical help is on the way. INFORMATION SYSTEMS It is important to be able to measure certain benchmarks, such as EMS response times, to improve the quality of the system. A computerized information system is necessary to track all calls from when they are received to when a unit is dispatched, arrives at the scene, departs the scene, and arrives at the hospital. Other important information includes patient demographics, chief complaint, and treatments initiated in the field. This information is invaluable to detect good and bad trends or to measure the effects of changes within a given system. TIERED RESPONSE A tiered response allows the ability to send EMS personnel of various levels of training to a given incident ( 10). The advantage of a tiered system is that large numbers of first responders can be positioned all around the community for quick response times to an incident. First responders may be fire fighters, police officers, volunteers, or EMTs, and they usually are trained in first aid, basic life support (BLS), or even defibrillation. They may arrive within a few minutes of a 911 call to deliver life-saving BLS or defibrillation while awaiting the arrival of the more highly trained paramedic several minutes later to deliver advanced life support (ALS) care as needed. VEHICLE DESIGN AND LOCATION Federal specifications (KKK-A-1822C) were introduced by the Department of Transportation that outline the minimum vehicle standards for all ambulances ( 9). When ambulances are positioned in fixed stations, fluctuations in call volume temporarily may leave certain geographic areas with minimal coverage while one unit is out on a call. Therefore, some systems now use a “system status management” model to move units to various posts for consistent coverage of the entire community ( 10). LIGHTS AND SIRENS Intuitively, ambulances should be able to transport sick patients to the hospital more quickly by using lights and sirens. This has been supported by studies, but the time gained is less than most would expect. Hunt et al ( 11) found that traveling under lights and sirens in a small city reduced the mean transport time from slightly less than 7 minutes to slightly more than 6 minutes. The importance of this issue is that rapid transport of patients creates a risk to EMS personnel, the occupants of other motor vehicles, and pedestrians. Every year ambulance crashes result in many injuries and even some fatalities. Approximately half the crashes occur when lights and sirens are used (11). EMS personnel must evaluate their criteria for lights and sirens.

MEDICAL DIRECTION Medical direction usually is supplied by a single physician medical director in an EMS system or by a committee comprised of representatives from hospitals within that community. The oversight has been described as on-line and off-line medical control. On-line medical control is the direction given to the EMT by radio or telephone while a patient encounter is occurring. Off-line medical control includes items such as design of the system and protocols. Perhaps a more descriptive division is prospective, immediate, and retrospective ( 12). Prospective medical control includes the development of policies and protocols, and the design of the EMS system (as in off-line control). Immediate medical control is the direction given during a patient encounter (as in on-line control), and retrospective medical control refers to investigating problems, measuring times, looking for trends, and so on.

EMERGENCY MEDICAL TECHNICIANS Considerable attention has been paid the training and certification of EMTs, establishing vehicular standards for ambulances, and developing communications systems. In the United States there are two levels of training for EMS personnel: Basic Life Support BLS includes noninvasive supportive measures, such as controlling hemorrhage, spinal immobilization, basic airway maneuvers, and CPR. Advanced Life Support ALS includes more invasive techniques, such as endotracheal intubation, intravenous (IV) cannulation, defibrillation, and administration of controlled medications. Basic standards of training for EMTs and requirements for certification and licensure are specified by state law. Three levels have been determined based on degree of training: EMT-Basic EMT-Basic training consists of training in BLS and of certification in cardiopulmonary resuscitation, basic airway management using a bag-valve mask, control of external hemorrhage, splinting and bandaging, and patient extrication from a vehicle. The typical period of training consists of 110 hours of instruction. EMT-D (defibrillation) training encompasses the skills described for the EMT-Basic and specific training on the use of a defibrillator. EMT-Intermediate EMT-Intermediate training consists of training in the skills described for EMT-Basic and various ALS skills, including advanced airway management and administration of intravenous fluids. In addition, the EMT-I training includes patient assessment and basic physiology. The range of training may require 110 to 1000 hours of instruction. EMT-Paramedic EMT-Paramedic training covers all the basic skills of the EMT-Basic a plus a broader array of emergency situations, basic physiology, and ALS skills such as endotracheal intubation, IV insertion, defibrillation, and medication administration. Training generally consists of more than 1000 hours of instruction spanning 6 months. EMT Training The original model training course for EMTs was developed by the National Highway Traffic Safety Administration and consisted of 81 hours of instruction ( 6). It covered general aspects of medical and traumatic emergencies, BLS, and patient extrication skills. Most states require a 110-hour basic curriculum for EMT-Basic

training. The National Registry of EMTs is the leading certifying and testing agency in the country. It requires recertification of EMTs every 2 years consisting of a refresher course, yearly CPR recertification, and documented continuing education. Whether improved outcome correlates with increased training is a question that has been raised but that requires extensive data to answer. In 1977, the University of Pittsburgh Emergency Medical Technician–Paramedic National Training Course was developed. It outlined 15 specific areas and formed the foundation on which a national standard could be established: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

the role of the EMT–paramedic human systems and patient assessment shock and fluid therapy pharmacology respiratory emergencies cardiovascular emergencies central nervous system soft-tissue injuries musculoskeletal emergencies medical emergencies obstetric–gynecologic emergencies pediatric and neonatal emergencies behavioral emergencies rescue techniques telemetry and communications

Not all states use the National Registry EMT–Paramedic examination, and many continue to use state-approved examinations or programs. Recertification of paramedics through the National Registry is required every 2 years and includes a refresher course, continuing education, advanced cardiac life support (ACLS) certification by the American Heart Association, and acknowledgment of satisfactory field performance by a medical director.

UNIQUE SETTINGS Prehospital care has been extended to parts of the country to which conventional EMS providers do not have easy access. The national parks, for instance, are large areas with rough terrain and many tourists. To provide prehospital care to ill and injured persons, some park rangers receive EMT-Intermediate training and are designated Parkmedics. They must determine how to maintain clinical skills in a low-call setting, and they receive specialized training in environmental emergencies and altitude illness. Ski patrols and lifeguards also receive BLS training and may obtain EMT certification.

FIELD INTERVENTIONS Most prehospital care is based on the theory that many illnesses, especially trauma and cardiac care, require rapid care for improved outcomes. Paramedics care for patients with every sort of disorder, but much of the attention and training focuses on the trauma patient and the cardiac patient. Perhaps this is because these are two groups of patients in whom good prehospital care can make a difference in survival. In addition, they have high morbidity and mortality rates, and they were the impetus for much of the development of EMS care in this country. Therefore, some prehospital interventions relevant to these disorders will be discussed in greater detail. The Trauma Patient All paramedic training courses include education in the management of the trauma patient. Many include the Basic Trauma Life Support (BTLS) course introduced in 1982 by the Alabama Chapter of the American College of Emergency Physicians ( 13). The course was modeled after the Advanced Trauma Life Support (ATLS) course with special attention to the unique environment encountered by the EMT. The first assessment occurs before patient contact is even made. That is, the EMT must assess the scene for hazards to determine whether it is safe to approach the victim so that he or she does not become a second victim. The primary survey of the patient includes rapid assessment of the airway, breathing, circulation, control of the cervical spine, and control of external hemorrhage. Airway management may involve the administration of oxygen and close observation to ensure that the patient's airway is and remains patent. It may involve assisting ventilation by bag-valve-mask or endotracheal intubation. The degree of management involves proper assessment by prehospital personnel, medical control, and level of EMT training. In some EMS systems, paramedics use paralytic medications to facilitate intubation. Next, the EMT treats shock and controls external hemorrhage. There is controversy concerning whether intravenous access should be obtained at the scene or en route to the hospital. The problem centers on how much prehospital time is consumed by this practice when only small amounts of fluid can be infused during a short urban transport. Often it is done en route. ATLS and BTLS teach aggressive fluid resuscitation for trauma patients in shock. However, much controversy has been raised over this issue. Bickell et al ( 14) reported that delayed fluid resuscitation for patients with hypovolemia from penetrating trauma had better outcomes. They found that patients with standard fluid resuscitation had greater dilutional coagulopathy and more postoperative complications. These findings have caused many to reevaluate their approach to the patient in shock from a stab or a gunshot wound. Care must be taken not to extrapolate these findings to blunt trauma, which is not addressed by this study. Chestnut et al ( 15) found that episodes of hypotension greatly increase the risk for death in patients with severe head injuries. Therefore, there may be subsets of trauma patients in whom hypotension is best not treated until the patient is in surgery and others in whom it is critical to prevent hypotension. Additional studies should help clarify these issues. Spinal immobilization should be used for any victim of significant trauma who has a potential spinal injury. Full immobilization includes a cervical collar, rigid long backboard, and tape or straps to hold the patient in a stable position on the board. There remains some controversy over the value of Military Anti-Shock Trousers (MAST). Although they probably increase peripheral vascular resistance, reduce venous pooling, increase preload, and splint some fractures, they have not been shown to reduce mortality and have fallen out of favor ( 3,8). Some EMS systems that used MAST in the past have abandoned them. They may still be useful for splinting pelvic fractures in patients with hypotension, especially in rural areas requiring long transport times. After the initial assessment, extrication, and treatment of immediate threats to life are completed, the trauma patient should be transported rapidly to a hospital for definitive care. Some controversy remains as to whether to “scoop and run” the trauma patient to the hospital as quickly as possible or “stay and play” to stabilize the patient in the field. It is debatable whether paramedics should perform initial lifesaving measures, such as emergency airway management or needle thoracostomy, at the scene or en route to the hospital. However, undue delays in the field must be avoided. The Cardiac Patient In the United States, approximately half a million people die each year of acute MI, and approximately half of those die within the first hour of the onset of symptoms (9). This is a significant medical problem and a great opportunity for prehospital care to decrease the mortality rate from cardiac disease. The major cause of sudden death after an acute MI is dysrhythmia, which is often amenable to treatment if the treatment is delivered quickly. Thrombolysis and angioplasty increase the chance for survival, but they are time dependent ( 16). Thus, it is critical for EMS personnel to respond quickly to patients with MI or cardiac arrest, deal with the life-threatening complications, and rapidly transport the patient for additional care. The National Heart Attack Alert Program Coordinating Committee reported on a number of features of EMS systems that are important for improving outcomes in patients with MI (9). Patients who suffer out-of-hospital cardiac arrest have better chances for survival if the arrest was witnessed, if they receive CPR within 4 minutes, and if they undergo defibrillation within 8 minutes ( 9,17). The “chain of survival” for victims of cardiac arrest includes, early access to EMS, early CPR, early defibrillation, and early ALS. Early access works best when patients call for help early and do not ignore symptoms that may represent an MI. It is important that there be a single emergency number to call (911) in a community, and even better if enhanced 911 is used so that help can arrive more quickly. Emergency dispatchers may even instruct a bystander to perform CPR before the arrival of trained help. Early CPR provides at least some blood flow to the heart and brain until providers

arrive who can perform defibrillation or other ALS therapy. First responders may arrive on scene before ALS providers and can initiate BLS care. Early defibrillation is probably the single most important intervention in increasing survival after cardiac arrest ( 18). Many first responders are now trained to defibrillate patients who have had cardiac arrest using an automated external defibrillator (AED). When placed on the patient, this device quickly analyzes the rhythm, charges up, and delivers a shock to the patient based on the rhythm discovered. The AED can help communities make defibrillation more readily available because first responders usually greatly outnumber paramedics. Early ALS care, including the administration of medications and airway management, may improve survival after cardiac arrest. Reports of survival rates after out-of-hospital cardiac arrest vary widely. Westfal et al ( 19) reported an overall survival rate of 2.1% in New York City. Of the witnessed cardiac arrests, 35% of patients had a return of spontaneous circulation, but only 2.8% of patients survived to discharge. Of those initially in ventricular fibrillation, 44% were given bystander CPR, and the survival rate rose to 7.3%. The mean response time to the scene was 4.5 minutes. However, in New York and other large cities, there are frequently delays in making patient contact because of the many high-rise buildings and multilevel subways. Similarly, Lombardi et al ( 20) reported an overall 1.6% survival rate in New York City. Again, the response time to the scene was 5.5 minutes, but the time to defibrillation was 12.4 minutes. This is in stark contrast to the 18% overall survival rate reported by Eisenberg et al ( 21) in King County, Washington. They also noted a survival rate of 34% for the subset of patients with witnessed cardiac arrest initially in ventricular fibrillation. White et al ( 18) reported a 49% survival rate for patients in ventricular fibrillation in Rochester, Minnesota, where, in addition to paramedics, they use police first responders equipped with AEDs. The mean call to shock time was 6 minutes, and it was significantly lower for survivors than for nonsurvivors. Recently, investigators have shown that measurement of end-tidal CO 2 can be useful in predicting which patients will ultimately survive cardiac arrest. This may become a useful tool for EMS systems to use in protocols defining when to halt resuscitative efforts ( 22,23).

PREHOSPITAL THROMBOLYTICS The thrombolytic era has effected some changes on EMS systems. Some advocate that paramedics should perform 12-lead electrocardiograms (ECG) in the field on patients with suspected MI and to transmit them to the receiving hospital. The idea is that it will shorten the “door to drug” time at the hospital for patients who ultimately are administered thrombolytics because preparations will have been made before the patient arrives, and the ECG will be ready. In systems in which this time interval already takes approximately 30 minutes without prehospital 12-lead ECGs, it is doubtful that this intervention could save more time, and it may not be cost effective. However, in areas that have significant hospital delays, it may be useful and is encouraged by the National Heart Attack Alert Program ( 9). In some EMS systems, paramedics administer thrombolytics in the field. Because thrombolytics reduce mortality rates when they are administered early, it is reasonable to consider the use of prehospital thrombolytics to reduce the time to treatment. However, studies have not yet demonstrated a significant reduction in mortality when prehospital thrombolysis is compared to ED thrombolysis ( 16). A number of practical barriers exist to the use of thrombolytics in the field, including the expense of 12-lead ECG capabilities, cellular phone ECG transmission, the drugs themselves, medicolegal issues, and the inability to evaluate fully the possibility of contraindications, such as gastrointestinal bleeding and aortic dissection. It may be a greater consideration in areas with long transport times to hospitals, where the time difference between prehospital and ED treatment is even longer.

AIR TRANSPORT History The use of the helicopter for the transport of critically injured patients originated in military conflicts. Although some air medical transport was conducted during both world wars, widespread use of helicopters for medical purposes began during the Korean War ( 24,25,26). The irregular terrain and small landing areas at MASH units favored the use of the helicopter instead of fixed-wing transport. The MASH units were strategically located to receive incoming wounded, who were secured on litters outside the helicopter. The use of helicopters contributed to reduced time to definitive medical care and to reduced mortality ( 24). More than 180,000 soldiers in Vietnam were airlifted by helicopter to surgical hospitals ( 26). The configuration of the helicopter was altered by then, allowing the patient to be transported inside the helicopter and to be attended by an ALS-trained flight crew. Instead of only a transport vehicle, the helicopter now allowed for earlier medical interventions en route to the definitive care hospital. Time to definitive care and mortality rates were decreased again. Civilian medical helicopter use began in the 1960s with aircraft designated for law enforcement and medical purposes ( 24). Federal funding by the National Highway Traffic Safety Administration of several helicopter aeromedical programs, using public service or military equipment, brought designated medical helicopters to the civilian arena. In 1972, St. Anthony's Hospital in Denver, Colorado instituted the first continuously operating civilian hospital-based helicopter program called Flight for Life (27). They flew in a single-engine Alouette 316 helicopter. Denver is close to mountainous terrain that is inaccessible to medical ground transport. The possibility that the 1976 Winter Olympics would be held in Denver prompted consideration of a hospital-based emergency medical helicopter service dedicated to medical transports in the event of serious injury. Although Denver did not obtain the bid for the Winter Olympics, plans for developing a civilian hospital-based helicopter program proceeded. The aircraft was medically configured and had as its goal a less than 5-minute liftoff from time of request for service. Integration with the EMS system was accomplished by establishing a helicopter communications center to coordinate flights and to disseminate information to first responders, EMTs, and law enforcement and public safety agencies. Radios were installed in the aircraft, enabling flight crew members to communicate with ground personnel en route to the scene of an accident. During the 1970s and 1980s, many new programs were formed as many hospitals and EMS systems began to view them as elite, high-tech extensions of medical care into the community. Aeromedical Programs Today The civilian emergency medical helicopter industry has grown beyond expectations. As of 1997, there were approximately 300 civilian aeromedical programs in the United States (28). Hospital-based programs are the most common type. Approximately 10% of transports are performed by public use programs, i.e., those directed by police and fire departments. Military aeromedical services also exist throughout the country. One of the most well-developed public service systems is the Maryland State Police aviation program, operating seven helicopter bases that serve the entire state of Maryland. Helicopter emergency programs can place a large economic burden on the sponsor hospital or agency. To be competitive with ground services, the early programs set the charge for transports well below the costs of the program. With increases in technology, level of training of the flight crew, and expansion from single- to twin-engine helicopters, costs have greatly increased. The average charge for a helicopter transport in 1995 was $3216 ( 29). Fee calculations vary widely and may consist of a base charge, hourly or mileage charge, and equipment or medical service charge. Increasingly, aeromedical services fall under capitated agreements or rates fixed by contracts. In 1986, the National Flight Nurses Association printed national practice standards for flight nurses. It was the intention of the association to ensure a high level of expert care offered by flight nurses across the country at the scene of an accident and during the transport of critically ill patients. An air medical crew national standard curriculum has been developed jointly by the U.S. Department of Transportation, Samaritan Air Evac, and the Association of Air Medical Services ( 30). It provides a guideline for the training of flight crew members; however, standardized certification has not been established. Many hospital-based programs construct their own educational training courses. Advantages of Air Transport Aeromedical helicopter transport offers several advantages. Flight crews, because of the concentrated experience in transporting critically ill patients coupled with a higher level of medical training and extended scope of practice, may improve patient outcome by treating disease earlier. The speed of the helicopter provides rapid transport without the problems of traffic or terrain. Patients transported by EMS helicopters are generally taken to higher levels of hospital care. One of the first articles reporting the effect of helicopter transport on trauma patient outcomes was published by Baxt and Moody in 1983 ( 24). Trauma patient outcome was predicted using the TRISS methodology for ground and air transport. TRISS combines calculation of the trauma score ( 31), a physiologic index of severity, and the injury severity score (32), an anatomic index of severity. Based on these two numbers, patient outcome is compared with probability for survival in a large trauma patient population to determine any effect of the variable studied. In Baxt's study ( 24), the TRISS methodology demonstrated that the outcome of patients transported by ground was statistically no different from outcomes in a large trauma patient population treated at a major trauma center ( 24). However, a statistically significant 52% reduction in predicted mortality rate for the group transported by helicopter was found. This was attributed to a highly trained medical crew (flight nurse–physician team) capable of performing a wide variety of procedures. The advantages of helicopter transport in rural communities are clear. Some of the differences, when compared to the urban setting, include longer transport times,

longer distances to trauma centers, and a generally lower level of prehospital care in less densely populated areas. Helicopters offer the advantage of rapid, interfacility, critical care transfer when the flight crew includes a nurse or a physician. Boyd ( 33) studied rural interhospital transfers of trauma patients, comparing ground and helicopter modes of transport. Using two similar cohorts, which differed only in the method of transport, he calculated the probability of survival based on the TRISS methodology. Patients transported by ground had the same mortality rate as predicted by TRISS calculations. Patients transported by air had a 25% reduction in predicted mortality rate. In this rural area of Georgia, time to definitive care at a trauma center was statistically greater in the ground-transported group. The rapid aeromedical transport may have contributed to the survival differences. In addition, air transport allows rural areas to maintain their crews and ambulances locally. Aircraft Helicopters must fulfill several requirements to be suitable for medical transport. Dependable performance is an absolute necessity. The aircraft must be airborne quickly, respond within a large radius, cruise at a high speed, and be accessible for patient loading and unloading. It must have the power to make a vertical ascent from a scene while fully loaded with one or two patients, a flight crew, equipment, and enough fuel. Lighter, less expensive, single-engine helicopters were used exclusively until 1980, when the larger twin-engine helicopters were introduced for EMS use. The twin-engine helicopter exceeds the number of single-engine helicopters in use today. The most popular hospital-based EMS helicopter is the MBB twin-engine BK-117. Manufactured jointly by West Germany's Messerschmitt–Bolkow–Blohm and Japan's Kawasaki, its rigid rotor system provides a highly maneuverable aircraft requiring a landing zone of only 60 × 60 feet. The minimal landing zone requirement lends itself well to accident scene responses. With a cruising speed of 155 miles per hour and a 150-mile radius, distant interhospital transports are achievable. The 200-cubic foot cabin space, which is separated from the aviation compartment, allows maximal double-patient transport. This additional space may accommodate such devices as the neonatal isolette, portable intra-aortic balloon pump, and other sophisticated medical equipment. In emergencies, the BK-117 has the best single-engine performance of all twin-engine helicopters ( 34). Safety Safety is an important concern of all aeromedical programs. Aeromedical helicopter accidents peaked in the early 1980s as providers with limited experience instituted new programs. The aeromedical helicopter accident rate at that time was more than double that of the rest of the helicopter industry ( 35). Since then, air programs have paid close attention to pilot staffing and training, flight standards, and strict maintenance schedules ( 36). These changes have been credited for the dramatic decrease in accident rates in the past 15 years. Adverse weather conditions and night flying are major factors in pilot error-attributable accidents ( 35). This is significant because 40% of helicopter EMS flying occurs at night. As a result of the accident trend, three industry organizations, the Association of Air Medical Services, Helicopter Association International, and the National Emergency Medical Service Pilots Association refined and improved visual flight rule (VFR) weather minimums for EMS helicopters, depending on the time of day and the length of flight (37). Most helicopter emergency medical services operate under VFR minimums, meaning that the pilot must have visual contact with the ground during all phases of flight. To reduce pilot fatigue, the Federal Aviation Administration now restricts the number of consecutive hours and the number of flying hours per shift. To fulfill these rest requirements, a busy program requires at least four pilots. In many programs, the pilot is blinded to the type of patient to be transported to avoid an emotional influence on the decision-making process. The pilot is given only the information necessary to make a weather decision before liftoff. This avoids acceptance of a transport for emotional reasons in marginal weather circumstances. Crew Composition The most common crew configurations are the flight nurse–Paramedic and the two-paramedic combinations. Physicians, emergency medical technicians, and respiratory therapists are also used as flight crew members in some programs. Baxt and Moody ( 38) compared the mortality rates of trauma patients transported by helicopter with either a flight nurse–physician crew or a flight nurse–paramedic crew. This prospective, randomized trial found that the mortality rate with the nurse–paramedic crew was the same as that predicted by the TRISS methodology. However, the mortality rate of patients transported by the nurse–doctor crew was significantly lower. Burney et al ( 39) compared the physician–nurse crew versus the two-nurse crew in a nonrandomized study and found no difference in mortality rates. A physician flight crew member probably makes a difference in selected, but not most, cases. Given that, it is difficult to see how it would be cost effective to staff helicopters with physicians in most settings. The most common crew is probably the flight nurse–paramedic because it takes advantage of the differences in their training. The paramedic usually has more training in patient extrication and scene management, whereas the nurse has more experience in critical care and in transferring patients on vasoactive infusions with invasive devices (Swan-Ganz catheter, intra-aortic balloon pump, transvenous pacer). Scope of Practice All hospital-based helicopter EMS systems offer ALS and are therefore equipped with paramedic equipment. This consists of pediatric and adult intubation equipment, intravenous catheters, intravenous fluids, advanced cardiac life support medications, a cardiac monitor with defibrillation capability, and spinal immobilization equipment. In addition, many EMS helicopters offer a higher level of care and carry more sophisticated equipment and medications, such as automated blood pressure cuffs, infusion pumps for various vasoactive medications, chest tube and central line equipment, heated humidified oxygen, end-tidal C O2–pulse oximeter monitors, neuromuscular blocking agents, and nebulized respiratory treatment. Flight crews often are trained in procedures that are usually not part of the ground paramedic scope of practice, such as the use of paralytics, thrombolytics, cricothyrotomy, and tube thoracostomy.

FUTURE TRENDS The greatest challenge facing helicopter programs in the near future is not medical but economic. Clearly, there is a niche for aeromedical transport within an EMS system, especially for long transport of sick patients. What is unclear is whether the advantages of air transport outweigh the costs, which can be tremendous. Most helicopter programs will have to become more economical. There may be creative staffing ideas to minimize the downtime of the highly trained flight crew between calls. Technology and miniaturization continue to improve the size and dependability of portable monitors and transport ventilators, which is much needed in the cramped quarters of a loaded helicopter. More outcome-based research is needed to solidify the position of helicopter programs as the highest evolution of prehospital care.

CONCLUSIONS Ground and air prehospital transport in the past 30 years have progressed from rudimentary, understandardized services to highly sophisticated and highly successful systems. Each mode has specific indications for use, and together they have contributed to the success of prehospital care. Prehospital medical care has been shown to save lives. However, economic factors will continue to place more pressure on EMS systems to justify costly aspects of care based on improved outcomes in controlled studies. The challenge for the next decade will be to refine and improve outcomes in prehospital care in a cost-effective manner. Portions of this chapter appeared in: Principles and practice of emergency medicine. 3d ed. Philadelphia: Lea & Febiger, 1992 and were authored by Sheryl G.A. Gabram, Lenworth M. Jacobs, and Ralph R. Garramone.

References 1. 2. 3. 4. 5. 6. 7. 8. 9.

Bukata R: Scrutiny of prehospital care reveals holes in logic. Emerg Med News 1996;23:8. Trunkey DD: Trauma. Sci Am 1983;249:28–35. Blackwell T: Prehospital care. Emerg Med Clin North Am 1993;11:1–12. Jacobs LM: Initial management and evaluation of the multisystem injured patient, part 1. J Nat Med Assoc 1987;79:361–370. Eisenberg M, Pantridge F, Cobb L, et al: The revolution and evolution of prehospital cardiac care. Arch Intern Med 1996;156:1611–1619. Rockwood CA, Mann CM, Farrington JD, et al: History of emergency medical services in the United States. J Trauma 1976;16:299–307. National Academy of Sciences National Research Council. Accidental death and disability: the neglected disease of modern society. Washington, DC: National Academy Press, 1966. Kallsen G, Nabors M: The use of priority medical dispatch to distinguish between high and low risk patients. Ann Emerg Med 1990;19:458–459. National Heart Attack Alert Program Coordinating Committee. Staffing and equipping emergency medical services systems: rapid identification and treatment of acute myocardial infarction. J Emerg Med 1995;13:58–65. 10. McCallum A, Rubes C: Prehospital interventions. Emerg Med Clin North Am 1996;14:1–12.

Am

11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39.

Hunt R, Brown L, Cabinum E, et al: Is ambulance transport time with lights and siren faster than that without? Ann Emerg Med 1995;25:507–511. Ayres R: Legal considerations in prehospital care. Emerg Med Clin North Am 1993;11:853–867. American College of Emergency Physicians, Alabama Chapter. Basic trauma life support. 2nd ed. Prentice Hall, Englewood Cliffs, NJ 1988. Bickell W, Wall M, Pepe P, et al: Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 1994;331:1105–1109. Chestnut R, Marshall L, Klauber M, et al: The role of secondary brain injury in determining outcome from severe head injury. J Trauma 1993;34:216–222. Weaver W: Time to thrombolytic treatment: factors affecting delay and their influence on outcome. J Am Coll Cardiol 1995;25:3S–9S. Eisenberg M, Bergner L, Hallstrom A: Paramedic programs and out-of-hospital cardiac arrest: 1. factors associated with successful resuscitation. Am J Public Health 1979;69:30–38. White R, Asplin B, Bugliosi T, et al: High discharge survival rate after out-of-hospital ventricular fibrillation with rapid defibrillation by police and paramedics. Ann Emerg Med 1996;28:480–485. Westfal R, Reissman S, Doering G: Out-of-hospital cardiac arrests: an 8-year New York City experience. Am J Emerg Med 1996;14:364–368. Lombardi G, Gallagher EJ, Gennis P: Outcome of out-of-hospital cardiac arrest in New York City: the pre-hospital arrest survival evaluation (phase) study. JAMA 1994;271:678–683. Eisenberg MS, Cummins RO, Larsen MP: Numerators, denominators, and survival rates: reporting survival from out-of-hospital cardiac arrest. Am J Emerg Med 1991;9:544–546. Asplin B, White R: Prognostic value of end-tidal carbon dioxide pressures during out-of-hospital cardiac arrest. Ann Emerg Med 1995;25:756–761. Wayne M, Levine R, Miller C: Use of end-tidal carbon dioxide to predict outcome in prehospital cardiac arrest. Ann Emerg Med 1995;25:762–767. Baxt W, Moody P: The impact of a rotorcraft aeromedical emergency care service on trauma mortality. JAMA 1983;249:3047–3051. Baxt W, Moody P, Cleveland H, et al: Hospital-based rotorcraft aeromedical emergency care services and trauma mortality: a multicenter study. Ann Emerg Med 1985;14:859–864. Neel S: Army aeromedical evacuation procedures in Vietnam. JAMA 1968;204:99–103. Thomas F: The development of the nation's oldest operating civilian hospital-sponsored aeromedical helicopter service. Aviat Space Environ Med 1988;59:567–570. Directory of Airmedical Programs. 1997. AirMed 1997;3:3:18–35. Mayfield T: 1996 Annual transport statistics and transport fees survey. AirMed 1996;2:14–19. US Department of Transportation, NHTSA. Air Medical Crew national standard curriculum. Pasadena: ASHBEAMS, 1988. Champion, HR, Sacco WJ, Carnazzo AJ, et al: Trauma score. Crit Care Med 1981;9:672. Baker SP, O'Neill B, Haddon W, Long WB: The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma 1974;14:187–196. Boyd CR, Corse KM, Campbell RC: Emergency interhospital transport of the major trauma patient: air versus ground. J Trauma 1989;29:789–793. Negrette AJ: Pilot report: BK117 A-3 agility joining function. Rotor Wing Int 1987. Analysis of 84 aeromedical helicopter accidents for the period 1975 to 1986. Worthington, OH: Aviation Safety Institute, 1986:H614-885-4242. DeLorenzo R: Military and civilian emergency aeromedical services: common goals and different approaches. Aviation, Space, and Environmental Medicine 1997;68:56–60. Hodges J: Aeromedical transport. Emerg Care Q 1989;4:1–12. Baxt W, Moody: The impact of a physician as part of the aeromedical prehospital team in patients with blunt trauma. JAMA 1987;257:3246–3250. Burney R, Hubert D, Passini L, et al: Variation in air medical outcomes by crew composition: a two-year follow-up. Ann Emerg Med 1995;25:187–192.

CHAPTER 153 DISASTER PLANNING AND OPERATION IN THE EMERGENCY DEPARTMENT Principles and Practice of Emergency Medicine

CHAPTER 153 DISASTER PLANNING AND OPERATION IN THE EMERGENCY DEPARTMENT Theresa M. Schwab and Eric K. Noji Introduction Definition and Classification of Disasters Types of Disaster Character of Mass Casualty Events Involving Emergency Departments Disaster Planning Disaster Operations The Hospital Disaster Plan Therapeutic Management During Disasters Aftermath of Disaster National Contacts Professional Medical Agencies Involved in Disaster Preparedness

INTRODUCTION The emergency medical service (EMS) system must have a designated plan and chain of command for potential disasters. This chapter offers a blueprint for such a plan. Natural disasters such as earthquakes, cyclones, tsunamis (tidal waves), floods, and volcanic eruptions have claimed approximately 3 million lives worldwide during the past 20 years, have adversely affected the lives of at least 800 million more people, and have caused property damage exceeding $50 billion ( 1,2). Worldwide, a major disaster occurs almost daily, and natural disasters that require international assistance for affected populations occur weekly ( 3). It is now estimated that the United States government spends an average of $1 billion dollars per week as a result of natural disasters ( 4). Although past disasters have produced their share of massive casualties, the future appears to be even more bleak. Growing population density in flood plains and in seismic and hurricane-prone areas, the development and transportation of thousands of toxic and hazardous materials, the potential risks that can occur from incidents at fixed-site nuclear and chemical facilities, the catastrophic possibilities from massive fires and explosions, and the rapid industrialization in developing countries all point to the probability of increasing disasters and casualties in the future ( 3,5,6). Recent catastrophes have included the Loma Prieta earthquake in 1989 ( 7), the Los Angeles riots and Hurricane Andrew in 1992 ( 8), the Iowa and Missouri county floods in 1993, the Northridge earthquake in 1994, the Oklahoma City Federal Building bombing in 1995, floods in Thailand ( 9), El Niño related disasters in California (1998), and the recent Peruvian earthquake, not to mention the disasters unfolding in Somalia, the former Yugoslavia, Cambodia, Afghanistan, Rwanda, Zaire, Burundi, and Chechnya. Because of these events, national and international attention has become focused on the problem of dealing effectively with natural and technological disasters ( 10,11). In fact, the United Nations General Assembly has designated the 1990s as The International Decade of Natural Disaster Reduction, during which a concerted international effort will be made by the world's scientific community to reduce the loss of life and damage caused by natural disasters ( 12). The purpose of this chapter is to discuss disaster planning and operations with particular emphasis on the emergency department (ED). Despite efficient field management of disaster victims, a rapid flow of victims from a disaster scene quickly can overwhelm a hospital ED ( 13,14,15). The point at which the ED becomes overwhelmed varies according to the time of day, the nature of the injuries, and the amount of preparation time before the arrival of victims ( 16,17,18,19 and 20). When it appears that normal procedures will be overwhelmed, EDs must have a specific set of protocols that direct the mobilization of personnel and equipment outside the ED and permit rapid assessment, stabilization, and definitive care for victims of mass casualty ( 21,22,23,24,25,26,27,28,29,30 and 31) and they must have the ability to refer for posttraumatic stress syndromes and other sequelae ( 32,33).

DEFINITION AND CLASSIFICATION OF DISASTERS From a health care perspective, the definition of a disaster is based on its consequences related to health and human services. A practical definition is that “a disaster is the result of a vast ecological breakdown in the relation between humans and their environment, a serious or sudden event (or slow, as in drought) on such a scale that the stricken community needs extraordinary efforts to cope with it, often with outside help or international aid” ( 3,34). According to the World Health Organization, a disaster can be defined as a sudden ecologic phenomenon of sufficient magnitude to require external assistance ( 35,36). At the community level, this can be defined operationally as any community emergency that seriously affects lives and property and exceeds the capacity of the community to respond effectively to that emergency (37). From the standpoint of the ED, a disaster exists when the number of patients, the severity of illness or injury, or the unique nature of the disease or injury are such that normal ED operations are no longer possible. Hence, an ED disaster is a situation in which patients in a given time frame cannot be given even minimal care without additional assistance ( 17,18,38). Circumstances that overwhelm resources and create disasters in small rural communities may be routine occurrences in other settings, such as large university teaching medical centers ( 23,39,40 and 41). Examples are a multivehicle accident involving four or five seriously injured persons or a family with carbon monoxide poisoning. On the other hand, more than 25 patients at one time can overwhelm even the best-staffed trauma center (15). Disasters resulting in large numbers of deaths and injuries are referred to as mass casualty incidents ( 16,42,43). However, disasters cannot be defined simply by the number of victims. Large university hospitals may not have the facilities to manage even two patients with chemical contamination ( 44,45,46,47). The arrival of one important political person with severe injuries (e.g., President of the United States, the Pope) can disrupt completely the normal operations of the most efficient ED (48,49). Regardless of how a disaster is defined, there is a point at which it is impossible for any ED to continue normal operations ( 18,50,51,52). At this point, it is imperative that the hospital and, more specifically, the ED implement a preestablished protocol to deal with such an extraordinary situation. These new protocols (e.g., mobilization of appropriate outside assistance) must be instituted rapidly to reduce potential morbidity and mortality. Hospital protocols must distinguish between internal and external disasters ( 53). External disasters are events that occur physically outside the hospital (transportation accidents, terrorist actions). Unless the outside disaster was a chemical accident and persons are contaminated, the hospital and its staff, patients, and visitors are in no immediate physical danger ( 54). Internal disasters are events that occur within the physical plant of the hospital itself (fire, laboratory accident involving radioactive material) that severely compromise the ability of the hospital to function ( 55,56). Of course, a disaster may be both internal and external—for example, an earthquake that severely damages the hospital ( 57,58). Such events may damage the infrastructure of the hospital and its equipment and injure or kill hospital staff, patients, and visitors. Whatever the type of disaster, the resultant destruction can overwhelm existing community medical care resources. For this reason, disasters can be classified as three levels based on the availability of existing resources ( 59): Level 1: disaster manageable within region, local EMS can provide adequate triage, stabilization and transport, local health care facilities able to diagnose and treat Level 2: local medical response capabilities exceeded, multijurisdictional aid required Level 3: local regional resources overwhelmed, state or federal support needed

TYPES OF DISASTER Disasters are classified as natural and manmade ( 60). Natural disasters include earthquakes, hurricanes, floods, tsunamis, fires, tornadoes, and extremes of temperature. Manmade disasters include transportation accidents, chemical or nuclear power plant accidents (technological disaster), and civil disturbances ( 61). A technological disaster may result from a natural disaster or vice versa. Examples include the multiple public utilities natural gas explosions in the Northridge earthquake and severe windstorms in the Soviet Union that spread radioactive material from an area contaminated by a nuclear power plant accident. This type of synergism is known as a NA-TECH disaster (3). Disasters can develop more slowly with multifactoral human causes, such as famines and civil wars. More than 130 armed conflicts continue to occur throughout the

world, creating an average of 10,000 new refugees each day ( 62,63). During such disasters, multiple crises develop because the infrastructure that sustains populations is destroyed. Accordingly, such disasters have been termed complex emergencies ( 8,62). Attempts are under way to develop a standardized nomenclature to describe disasters more definitively. One such model taxonomy system is termed PICE or Potential Injury Creating Event. PICE describes a disaster based on its potential to create additional casualties, the effect on local resources, the extent of geographic involvement, and the likelihood that outside medical assistance will be required. PICE is, as yet, unstudied ( 64).

CHARACTER OF MASS CASUALTY EVENTS INVOLVING EMERGENCY DEPARTMENTS Extensive disaster research during the past 30 years or so has shown that EDs experience great difficulty coping with even moderate numbers of patients after a disaster (65,66 and 67). The reasons for this include confusion, lack of planning, and lack of emergency training. Hospitals are often not well integrated into overall community disaster planning (68). Hospital disaster plans exist only on paper and are rarely referred to, let alone carried out, during a real disaster. Shortcomings of disaster plans include: 1. 2. 3. 4. 5. 6.

delayed or improper notification poor delineation of command structure overloaded or broken communications networks improper or incomplete identification lack of supplies lack of public relations

What usually happens in the ED when a disaster occurs in the community? Transportation of patients to the ED is usually uncoordinated, and there is no thought to the equitable distribution of patients ( 69). As a result, nearby hospitals usually are overwhelmed with the majority of severely injured patients, whereas those farther away see few patients (70). There is also a pattern to ED patient flow during a disaster. Most casualties are transported to the hospital in a relatively short period—i.e., most patients arrive at the ED within 1 1/2hours after the disaster has occurred ( 14). On the whole, most patients taken to an ED in a disaster have minor injuries and do not require advanced trauma services ( 70). Victims of mass casualties may arrive at hospitals by various means, including ambulances, private automobiles, police vehicles, cabs, and on foot ( 71,72,73 and 74). As a result, hospitals may receive patients in all sorts of unplanned ways, and the patient flow is essentially not under the control of the formal EMS system ( 14). Ambulatory patients, vocal families, and media may arrive at the ED before the more serious patients. This is because they are able to leave the disaster site in taxis, buses, private cars, vans, and police vehicles. The more severely injured, who often need extrication, arrive at a later stage. Less severely injured patients may be treated before more seriously injured patients ( 14). A large number of ambulatory patients arriving early can create overcrowding in the ED, and the established triage process may be abandoned, resulting in confusion in the efforts to provide treatment ( 75). Patients in the initial phase of a disaster will have different conditions than those brought to the ED later. Initial injuries may be caused by trauma or environmental exposure. Subsequent health problems are caused by lack of routine medical care and pharmaceutical services ( 62). Overcrowding combined with possible food, power, water, or sanitation interruption can create nutritional emergencies and epidemics of infectious disease. It has been found that in the absence of extreme cold stress to a disaster-affected population, acute waterborne illnesses at disaster sites pose the greatest immediate threat to health and welfare (62,63,64,65,66,67,68,69,70,71,72,73,74,75 and 76).

DISASTER PLANNING Overview Roles, responsibilities, and working relationships among those responsible for disaster operations should be clarified in the planning process to lessen the confusion that invariably occurs during a disaster. Selected protocols should require personnel to perform functions that are relatively similar to their day-to-day activities ( 77,78 and 79). The disaster planning process should begin by answering the following questions: 1. What types of disasters are most likely to occur in the community (e.g., hazard analysis) ( 80). 2. What are the disaster planning requirements of the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) and other accreditation bodies (e.g., city, and state health agencies)? ( 81) 3. What are the capabilities and responsibilities of the hospital and its medical staff? ( 28) Hazard Analysis Hospital disaster planners must prepare for those disasters most likely to occur in their communities ( 24). Hospitals along the Gulf Coast of the United States should plan for hurricanes ( 72), those in California should plan for earthquakes ( 57), those near chemical plants should have facilities for decontamination ( 45). Consideration should be given to the proximity of large transportation facilities (airports, harbors) and areas in which large numbers of people assemble (festivals, stadiums, amusement parks). Accidents in these types of facilities can generate large numbers of casualties ( 82,83). It is also important to have knowledge of those disasters most prevalent in the area because different disasters are characterized by different morbidity and mortality patterns and, thus, different health care requirements (60,80,84,85). For example, earthquakes cause numerous deaths and severe injuries ( 86). Hurricanes cause severe property damage, though deaths are usually few and injuries minor (35). Pulmonary irritation may result from fires or accidents involving hazardous chemicals that require large supplies of oxygen, as the Bhopal chemical accident in 1984 demonstrated (44,87). Fortunately, hurricanes and other predictable disasters have several day's lead time, and preparations for management can begin early if disaster managers heed warning signals. JCAHO Requirements for Hospital Disaster Planning There are other motivations for hospitals to plan for potential disasters. The JCAHO requires that member hospitals have a written plan for the timely care of casualties arising from external and internal disasters. Hospitals also must document the rehearsal of these plans ( Fig. 153.1) (81).

Figure 153.1. Joint Commission disaster planning requirements for hospitals. (Reproduced with permission from Standards, Management of the environment of care. EC16. In: Comprehensive accreditation manual for hospitals: The official handbook. Oakbrook Terrace, IL: JCAHO, 1996.)

Capabilities of Hospitals to Manage a Disaster

A plan must be based on the institution's capabilities, which may range from basic first aid to more sophisticated trauma and intensive care services. Each hospital's bed capacity and average bed availability should be known, as should additional areas that could be set up for triage, staging, and resuscitation ( 17). Hospital treatment capacity (HTC) can be defined operationally as the number of casualties that can be treated in 1 hour according to normal medical standards ( 88). Several factors affect HTC, among them the total number of emergency physicians and nurses, surgeons, anesthesiologists, operating rooms, and intensive care beds. If the disaster takes place at night or on the weekend, the HTC will be lower than the HTC during a weekday morning. As a rough figure obtained empirically through analyses of several disasters and simulations involving hospitals of different sizes, HTC can be estimated at 3% of the total number of beds ( 88). Based on military experience, one can also estimate a hospital's surgical capacity, that is, the number of seriously injured patients that can be operated on within a 12-hour period, as follows: number of operating rooms = 7 × 0.25 ( 89). Thus, a 300-bed hospital with five operating rooms should be able to care for eight or nine seriously injured disaster victims within a 12-hour time span. Unless there is considerable preplanning, this does not mean that this hospital can handle 36 casualties in 48 hours. Instruments and supplies are likely to be limiting factors. Limited staffing can adversely affect these estimates. A hospital also has a responsibility to inform those responsible for community disaster planning and response (police, fire rescue, EMS) of its emergency care capabilities and limitations in handling a disaster, both before and during a disaster ( 24,90). These reports should be updated continually as patients are discharged and additional staff become available to care for the patients. Hospital–Community Cooperation in Disaster Planning Many failures of disaster planning can be attributed to the fact that few localities have a coordinated, communitywide plan for disaster medical care ( 91). For the successful implementation of disaster plans, it is imperative that every hospital integrate its own disaster plan with those of the community and other disaster management agencies (29). This is particularly important with regard to disaster notification and communications, transportation of casualties, and provisions for dispatch of hospital medical teams to a disaster site. The number of community agencies that have some responsibility for disaster planning and response can be bewildering (92,93). Some of these are listed in Table 153.1.

Table 153.1. Community Agencies Involved in Disaster Planning

Other organizations a hospital may interact with during the disaster planning process may include the military, disaster medical assistance teams, local chapters of the Red Cross and other volunteer agencies, and state and federal agencies such as the Federal Emergency Management Agency (FEMA). Medical planning for disasters in the community is usually the responsibility of local EMS councils ( 39,78). Such councils include physicians, representatives from the local ambulance services and fire departments, personnel from nonmedical and government agencies, and an EMS director. It is essential that physicians involved in community disaster planning be familiar with the local EMS communications and treatment protocols ( 94,95). The hospital must develop its external disaster plan in conjunction with other emergency facilities in the community. For example, mutual aid agreements should be prearranged with hospitals outside the immediate area if hospital capacities are exceeded ( 96,97 and 98). There should be preplanning for referral to area tertiary centers and special units (burn, spinal cord, pediatric trauma centers) ( 23,99). Hospital disaster planners should anticipate that information about specific hazards (chemicals, radiation), expert personnel (poison control), and special supplies (antidotes) not readily available may be needed ( 46,100). Plans should consider how to access these resources rapidly. Alternative vendors should be obtained, both inside and outside the immediate area, for food, water, pharmaceutical and other supplies, and oxygen ( 59). Logistic plans for obtaining these necessities should be delineated.

DISASTER OPERATIONS On-Site Medical Care Determining how much and what type of care to administer at the disaster site depends on several factors ( 101). If the number of patients is small and sufficient prehospital personnel and transportation resources are available, on-site medical care can proceed in a fairly normal manner, with rapid stabilization and transportation to nearby hospitals. When extrication is prolonged, it is important that potentially lifesaving interventions be instituted, such as intravenous fluids for hypovolemic shock (102). On the other hand, early, rapid transportation with a minimum of treatment should be practiced when there is danger to rescuers and casualties from fire, explosion, falling buildings, hazardous materials, and extreme weather conditions ( 45). When the number of casualties exceeds transportation capacities, advanced field medical treatment may be beneficial because it may be hours before seriously injured patients can be evacuated ( 101,103). This may necessitate the establishment of field hospitals with operating theater capabilities ( 104,105). Such a field hospital may be set up in a large building such as a school or a church. Casualties are brought here from the disaster site for additional assessment and initial treatment of their injuries. After a period of observation and stabilization, they are either sent home or transported to a hospital. Field hospitals may become an absolute necessity, particularly in disasters such as earthquakes in which massive structural damage may occur. As described, evacuation of less injured, ambulatory patients rapidly may overwhelm local hospitals before the arrival of more severely injured patients ( 14). Under these conditions, it may be better not to evacuate them but to treat them locally. Incident Command System The incident command system (ICS), also known as the incident management system (IMS), are organizational structures that manage incidents. The ICS is used extensively by fire, police, emergency medical services, county and state disaster planning agencies and the military. In 1970, the ICS was developed by a southern California organization known as FIRESCOPE (Firefighting Resources of California Organized for Potential Emergencies). Its creation was a response to the difficulties experienced managing major wildland fires ( 106). The ICS is now almost universally used by the above agencies as a disaster management tool. The ICS defines a management structure that incorporates the following elements: the use of a common, standard terminology with predesignated organizational functions, facilities, and resources; a modular command structure with the ability to expand or contract, depending on the requirements of a specific incident; integrated communications with the use of nontechnical language; a unified command structure with consolidated action plans; manageable span of control; and comprehensive resource management (106). The specific nature of a disaster does not change the overall command structure but will influence the type of resources used and the tasks that must be performed. The ICS details that a command post must be set up as the first functional area or sector after an incident ( 106). There is to be a single overall incident commander

appointed from the agency with the greatest jurisdictional involvement (e.g., fire for chemical gas explosion, police for hostage incident or bombing). Should the incident be multijurisdictional, key representatives from each agency take charge of the command post and share responsibility. This is an example of unified command. The command post and the overall incident commander oversee responsibility for the entire incident. As part of a large incident, multiple command posts or sectors, each with a single mission, are created. Talk between commanders is limited to simple nontechnical language and involves only whether they have met or cannot meet their objective, discovered a safety problem, and require more resources. During the past 20 years, the ICS has been gaining support and is used by most prehospital, emergency, and disaster planning agencies. Its design has been proven useful in many emergencies ( 106). The required complexity of hospitals to manage disasters, either external or internal, resembles what is required of the above agencies during a large-scale multijurisdictional incident. Adoption of the ideas of functional sectors and a control network designated by the ICS framework appears to offer great help for the management of hospital disaster responses. The JCAHO requires that hospitals have internal and external disaster plans, but it does not specify command structure (81). It has been suggested by many state planning agencies that the ICS be integrated into the hospital disaster plan. The Hospital Emergency Incident Command System (HEICS) manual prepared by the State of California EMS Authority contains the information necessary to set up an ICS-type structure for hospitals ( 107). In addition, the ICS structure not only aids hospital emergency responses, it can provide the necessary link to out-of-hospital support agencies. Communication from Disaster Site or Disaster Operations Center to Hospital The local emergency communications or disaster operations center should alert hospitals in the affected area of a possible mass or multiple casualty situation. This report should include the number of injured persons, specifically the number of seriously injured persons and the number for whom ambulatory treatment is sufficient (45). Hospitals should report to the local emergency communications center the bed availability, number of casualties received thus far, number of additional casualties that hospital is prepared to accept, and specific items in short supply. Distribution of Casualties to Receiving Hospitals Experience has shown that victims of a disaster usually are distributed unequally among receiving hospitals ( 14,51). Typically, the hospital closest to the disaster site receives an inordinately large number of disaster victims and the most critically injured. It is important that the casualty load be spread to available hospitals in such a way that the injured receive prompt and appropriate treatment and that specific hospitals are not overwhelmed. This can be accomplished by predetermining the distribution of patients. Such a list should specify how many critically injured patients go to each participating hospital and in what order. An example of a patient distribution list or matrix is seen in Figure 153.2.

Figure 153.2. An example of a patient distribution matrix used in a disaster setting. (Reproduced from Fresno County EMS, Policies and Procedures 1995.)

Improper casualty destination and hospital overloading may be unavoidable because of large numbers of critically injured patients, blocked transportation routes, and weather conditions. To decrease the possibility of this occurrence, it is important that good communications be maintained between hospitals and on-site EMS command. If this situation is anticipated, the on-scene commander or other appropriate personnel should be alerted immediately by the potentially overloaded hospital to avoid unnecessary patient transportation to this hospital. In this situation, the less injured and more stable can be sent to outlying hospitals. Secondary triage from one hospital to another may be necessary if the hospital's capability to handle victims has been exceeded ( 41). Patients with special problems, such as major burns, carbon monoxide poisoning, and spinal cord injuries, may have to be transferred directly to specialized units, although it may not be possible for these units to accept a large number of injured (23). On-Site Disaster Medical Teams from Hospitals/Urban Search and Rescue On-site disaster medical teams dispatched from local hospitals may be of value if victims require prolonged extrication, transportation routes are blocked, easy evacuation to hospitals is prevented, or casualties are of such magnitude that they exceed transportation capacity ( 108,109). Such a team should be dispatched with great caution. Most physicians and nurses function well in an in-hospital setting; few, however, are prepared to work under austere field conditions by either training or experience (101). Such hospital-based teams should not come from the ED staff until backup staff has arrived to care for patients arriving from the disaster site or are already present. The resources for such teams should be planned carefully on a regional basis ( 109). The capability to send hospital teams to a disaster site can be developed in several ways. For example, a physician on-site triage team can come from teaching hospitals or be created from a pool of doctors in office practice. At least one institution from each region should maintain such capability. The designated hospital should store disaster triage kits containing essential resuscitation and stabilization equipment in the ED for such circumstances. It would be valuable for physicians or hospital personnel who are designated to be part of a team to be dispatched to a disaster site to receive some training in disaster medical care ( 110,111,112 and 113). URBAN SEARCH-AND-RESCUE TEAMS Hurricane Hugo and the Loma Prieta earthquake highlighted a national deficiency in heavy-rescue preparedness and search-and-rescue capabilities. After these events, FEMA, under congressional and presidential mandate, was given authority to implement a national-scale urban search-and-rescue capability. Urban search and rescue is the science of locating, reaching, medically treating, and safely extricating deeply entombed survivors of collapsed structures. It involves specialists in search, heavy rescue, medical services, hazardous materials, structural engineering, communications, and management ( 114). This capability is applicable to heavy structural collapse with the possibility of prolonged entombment associated with major problems in finding, reaching, and removing victims ( 114). The FEMA Urban Search and Rescue Task Force has 56 positions and operates 24 hours a day. Urban search-and-rescue task forces must be deployable within 6 hours and are equipped to run double-shift, continuous 24-hour operations and to be self-sufficient for up to 72 hours. The multiple components seen in Figure 153.3 include the following:

Figure 153.3. FEMA Urban Search and Rescue Task Force. (Reproduced with permission from Barbaera JA, Macintyre A. Urban search and rescue. Emerg Med Clin North Am 1996;14:399–412.)

1. Search: contains both canine and technical capabilities to find live victims and to assist medical personnel in gaining proximity during the extrication process 2. Rescue: uses structural engineering knowledge and portable, powerful equipment to penetrate steel and reinforced concrete without additionally endangering victims or rescuers 3. Medical: includes emergency physicians and paramedics to provide medical care to victims while they are entrapped and at the scene if transport to a definitive care facility cannot be accomplished 4. Technical: contains multiple personnel with expertise in communications, structural engineering, logistics, hazardous materials, and management Although definitive care of the trauma victim with internal injuries remains in the operating room (the “golden hour” rule of trauma care), the unique medical injuries sustained by entombed victims make on-site medical care effective in decreasing morbidity and mortality. This includes the high possibility of inhalational injury caused by dust impaction and particulate injury and hypovolemia secondary to dehydration, blunt trauma, lacerations with blood loss, and crust injury ( 114). Medical teams are capable of performing intubation by various means, obtaining intravascular access, and multiple other procedures. This is often provided while the victim is entrapped. Appropriate pain control can facilitate the extrication procedure. Care of task force personnel and basic veterinary care for the canines is also under the purview of the medical team. The Emergency Department The ED is the most critical part of the hospital's initial response to virtually any type of external disaster. It is the part of the hospital that usually receives first notification that a disaster has occurred, and it is usually the entry point for incoming victims ( 67). INITIAL RESPONSE When a call is made to the hospital informing it of a disaster, the receiver of the call must have a procedure to follow for verification of the incident. A disaster notification form is used by some facilities to remind the staff of the questions they are to ask ( Fig. 153.4).

Figure 153.4. Disaster notification form (Reproduced with permission from Seliger JS, Simoneau JK, eds. Emergency preparedness: disaster planning for health facilities. Baltimore: Aspen Publishers, 1986.)

The appropriate hospital official or administrator on duty is then given this information. When the ED is notified by hospital administration (now disaster control) that the external disaster plan is in effect, it sets in motion a series of activities. The information obtained from the call is given to the nurse in charge, the nursing and medical personnel in the department are notified of the impending arrival of casualties, and the ED's plan for calling additional staff is activated. An initial needs assessment is conducted by the nurse and physician in charge based on the available information. They must evaluate the current status of the patients in the department and make the appropriate decisions concerning their care and disposition. Among the decisions are those related to the admission, discharge, or transfer of patients, and decisions about the priority of patient care. To facilitate reception and care of a large number of casualties, all nonemergency patients should be discharged from the ED with responsible friends and relatives. Based on this initial assessment of the current patient load, the number of patients the department can receive is determined and communicated to the prehospital disaster communications center. The nurse and the physician in charge then determine whether more physician and nursing coverage is required in the department, and they assign staff to the areas in the department to be used during the disaster. As patients begin to arrive, it is critical that those in charge immediately recognize signs of staff overload before the problem gets out of hand. A waiting room area for family members must be designated away from the ED so that the area is not congested when casualties arrive ( 115). PERSONNEL NOTIFICATION The director of the ED or his designate should have a telephone list of appropriate personnel to be called in to work during a disaster. Lists of addresses and telephone numbers of these persons should be distributed to all key personnel if it is impossible to locate the director or his or her assistant. Every position, address, and telephone number listed should be updated frequently. If hospital telephone communications have been disrupted, ED personnel may have to be reached by radio or television announcement (if power lines are down). Alternatively, a calling station remote from the hospital, such as a nurse's residence, may be able to handle this extensive calling job without taxing the hospital's telephone system. SECURITY AND TRAFFIC CONTROL Hospital security personnel play a key role in the ED by diverting nonessential vehicles and ensuring a smooth, one-way flow of traffic to the ambulance entrance. RECEPTION OF PATIENTS Many patients arrive independently of the formal EMS system (14). They are brought by neighbors or friends, or they may even hitchhike. It is important to recognize this because reports from the field of numbers of patients to be expected by ambulance may greatly underestimate the total number of patients who actually arrive at the ED. All too often, the initial wave of casualties arriving at the ED are those with less severe injuries who have been able to leave the site of a disaster without too much difficulty. The more severely injured, who often need extrication, arrive later ( 70). All available litters and wheelchairs should be taken to the ambulance ramp immediately on announcement of the disaster status. Disaster victims are met at the receiving area by hospital escorts, who assist the EMTs in transferring patients to wheelchairs or stretchers. Essential equipment such as endotracheal tubes, intravenous solutions, cervical collars, splints, and bandages should be placed near to the ambulance entrance to permit convenient restocking of the ambulance and rapid return to the disaster site.

Disaster Medical Assistance Teams Under the auspices of the federal government, the Department of Health's National Disaster Medical System (NDMS) was specifically designed to meet the medical needs of a civilian population affected by disaster. The current NDMS is sponsored by four government agencies, the Department of Public Health, the Department of Defense, the Department of Veterans Affairs, and FEMA. In 1984, the NDMS was given authority to create disaster medical assistance teams (DMATs). These DMATs are capable of deployment to the disaster area or receiving large numbers of evacuees destined for the contingency hospital beds in other areas should local hospital beds become overwhelmed. The teams are sponsored locally and are primarily available as state assets that can be “federalized” as needed ( 116). DMATs are capable of the following: 1. Within a disaster area, teams may provide medical care in a field setting, augment medical care at a surviving hospital or clinic, or provide specialty care at either site. Teams may be activated from within the disaster area or may respond from a nearby unaffected area through mutual aid. 2. A team may function at a casualty staging area, receive relatively stable patients from within the disaster area, and prepare them for long-range transport to unaffected portions of the state or country. 3. Outside the disaster area, a DMAT may function as a casualty reception team, meeting patients at the arrival point, offloading patients from incoming transport, providing medical care as needed at the arrival point, providing triage and medical assessment of patients, and assigning them to participating hospitals or to appropriate receiving hospitals within the NDMS hospital system based on patient care needs ( 117).

THE HOSPITAL DISASTER PLAN Basic Requirements of Hospital Planning Hospital disaster planning is the responsibility of administration, nursing, and the entire medical staff ( 38,95). As mentioned, a good hospital disaster plan should be coordinated with community organizations including regional EMS, fire, rescue, police, civil defense, utilities, Red Cross, and Salvation Army ( 92,93). It should provide an organized response of the hospital for the management of casualties transported to the hospital from the disaster site. Finally, it should plan for disasters arising within or near the hospital that require hospital evacuation ( 54,56) (Fig. 153.5).

Figure 153.5. Table of contents for a hospital disaster manual. (Reproduced with permission from Seliger JS, Simoneau JK. Emergency preparedness: disaster planning for health facilities. Baltimore: Aspen Publishers, 1986.)

Disaster research has demonstrated that staff who perform most efficiently are those who perform relatively familiar tasks ( 69,70). The disaster plan should take this into account by relying on standard operating procedures as much as possible. The plan must describe several key functions. These include: 1. 2. 3. 4. 5. 6. 7.

activation of the plan assessment of the hospital's capacity establishment of a disaster command communications supplies hospital disaster administrative and treatment areas training and drills

Activation of the Disaster Plan It is essential that the plan designate someone who will be responsible for putting the hospital's disaster plan into effect. An alternative person or persons who have this authority also should be specified. Situations that warrant activation of the plan should be defined operationally (i.e., definition of disaster). This, of course, varies from hospital to hospital and cannot be defined simply as the number of incoming casualties (see previous section Definition and Classification of Disasters ). For example, the ED disaster manual must define how the on-duty physician and nurse determine to what degree to mobilize and when to involve the administrator or nursing supervisor (37). After activation of the plan, there must be immediate mobilization of all disaster resources likely to be needed. These include personnel, supplies, equipment, communications, and transportation. Assessment of the Hospital's Capacity Before the hospital can receive casualties, it must be determined whether the hospital itself has sustained any structural damage or loss of capability as a result of a disaster (55,57,118,119). These include blocked passageways; inoperable elevators; potential for fire, explosion, or building collapse; failure of any utility; loss of equipment or supplies, including oxygen; contamination of water; and outside access problems. Damage assessment is usually the responsibility of the plant safety officer or hospital engineer. If the hospital's structural integrity has been compromised, it may be necessary to evacuate staff and patients. Once it is determined that the hospital is safe, the hospital must determine how many casualties from the disaster site it can manage. This may be limited by available personnel, beds, and supplies, by the type of disaster, and by the availability of other community resources. At the time of disaster notification, it is necessary to know the status of many of the hospital's capabilities—how many beds are available, how much blood is available, how many personnel are on duty, what damage has been done, how many operating rooms are in use, which doctors are present, and so forth. Either someone must tour the hospital to accumulate this information or a form for reporting it must be available in each department ahead of time. Establishment of Disaster Command A command site within the hospital should be established, preferably in a predesignated area (e.g., hospital disaster control center). This center should have communications ability with the patient receiving area (triage site), patient care areas, and with regional EMS, police, fire, and government authorities. Provisions for multiple modes of communication (telephones, cellular phones, two-way radios, runners) should be made. The command personnel should include at least a physician, a nurse, and an administrator ( 38,53). A hospital command structure modeled after the ICS (see previous section Disaster Operations/ICS) may simplify communication internally and with outside agencies. Communication

Establishment of good communications is critical in any disaster or mass-casualty situation ( 120). Experience, however, has shown that this essential function is difficult to achieve for several reasons ( 14). Telephones frequently become inoperative because of switchboard overload and damage to telephone lines and other equipment. A major goal should be full use of all possible communications resources including citizens' band groups, radiotelephone subscribers, cellular phones, blackboards, intercoms, closed-circuit television, short-wave radio, and radio-equipped persons of all kinds and even messenger and courier services ( 13,42). Cellular communications have proven unreliable in earthquakes ( 105). Interhospital communication is of utmost importance. This communication may be necessary because of shortages of supplies such as blood or intravenous fluids, certain equipment such as incubators or surgical instruments, or personnel such as nurses, x-ray technicians, or physicians ( 96,97 and 98). An overloaded hospital may want to transfer patients to another hospital with which this arrangement has been made ahead of time. Unfortunately, interhospital communications may present a weak link in the community's disaster response. After one Los Angeles earthquake, 67% of hospitals had difficulty with interhospital communications ( 121). The Federal Communications Commission (FCC) has designated multiple radio frequencies solely available for EMS radio services (FCC 90.27(a)(b)). These frequencies are used for daily EMS operations and dispatch. The FCC also designates a particular radio frequency (155.340) for use as a “mutual aid” coordination channel. (FCC 90.27(c)( 5). This channel authorizes the building-to-building (point-to-point) communication necessary in events requiring mutual aid. Hospital networks can take advantage of this frequency as an additional communications system. This can help ensure the rapid transfer of information in disasters. In California, 155.340 is designated for use by the Hospital Emergency Administrative Radio System under the Statewide Mutual Aid Radio System Plan ( 122). Under these systems, frequency 155.340 is used for interhospital communications in disasters or extreme emergencies. Supplies During a disaster, necessary supplies and equipment must be ready for immediate distribution to appropriate locations in the hospital (e.g., stretchers and wheelchairs to the receiving area). Each hospital must estimate the amount of supplies that will be needed in stock over and above its regular hospital supply. In most instances, this will not have to be increased because most hospitals already have a month's supply of many items in stock ( 37,53). Hospital Disaster Administrative and Treatment Areas As part of disaster planning, it is essential that certain areas of the hospital be designated for specific functions such as reception of casualties, treatment, and discharge of patients. The plan should be specific as to the function of these areas, staffing requirements, and basic supplies to be used. The areas to be incorporated in each plan are described in the following sections. DISASTER CONTROL CENTER A disaster control center must be established to provide overall command and coordination of the hospital's disaster response activities. These activities include activation of the plan, coordination of hospital activities with those at the disaster site, and adjusting the plan as necessary. Good communication is essential for these coordination activities and must be immediately available by means of telephone, radio, and messengers. Disaster control responsibilities include opening up additional hospital wards or clinics, obtaining outside assistance, evacuation of endangered patients, assignment of staff to treatment areas, and revision of original job assignments. TRIAGE To maximize efficiency, entry of all patients should be restricted to only one location, the triage area. The location of the disaster triage area may differ from the normal operating site. This is often necessary because the large number of patients in a disaster may overwhelm the often small physical plant space used for most triage areas. Weather permitting, a triage area immediately outside the ED can provide additional space and be an alternative site if the hospital has sustained structural damage (105). The primary function of a disaster triage area is rapid assessment of all incoming casualties, the assignment of priorities for management, and classification of dispositions (i.e., distribution of patients to various patient care areas in the hospital) ( 123,124). Without a triage area to manage the patient flow, the major treatment area may become overwhelmed. PATIENT CARE STATIONS Suggested means of organizing patient care stations are described as follows: Major Trauma and Medicine From the triage location, most if not all seriously injured patients are sent to the major trauma–medicine area (e.g., trauma and cardiac resuscitation, treatment of hypovolemic shock). This is usually in the ED. This should be staffed by emergency physicians or any other physicians qualified to handle rapid resuscitation of injured or critically ill patients. Minor Trauma–Primary Care In most disasters, most patients are not seriously injured. A great percentage of these are classified as the walking wounded ( 15). These low-priority patients can be sent to an urgent care area often designated as the minor trauma–primary care area for definitive care, including splinting of fractures, primary closure of lacerations, and tetanus prophylaxis. This area can be established in the hospital's outpatient clinics. Staffing in these areas can be a useful place for outpatient physicians reporting to the hospital to aid in disaster relief efforts. ADMISSION PRESURGICAL HOLDING Most patients stabilized in the major trauma area (ED) are sent to the admission presurgical holding area. SURGERY The number of operating rooms that can be staffed is the main limiting factor in the provision of definitive care for a large number of severely injured patients ( 88,89). The most experienced surgeon available must evaluate patients and assign surgeons as rapidly as possible. MORGUE Many disasters can result in a large number of fatalities, requiring the expansion of morgue capacities or the temporary use of other facilities such as a church or a stadium (125). Forensic issues may be important and guidelines established for analysis. DECONTAMINATION A hazardous material (hazmat) is any substance that is potentially toxic to a biologic system and includes chemical, biologic, and disease-causing agents (Code of Federal Regulations, 29, 1910.1030 ( 129). These hazards are regulated by the Occupational Health and Safety Administration (OSHA). Other agencies involved in the regulation or support of hazmat incidents include FEMA, the Environmental Protection Agency, the National Center for Environmental Health of the Centers for Disease Control, and the National Fire Protection Agency. JCAHO requires that hospitals have provisions for emergency treatment and decontamination of patients who are radioactively or chemically contaminated ( 81). Some specific guidelines that hospitals must meet are outlined in Figure 153.6. JCAHO standards are incomplete in that there is no direction as to the hospital's role

in the decontamination operation, training requirements of ED personnel, and the level of protective equipment required. An ED whose staff has not received appropriate training and personal protective equipment is in violation of OSHA standards (29 CFR 1910.120; 1910.1200; 1910.132). Should a contaminated patient be brought to an unprepared ED (in terms of training and equipment), the ED is in violation of federal law ( 126). Choosing not to provide care to a contaminated person because of lack of hazmat training is a potential COBRA violation.

Figure 153.6. JCAHO Standards. Partial listing of Joint Commission hazardous material requirements for hospitals. (Reproduced with permission from Levitin HW, Siegelson HJ. Hazardous materials. Disaster medical planning and response. Emerg Med Clin North Am 1996;14:327–348.)

Hospitals must prepare to treat victims of hazmat before an incident requires this resource ( 127,128). Hospitals must provide the specialized training and protective equipment and develop the necessary protocol to treat contaminated patients. Unfortunately, most hospitals are poorly prepared to treat these patients despite federal, state, and JCAHO standards and in spite of the regulatory and certification organizations described ( 126). Hospitals cannot rely on decontamination of patients to occur in the prehospital arena, nor can they assume that patients will go to appropriate designated facilities. All hospitals should have the capability to treat several patients; the usual number of hazmat victims is limited to one or two ( 126). The goals of treatment are to reduce external contamination, contain the contamination that remains, and prevent the additional spread of potentially dangerous substances (44,45,46 and 47). The sooner a patient has been decontaminated, the sooner he or she can be treated as a “normal” accident victim. To accomplish this, three things must be achieved: 1. Terminate exposure to toxic materials. 2. Stabilize the patient. 3. Initiate proper definitive care. PSYCHIATRY In disasters involving casualties and even property damage with loss of possessions, there can be much anxiety, depression, and psychotic episodes ( 42,65,129). Hysterical persons, whether patients, visitors, or staff, can be extremely disruptive to hospital disaster operations ( 14). A separate isolated area must be predesignated to receive persons in need of psychologic intervention ( 115). Safety of the health care team must be maintained as well. FAMILY WAITING AND DISCHARGE AREA As experience in disasters has shown, families and friends converge en masse to the hospital seeking information about victims ( 51,68). This convergence can interfere seriously with efforts by the hospital to respond effectively to the situation. For this reason, a separate area must be predesignated for family members seeking information. This area may be used to discharge in-hospital patients and victims of the disaster. TRAINING AND DRILLS Regular training and drills help to familiarize staff with their disaster roles and responsibilities ( 90,111,112,113,130,131,132 and 133). They also serve to point out weaknesses or omissions in the plan that require additions or revisions. Drills can range from full-scale, communitywide simulations with moulage victims to table-top triage games to minidrills that test only certain components of the disaster plan such as call-up of personnel and test of communications ( 42). The absolute necessity of training and drills cannot be overstated. The fact is that most disasters in the United States are not of extraordinary magnitude, and many of the logistical problems faced in disasters are not caused by shortages of medical resources but from failures to coordinate their distribution ( 91). Because most EMS providers and hospitals have written disaster plans, this can lull providers into the belief that they are prepared. This is known as the paper plan syndrome ( 134). Unless adequate training precedes disaster drilling, the disaster plan is often not adhered to ( 135). Therefore, the written disaster plan is only the first step in disaster preparedness and must be accompanied by regular training programs and drilling if patient morbidity and mortality are to be kept to a minimum. One of the unfortunate realities is that there is a high prevalence of apathy toward disaster planning, and this attitude is probably a major impediment to disaster preparedness (91). Disaster planning must compete with regular personnel activities. Certainly the interest in disaster planning is inversely proportional to the time elapsed from a recent disaster ( 134). Although there is no clear method to overcome this phenomenon, training and drilling with reference to or in the context of a recent disaster may heighten interest and participation.

THERAPEUTIC MANAGEMENT DURING DISASTERS Triage PURPOSES Generally, triage can be defined as the prioritization of patient care based on the severity of injury or illness, the prognosis, and the availability of resources ( 123,124). The purpose of triaging patients arriving in the ED is to determine the predesignated care area to which the patient should be sent ( 13,17). The location to which the patients are triaged establishes priorities for care. For example, some victims may need immediate decontamination as they arrive, regardless of the severity of injury. Those requiring immediate care (respiratory failure, shock) are taken to resuscitation areas, whereas the dead are moved directly to the morgue ( 136). The severely, but less critically, injured are taken to the major trauma–medical area, where they are assessed additionally and initial treatment is begun. The walking injured are directed to the minor surgery–primary care treatment area, often located in outpatient clinic areas. There must be the ability to reassess and retriage on an ongoing basis to detect deterioration or changes. PERSONNEL A team consisting of a physician (preferably an emergency physician or a surgeon), an ED nurse, and a medical records or admitting clerk should receive every patient (25). In extraordinary situations, several triage teams may be required to handle the casualty load ( 41,74). The physician performing patient triage should be acknowledge as in command in the triage area. He or she should be clearly identified by a vest or other garment and must understand all triage options. If a physician is unavailable, an emergency nurse with training in the concepts of casualty triage and emergency patient assessment can be designated as the triage officer ( Fig. 153.7).

Figure 153.7. Responsibilities of triage area personnel. (Reproduced with permission from Seliger JS, Simoneau JK. Emergency preparedness: disaster planning for health facilities. Baltimore: Aspen Publishers, 1986.)

RESPONSIBILITIES Even though patients may have been triaged at the scene, they should undergo a second process of triage on arrival at the hospital, preferably at the ambulance entrance to the ED (13,43). Responsibilities of members of the triage team include: 1. assigning disaster patients to appropriate treatment areas (e.g., resuscitation room, major surgical, minor surgical) according to the assessment of their immediate needs and the availability of resources 2. instituting the most basic of life support measures, such as opening the airway, controlling external hemorrhage and possibly cardiopulmonary resuscitation Assessment of severity of injury should be accomplished by conducting a rapid primary survey supplemented by obtaining prehospital information from the patient or prehospital personnel. The triage team communicates information on number of casualties, severity of injuries, and need for additional resources to both the ED and the hospital disaster control center. If telephone lines are busy, this notification can be accomplished by using runners or by the use of portable radios. Similarly, triage personnel must be informed about the capability of the various treatment areas (e.g., major and minor surgery) to handle additional casualties or special problems such as burns. They also must know about the establishment and location of overflow areas. The triage physician should be aware of the location of a family waiting and public relations area within the institution because family, friends, and the media inevitably appear in the triage area. Every effort should be made by the security staff to keep them out of patient care areas until after the staff has dealt with the needs of the patients. The admitting clerk's role as part of the triage team is to complete tags, attach them to victims, and retrieve valuables and clothing for bagging ( 19,137). He or she then tags the bag and completes the Triage Area Casualty Log ( Fig. 153.8 and Fig. 153.9).

Figure 153.8. Example of disaster tag. (Reproduced with permission from Wieland P, Hattan DK. Disaster decision making in the acute facility. In: Garcia LM, ed. Disaster nursing: planning, assessment, and intervention. Baltimore: Aspen Publishers, 1985.)

Figure 153.9. Example of disaster tag. (Reproduced with permission from Simoneau JK. Disaster management. In: Sheehy SA, Barber JM, eds. Emergency nursing: principles and practice. 2nd ed. St. Louis: CV Mosby, 1985.)

PRINCIPLES OF TRIAGE The approach to patient evaluation and treatment is different under disaster situations resulting in large numbers of casualties ( 19,138,139). The triage physician's goal is to evaluate incoming patients rapidly to decide where to distribute them (e.g., to major or minor surgery). If there are mass casualties, one no longer has the luxury of concentrating all resources on the management of a single critical patient. To accomplish the most good for the greatest number of patients, the triage team must evaluate all patients arriving in the ED and classify their conditions with regard to severity of injury and need for treatment. Although some principles of medical care are unchanged in a mass casualty incident, other principles of patient care must be altered to achieve the best overall result ( 140). There is clearly no role for resuscitation, let alone definitive care, at this stage. Care should be limited to manually opening airways and controlling external hemorrhage ( 105). (Table 153.2 and Table 153.3).

Table 153.2. Routine Medical Practices Altered in a Mass Casualty Situation

Table 153.3. Routine Medical Practices Unaltered in a Mass Casualty Situation

The most common triage classification involves assigning patients one of four colors (red, yellow, green, or black) depending on injury severity and prognosis ( Table 153.4). One common prehospital method of categorizing patients to a color category system is S.T.A.R.T. or Simple Triage and Rapid Treatment. This system classifies victims according to their ability to walk, their mental status, the presence or absence of ventilation, and capillary perfusion ( 141). In addition to the nature and urgency of the patient's systemic condition, triage decisions must be sensitive to such factors affecting prognosis as age, general health, and physical condition of the patient and to the qualifications of the responders and the availability of key supplies and equipment ( 140).

Table 153.4. Triage Categories

Patients with catastrophic injuries who have a minimal chance for survival despite optimal medical care should be classified as expectant (e.g., those with burns involving 95% of the body surface area). Spending time on patients who are not likely to survive leaves other patients who can be saved awaiting care. If too much time intercedes, these patients also may become expectant. The goal with these patients should be adequate pain control and time to be with friends and family. Patient Care in the Emergency Department The purpose of this section is not to review all aspects of mass casualty care (e.g., advanced trauma life support, decontamination of chemical injuries) but to address some concepts of care not found in the routine management of emergency patients. Knowledge of possible disaster types and anticipation of associated injury patterns can help minimize morbidity and mortality. For example, victims of earthquakes who have been trapped by rubble for several hours or days should be watched closely for signs and symptoms of crush syndrome, such as cardiac arrhythmias and renal failure. Fulminant pulmonary edema from dust inhalation may be a delayed cause of death for victims of building collapse ( 142). (See Chapter 15, Chapter 17, and Chapter 139.) WOUND INFECTION Wound infections may occur in virtually all types of disasters. Infected wounds and gangrene were major problems after the Armenian earthquake ( 142). In hurricanes or tornadoes, persons may be cut by flying glass and other potentially highly contaminated material ( 35,36). Because of this, all wounds should be copiously flushed with saline. Primary closure of heavily contaminated wounds may result in major complications, as was the case after the Armero volcanic eruption in Colombia. If lacerations are old (older than 6 to 12 hours) or appear contaminated, they should be treated by debridement and left open for primary delayed closure in a 3-day period (89). This will allow observation of the wound for the possible development of infection. All patients should receive a tetanus booster and, if highly contaminated, tetanus immune globulin (Hypertet). RADIOGRAPHIC AND LABORATORY STUDIES Radiographic and laboratory studies should be used extremely judiciously in a mass casualty situation and only if the results of such tests will change therapeutic intervention (13,37). For example, radiographs of closed, nonangulated, potential fractures can be safely delayed for 24 to 48 hours, during which time effective splinting, elevation, and ice can be used. Skull films are never indicated if there are mass casualties ( 30). If a patient has neurologic impairment, computed tomography of the head should be performed. A chest film is needed in patients with chest pain, dyspnea, or abnormal chest wall motion. In trauma, the abdominal film does not provide much useful information. In contrast, radiographs of the cervical spine, pelvis, and femur should be taken, and the potential seriousness of injuries thus detected (permanent neurologic impairment, potential blood loss) should be considered. There are minimal indications for blood work. For example, in patients with hemorrhagic shock, one should clearly obtain a baseline hematocrit in addition to type and cross-matching for blood. Urine dipstick for blood may be useful to detect kidney or urinary tract injuries. In patients who are short of breath or who demonstrate ventilatory impairment, baseline arterial blood gases or pulse oximetry may be useful. All other laboratory studies should be considered accessories and should be ordered only in specific circumstances (e.g., carboxyhemoglobin in patients with smoke inhalation).

BLOOD BANK For disasters involving many casualties, it is recommended that the blood bank have at least 50 units of blood available ( 143). It is also important that the bank have ready access to a source of volunteer donors who can be mobilized rapidly. Other potential sources of blood include friends and family members of patients, as well as the walking injured. PATIENT IDENTIFICATION AND RECORD KEEPING Emergency department records of disaster victims usually have been poor to nonexistent ( 14). The general absence of detailed and systematic record keeping in disasters, except for patients admitted to hospitals for surgery or to intensive care units, has all kinds of implications ranging from problems of lost billing and insurance collection to the difficulty of making any evaluations of the quality of medical care given and the possible efficacy of treatment procedures ( 129). Documentation of the patient's hospital course should start in the triage area ( 19,137). Proper tagging with a hospital disaster tag is essential for proper identification, documentation of medical care, and information for relatives and the news media ( Fig. 153.8 and Fig. 153.9). One member of the triage team (admitting or medical records clerk) should be assigned the job of recording the victim's name on the disaster tag along with the triaged destination of the patient. If identification of the patient is not available, race, sex, and approximate age should be noted on the tag. An initial diagnostic impression should be registered on the tag. This information is entered into a department log and placed in a triage log book. MEDIA CONTROL In a disaster, the hospital may become inundated by members of the media more than by disaster victims ( 92,93). This impair the performance of an already stressed hospital staff (75). For this reason, members of the press and other news media representatives should be directed to a room or office of the hospital away from the ED or other areas in which patient care is delivered ( 115). The press room should be supervised closely by a hospital administrator or public relations specialist. This person should be in direct contact with the disaster control center. Hospital staff must leave all communications with the media to this person and should direct any member of the media to the public relations area so that consistent information is given by the hospital. FAMILY MEMBERS The presence of large numbers of people seeking news of friends and relatives can greatly impair effective disaster control activity. For this reason, a separate area must be predesignated for family members seeking information (115). Family members should not be allowed into patient care areas except to see patients who are critically ill or have died. The hospital telephone operator will be inundated with calls from concerned family members regarding the presence and status of patients. These calls should be directed to a single predesignated desk or office.

AFTERMATH OF DISASTER As soon as possible, efforts should be directed toward returning the hospital to normal operations. Besides restocking and cleaning, consideration must be given to the emotional stress experienced by prehospital and hospital staff. Short- and long-term emotional problems, particularly among rescuers, have been reported on numerous occasions (144). All those involved should be encouraged to talk with one another and with counselors as needed. Deficiencies in a hospital's plan that are revealed during a disaster should be carefully recorded, reviewed, and criticized. Immediate steps should then be taken to correct any flaws in the plan.

NATIONAL CONTACTS Federal Emergency Management Agency, 500 C Street, SW, Washington, DC 20472. Office of Emergency Preparedness and Disaster Relief, Pan American Health Organization, 525 23rd Street, NW, Washington, DC 20037; (202) 861-4325. Disaster Research Center, University of Delaware, Newark, DE 19716; (302) 451-6618. American Academy of Emergency Medicine, 611 E. Wells Street, Milwaukee, WI 53202; (800) 884-AAEM. American College of Emergency Physicians, PO Box 619911, Dallas, TX 75261; (800) 798-1822. National Association of EMS Physicians, 230 McKee Place, Suite 500, Pittsburgh, PA 15213; (800) 228-3677. Disaster Research and Training Program, The Johns Hopkins University Department of Emergency Medicine, 600 N. Wolfe Street, Baltimore, MD 21205; (301) 955-8708. Office of Emergency Preparedness and NDMS, US Department of Health and Human Services, 5600 Fishers Lane, Room 4-81, Rockville, MD 20857. Office of US Foreign Disaster Assistance, US State Department, Room 1262A, Washington, DC 20523; (202) 647-7545. National Study Center for Trauma and EMS, University of Maryland, 22 S. Greene Street, Baltimore, MD 21201. Agency for Toxic Substances and Disease Registry, 1600 Clifton Road, NE, Atlanta, GA 30333; (404) 488-4100. Office of the UN Disaster Relief Coordinator, United Nations, Room S-2935, New York, NY 10017. World Association for Emergency and Disaster Medicine, c/o Dr. Peter Baskett, Department of Anaesthesia, Frenchay Hospital, Bristol BS16 1LE, UK. American Red Cross, National Headquarters, 17th and D Streets, NW, Washington, DC 20006. Emergency Management Institute, 16825 South Seton Avenue, Emmitsburg, MD 21727. International Civil Defense Organization, 10-12 Chemin de Surville, CH-1213 Petit-Lancy, Geneva, Switzerland. Center for Research on the Epidemiology of Disasters, Catholic University of Louvain 30-34, Clos-Chapelle-aux-Champs 30, 1200 Brussels, Belgium. Emergency Preparedness Program, Partners of the Americas, 1424 K Street, NW #700, Washington, DC 20005. Office of Emergency Preparedness, Health Resources and Services Administration, 5600 Fishers Lane, Room 13A-22, Rockville, MD 20857. International Association of Fire Chiefs, 1329 18th Street, NW, Washington, DC 20036. Joint Commission on the Accreditation of Healthcare Organizations, 875 N. Michigan Avenue, Chicago, IL 60611.

National Association for Search and Rescue, PO Box 3709, Fairfax, VA 22038. National Association of EMS Physicians, 190 Lothrop Street, Pittsburgh, PA 15213. American Hospital Association, 840 N. Lake Shore Drive, Chicago, IL 60611. California Specialized Training Institute, Division of California Office of Emergency Services, P.O. Box 8104, San Luis Obispo, CA 93403-8104. Chemical Manufacturers Association, Chemical Awareness and Emergency Response Program, 2501 M Street, NW, Washington, DC 20037. World Health Organization, Office of Emergency Relief Operations, 20 Avenue Appia, 1211 Geneva, 27, Switzerland. Intertect, PO Box 565502, Dallas, TX 75356. University of Wisconsin–Extension, Disaster Management Center, Department of Engineering Professional Development, 432 N. Lake Street, Madison, WI 53706. Casualty Surgeons Association, The Royal College of Surgeons, 35/43 Lincolns Inn Fields, London WC2A 3PN, UK. Radiation Emergency Assistance Center/Training Site, Medical and Health Sciences Division, Oak Ridge Associated Universities, Box 117, Oak Ridge, TN 37831. Emergency Training Institute, Miller Landing Building 200, 150 N. Miller Road, Akron, OH 44313. Emergency Services Branch, National Institute of Mental Health, 5600 Fishers Lane, Rockville, MD 20857. Medicine de Catastrophe, Hospital Henri Mondor, 51, Av. du Marechal de Lattre de Tassigny, F-94010 Creteil, France. European Center for Disaster Medicine, State Hospital, 47031 Republic of San Marino. CHEMTREC (Chemical Transportation Emergency Center); 1-800-424-9300.

PROFESSIONAL MEDICAL AGENCIES INVOLVED IN DISASTER PREPAREDNESS County and state medical societies Hospital council Nursing association Dental association Podiatry association Pharmaceutical association Veterinarian association Industrial medical association City, county, and state health departments References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41.

National Research Council. Confronting natural disasters: an international decade for natural hazard reduction. Washington, DC: National Academy Press. 1987:1–67 Office of US Foreign Disaster Assistance. Disaster history: significant data on major disasters worldwide, 1900–present. Washington, DC: Agency for International Development, 1995. Noji EK: Disaster epidemiology. Emerg Med Clin North Am Disaster Medicine 1996;14:289–300. Subcommittee on Natural Disaster Reduction. Committee on the Environment and Natural Resources: Final Report. Washington, DC: National Science and Technology Council, Nov. 7, 1994. Wijkman A, Timberlake L: Natural disasters: acts of God or acts of man. New York: Earthscan, 1984. Hagman G: Prevention better than cure. Stockholm: Swedish Red Cross, 1984. Martchenke J, Lynch T, Pointer J, et al: Aeromedical helicopter use following the 1989 Loma Prieta earthquake. Aviat Space Environ Med 1995;66:359–363. McNabb SJ, Kelso KY, Wilson SA, et al: Hurricane Andrew-related injuries and illnesses, Louisiana, 1992. South Med J 1995;88:615–618. Wickramanayake E, Shook GA, Rojnkureesatien T: Rehabilitation planning for flood affected areas of Thailand: experience from Phipun District. Disasters 1995;19:348–355. Waeckerle JF: Disaster planning and response. N Engl J Med 1991;324:815–821. Burkle FM: Complex, humanitarian emergencies: I. concept and participants. Prehospital Disaster Med 1995;10:36–42. International Ad Hoc Group of Experts. Implementing the international decade for natural disaster reduction: a report to the Secretary General of the United Nations. Geneva: United Nations, 1989. Aghababian RV: Hospital disaster planning. Top Emerg Med 1986;7:446. Quarantelli EL: Delivery of emergency medical services in disasters: assumptions and realities.New York: Irvington, 1983. Woods D: Disasters: how would your hospital cope with 50 casualties? Can Med Assoc J 1977;116:1195. Butman A: The challenge of casualties en masse. Emerg Med 1983;15:110. Contzen H: Preparations in hospital for the treatment of mass casualties. Journal of World Association for Emergency & Disaster Medicine 1985;1:118. Cowan M, Butman AM, Bosner LV: Mass casualty planning: model for in-hospital disaster response. Journal of World Association for Emergency & Disaster Medicine 1986;2:83. Irving M: Major disasters: hospital admission procedures. Br J Surg 1976;63:703. Kennedy W: Some preliminary observations on a hospital response to the Jackson, Mississippi tornado of March 3, 1966. Disaster Research Center report no. 17. Columbus: The Ohio State University, 1967. Baker EJ: The management of mass casualty disasters. Top Emerg Med 1979;1:149. Blanshan SA: A time model: hospital organization response to disaster. Beverly Hills: Sage Publications, 1978:173–198. Jacobs L, Goody M, Sinclair A: The role of the trauma center in disaster management. J Trauma 1982;23:697. Katz LB, Pascarelli EF: Planning and developing a community hospital disaster program. Emerg Med Serv 1978;Sept/Oct:70. Koslowski I: Emergency and disaster medicine: assignments and perspectives. Journal of World Association for Emergency and Disaster Medicine 1985;1:255. Mezzetti F: A hospital emergency plan. Journal of World Association for Emergency & Disaster Medicine 1985;1:266. Rutherford WH: Disaster procedures. Br Med J 1975;1:443. Savage PE: Disasters and hospital planning: a manual for doctors, nurses and administration.Oxford: Pergamon Press, 1979. Seliger JS, Simoneau JK: Emergency preparedness: disaster planning for health facilities. Rockville, MD: Aspen Publishers, 1986. Williams DJ: Major disasters. Disaster planning in hospitals. Br J Hosp Med 1979;22:308–317. Meyer MU, Graeter CJ: Health professional's role in disaster planning: a strategic management approach. AAOHN J 1995;43:251–262. Trappler B, Friedman S: Posttraumatic stress disorder in survivors of the Brooklyn Bridge shooting. Am J Psychiatry 1996;153:705–707. Garrison CZ, Bryant ES, Addy CL, et al: Posttraumatic stress disorder in adolescents after Hurricane Andrew. J Am Acad Child Adolesc Psychiatry 1995;34:1193–1201. Gunn SWA: The language of disasters. Prehospital Disaster Med (Special Report) 1990;5:1–25. Emergency health management after natural disaster. Washington, DC: Pan American Health Organization, 1981. Emergency care in natural disasters: Views of an international seminar. WHO Chron 1980;34:96. Jenkins AL, van de Leuv JH, eds: Disaster planning in emergency department organization and management. 2nd ed. St. Louis, CV Mosby, 1978. de Boer J, Baillie TW, eds: Disasters: medical organization. London: Pergamon, 1980. Holloway R: Medical disaster planning in urban areas. NY J Med 1971;1:591–595. Melton RT, Riner RM: Revising the rural hospital disaster plan: a role for the EMS system in managing the multiple casualty incident. Ann Emerg Med 1981;10:39–44. Li TC, et al: Medicine in a disrupted society: the role of the academic medical center. Am J Med 1981;70:998.

42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144.

Butman AM: Emergency training: responding to the mass casualty incident: a guide for EMS personnel. Westport, CT: Educational Direction, 1982. Cowley RA, ed: Proceedings of mass casualties: a lessons learned approach. 1982;13–17. Cashman JR: Hazardous materials emergencies: response and control. Lancaster, PA: Technomic Publishing, 1988. Currance PL, Bronstein AC: Emergency care for hazardous materials exposure. St. Louis: CV Mosby, 1988. Leonard RB: Community planning for hazardous materials. Top Emerg Med 1986;7:55. Stutz DR, Ricks R, Olsen M: Hazardous materials injuries: a handbook of prehospital care. Greenbelt, MD, Bradford Communications Corp., 1982. Edelstein S, Giordano J: Presidential assassination attempt. In: Cowley RA, ed. Proceedings of mass casualties: a lessons learned approach. 1982;17–28. O'Leary DS: Managing a hospital under crisis. In: Cowley RA, ed. Proceedings of mass casualties: a lessons learned approach. 1982;127–140. Blanshan S: A time model: hospital organizational response to disaster. In: Quarantelli EL. Disaster: theory and research. 1978;173–198. Quarantelli EL: The community general hospital: its immediate problem in disasters. Am Behav Sci 1970;13:380. Weiss DB: Organization of hospital medical care of mass casualties in peacetime disasters. Int Surg 1982;67:400. Garcia LM: Disaster nursing: planning, assessment, and intervention. Rockville, MD: Aspen Systems, 1985. Tresalti E: Organization of hospital for extrahospital emergencies. Journal of World Association for Emergency & Disaster Medicine 1985;1:284. Seaver DJ: Coping with internal disaster is a hospital priority. Hospitals 1997;51:167–172. Tresalti E: Organization of hospital for intrahospital emergencies. Journal of World Association for Emergency & Disaster Medicine 1985;1:285. Reitherman R: How to prepare a hospital for an earthquake. J Emerg Med 1986;4:119. Zeballos JL: Health effects of the Mexico earthquake—19th Sept. 1985. Disasters 1986;10:141. Lewis CP, Aghababian RV: Disaster planning, part I: overview of hospital and emergency department planning for internal and external disaster. Emerg Med Clin North Am Disaster Med 1996;14:439–452. Western K: The epidemiology of natural and man-made disasters: the present state of the art. University of London. 1972. Dissertation. Seaman J: The effects of disaster on health: a summary. Disasters 1980;4:14. SAEM Disaster Medicine White Paper Subcommittee. Disaster medicine: current assessment and blueprint for the future. Special contribution. Acad Emerg Med 1995;2:1068–1076. Toole MJ, Waldman RJ: Refugees and displaced persons: war, hunger and public health. JAMA 1993;270:600–605. Koenig KL, Dinerman N, Kuehl AE: PICE nomenclature: a new system to describe disasters. Prehospital Disaster Med 1994;9:S65. Abstract. Drabek TE: Human system responses to disaster. New York: Springer–Verlag, 1986. Dynes R, Quarantelli EL, Kreps G: A perspective on disaster planning. 3rd ed. Columbus: Ohio State University, 1981. Dynes RR: Emergency medical services delivery in disasters. In: Collected papers in emergency medical services and traumatology. Baltimore: University of Maryland, 1979:56–58. Quarantelli EL: The delivery of disaster emergency medical services: recommendations from systematic field studies. Disaster Med 1983;1:41. Tierney K: Emergency medical preparedness and responses in disasters: the need for interorganizational coordination. Public Admin Rev 1985;45:77. Tierney KJ, Taylor VA: EMS delivery in mass emergencies: preliminary research findings. Mass Emerg 1977;2:151. Bozza–Marrubini M: Three major disasters in Italy: experience of Niguarda Hospital of Milan as ‘base hospital.' JWAEDM 1985;1:414. Foster C: Texas hospital battles Hurricane Beulah. Hosp Management 1967;104:70. Lewis F, Trunkey D: Autopsy of a disaster: the Martinez bus accident. J Trauma 1980;20:861. Orr M, Robinson A: The Hyatt Regency skywalk collapse: an EMS-based disaster response. Ann Emerg Med 1983;12:601. Taylor VA: Hospital emergency facilities in a disaster: an analysis of organizational adaptation to stress. Disaster Research Center preliminary paper no. 11. Columbus: The Ohio State University, 1974. Toole MJ, Waldman RJ: Prevention of excess mortality in refugee and displaced populations in developing countries. JAMA 1990;263:3296–3302. Bliss AR: Major disaster planning. Br Med J 1984;288:1433. Jacobs LM, Ramp JM, Breay JM: An emergency medical system approach to disaster planning. J Trauma 1979;19:157. Keller EL: A realistic approach to disaster planning. Hosp Med Staff 1977;May:18–23. Guha–Sapir D, Lechat MF: Information systems and needs assessment in natural disasters: an approach for better disaster relief management. Disasters 1986;10:232. Joint Commission on the Accreditation of Healthcare Organizations. Comprehensive accreditation manual for hospitals: the official handbook/1997. Chicago: Authors, 1996. Mohler SR, et al: Medical management in a disaster. Aviat Space Environ Med 1980;51. McSwain NE, Rodriguez C: Disaster medical care: Mardi Gras. J Trauma 1982;22:235. Binder S, Sanderson LM: The role of the epidemiologist in natural disasters. Ann Emerg Med 1987;16:1081. Noji EK, Sivertson KT: Injury prevention in natural disasters: a theoretical framework. Disasters 1987;11:290. Zhi-Yong S: Medical support in the Tangshan earthquake: a review of the management of mass casualties and certain major injuries. J Trauma 1987;27:1130. Buerk CA, Batdorf JW, Cammack KV, et al: The MGM Grand Hotel fire: lessons learned from a major disaster. Arch Surg 1982;117:644. de Boer J, Brismar B, Eldar R, et al: The medical severity index of disasters. J Emerg Med 1989;7:269. Burkle FM, Sanner PH, Wolcott BW, eds: Disaster medicine. New York: Medical Examination Publishing, 1984. Davies LF: Community disaster planning and training. Emerg Med Serv 1986;15:42. Auf der Heide E: Disaster planning, II: disaster problems, issues, and challenges identified in the research literature. Emerg Med Clin North Am Disaster Med 1996;14:453–480. Quarantelli EL: Human resources and organizational behaviors in community disasters and their relationship to planning. Columbus, OH: Disaster Research Center, The Ohio State University, 1982. Quarantelli EL, Dynes RR: Different types of organizations in disaster responses and their organizational problems. Columbus, OH: Disaster Research Center, The Ohio State University, 1977. American College of Emergency Physicians. The role of the emergency physician in mass casualty/disaster management. JACEP 1976;5:901. Dimick A: Role of medical staff in disaster planning and operation. In: Proceedings of the U.S.A. Bicentennial EMS and Traumatology Conference. Baltimore: U.S. Department of Health, Education, and Welfare, 1976. Eldar R: A multi-hospital system for disaster situations. Disasters 1981;9:112. Marsden AK: Coordination of major accident services within a British health region. JWAEDM 1987;3:57. Rowal JS: Four hospitals join in planning city-wide disaster alert. Hospital Topics 1970;48:24. Keogh J: Management of mass burn casualties in a hospital with a burn unit. Med J Aust 1980;1:303–305. Golec J, Gurney PJ: The problems of needs assessment in the delivery of EMS. Mass Emergencies 1977;2:169. Oyen O: The on-scene medical organization. Journal of World Association for Emergency & Disaster Medicine 1985;1:115. Safar P: Resuscitation potentials in mass disasters. Journal of World Association for Emergency & Disaster Medicine 1986;2:34. Baskett P, Weller R: Medicine for disasters. London: Wright, 1988. Nancekievill D, Finch P: The role of hospital mobile medical teams at a major accident. In: Cowley RA, ed. Proceedings of mass casualties: a lessons learned approach. 1982:147–156. Schultz CH, Koenig KL, Noji EK: A medical disaster response to reduce immediate mortality after an earthquake. N Engl J Med 1996;334:438–444. Londorf D: Hospital application of the incident management system. Prehospital Disaster Med 1995;10:184–188. The Hospital Emergency Incident Command System. Long Beach, CA: Orange County Health Care Agency, Emergency Medical Services, May 1993. Alcouloumre E: The role of the physician at a medical disaster: hospital emergency response teams. Journal of World Association for Emergency & Disaster Medicine 1986;2:128. Gerace RV: Role of medical teams in a community disaster plan. CMA J 1979;120:923. Thompson P: Issues in disaster management training. Disasters 1983;7:37. Defeu N, Huguenard P: Teaching disaster medicine in France. In: Cowley RA, ed. Proceedings of mass casualties: a lessons learned approach. 1982:289–294. Feldstein B: Disaster medicine training in France. Ann Emerg Med 1983;12:621. Feldstein B, Gallery M, Sanner P, et al: Disaster training for emergency physicians in the United States: a systems approach. Ann Emerg Med 1985;14:36. Barbera JA, Macintyre A: Urban search and rescue. Emerg Med Clin North Am Disaster Med 1996;14:399–412. Roth JA: Staff and client control strategies in urban hospital emergency services. Urban Life and Culture 1972;39–60. Roth PB, Gaffney JK: The federal response plan and disaster medical assistance teams in domestic disasters. Emerg Med Clin North Am Disaster Med 1996;14:371–382. National Disaster Medical System, Disaster Medical Assistance Team Manual. Washington DC: NDMS, September 1995. Rutherford WM: Experience in the accident and emergency department of the Royal Victoria Hospital with patients from civil disturbances in Belfast 1969–1972 with a review of disasters in the United Kingdom 1951–1971. Injury 1973;4:189. Roeschlaub EL: Hospitals in riot-torn cities meet patient needs head on. Hosp Topics 1968;46:57. Storer D: Disaster planning: communications. Ohio Med J 1979;6:401. Bouzarth WF, Mariano JP, Smith JS: Disaster preparedness. In: Schwartz GR, ed. Principles and practice of emergency medicine. Philadelphia: WB Saunders, 1986:612. State of California, Governors Office of Emergency Services. Statewide Mutual Aid Radio System Plan. 1986:13. Rund D, Rausch T: Triage. St. Louis: CV Mosby, 1981. Rutherford WH: Sorting patients, sometimes called triage. Disaster Med 1983;1:121. Hooft PJ, Noji EK, Van de Voorde HP: Fatality management in mass-casualty incidents. Forensic Sci Int 1989;40:3. Levitin HW, Siegelson HJ: Hazardous materials: disaster medical planning and response. Emerg Med Clin North Am Disaster Med 1996;14:327–348. Cox RD: Decontamination and management of hazardous materials exposure victims in the emergency department. Ann Emerg Med 1994;23:761. Kirk MA, Cisek J, Rose SR: Emergency department response to hazardous materials incidents. Emerg Med Clin North Am 1994;12:461. Logue JN, Melick ME, Hansen H: Research issues and directions in the epidemiology of health effects of disasters. Epidemiol Rev 1981;3:140. Cloutier MG, Cowan ML: Disaster medicine training through simulations for fourth-year students. J Med Ed 1986;61:408. Hell K: Training of physicians in disaster medicine in Sweden. JWAEDM 1985;1:106. Hell K: Training of physicians in disaster medicine. Disaster Med 1983;1:107. Thompson P: Issues in disaster management training. Disasters 1983;7:37. Auf der Heide E: Disaster response: principles of preparation and coordination. St. Louis: CV Mosby, 1989. Quarantelli EL: Delivery of emergency medical care in disasters: assumptions and realities. New York: Irvington Publishers, 1983. Evans RF: Major disasters: the patient with multiple injuries. Br J Hosp Med 1979;22:329. Finch PM, et al: Early documentation of disaster victims. Anaesthesia 1982;37:1185. Byrd TR: Disaster medicine: toward a more rational approach. Military Med 1980;145:270–273. Dubouloz M: An introduction to disaster medicine. Bull Int Civil Defence August 1983;25. Roding H: Triage and its ethical problems. JWAEDM 1987;3:10. Gans L, Kennedy T: Management of unique clinical entities in disaster medicine. Emerg Med Clin North Am Disaster Med 1996;14:301–326. Noji EK: Medical and healthcare aspects of the 1988 earthquake in Soviet Armenia. Earthquake Spectra 1989;(suppl):101–107. Sandler SG: Strategies for blood management in mass casualty incidents. In: Cowley RA, ed. Proceedings of mass casualties: a lessons learned approach. 1982:229–234. Waeckerle JF: The skywalk collapse: a personal response. Ann Emerg Med 1983;12:651.

Chapter 154.1 Germany Principles and Practice of Emergency Medicine

CHAPTER 154 INTERNATIONAL PERSPECTIVES OF EMS SYSTEMS DEVELOPMENT

1 Germany Markus D.W. Lipp and Andreas R. Thierbach Capsule Introduction Organization Education and Training of EMS Personnel Response Procedures in the EMS Senior Emergency Physicians Medical Director Rapid Response Units In the 1st, 2nd, and 3rd editions we covered a wide range of EMS including: Hungary, Tokyo, Stockholm, Israel, Tel-Aviv, Canada, France, Japan, Germany (West), Australia, and the USSR. In view of the systemic changes, in the 4th edition we highlight Russia (since the breakup of the USSR), Germany (with the consolidation of East and West Germany), and Australia, which had increases in dealing with rural populations.

CAPSULE Organization and guarantee of the prehospital emergency medical service (EMS) are the sole responsibility of the 16 states. Because of political considerations, differences in EMS structure exist between states in Germany, but the main principles are comparable throughout the country. The structure of the EMS in Germany is based on strong medical control and the philosophy to provide emergency care at the scene by emergency physicians. The main components of the EMS are well-trained emergency physicians and paramedics as well as adequate medical and technical equipment. Transport is provided by ground vehicles and helicopters. For quality management, the position of a medical director (physician with additional training and experience) has been introduced. In disaster situations, the EMS is backed by senior emergency physicians and rapid response units.

INTRODUCTION The location of Germany is in central Europe, bordering the Baltic Sea and North Sea, between the Netherlands and France in the west, Switzerland and Austria in the south, Czech Republic and Poland in the east and Denmark in the north. Germany has a population of 81.3 million inhabitants and an area of 356,910 square kilometers after the reunification of the formerly separated Federal Republic of Germany, the German Democratic Republic and Berlin in 1990. Politically, the Federal Republic of Germany is subdivided into 16 states. The organization and guarantee of the prehospital EMS are the sole responsibility of the government of each state. Because of political considerations, differences in EMS structure exist between states in Germany, but the main principles are comparable throughout the country. In the six states of the former German Democratic Republic, EMS systems have been reorganized totally to the same level of the “old” states. The EMS of Germany has developed rapidly since 1957, when Bauer and Frey introduced the first “Clinomobile,” an ambulance car, manned with a physician and assistance personnel (nurse and driver in these days, “compact system”), designed to provide medical support to patients at the emergency site. That was the beginning of the German philosophy “Bring medical care to the patient, not the unstabilized patient into the hospital.” Between 1968 and 1980 the concept of these mobile intensive care units (MICU) became established all over the former West Germany. After the reunification of the country, this principle has also been introduced in the new states of Germany. Parallel to this growing medical involvement, the number of paramedic-manned ambulances, operated by volunteer assistance organizations, fire brigades, and private companies grew. A major problem during this time period was that rescue vehicles were being dispatched by many noncooperating rescue coordination centers, and at times a race to the patient occurred. This situation changed in 1973, when the concept of a modern EMS was established by the proposals of a joint committee of the federal and state governments. The goals were to be laid down by details in the 16 state laws for: tasks of the EMS, structure of the EMS (central coordination and dispatching, personnel and technical demands), financing and supervision. Based on this proposal, in all states of Germany, specific laws concerning the EMS were passed. As outlined, the structure of the EMS in Germany is based on strong medical control; the main components of the EMS are well-trained emergency physicians and paramedics as well as adequate medical and technical equipment ( 1).

ORGANIZATION Fire Brigade and Medical Rescue Organizations In 1991 36.9% of all EMS rescue activities were provided by the fire brigade, in particular in the cities and in the northern states up to 61.2%. The other German medical rescue organizations are different in origin and age. The “Deutsche Rote Kreuz” (DRK) is 130 years old and is part of the International Red Cross Societies. The “Arbeiter-Samariter-Bund” (ASB) was founded in 1889 and had its roots in the workers' movement. Today it is a nonpolitical medical rescue organization, providing EMS in all states of Germany. “Johanniter Unfall-Hilfe” (JUH) and “Malteser-Hilfsdienst” (MHD) have their origin in the Protestant and Catholic churches, respectively, and started their activities in the EMS in 1952 and 1953. Fire brigade and medical rescue organizations provide vehicles and medical equipment. They are also employees of the paramedics, not of the emergency physicians. Rescue Coordination Center Germany is divided into multiple EMS districts, often identicalwith the political topographic structure of the particular region. Every rescue coordination center (RCC) activates and coordinates within its area all activities of ground rescue vehicles and rescue helicopters. The RCC also coordinates bed availability and the transport of critically ill patients to the appropriate hospitals. The RCC relays information from the rescue team to the receiving hospital or other specialty facilities (i.e., a detoxification center) as necessary. All RCCs are state controlled institutions, operated by the fire brigade or medical rescue organizations. In the northern and most of the new states RCCs coordinate fire brigade and EMS; in the southern area both services run separate dispatch centers. Most dispatchers are paramedics or fire fighters, a special training for EMS-RCC dispatchers still does not exist. Communication The center of the communication process is the RCC. Permanent open telephone lines are established to all rescue stations, the dispatch centers of police and fire departments (only if the EMS runs a separate RCC) as well as major receiving hospitals. Two-way radio communication devices, beepers, and in some centers, computerized information retrieval systems are used. Emergency calls from various sources, including individuals, police, and fire brigade are channeled to the RCC. The countrywide emergency telephone number is 112 (fire brigade and EMS), but in some parts of Germany the RCC can also be reached by dialing different and individual numbers, implemented by medical rescue organizations. This problem results in some confusion of patients, and under certain circumstances up to 72% of all emergency calls are not directed primarily to the RCC ( 2). Ground Vehicles The various types of EMS ground vehicles include: smaller ambulances (KTW), used for transport of noncritically ill patients; emergency ambulances (RTW), primarily designed for the stabilization of critically ill patients; MICUs, generally dispatched with an emergency physician: and, finally, cars designed for the transport of the

emergency physician (NEF). The medical rescue equipment of the ground rescue vehicles is tailored to adapt to specific roles and specified in law. KTWs, normally used for the transport of the noncritically ill patients only, are equipped with a litter, transport chair, oxygen tank, suction device ventilation masks and bags for artificial respiration, intravenous infusion supplies, dressings, and bandages. In reality, most of the KTWs are equipped above the minimum requirements. The actual financial situation caused some medical rescue organizations to reduce the equipment again to the legal level. However, the BLS resuscitation equipment is found in all ambulances; that allows the RCCs to dispatch even a KTW as the next available vehicle first, followed by an RTW, in an effort to reduce the response time. Most KTWs are dispatched with two semi-trained paramedics (RS). RTWs are used for on-site emergency care and transport of critical ill patients. They have to be supplied additionally to the equipment of a KTW with a vacuum mattress, electrocardiogram (ECG) and defibrillator, and complete resuscitation kits for adults and children including endotracheal intubation instruments, surgical instruments, and emergency drugs. The crew consists of two fully trained paramedics (RA). Actually, the number of RTWs equipped with semi-automatic defibrillators is increasing: the fire brigade of Hamburg has just implemented these defibrillators on all 63 RTWs. By law, the equipment of a MICU, which is generally dispatched with a certified emergency physician and two fully trained paramedics (RA), does not differ from the material of RTWs. But in reality, the equipment exceeds the legal requirements by far: automatically working respirators, blood pressure monitors, 12-lead ECG, pulse oxymetry, and capnography. Cars designed for the transport of the emergency physician to the emergency site (NEF, operating in a so-called “rendezvous system”) are equipped with advanced cardiac life support (ACLS) kits (for adults and children), oxygen, defibrillator/ECG and emergency drugs. Helicopter Rescue System To complement the ground EMS system, there is a network of 48 EMS helicopter stations throughout all parts of Germany (RTH). The helicopter rescue system covers 90% of Germany. This system allows quick response time even in the rural areas, smooth transport of the patient, and rapid transfer to a medical center if necessary (3). The use of most helicopters is limited by weather and daylight conditions, due to the fact that only a few helicopters of the German army and the disaster control are equipped with night flight capabilities. The crew consists of a certified emergency physician, a fully trained paramedic (RA), a flight officer, and a pilot. The system is not used only for transport of patients after medical treatment at the scene, up to one-half of the patients are transported by a ground rescue vehicle after receiving medical treatment by the emergency physician of the helicopter ( 4). The simultaneous dispatching of ground rescue vehicles and a helicopter has been demonstrated to have some advantages. At the emergency site, the paramedics can start to restore or maintain vital functions (e.g., BLS or ACLS). If they arrive earlier, an emergency ambulance provides a dry, warm, well-lighted “emergency room” for the initial medical treatment of the patients, a great advantage especially during rough weather conditions. The helicopters used in the German EMS are generally equipped in the same way as the emergency ambulances in respect to the medical aspects. The smallest helicopter operated, BO 105, has a restricted cabin area, and, therefore, stabilization must occur before flight. The BK 117 and the Bell UH1D provide an unobstructed cabin area, so that treatment during flight is possible. The old larger crafts, such as the Bell UH1D, are also operated as “search and rescue” crafts. Most of the helicopters have high maneuverability and small external dimensions, and are twin engine operated. Only a few helicopters, mainly operated by the army, are allowed to fly at night. The takeoff time after alerting should be less than 2 minutes. Statistics in 1985 for the helicopter located at Munich showed that the in-flight time after takeoff was approximately 10 minutes with an average distance of 30 km to the emergency site. The helicopters are mostly located at major hospitals and operated by the disaster control, the German army, the German automobile association and a private rescue organization (German Air Rescue). The air rescue system is used as a primary transport facility as well as for secondary transports.

EDUCATION AND TRAINING OF EMS PERSONNEL Emergency Physicians In Germany, emergency physicians routinely staff ambulances to render medical treatment to the emergency patient. At the scene, it is the responsibility of the emergency physician to provide the whole range of the necessary medical care to the patient. That contains all procedures of advanced trauma life support (ATLS) and ACLS as well as pain management and invasive procedures. The emergency physician must have knowledge of pathophysiology, symptoms, and treatment of typical emergencies in the specialties of surgery, internal medicine, pediatrics, and anesthesiology. On the administrative side, emergency physicians must know the structure of the local health and rescue system, e.g., locations, departments, and capabilities of the hospitals in their particular area. In contrast to other countries, Germany has no specific emergency departments within hospitals. Emergency medicine is a component in the education of anesthetists, as well as internal specialists and surgeons. Although anesthetists often meet the demands for emergency physicians best, in Germany surgeons, internal specialists, pediatricians, and general practitioners also work as emergency physicians. To ensure standards, physicians have to complete successfully a specialty training program and gain clinical experience of at least 18 months after becoming a specialist, of which 6 months is experience in an ICU. During this period, the techniques of emergency medicine, artificial ventilation, endotracheal intubation, and peripheral and central venipuncture, to name a few, are perfected. Additionally, an 80-hour program of theoretical education on special topics of emergency medicine must be successfully completed ( 5). Finally, before being certified as an “emergency physician” by the local health authority, the physician must treat at least ten emergency patients in the prehospital setting under the supervision of a senior emergency physician. Paramedics Before September 1989, the only training of a semi-trained paramedic (RS) consisted of 520 hours, divided as follows: 160 hours of theoretic education, 160 hours of practical training in a hospital, 160 hours of practical training in an ambulance, and 40 hours of a final theoretic course. After passing a state certification test consisting of oral, written and practical examinations, the candidate is allowed to work. The aim of the described training was to enable the paramedics (RS) to restore or maintain vital functions (e.g., cardiopulmonary resuscitation [CPR]), but without independent application of drugs and to assist emergency physicians in their treatment. Paramedics (RS), however, had no profession comparable to that of any other workers in the German health system. In September 1989, education of paramedics was changed fundamentally: the theoretic and practical training at school was extended to a 1200-hour course and an additional 1600-hour practical education at special ambulance dispatching stations. The training now lasts two years and ends with an extensive state certification procedure. Fully trained paramedics (RA) who have achieved this certification are given an official profession, titled “Rettungsassistent.” Paramedics may work as full-time employees (fire brigade and private ambulance companies or medical rescue organizations) or as volunteers (medical rescue organizations only). Due to German law, paramedics (RA) are not allowed to administer any drugs, perform intubation or myocardial defibrillation, or establish an IV access. To overcome these forensic limitations in time-critical situations (e.g., CPR), a nationwide program has been launched by the Federal Physicians Chamber. Lifesaving procedures such as early defibrillation, endotracheal intubation, administration of epinephrine are now permitted under certain conditions: A definitive and clear indication has to be given, the RA had passed a special physician-based training in these procedures (repeated every year) and an emergency physician is alerted, but has not reached the scene in the given moment. The program is controlled by authorized physicians. After having performed such action, the paramedic has to hand in a written report to the supervising physicians, if necessary followed by an interview.

RESPONSE PROCEDURES IN THE EMS After taking down the essential and necessary information of an emergency call, the paramedic on duty has to decide which rescue team or vehicle is to be sent out.

The activation time of an ambulance after alerting should be less than 45 seconds. Emergency calls that describe critically ill patients lead to the notification of an emergency physician, and the specific indications are prioritized at all RCC. The transport of the physicians is either carried out by a MICU, normally located at the hospital (compact system) or by a special designed car (rendezvous system) with the emergency ambulance arriving separately. The compact system is still operated in some cities and towns, whereas the rendezvous system is operated in the most rural areas. In an emergency, three dispatch strategies are used: the “next available vehicle” strategy, the “assignment” strategy, and the “multiple-purposes vehicle” strategy. The “next standing vehicle” strategy means that the nearest rescue vehicle (KTW, RTW, or MICU), which is actually situated at the emergency site, has to be alerted, regardless of its configuration or equipment. The main advantage of this principle is the short response time (e.g., less than 8.8 minutes in 85% of all emergencies in the town of Karlsruhe). A disadvantage, however, is that in some cases, critically ill patients have to be treated or even transported in underequipped small ambulances. The “assignment” strategy means that only emergency ambulances (RTW or MICU) are sent to an emergency patient and the smaller ambulances (KTW) are reserved for nonurgent transport of noncritically ill patients. The advantage of this principle is that patients can be treated with appropriate medical equipment before and during the transport. Disadvantages are the slightly extended response time compared to the “next available vehicle” strategy and the increased costs for the whole EMS. Use of the EMS vehicles system is for primary and secondary transports. “Primary transport” describes an immediate transport of medical personnel (emergency physicians and paramedics) to the emergency site within lifesaving minutes, for treatment and stabilization of casualties at the scene followed by medically supervised transport to an appropriate hospital. Primary transports have absolute priority over any other requests to the EMS. A “secondary transport” is carried out if a patient has been stabilized and treated in a hospital and then has to be transferred to a specialized center. Both primary and secondary transports are carried out by ground and air rescue systems.

SENIOR EMERGENCY PHYSICIANS In contrast to emergency physicians described previously, the senior emergency physician (SEP) has the task of the medical command, triage, and supervision in the case of a disaster situation (road or fire accident with more than 5 [in some areas 10] patients, explosion, airplane crash, train accident, or shipwreck) ( 6). A SEP does not primarily treat single patients at the emergency site and accompany patients to the hospital. They remain at the location of the disaster or accident. Provided with adequate technical equipment (e.g., radio communication), the SEP organizes the medical care given by the emergency physician and paramedics and prioritizes transport to the appropriate hospitals. During the resuscitation efforts, the SEP must be in close contact with the commanders of all agencies involved, e.g., the police and fire brigade. Because of these demands, a SEP must have extensive clinical experience (consultant level) and knowledge in emergency medicine, and the organization of the local emergency system. In a disaster medicine training program of 40 hours, physicians gain knowledge of and a tactical approach to diagnostics and medical decisions under disaster conditions. Technical experience and familiarity with equipment and radio communication service are gained through repeated mock exercises, and the much-needed skills and knowledge are acquired and refreshed.

MEDICAL DIRECTOR The need for total quality management in prehospital emergency medicine led to the implementation of the first medical directors ( 4,6). Tasks of these physicians are: Supervision and control of all EMS actions, provided by emergency physicians and RA/RS. Quality control in the RCC. Directions in equipment and standing orders. Control of continuous medical education of emergency physicians and RA/RS. Enforcement of all laws and rules concerning the EMS. To fulfill the tasks, the medical director has to pass an additional training course (quality management, economics, hygiene, law), and to avoid any bias from medical rescue organizations, the position should be based at the state authority. Actually, medical directors are implemented in some new states as well as in Cologne and Hamburg.

RAPID RESPONSE UNITS The analysis of EMS actions after several disasters occurring showed that the everyday emergency system was unable to rescue all patients promptly and properly. A common concurrence was that untrained personnel went into action, with ambulances and staff from other areas becoming involved. The drain of resources from diversion away from daily operational system needs created a dilemma. To address this challenge, the concept of “rapid respond units” (RRU) was developed. Their aim is to provide: Quick additive support to the daily emergency service with well-trained staff and adequate equipment in case of greater accidents or disaster. Adequate prehospital care to most or even all patients. Partial or even total replacement of the daily emergency service from other areas. This concept was realized in several areas of Germany between 1988 and 1990; the requirements for such a RRU are listed in Table 154–1.1 The medical and technical equipment of rapid respond units is designed to provide medical treatment to 50 patients, 10 of them seriously ill. It contains instruments for endotracheal intubation, artificial ventilation, injection material, multiple sets for IV lines and infusion solutions, emergency drugs (including anesthetics), emergency surgery sets, and bandaging material. It also contains radio communication equipment, 25 stretchers, a tent, and triage registration forms. Due to different geographical, political and structural settings, RRUs are slightly different in equipment and staffing throughout Germany, but the overall structure is comparable.

Table 154–1.1. Fast-Responding Rescue Squad Requirements

The staff consists of certified emergency physicians and semi-trained as well as fully trained paramedics. Normally all staff members belong to either the special disaster crew or the local EMS. Some are volunteers with basic experience in prehospital care. In addition to their training, all members are educated in the unique triage approach and medical requirements of disaster medicine. The criteria for alarming RRUs are similar to the alarm criteria of SEPs: larger accidents (more than 8 to 10 patients) or disasters (e.g., explosion, airplane crash, train accident, or shipwreck).

References 1. Lipp M: Preclinical emergency medicine systems: international comparisons. Anaesthesist 1993;42:623–629. 2. Lipp M, Mihaljevic V, Dick W: Analysis of telephone calls placed to fire brigade, emergency medical services, and general practitioners' emergency services in an emergency medical service system. Anaesthesist 1994;43:187–193. 3. Lampl L, Helm J, Weidringer JW, et al: Stellenwert der differenten Formen der Lufrettung im Konzept des Rettungsdienstes. Der Notarzt 1996;12:145–149. 4. Felleiter P: Qualitaätsmanagement in der Luftrettung. Der Notarzt 1996;12:152–157. 5. Lipp MDW: Fachkundenachweis “Rettungsdienst.” Notfallmedizin 1995;21:37–41. 6. Lipp M, Dick W, Ahnefeld FW, et al: Integrales Konzept Rettungsdients/Grobschadenslage. Notfallmedizin 1995;21:589–592.

Suggested Readings Ahnefeld FW, Weibauer W, Lippert H-D, et al: Rettungsdienst im Spannungsfeld zwischen Politik, Recht und Medizin. Dt Ärztebl 1995;92:A-674–678. Ahnefeld FW, Dick W, Schuster HP: Die aärztliche Aufgabenstellung im deutschen Rettungsdienst. Notfallmedizin 1995;21:165–169. Klingshirn H: Der aärztliche Leiter Rettungsdienst. Notfallmedizin 1996;22:101–103. Ufer MR: Strukturwandel im Notarztdienst aufgrund höchstrichterlicher Rechtsprechung. Notfallmedizin 1996;22:94–96.

Chapter 154.2 Emergency Care “Skoraya” in Russia Principles and Practice of Emergency Medicine

CHAPTER 154 INTERNATIONAL PERSPECTIVES OF EMS SYSTEMS DEVELOPMENT

2 Emergency Care “Skoraya” in Russia Michail V. Grinev Capsule Introduction Organization The City Administration of Emergency Service Ambulance Substations Hospital Stage Emergency Care Hospital Structures Research Institute of Emergency Medicine Rural Service of Emergency Care

CAPSULE “Skoraya” in Russia is the system that provides emergency care in the prehospital stage in case of life-threatening conditions and traumatic injuries, and admits these patients to hospitals. The medical doctor's team prevails in the ambulance structure in large cities. Such a system of prehospital medical service allows doctors to assist patients early. Information from the place of the accident is received at the ambulance station by “03” calls. The operator directs the ambulance from the nearest substation. Large multifield hospitals (800 to 1000 beds) service different regions and perform all kinds of medical care. There are two Research Institutes of Emergency Medicine that address the scientific problems of emergency medicine and help to apply new methods in clinical practice.

INTRODUCTION In Russia “Skoraya” is a state-supported structure that provides emergency care at the prehospital stage in cases of traumatic injuries, accidental life-threatening conditions, as well as transfering patients to hospitals. Distinguished from other countries, Russian “Skoraya” provides early and adequate first aid and sometimes specialized care. Currently in Russia (1998), there are more than 430 independent ambulance stations and departments, and the 2691 departments that were part of the structure of other medical establishments. Of these, there were 1179 units in rural areas. The teams of ambulances answered more than 43 million calls and gave first aid to more than 47 million persons. In 1993 the number of stations (departments) increased by 64 units (2%) and the number of persons who were attended increased by 8.2%. In 1992, two Research Institutes of Emergency Medicine and 53 hospitals of emergency care functioned in Russia.

ORGANIZATION There is a typical structure of emergency care in each city with more than 500,000 inhabitants. The composition is standard and includes the following units: Administration (management) Operators Quality insurance Chemists (first-aid kit) Subdivisions of emergency care (including research institutions)

THE CITY ADMINISTRATION OF EMERGENCY SERVICE The role of the city administration is to provide a chief doctor, two deputies in management technical service, and the staff, technical equipment, materials, etc. Also, the administration must get in touch with the militia and fire service as well as different services of other cities. Operative Department Operative department is in charge of receiving toll-free “03” calls. This is the first stage of emergency care. The department's senior doctor is responsible for staffing the system of emergency care including ambulance teams. The operative department is the center of incoming calls and distributing the work among the first aid staff members. It is here the operator fills in a special card for each call and this card is passed over to another operator who gives instructions to the nearest ambulance substations and dispatches the first aid team. In doubtful cases, the ambulance doctors can get advice from specialists. The operative department connects “SKORAYA” with polyclinics, dispensaries, and hospitals. There is a possibility for each city to have this continuous type of first aid. The principle task of this department is the even distribution of patients among hospitals depending on the degree of severity of conditions and resources of hospitals. The Department of Quality Insurance This department controls the work of the stations and analyzes the fatal cases that occur in the prehospital stage and reviews all the filled cards after patients are seen by the surgery department doctors. The inquiry service receives these cards and keeps the information about the patients who received emergency care. The doctors of this department investigate causes of deaths, write reports, instructions, and requirements for new methods of diagnostic and treatment procedures for “SKORAYA”.

AMBULANCE SUBSTATIONS Ambulance substations are separate subdivisions that carry out regional first aid. The radius of their region is 5 km, approximately 1 ambulance for 10,000 inhabitants. The typical structure of substations include an admission room for walk-in patients, a room for receiving calls, and a room for the staff. The staff of a substation consists of following medical teams: 1. 2. 3. 4.

Medical doctor, doctor's assistant, driver—basic medical team. Medical doctor, two doctor's assistants, driver—intensive care team. Feldsher (senior nurse) and driver—general medical transport team. Midwife and driver—obstetric transport team.

The medical teams of large cities accept 15 to 20 calls every 24 hours.

HOSPITAL STAGE Patients that present with shock-induced trauma in severe condition have a higher level of mortality and disability. The main treatment of such patients is to optimize the outcome of management using the prognostic scale of shock. There is also the algorithm of tactic according to this scale. An optimal tactical algorithm in patients with polytrauma has to be quantitative, i.e., objective estimate of the shock-induced injuries, as well as varying degrees of

seriousness of the patient's condition in relation to the surgery that is planned. The exponent ( T) was chosen as the object of prognosis, which characterizes life expectancy in hours when the prognosis is unfavorable ( T) or expected duration of shock (also in hours) when the prognosis is favorable ( T). The rule may be expressed in a rather simple formula obtained by multifactorial regression analyses:

where: AP = arterial pressure P = pulse rate A = age of the patient K = estimate of shock-induced trauma, obtained from Table 154–2.1.

Table 154–2.1. Evaluation of Injury Influence on Shock Development

Currently, it is not necessary to determine the prognosis of shock by this formula. Based on a pocket computer system, the prognostic index is calculated within 1 to 2 minutes. The prognostic criteria ( T) became the basis of the management of victims with shock-induced trauma (Fig 154–2.1). The range of the tactic was based on the time of unstable hemodynamic, i.e., shock. A group of patients who had T less than 12 were favorable for the operative treatment. In this group, it is possible to use all kinds of operative treatment (osteosynthesis, debridement of wounds, plastic operations).

Figure 154–2.1. Triage for ambulance patients in Russia with prognosis of I to III based on injury and time. I, beneficial prognosis, II, doubtful prognosis; III, unfavorable prognosis.

The second group of patients presents in a more serious condition, when an integral prognostic index T is between 12 and 24. This group of patients was doubtful for operative treatment and that is why the range of surgical treatment was limited. The operations are performed according to strict indications; plastic surgery, vessel suturing, and intraosseous osteosynthesis are contraindicated. Transosseus osteosynthesis are simply performed with distraction compression apparatus. Debridement is performed without elements of plastic surgery and wound suturing. Amputation is also performed using the simplest method. The third group of patients present in extremely grave condition; they have poor prognosis for operative treatment ( T more than 24 and negative values of T) and require more than 24 hours of resuscitation therapy. In this group of patients, only conservative therapy of fractures is warranted; skeletal tractions also apply. The bleeding is stopped by ligature; cutting off the crushed limbs below the tourniquet is performed by the simple method without sewing of the wound. Certainly, in all of these groups urgent operations are performed, such as bleeding into abdomen or thorax, intracranial hematoma, and injuries of the parenchimal or hollow organ. All kinds of operations that are performed when extremities are injured call for urgent operation. The increase of operative activity from 12 to 38.5%, based on the objectified tactic of treatment according to prognostic index + T, has not increased total mortality (12 and 9.8%). It turned out that 55% of the patients belonged to the group of favorable prognosis, and they received the full range of surgical treatment. The range of treatment was limited in 6.5% and conservative methods prevailed in 38%. Total mortality of the victims with shock producing trauma was 35%. Among them, 22% died during the shock period, and 13% in the postshock period. Of great interest are comparative data in the mortality in cases of different tactic. The group of patients with the favorable prognosis for operation had a lower mortality rate (by 1.7 times) than the patients who were treated conservatively. The total mortality (12%) in this group should be identified as low, because the percentage of these patients in shock was high (39%). Among other things, there was evidence of low informative value of the severity of the shock and low suitability for tactic schemes of treatment. The most important result of objective tactic treatment of shock producing trauma is the significant lessening of disability by more than three times (from 46.5 to 13%). So the analyses used on large populations provided safe diagnosis operative treatment. The decrease of the mortality due to operative treatment in an acute period of shock was reached by using antishock components of the operative treatment (reliable termination of bleeding, firm fixation of bones, etc.).

EMERGENCY CARE HOSPITAL STRUCTURES The emergency medicine hospitals are multi-field with 800 to 1000 beds. There are surgical, therapeutic, gynecology, traumatology, and toxicology departments, and a burn unit. Hospitals are able to have combined trauma departments, neurosurgery, urology, thorax surgery, and others. The number and type of departments depend on the necessity of each city. Each hospital is led by a chief medical director, chief surgeon, chief internist, and administration staff. There is 24-hour service, guided by the chief doctor on duty.

RESEARCH INSTITUTE OF EMERGENCY MEDICINE In Russia, there are two Research Institute of Emergency Medicine; one in Moscow, the other in St. Petersburg. The main function of these institutes is to improve the organization of first aid in the hospital and prehospital stage, diagnostic methods, and management of emergency diseases by applying them in the practice. Both institutes have a powerful research clinic base 1000 beds. There are between 1000 to 5000 persons on staff in each facility. Research and clinical staff investigate the actual problems of emergency medicine.

RURAL SERVICE OF EMERGENCY CARE

The emergency medical care in the provinces are performed by rural hospitals. Departments of emergency or the autonomic stations of emergency care are located near rural hospitals. The autonomic stations are usually located in remote villages. There is a doctor on duty at each station. This doctor is called when there are complicated cases, to assist other doctors, or in case of organizational problems.

Chapter 154.3 Australia Principles and Practice of Emergency Medicine

CHAPTER 154 INTERNATIONAL PERSPECTIVES OF EMS SYSTEMS DEVELOPMENT

3 Australia Harry F. Oxer Capsule Introduction Background Unique Problems of Australia Role of the St. John Ambulance Organization Medical Control of Ambulances Advanced Life Support Education and Training List of Medical Directors of Ambulance Services

CAPSULE Emergency medical service (EMS) in Australia is provided by general practitioners, locum services, and hospital emergency departments (EDs). Ambulance services vary according to area, but all services are now teaching defibrillation and monitoring to all paid ambulance officers. In some areas, e.g., Western Australia, shock advisory defibrillators are now also used by the large force of volunteer ambulance officers, who are trained to a level similar to EMT-B. Aircraft are used extensively for retrieval because of the distances involved. The Royal Flying Doctor Service also provides primary health care to remote stations.

INTRODUCTION EMS in Australia is provided by a three-pronged system. General medical practitioners provide a first-line service, mainly for minor problems, but are often called first in an emergency. Locum services, staffed mainly by younger physicians, provide after-hours service for urgent calls. Both of these groups provide house-call service, though this is becoming less frequent. Ambulance services provide the next level of EMS, and are usually a state-wide operation, either state-run or state-subsidized. The levels of service provided vary somewhat from city to city, and in rural areas. A core curriculum of ambulance knowledge and skills was established by an expert committee, and this has been the basis of ambulance training in all states and territories for some years. The way in which training is carried out varies from state to state. Some states have trained some of their officers in advanced life support (ALS) skills to “paramedic” standards, but the main thrust now is to take selected skills, particularly defibrillation and monitoring, and teach them to all paid ambulance officers.

BACKGROUND Australia is a large, semi-arid island continent, roughly the same size as continental United States, but with a population of only some 18,000,000. Most of these are concentrated in the coastal regions, and 60% live in the capital cities. Three to four million people live in each of the cities of Sydney and Melbourne. Adelaide, Brisbane, and Perth have roughly one million each. Hobart, Canberra, and Darwin are smaller. There are six states and two territories. Although some of the health funding is received from the federal government, allocation of health resources is at state level.

UNIQUE PROBLEMS OF AUSTRALIA Australia has some special problems because of its huge, sparsely populated areas. These unique outback areas are serviced mostly by volunteer ambulance officers, backed up by air ambulance services or the Royal Flying Doctor Service. Although there has been some development of “paramedic” type systems in some of the larger cities, the current demand for additional ALS skills is centered mainly on the provision of cardiac monitoring and defibrillation facilities on most ambulances. This situation has been achieved for many years in Western Australia, Tasmania, and the Australian Capital Territory, and has been introduced in South Australia, New South Wales and the Northern Territory. The third group of providers of emergency facilities is made up of the EDs of the public hospitals, and in the larger cities, the teaching hospitals. These departments sometimes also have a primary care department in association with the ED, which provides a service similar to that provided by general practitioners, especially in inner city areas. An increasing number of private emergency departments are being set up in the major cities.

ROLE OF THE ST. JOHN AMBULANCE For over 100 years, first aid has been widely taught to the general public by several organizations, particularly by the St. John Ambulance. This largely voluntary organization began teaching first aid in Australia in 1883, and from then onward, both it and its uniformed volunteer arm, the St. John Ambulance Brigade, provided some form of ambulance transport in most states. In the 1880s, hand-held wheeled trolleys were the only facility available, and patient care was minimal. The provision of ambulance services by St. John was a mixed success story. In New South Wales and Victoria, the state governments took over ambulance services by the early 1920s. In Tasmania, it was 1965 before the state took over from St. John, and in 1995 in South Australia. In Western Australia, and the Northern Territory, the St. John Ambulance adopted sound management and training strategies, and developed efficient and effective ambulance administrations, which continue to operate. Queensland has the Queensland Ambulance Transport Board, which is covered by a State Act of Parliament. Its organization is complex, and over the huge area of the state, ambulance centers until recently have had considerable autonomy. The state is now accepting responsibility for them. The Australian Capital Territory, a small enclave surrounding the capital, Canberra, has an ambulance service that is directly controlled by the federal government.

ORGANIZATION There is no overall EMS organization in Australia. Services are provided by individuals or groups of general medical practitioners, by the various ambulance authorities, and by the EDs or primary care departments of the various hospitals. The links between these groups are informal, but are nevertheless effective. Physicians Many general medical practitioners, particularly those working in group practices, or in country and remote outback areas, continue to provide a 24-hour medical service for their patients. They offer round-the-clock service at their clinics, or if necessary, will make house calls after-hours. There are also after-hours “locum” or

deputizing services in most major towns and cities. Hospitals Since the formation in 1983 of the Australian College for Emergency Medicine, EDs in most of the major “teaching hospitals” in capital cities of Australia are now staffed by physicians fully trained in emergency medicine. There is a training program in place, and registrars in training are common. Such departments are staffed on a 24-hour basis. Until 1990, it was uncommon to have a consultant physically in the department all 24 hours. Senior registrars in training were likely to be on duty after 11 PM, and through the night, with a consultant available on call. The standard of emergency care available in such major hospitals is extremely high, and rising steadily. The Australian College of Emergency Medicine is still relatively new, however, and the supply of fully trained emergency physicians is still not sufficient to staff many of the other hospitals. Outer suburban and country hospitals continue to be served by either local general practitioners or junior medical staff in training in surgical or medical specialties. They vary in the facilities they provide according to the number of people served. When there is no local medical practitioner in the immediate area, nursing staff carry out relevant primary care with telephone consultation as necessary. The country medical services rely heavily on secondary retrieval of patients requiring further medical care. This is carried out either by helicopter in some areas close to large centers, or more often by fixed-wing aircraft operated by the Royal Flying Doctor Service or the ambulance services. Ambulance In all major cities in Australia, “000” is the emergency telephone number, and has been for many years. When this number is dialed, a dedicated emergency switchboard connects the caller to police, fire, or ambulance. All states are working toward this number becoming universal throughout the whole country. This has already been achieved in Western Australia. There is as yet no direct relationship between ambulance services and police or fire departments in Australia, though one or two states are considering the concept. Each ambulance service has its own emergency switchboard, and is responsible for taking the calls, allocating resources, and dispatching vehicles in an appropriate response. Generally, ambulance services operate under the health umbrella, but in close operational liaison with police and fire services. Ambulance services in each state are operated by a central nonprofit body. In New South Wales, South Australia, Victoria, Tasmania, and Queensland, the authority is set up under an act of state parliament. Moves are afoot to attain more central control and organization. In Western Australia, and the Northern Territory, ambulance services are provided by the St. John Ambulance. Although originally almost entirely voluntary, in these states St. John has reorganized to become a modern management organization. Volunteers are still used in country areas and regional towns, to supplement paid staff. Their training is the same as that of paid officers. As an example of ambulance organization in a large sparsely populated state, Perth, the capital city of Western Australia, and nine other cities or larger areas have professional paid ambulance officers. One hundred twenty other centers scattered throughout this vast area, which covers more than one-third of Australia, are staffed by volunteers. These officers receive training from traveling training teams. Numbers of patients transported from these remote areas may be low, causing potential problems with skills maintenance. Utilization The mix of patients differs from city to city in Australia and considerably, in most cases, from that reported in the United States of America. Seat belts are almost universally worn in Australia, greatly reducing the amount of facial and chest trauma in accidents. Although the incidence of assault with weapons is rising in the larger cities, it is still small by comparison with reported North American experience. Penetrating body cavity trauma is rare in most services. As a result, the number of seriously hypovolemic patients seen by an individual ambulance officer in most areas is small. Utilization varies from state to state. Some states provide an extensive service, including clinic transport (patient transportation for day hospital geriatric and rehabilitation patients), ambulance transport (first response in medical emergencies and accidents), and secondary transportation for patients being admitted, discharged, or transferred from or between hospitals. There may also be a paramedic service. In other states, such as Western Australia, a conscious effort has been made to limit the use of expensively staffed and equipped ambulances to those needing special skills and or facilities. This has reduced considerably the number of “taxi” transports carried out by the main ambulance service and has enabled Perth, a city of a million people, to be covered by a fleet of 26 front-line ambulances. Brisbane, the capital of Queensland, is a city of similar population and has well over 100 vehicles to cover the wide range of tasks undertaken by its ambulance service. In Perth, Western Australia, about 300 patients are carried daily on weekdays, and fewer on weekends and holidays. Table 154–3.1 and Table 154–3.2 give an indication of the main categories of patients, which make up a little less than one-half the workload. The rest consist of many smaller groups and patients who are not “ill” but nevertheless need ambulance transport. Within the limits of the differing ways in which ambulance services are provided, these distributions are fairly representative of ambulance workloads throughout Australia, although Melbourne and Sydney, the two largest cities, show an upsurge in trauma resulting from accident and assault.

Table 154–3.1. Main Categories of Ambulance Patients in Perth for Two Typical Months

Table 154–3.2. Breakdown of Trauma Over the Same Perioda

MEDICAL CONTROL OF AMBULANCES With the exception of one or two of the “paramedic” trained groups, there is no direct control of ambulances from a hospital or by radio. Even in these cases, ambulance officers work almost entirely by protocol. They may, but do not have to, seek advice from a hospital. This system has been found to work well in Australia, and there are no medicolegal reasons why they should operate otherwise. Early ambulance services were guided by medical advisory committees of voluntary medical officers. Sometimes their advice was ignored or only partially implemented. Western Australia was the first state to appoint a medical director in 1976, with full authority over medical aspects of ambulance care. Physicians are now involved in ambulance service in every state in some capacity, and each year hold meetings as a subcommittee of the Convention of Ambulance Authorities of Australia and New Zealand. This meeting is a valuable forum for the exchange of ideas and information. The group reviews common medical dilemmas in ambulance service and submits recommendations each year for consideration at the Convention's meeting. Quality control of ambulance operations varies in nature and degree. In all states, however, mechanisms for review of case sheets exist, especially when ALS techniques are involved. Such case sheets are reviewed, with ambulance officer feedback. There is a growing data base of computerized information, which allows analysis of ambulance techniques used, ambulance cases transported, and results of prehospital ambulance care. Administration Ambulance administration in the early days was in the hands of senior uniformed ambulance officers. In virtually all states now, however, professional administrators and managers are teamed with the senior ambulance officers to handle specialized management functions. Most states have a general manager or chief executive, with specialists in finance and industrial and personnel officers in their management team. Finance There are detailed differences in the financing of the various ambulance services, but generally funding comes from a mixture of government subsidies or contracts, fees charged for transport (based on a call-out charge plus a distance charge), and subscriptions received from members of an ambulance insurance fund. Subscribers to these funds receive free transport, providing that their reason for transport falls within those accepted by the fund. Those not covered by any form of insurance are likely to receive a substantial account for ambulance transport. In some indigent and impecunious groups, costs related to transport have to be written off against the government subsidy. Prehospital Treatment A major difference between EMS in North America and ambulance services in Australia is that in Australia there is no need or wish for direct physician control of ambulance officers when carrying out a particular patient care episode. Ambulance officers work under protocol guidelines developed by their medical control system. Medical radio communications are used only to advise hospitals of the type of case that is being brought in, not to seek medical direction.

ADVANCED LIFE SUPPORT The first Australian system for mobile ALS began during 1969 in Perth, Western Australia, with the introduction of a coronary care ambulance staffed by ambulance officers and a nurse and physician from the Royal Perth Hospital. This was probably the second such unit in the world, following the lead of Pantridge in Belfast, Northern Ireland. Similar systems followed in Melbourne in 1971, and in Sydney in 1973. During the 1970s, it was decided that such services could serve only a limited group of patients within their operating radius, and that medical and nursing staff were inappropriate as staff for these ambulances. In the late 1970s in Perth, it was decided to equip all operational ambulances in the greater Perth area progressively with monitor-defibrillators, and this was completed by 1978. All fully trained ambulance officers were authorized to defibrillate by 1980. In Melbourne and Sydney, the decision was made to train selected ambulance officers in ALS skills and equip a small number of specialized ambulances as mobile ALS units. This system continues in some major cities. Other states and territories reviewed the development of mobile intensive care ambulances, and then made a conscious decision not to introduce these specialized units. They have chosen rather to upgrade the skills of all their ambulance officers progressively in selected ALS skills. In most states now, all officers are offered training in some ALS skills, including defibrillation. Currently, all Perth ambulance officers are able to monitor and defibrillate, and to perform only certain ALS skills, such as military antishock trousers (MAST), measurement of peak airway flows, nebulized treatment for asthma, cricothyrotomy, and management of the cannulated or intubated patient. Eleven medications are carried and used including intramuscular drugs. The skills of intubation and cannulation have not yet been introduced, but are under continual review. Data do not yet support their benefit in improving outcome in a significant number of patients, despite their widespread use in ambulance services. “Paramedic” type programs have been implemented to a variable extent in New South Wales, Victoria, South Australia, Tasmania, the Australian Capital Territory, and the Northern Territory. Western Australia teaches to its paramedics selected skills and interventions that have been shown to produce benefit. There is a widespread presumption that more and more ALS must be better than “lesser care.” It is surprisingly difficult to find evidence to support any related improvements in morbidity or mortality, with the one outstanding exception of early prehospital defibrillation. Many accepted skills do not measure up well when subjected to such analysis, but are impossible to remove from service once they are entrenched. The advent of thrombolytic therapy for acute myocardial ischemia raised the question: Should paramedics be trained to begin therapy? Most Australian cardiologists and emergency physicians prefer that the patient be brought quickly to a hospital where this therapy can be administered. In areas where the response times are under 15 minutes, such as in Perth, there seems little point in beginning such therapy outside the hospital. Prehospital Management in Rural Areas In remote areas such as large areas of Western Australia, ambulance services are provided by volunteers. They receive training on weekends, by traveling teams from the ambulance training center. Volunteer ambulance officers are trained to a level similar to that of emergency medical technicians (EMT-Bs) in the United States, involving about 120 hours of training. In some of the country areas, where numbers cannot justify many full-time ambulance officers, ambulances are staffed by full-time officers, supplemented by trained volunteers. Although there may be a need for intravenous infusion in some country cases, the small number of cases handled by many of the rural ambulance services makes it impractical to offer advanced skills training and maintain skills. As a practical compromise, patients are brought by ambulance to the nearest nursing post or medical practitioner, where initial treatment and stabilization are carried out. Patients are secondarily retrieved as necessary by the teams of the Royal Flying Doctor Service or the Air Ambulance.

EDUCATION AND TRAINING

General Practitioners General practitioners, in addition to their routine medical training and required intern and resident posts, often complete an additional 2 to 3 years of training aimed at producing a well-rounded and relevantly trained general practitioner. This vocational training has been provided under the auspices of the Royal Australian College of General Practitioners. Training is provided mainly in association with city teaching hospitals, and involves rotation through a number of specialist departments and EDs. Training in Advanced Trauma Life Support (ATLS) is increasingly being taken up. Emergency Physicians In the larger cities, emergency care is provided by the EDs of the major hospitals. These are now mostly staffed by physicians specifically trained in emergency medicine. The number of such trained emergency physicians is growing. Rural and smaller hospitals are still staffed mainly by general practitioners, on a roster call basis. Such hospitals may also have junior medical staff. The formation of the Australasian College for Emergency Medicine was a significant step forward for emergency medicine in Australia. A formal fellowship training program, with courses and examinations, has attracted many young physicians toward a career in emergency medicine. The support from the College for the Ambulance Services has been exceptionally strong and generous. Nurses The widespread movement of nurse training into more academic environments is well-established in Australia. Nursing courses are being offered in emergency medicine, focused for those who are likely to work unsupported or in rural areas. These courses are practically based and skill-oriented to enable nurses to manage acute medical problems. Much nursing emergency training, however, still occurs on the job and in the EDs of major hospitals. Some trained nurses transfer to the ambulance services and are retrained as ambulance officers. Ambulance Officers (Emergency Medical Technicians) The term “emergency medical technician” is not used in Australia. Historically, they have been known as ambulance officers (“Bearers” in Queensland). Training of ambulance officers beyond the level required for the St. John Ambulance First Aid volunteers began in Victoria and New South Wales in the early 1960s, and other states quickly followed. Since the mid 1970s, ambulance officer training has been formalized and ambulance-based. All Australian states and territories with testing now have a central ambulance training school, providing training for ambulance officers at all levels. In addition, such training centers usually have mobile training teams that can visit country and remote areas and carry out training for professional and volunteer officers. During the 1970s, a National Education Committee met under the Chairmanship of Dr. Harry Oxer, the Medical Director of the ambulance service in Western Australia. They developed a practical and job-oriented curriculum for ambulance officer training. This became and has remained the basis for all Australian ambulance officer training courses. Coincidentally, this curriculum was published at the same time as the blue and white Department of Transportation documents in the United States, indicating that Australia and the United States were working along similar lines at the same time. Accreditation of courses has mainly been through colleges of advanced education, but there is a current fashion to seek university accreditation for ambulance officer training. Training is still ambulance based rather than institution based preemployment. Vehicles Most ambulances in Australia have fiberglass bodies custom-built on a light van chassis, with a V8 engine and power steering. Ambulances operating in areas outside the main cities are fitted with a “Roo-Bar.” This is a device similar to a cow-catcher that saves the vehicle from being wrecked by an impact with a 6-foot kangaroo. These animals are not an endangered species, as some reports suggest, but are often in plague proportions, and are a real menace in rural areas after dark. On one classic patient retrieval from the Eyre Highway, across the Nullabor Plain in the south of the continent, both the initial responding ambulance and its back-up were wrecked after hitting kangaroos. The patient eventually arrived back at a country hospital in a third vehicle from this retrieval, which was well over 200 miles. The kangaroos apparently did not survive the impacts, but the patient was not additionally injured. Ambulances usually carry two main stretchers, one of the self-loading type and the other usually of a simpler and less expensive type. Equipment Prehospital management in all services consists of assessment, provision of oxygen, appropriate splinting, and the offering of analgesia by inhalation. Some services use a 50/50 combination of nitrous oxide and oxygen; others use a low analgesic concentration of inhaled methoxyflurane. Both provide effective reversible prehospital analgesia of short duration. In addition, the paramedic groups in some cities administer intravenous narcotic analgesia. As a result of seeing the effective ambulance use of inhaled analgesia techniques, many hospitals have adopted this ambulance technology to their short-term pain relief requirements. All services offer nebulized salbutamol for management of reactive airway diseases. Resuscitation equipment may be oxygen-powered, use a self-filling bag, or soft bag circle system with Co2. The “Jordon Frame” is commonly used for the multiple injury patient rather than the “scoop” stretcher. It is an Australian invention in which a frame is built around the patient, then flexible slats are slid under relevant parts of the patient to support the patient and build the stretcher. All ambulances carry assorted bandages, immobilization splints, including traction and air splints, and most carry the MAST. Cannulation, intubation, and the use of intravenous medications are restricted to services with some staff trained in full “paramedic” skills. Many other ambulances, however, carry this equipment for the use of a physician at the scene. Officers are trained to care for cannulated or intubated patients in transport. There are currently no medicolegal impediments, and doctors often treat patients at the scene. Aircraft Aircraft are extensively used outside the major cities in Australia because of the vast distances involved. Some retrievals to capital cities, e.g., in Western Australia, exceed 2000 km. Helicopters are used in some cities where the specific geographic or traffic problems make their use an advantage for patient retrieval. Other cities, however, have successfully resisted the evangelistic approach of helicopter operators and manufacturers where use of such facilities would confer no patient care advantages in terms of decreased mortality or morbidity. Distance retrievals are carried out by dedicated air ambulance aircraft, operated by either the ambulance service or, particularly in the more remote areas, the aircraft of the Royal Flying Doctor Services of Australia. All such aircraft are fully and professionally equipped and staffed by especially trained flight nurses, and have aeromedically trained physicians available to take part in retrieval where appropriate. Aircraft provide a secondary response, and are rarely the primary responder to an accident or emergency situation. They work closely with the local ambulance services and medical practitioners, and with the remote bush nursing posts. In Western Australia, which occupies more than one third of the area of Australia, there are some 18 Royal Flying Doctor Service aircraft, organized in 3 divisions. These are all light, twin-engine aircraft. Several are turboprop-equipped and pressurized to enable them to retrieve patients effectively over the long distances involved. Others are light twin-engined planes with the ability to handle the rough, relatively unprepared gravel outback landing strips. The Royal Flying Doctor Service also provides primary health care by operating regular medical clinics at remote sheep and cattle stations in the outback, and at aboriginal, mining, and other remote communities. Communications

Ambulance communications in city areas are by VHF radio or UHF. HF radio is still needed for some of the extremely long distances and remote areas, but with the advent of satellite radio and telephones, this is being phased out.

LIST OF MEDICAL DIRECTORS OF AMBULANCE SERVICES Dr. H. Oxer, Medical Director, St. John Ambulance Association, 209 Great Western Highway, P.O. Box 183, Belmont, WA 6104. Prof. Tony Bell, Regional Supervisory Physician, Intensive Care Unit, Royal Hobart Hospital, G.P.O. Box 1061L, Hobart, TAS 7001. Dr. Barbara-Ann Adelstein, P.O. Box 640, Strathfield, N.S.W. 2135. Dr. D. Crone, N.Z. Dr. Frank Archer, Ambulance Services' Medical Officer, Ambulance Officers' Training Centre, 69 Queens Road, Melbourne, VIC 3004. Dr. Hugh Grantham, Medical Director, Ambulance Service Training, SA 5042. Dr. Richard Banham, Medical Director, Queensland Ambulance, Services Board, P.O. Box 251, South Brisbane, QLD 4101. Dr. Lionel Crompton, Commissioner, St. John Ambulance NT Inc., 51 Dripstone Road, Casuarina, NT 5792. Suggested Readings Dawson DA: Ambulance officer selection: predicting training performance. Aust Psychol 1988;23:69. Doman AS: Paramedic ambulance services in NSW: analysis of response times, case mix and catchment area. Community Health Study 1984;8:140. Abstract. Hamilton T: Medical and nursing response to disaster. Emergency Response 1983;7:21. Hockings BE: Transportation of the patient with a myocardial infarction. Patient Manage 1986;10:15. Howie-Willis I: Centenary of the Order of St. John in Australia. Sterilization Aust 1983;3:24. Lyle D, Potter D, Goldstein G, et al: The delivery of emergency trauma care in the Sydney region. Community Health Stud 1987;11:226. Robinson R: Occupational stress: a study of ambulance officers in Victoria. Aust Psychol 1987;22:119 and 1987;23:69. Selecki BR: Experience with spinal injuries in New South Wales. Aust NZJ Surg 1986;56:585. Simpson DA: Logistics of early management of head and spinal injuries. Aust NZJ Surg 1986;56:585. Toscano J: Prevention of neurological deterioration before admission to a spinal cord injury unit. Paraplegia 1988;26:143. Willis E, McCarthy L: From first aid to paramedical: ambulance officers in the health division of labour.

Community Health Stud 1986;10:57.

Chapter 154.4 Terrorism: EMS Issues and Management Principles and Practice of Emergency Medicine

CHAPTER 154 INTERNATIONAL PERSPECTIVES OF EMS SYSTEMS DEVELOPMENT

4 Terrorism: EMS Issues and Management John E. Prescott and Thom A. Mayer Capsule Introduction The Emergence of Terrorism Modern Terrorism The Role of Federal Emergency Management Agency Medical Considerations Terrorist Incidents Medical Casualties of Terrorism EMS Response Special Concerns VIPS Conclusion

CAPSULE Over the past two decades, much of the world has been affected by repeated acts of terrorism. Valuable medical information has been learned from many of these incidents, and gradually a distinct body of medical knowledge has evolved. A key lesson is that the proper emergency medical response to terrorism requires an understanding of the various types of terrorist acts and resulting patient injuries. The thoughtful coordination of several local and federal agencies must also occur if the effects of terrorism are to be minimized.

INTRODUCTION Within the United States, adequate preparations for handling the medical consequences of terrorism are generally lacking. Traditionally, terrorist acts have been considered only from a law enforcement perspective. More importantly, many of the leaders in medical, legal, and governmental authority are not aware of the significant differences between terrorist acts and other multiple-casualty incidents. Additionally, these leaders falsely assume that emergency personnel are fully prepared to handle any medical situation, including terrorism. Although it is clear that the medical effects of any incident are initially the responsibility of local emergency medical services (EMS) systems, it cannot be assumed that readiness for other disasters has prepared these systems to deal with terrorism. Preparations for the special medical requirements inherent to a terrorist incident are not usually addressed in most community disaster plans, and medical personnel are not typically involved in antiterrorist planning. This overconfidence and lack of medical readiness can be directly related to increased patient morbidity and mortality ( 1,2). This chapter explores the phenomenon known as terrorism and delineates how it can and does affect the medical community. A description of the commonly encountered terrorist incidents and their medical casualties and key points in the suggested EMS response are provided. The similarities and differences between specific acts of terrorism and other multiple-casualty incidents are also discussed.

THE EMERGENCE OF TERRORISM Definition Terrorism is the unlawful use of force or violence against persons or property to intimidate or coerce a government, the civilian population, or any segment thereof, to further political or social objectives ( 3). Militant religious factions have also used terrorism to further specific sectarian goals. Generating fear in individuals or society itself is the terrorist's prime goal. The use of terrorism to control large numbers of people can be traced back to the beginnings of civilization. Recognition of the political usefulness of fear is demonstrated by an ancient Chinese proverb that states, “Kill one, frighten ten thousand.” During the state-sponsored Reign of Terror in France in 1793, a small group of individuals controlled approximately 28 million people. As Robespierre stated, “Fear paralyzed the opposition.” Throughout the nineteenth and twentieth centuries, numerous examples of group and state-sponsored terrorism have occurred.

MODERN TERRORISM The emergence of the present wave of terrorism can be traced to the simultaneous development of several factors. Over the past 50 years, traditional warfare has become increasingly expensive for countries and factions to wage and win. In contrast, terrorism is a relatively inexpensive method that can be used to influence government policy and society. The development of rapid, worldwide transportation has allowed terrorists to leave the site of an incident quickly and thus usually act without fear of direct retribution. Smaller and more powerful explosives and weapons have also aided the terrorist's ability to infiltrate society and inflict greater damage. The concentration of populations and important civic resources into smaller areas has given the terrorist the opportunity to cause greater damage with each incident. Finally, there has been a worldwide erosion of the concept of the noncombatant. For the terrorist, society, not simply the government or police, has become the target. Yet terrorism would not have become a popular weapon if it were not for the rapid and unprecedented development of sophisticated communciations systems. Terrorist acts have become media events, often captivating millions of people in carefully orchestrated incidents. Instantaneous reporting of each occurrence aids the terrorist in his ultimate goal of instilling fear. Bombing, which was once an act of random violence, is now carefully planned to achieve maximum publicity and psychologic effect on the target population. The last few years have seen the emergence of new and varied forms of terrorism. Narcoterrorism has surfaced as a means of increasing the influence of illegal drug cartels. Acts of terrorism against the environment and by environmental groups have also been reported with increasing frequency. The propensity of terrorists toward “superviolence” has risen with the increased availability of more powerful explosives. The threat of nuclear, biologic, and chemical terrorism is gradually becoming a reality. The United States Few modern countries have been spared the effects of terrorism. Indeed, the emergence of state-sponsored terrorism and the development of terror networks are well established (3). Although the United States has experienced few true terrorist incidents, it remains particularly vulnerable to terrorism. Its worldwide geopolical involvement marks it as an adversary to many groups. Additionally, its open borders, large size, and free society allow terrorists easy access to virtually any place within the country. Attacks against and within the United States are covered by the media in great detail. THE OKLAHOMA CITY BOMBING While large terrorist incidents are relatively rare, the 1995 Oklahoma City bombing of the federal building demonstrated a need to prepare. A “routine” medical day was transformed within minutes into a chaotic “trauma center” ( 4). External and internal injuries were common and triage was performed by resident physicians in the University Hospital emergency department (5). The range of casualties and destructive effects of the bombing (759 injured, 167 fatalities of which 19 were children [6]) led to psychological stress in the survivors and medical caregivers themselves. The incident underscored the need to have plans in place, but simulated disasters require specific planning for such large scale tragedies. Potential terrorist targets are not limited to government offices or military installations. Anywhere large groups of Americans gather or important natural resources are stored may be marked for destruction. Incidents could develop and involve sports arenas, factories, energy facilities, amusement parks, shopping malls, airports, and

hazardous cargo shipments. Ensuring that United States interests abroad are protected is the responsibility of the State Department. Within the United States, the Federal Bureau of Investigation (FBI) is the lead federal agency in combatting terrorism. Its mission is primarily twofold: to prevent terrorist acts before they occur and, should they occur, investigate the incident so that the terrorists are brought to justice. To that end, the FBI maintains a large database detailing terrorist incidents, suspected terrorist groups, and terrorist-related activity that has occurred in the United States. The FBI has been largely successful in keeping terrorism from affecting the American public, but with limited resources and the almost daily formation of new terrorist factions, the FBI cannot reliably preempt terrorist acts ( 7). In addition, nonfederal agent medical casualties resulting from a terrorist act are not the responsibility of the FBI, and no special plan exists for their care. During and after a terrorist incident, the FBI relies totally on local EMS systems for medical support.

THE ROLE OF FEDERAL EMERGENCY MANAGEMENT AGENCY Within the federal government, the Federal Emergency Management Agency (FEMA) has a threefold mission related to terrorism. The FEMA is responsible for ensuring that the resources of the federal government are coordinated with those of state and local governments during any disaster, including large-scale terrorist incidents. It is also charged with the identification and utilization of private sector resources during major crises. The second area of responsibility is the development of a proactive methodology to prevent terrorism or mitigate its potential consequences. Finally, the FEMA is charged with developing mechanisms for the integrated exercise and evaluation of plans and procedures ( 8). During the past several years, FEMA has had increasing influence in preparing local communities for terrorism. However, most municipalities, even those with well-developed antiterrorist units, have failed to consider the medical implications of a terrorist act. Only scant information is available to individuals or groups seeking detailed guidance regarding response to terrorist acts.

MEDICAL CONSIDERATIONS Emergency physicians and other medical personnel can have a significant impact on reducing the morbidity and mortality of terrorist casualties and, therefore, minimizing the effect of terrorism. Their role and those of all responding medical personnel must be clearly defined and adaptable to a variety of terrorist scenarios. By delineating responsibilities and knowing the types of injuries to expect from specific terrorist acts, medical personnel can better assist law enforcement agents during the resolution of any terrorist incident. In the field, EMS personnel may be called on to provide initial triage, stabilization, and transportation in highly volatile and tense situations. Similarly, emergency physicians and other hospital personnel may face unusual injuries and overwhelming casualties while being closely scrutinized by the press. Clearly, the support function of medical care providers cannot be successfully determined while an incident is taking place. Specific acts of terrorism may mimic to a degree the situations and injuries medical personnel face in war. The threat of personal injury from renewed violence and the need for strict security are often present. Safety concerns range from secondary incidents caused by delayed bombs to the presence of snipers. Also, injuries resulting from automatic weapons and explosions are common in terrorist victims. Medical casualties of terrorism, however, are usually not healthy young men. Many terrorist acts generate patients who often represent a cross-section of society. Victims can be from any age category and often have preexisting diseases necessitating individualized resuscitation. Most civilian medical personnel receive little training regarding “military injuries” and, therefore, may not be prepared to handle the medical or psychologic casualties of terrorism, and post-traumatic stress disorder may be found in the rescuers ( 9).

TERRORIST INCIDENTS Several common elements can be found in every terrorist incident. Each act is deliberate, preconceived, and purposeful violence directed against society and is intended to cause maximum fear. Realization that other human beings were the cause of unexpected suffering often causes profound psychologic stress to the victims. Responding medical personnel may also experience a level of psychologic stress greater than that resulting from unexpected natural disasters or other multiple casualty incidents. Post-Traumatic Stress Disorder These nervous or psychiatric conditions are a real event in the medical personnel ( 10,11), although factitious disorders for personal gain may also occur ( 12). After the bombing of the World Trade Center hospitals were flooded with patients experiencing medical and psychological trauma ( 13). The overall approach is to arrange for postevent discussions and to have contact people to whom an individual with psychological problems can be referred to. Every terrorist act also rapidly becomes a media and a political event. Antiterrorist police and medical personnel can be expected to have all of their actions closely monitored and examined. Depending on the nature and magnitude of the specific act, politicians and reporters may interfere with on-scene operations or attempt to violate scene security. Terrorist incidents resulting in medical casualties can be divided into four major categories: bombings, shootings, hostage taking and kidnapping, and mass murders and assassinations. Although there are obvious differences in each of the specific acts, hostage taking and kidnapping bear enough similarities to be considered together, as do assassination and mass murder. Bombings Bombings are the common terrorist act. As seen in mail bombs (e.g., Unabomber and others), the World Trade Center bombing and the Oklahoma City bombing, bombs are often chosen by terrorist because they are relatively inexpensive and can be easily concealed, transported, and remotely detonated. Danger to the terrorist is usually limited to bomb preparation and delivery of the explosive. Time-delayed fuses give terrorists the opportunity to leave the immediate vicinity of the blast before it occurs. As terrorist weapons, bombs can produce massive instantaneous destruction against a target population. Factors such as the environment, position of occupants, amount of explosive, number of people around the bomb, and simultaneous structure collapse determine the ultimate casualty total ( 1). Bombs produce injury through the explosive combustion or decomposition of a material that creates an expanding mass of heated gas. The high pressure of this expanding gas gives rise to a shock wave in a fluid medium such as air or water. The idealized shock wave is a steep frontal pressure pulse that rapidly rises to a maximum pressure and then decays over a longer period of time (14). As the wavefront expands, it rapidly loses force and speed. The measured peak pressure and the duration of the overpressure wave determine blast damage. Reflection of the pressure wave off a solid object may cause greater damage and injuries than the initial pressure wave. Reflective blast effects depend on the strength of the incoming wave and the orientation of a solid surface to the shock wave. This principle is used with a great deal of success (and on a much smaller scale) by extracorporeal lithotriptors ( 15). Much of the research on blast effects has been done in idealized field settings using military ordnance. Under such conditions, there is an absence of reflecting objects, which could alter pressure waveform and the peak pressure of the explosion. Therefore, strict extrapolation to indoor smaller explosions may be misleading. The ultimate destructive force of a blast, however, depends on the size of the explosive charge, the surrounding medium, and distance from the explosion epicenter. For the common high explosive used in civilian terrorist bombs, the duration of the positive pressure is 2 and 10 ms for charges of 50 and 4000 lbs. respectively ( 14). This is in contrast to military bombs, in which the duration may be greatly prolonged. If the shock wave is transmitted in a dense medium such as water, the effects are far more lethal because of the increased velocity and longer positive pressure duration of the blast wave ( 16,17 and 18). The overpressure produced by explosions produces four general categories of effects ( 19). Primary blast effect is the result of direct exposure to the pressure wave. Secondary blast effect results from the debris set into motion as a direct result of the blast. Tertiary blast effect is caused by whole-body displacement during the explosion. A fourth, miscellaneous category encompasses all other injuries resulting from the balst (burns, toxic inhalation injury). Terrorist bombings produce a preponderance of secondary and tertiary blast effects, i.e., most victims are struck by flying debris or thrown against a stationary object. Casualty totals from bombings may reflect the changing political or social goals of the terrorists. Hadden et al. ( 20) postulated that in Northern Ireland casualties would have been significantly higher if many bombing incidents had not been preceded by a warning. Bombings may cause various types and degrees of injuries ( 21). Complete body disruption occurs when the victim is in extremely close proximity to the actual detonation point. Depending on the force of the blast, only body fragments may remain. Traumatic amputations represent the effects of explosive injury. Masonry injuries result from the collapse of buildings or other structures. Flying missiles cause extensive soft-tissue wounds and are responsible for most of the injuries caused

during a bomb blast. Burns also occur during bombings but are usually secondary to the flash and are, therefore, mostly superficial. Blast injury is caused by the sudden overpressure secondary to the explosive force of the bomb. Psychologic injuries are evident in most patients. Inhalation injury is seen as a result of combustion from secondary fires. Primary blast injury depends on overpressure duration and the peak overpressure. Tissue injury is thought to occur through either spallation, implosion, or inertial effects; however, the exact mechanism has yet to be elucidated ( 16). Lesions are typically located in the air-containing organs. The ears, lungs, and gastrointestinal tract are most commonly affected. Tympanic membrane rupture is frequently reported in patients after a terrorist bombing. Blast injury to the lungs is not unlike a serious pulmonary contusion from other blunt chest trauma except that there are no rib fractures or chest wall injury. Air embolization may result from alveolar-pulmonary venous fistulae. Primary blast injury affecting the lungs is rarely reported in patients surviving terrorist bombings. The vast majority of injuries that are treated are caused by the secondary and tertiary effects of the blast. Most of these are minor and involve the head, neck, and extremities. Clothing appears to have a significant protective effect. Puncture lacerations, abrasions, subcutaneous foreign bodies and contusions are frequently treated. In a collective review, Cooper et al. ( 19) reported that 85% of all bombing victims were treated as outpatients. Severe head injury was the most common cause of death. Injuries to the chest and abdomen were rare but, when present, were associated with high mortality. Approximately 9% of all victims in Hadden's study of over 1500 patients in Northern Ireland required surgical intervention. Adler et al. ( 22) and Brismar and Bergenwald (23) reported significant numbers of patients requiring plastic surgery. Flash burns, fractures, serious soft tissue damage, and eardrum rupture are common in people situated close to an exploding device, who usually require admission. In each study, a much higher than expected number of patients suffered from significant psychological stress. Most were treated as outpatients with resolution of symptoms with time. Shootings Many patients, with a variety of gunshot wounds, are seen as a result of terrorism. Shooting victims may present after a failed assassination attempt. Many injured individuals, however, are the innocent victims of random gunfire or have been caught in the crossfire between terrorists and the authorities. High-velocity military weapons are standard for most terrorists. In contrast to nonmilitary patients, victims of these weapons usually have multiple wounds. Considering all terrorism-related injuries, patients with gunshot wounds have the highest overall admission rate. Fackler ( 24) notes that the potential for tissue destruction from gunshot wounds depends on projectile mass and striking velocity. Tissue damage is related to the projectile shape, projectile construction, and target tissue type. Extensive debridement of wounds without evidence of tissue damage is not recommended. Poison Gas The major example of a poison gas terrorist attack occurred in Matsumoto, Japan on June 27, 1994 ( 25,26). About 600 residents and rescue staff were poisoned with at least seven deaths. The effects were related to the inhibition of acetylcholinesterase. Exposure of many people occurred due to release of sarin gas in a residential area of the city. Certainly with the known Iraqi use of chemical warfare in the past as well as some likelihood of use in the Gulf War ( 27), we may be witnessing the beginning of chemical terrorist gas attacks. The toxicity of such gases as sarin is due to acute and chronic effects and can be treated as an organophosphate intoxication (28,29). Hostage Taking and Kidnapping During these incidents, hostages are typically held for their bargaining worth (money, political policy changes, etc.) and are used to manipulate a government's political decisions. Terrorists also kidnap victims to obtain information or to exact revenge for “crimes” committed against the terrorist group. Hostages may be tortured and suffer from sleep, food, and water deprivation. Victims who are trapped in burning buildings or involved in aircraft assaults are at high risk for upper airway injury, smoke inhalation, and carbon monoxide or polyvinyl chloride inhalation. During hostage situations, authorities are usually faced with the dilemma of negotiating with the terrorists versus attempting a hostage rescue. Negotiations leading to acquiescence to terrorist demands can be interpreted as a sign of weakness by the government. Rescue attempts may result in significant numbers of casualties among the hostages and antiterrorist personnel. For the individual victim, there is a profound degree of psychologic stress. Intense feelings of fear and hopelessness can literally paralyze patients. Victims with chronic but stable medical conditions may undergo rapid decompensation. If a rescue is accomplished, hostages may initially be treated as “prisoners” while a thorough search is made for the terrorists. This may add to the sense of personal violation victims commonly experience. Because of the nature of the incident, medical personnel are usually given time to prepare their response. Frequently, they are asked to provide input regarding the medical condition of the hostages and terrorists. Concerns about water, food, sleep, and hygiene become important during prolonged incidents. Mass Murder and Assassinations Motives for this type of terrorism are usually to exact revenge for perceived past injustices and to create panic among the population. Typically, these acts are carried out against select government groups or prominent individuals. Often they are interpreted as an indication of the terrorists' ability to inflict harm without fear of retribution. The boundaries between each type of terrorist incident are not always clear-cut. Police interdiction, a sudden change in the weather, or alterations in scheduled events can all force terrorists to abandon their original plans. In several instances, planned terrorist incidents have developed into even more bizarre and unexpected situations.

MEDICAL CASUALTIES OF TERRORISM As with other patients suffering from serious medical conditions, there are guidelines to handling terrorist casualties that will improve their prognosis. The use of well-established triage and treatment protocols for trauma casualties is required. Additionally, an appreciation of several other factors will further reduce morbidity and mortality. Terrorist casualties can be of any age and may have various underlying medical conditions. During initial triage and treatment, they are often unable to relate important facts about the actual terrorist event or their general health. Physicians must, therefore, depend to a greater degree on careful physical examination and pertinent laboratory testing to assist diagnosis and treatment. During their examination, all patients must be fully stripped. An inspection for occult wounds is absolutely necessary for victims of bombings. Additionally, all patients must be searched for concealed weapons. It is not uncommon for terrorists and antiterrorist personnel to carry small, discreetly hidden weapons or explosives on their person. As with all trauma patients, every body orifice should be examined. Traumatic wounds should not be primarily repaired because of increased likelihood of infection. Emergency personnel should make it their policy to render assistance based on the patient's injuries without regard to their own role in the incident. Within Lebanon and Northern Ireland, health care workers have been spared from most violent acts because of their neutrality. At all times, emergency personnel should practice professional, nondiscriminatory, and nonthreatening medical care. Responsibility for particular terrorist acts (bombings, shootings) may be difficult to determine initially. For the peace of the community, it is extremely important to have detailed forensic investigations performed by experienced and impartial experts. Photography is particularly useful in documenting the exact location and nature of injuries (21). A large number of psychologic injuries can result from a terrorist incident. The actual victims, their families, individuals present on the scene but not physically injured, and responding personnel, can all suffer varying degrees of psychologic stress. There are several contributing factors. For many victims, the overwhelming sensation

of fear, combined with the total lack of control over events, overwhelms normal coping mechanisms. Also, the acuity of the event and the terrorist's use of sensory deprivation does not allow individuals time to put into place their normal psychologic defenses. As a result, many terrorist victims go through prolonged stages of denial and disbelief. For others with post-traumatic stress disorder, there is no relief from recurring memories of the incident ( 30). Hostages can feel guilt and depression because of their behavior during the incident. Some 20 to 50% have depression, insomnia, anxiety, phobias, and obsessions. In studies of bombing victims, both Hadden et al. ( 20) and Pyper et al. (31) found a much greater number of patients with psychologic injuries than expected.

EMS RESPONSE The key to an effective EMS response to a terrorist incident is planning. Although many communities have developed increasingly sophisticated antiterrorist systems, they have been slow to implement integrated medical support. During any terrorist crisis, the EMS is asked to provide medical triage, resuscitation, stabilization, and transport to victims, police, and terrorists who are injured. Failure to include emergency personnel in the planning stages of the response jeopardizes the likelihood of the EMS being able to care maximally for all casualties. Communities should perform their own terrorism threat analysis and determine in advance possible scenarios. Unique factors and unusual circumstances for each situation should then be identified and preparations made to deal with them. Although the basic role for the EMS must be defined, sufficient flexibility must be incorporated to allow medical personnel to adapt to the situation. Unexpected complications occur commonly and may range from a prolonged hostage situation to the explosion of a secondary device. Because of the unusual circumstances of most terrorist incidents, responders from medical and law enforcement professions must cross-train and be knowledgeable about the types of injuries likely to be encountered, security aspects, scene integrity, and types of weapons commonly used. For example, in Washington DC, a Metropolitan Medical Strike Team (MMST) was formed to prepare for possible disasters. Working with the USPHS and Office of Disaster Preparedness, many detailed plans were formulated. These can be accessed through this office. On-Scene EMS personnel must work closely with law enforcement personnel once they arrive on the site. They should not enter the incident scene until they are cleared by the commander. Once that has been done, EMS personnel should then immediately determine the severity of the situation and, if possible, the number and types of casualties. Because many medical personnel are not familiar with the scope or treatment of various types of terrorist injuries, overtriage can result. Care must be taken to prevent patients from being sent to the wrong facility or experiencing delayed care ( 1). Radio communication to either the base station or supporting area hospital, as well as with other responding agencies, is essential. Strict noise, light, and radio discipline should be maintained while a threat is present. EMS personnel may be asked by the incident commander to provide input about the medical and psychologic condition of hostages and/or the terrorists, the number and types of casualties, their medical treatment and transportation requirements, and search and rescue ( 2,32). During and after any incident, the presence of the EMS aids in reducing the anxiety and panic of the victims and responding personnel. Depending on the incident, first responders may have to alter their normal treatment protocols. If the scene remains unsecured, select patients may have to forgo on-scene stabilization. Unless specific medical personnel from the hospital have extensive experience in handling terrorist casualties, the use of special medical teams is not warranted. Hospital Medical personnel within hospitals have the task of providing definitive care to terrorism victims. They must be knowledgeable about the types of injuries they can expect from any type of situation and must know their capabilities and limitations for dealing with these injuries. The availability of critical care and other hospital beds must be communicated to on-scene personnel so that patients can be appropriately transported. Internally, the hospital should determine its own supply, equipment, and personnel needs. Additional security is needed to control the expected influx of relatives and media. Communication with on-scene personnel and other health facilities is required to maximize efficiency.

SPECIAL CONCERNS The Media As with other disasters, the media quickly descend onto the scene of any terrorist incident. Responding personnel have an obligation to provide the press with clear and timely information about the incident. If information is not forthcoming, the media may become even more demanding. If possible, news briefings should be held at regular intervals, as far away from the incident site and treatment areas as possible. Weapons Handling Medical personnel may be faced with caring for patients who are still carrying weapons or explosives. Every attempt should be made to search all patients before their arrival at the hospital. Law enforcement personnel should be present to unload all weapons, and provisions must be made for the registration and storage of these devices in secure areas.

VIPS Politicians and other dignitaries are often the victims of terrorism. When such a situation occurs, emergency personnel must render care under strict security conditions and may initially feel intimidated. If a medical staff is travelling with the dignitary, they may insist on being present during medical treatment. By their nature, such situations will be tense. Much can be accomplished quickly, however, if all personnel identify themselves, describe their position and medical function, and state what they perceive the immediate needs of the injured to be. Senior personnel from the FBI and Secret Service should be identified and informed of medical necessities. All hospital services may be affected during the incident and routine care severely limited. The entire hospital staff must practice strict confidentiality. Ethical Issues Medical personnel may experience difficult ethical and personal decisions when asked to treat not only the victims of a terrorist incident but the terrorists themselves. Problematic triage and treatment decisions may also occur when pressure to care for a particular individual or group of patients first is applied, i.e., wounded police. Evidence Collection This is extremely important to law enforcement personnel and may lead to the determination of responsibility for the terrorist act. Therefore, it should be emphasized at every level of care. When possible, the location of the victim must be carefully noted. The victim's clothes and any missiles removed from patients should be saved for analysis. Wound location should also be carefully documented, as well as all pertinent statements by the victims. The dead should not be moved until their exact position and location are carefully documented. Photography and videotaping are particularly useful, both on-scene and in the hospital. Drills The value of disaster preparedness exercises is well known. Such drills test the coordination and communication of all responding agencies. One such model is presented and emphasizes the extent of planning and debriefing required ( 33). Realistic terrorism exercises should be planned and executed with minimal publicity, however. The general public may react with unnecessary fear if the community was thought to be under significant threat.

CONCLUSION Society expects emergency personnel to meet the unique medical challenges presented by terrorism. Success in this endeavor is largely determined by four factors. First, the threat of terrorism must be appreciated and understood by emergency personnel. Second, medical personnel must be fully prepared to care for the

casualties of terrorist incidents. Third, the EMS must play an integral role in the larger, community-wide response to terrorism. Such a role can be assured only through coordinated preplanning with all responding agencies. Finally, society and emergency personnel must keep the terrorism issue in perspective. An appreciation of the potential threat allows a realistic allocation of community resources and prevents unrealistic expectations. Past and current trends in terrorism have been examined. The future, however, may bring radically different situations and challenges to emergency personnel. Continued diligence and planning are required to ensure preparedness. References 1. Frykberg MD, Tepas JJ: Terrorist bombings—lessons learned from Belfast to Beirut. Ann Surg 1988;208:569. 2. Degeneste HI, Sullivan JP: EMS, the police response to terrorism. The Police Chief 1987;May:36–40. 3. U.S. Department of Justice. Terrorism in the United States—1988. Terrorist Research and Analytical Center, Counterterrorism Section, Criminal Investigative Division, Federal Bureau of Investigation, 1988. 4. Spengler C. The Oklahoma City bombing: a personal account. J Child Neurol 1995;10(5):392–398. 5. Atkinson R, Keylon K, et al: Disaster nursing in the Oklahoma City bombing. Insight 1995;20(3):30–31. 6. Mallonnee S, Shariat S, Stennies G, et al: Physical injuries and fatalities resulting from the Oklahoma City bombing. JAMA 1996;276:382. 7. FBI: more threats against Americans. Washington Times, Sept. 12, 1989. 8. Guiffrida LO, Salcedo FS: Terrorism.... what can we do? Emerg Manag Rev 1984;1:10. 9. Dolev E: Medical aspects of terrorist activities. Milit Med 1988;153:243. 10. Trappler B, Friedman S: Posttraumatic stress disorder in survivors of the Brooklyn Bridge shooting. Am J Psychiatry 1996;153(5):705–707. 11. Gellert GA: Humanitarian responses to mass violence perpetrated against vulnerable populations. Br Med J, 1995;311(7011):995–1001. 12. Neal LA, Rose MC: Factitious post traumatic stress disorder: a case report. Med Sci Law 1995;35(4):352–354. 13. Steefel L: The World Trade Center disaster. Healing the unseen wounds. J Psychosoc Nurs Ment Health Serv 1993;31(6):5–7. 14. Stapczynski JS: Blast injuries. Ann Emerg Med 1982;11:687. 15. Pode D, Landau E, Lijovetsky G, et al: Isolated pulmonary blast injury in rats—a new model using the extracorporeal shock-wave lithotriptor. Milit Med 1989;154:288. 16. Phillips YY: Primary blast injuries. Ann Emerg Med 1986;15:1446. 17. Bafford KD, McFarlone C: Urban bomb blast injuries: patterns of injury and treatment. Surg Ann J 1993;25:29. 18. Karmy-Jones R, Kissinger D, Goloevsky M: Bomb-Related Injuries. Milit Med 1994;159:536. 19. Cooper GJ, Maynard RL, Cross NL, et al: Casualties from terrorist bombings. J Trauma 1983;23:955. 20. Hadden WA, Rutherford WH, Merret JD: The injuries of terrorist bombing: a study of 1532 consecutive patients. Br J Surg 1978;65:525. 21. Marshall TK: A pathologist's view of terrorist violence. Forensic Sci Int 1988;36:57. 22. Adler J, Golan E, Golan J, et al: Terrorist bombing experience during 1975–1979. Casualties admitted to the Shaare Zedek Medical Center. Isr J Med Sci 1983;19:189. 23. Brismar B, Bergenwald L: The terrorist bomb explosion in Bologna, Italy, 1980: an analysis of the effects and injuries sustained. J Trauma 1982;22:216. 24. Fackler ML: Ballistic injury. Ann Emerg Med 1986;15:1451. 25. Morita H, Yanagisawa N, Nakajima T, et al: Sarin poisoning in Matsumoto, Japan. Lancet 1995;346(July 29):291. 26. Yanagisawa N, ed: Report for toxic gas attack in Matsumoto. Matsumoto Local Medical Council. 1995 Matsumoto, Japan. 27. Macilain C: Study proves Iraq used nerve gas [news]. Nature 1993;363:3. 28. Anzueto A, de Lemos RA, et al: Acute inhalation toxicity of soman and sarin in baboons. Fundaml Appl Toxical 1990;14:676–687. 29. Husain K, Vijayaraghavan R, Pant SC, et al: Delayed neurotoxic effect of sarin in mice after repeated inhalation exposure. J Appl Toxicol 1993;13:143–145. 30. Duffy JC: Common psychological themes in societies' reaction to terrorism and disasters. Milit Med 1988;153:387. 31. Pyper PC, Graham WJ: Analysis of terrorist injuries treated at Craigavon Area Hospital, Northern Ireland, 1972–1980. Injury 1983;14:332. 32. Vayer JS, Adams R: Responding to terrorism—keeping emergency workers out of the crossfire. Firehouse 1987;June:101–102. 33. Spain EL: Developing a simulated disaster. Nurs Manage 1995;26(12):48H, 48K.

CHAPTER 155 INTRODUCTION TO MANAGEMENT: DEFINITIONS, UTILIZATION, AND WORKFORCE ISSUES Principles and Practice of Emergency Medicine

CHAPTER 155 INTRODUCTION TO MANAGEMENT: DEFINITIONS, UTILIZATION, AND WORKFORCE ISSUES James S. Cohen Introduction Urgent or Not? What is the Cost of Providing ED Care? What Factors will Determine Future ED Utilization Levels? ED Physician Workforce Needs Shift Lengths Trauma Center Evolution The Future

INTRODUCTION How does one define the specialty of emergency medicine? How did we arrive at our present circumstances? Where is the specialty going? Inherent in any discussion of the future of emergency medicine should be some consideration of what or rather, who defines an emergency medical condition. For the past 30 to 40 years it has been the patient with a cornucopia of undifferentiated symptoms who has defined the practice of emergency medicine. It was not always this way, and if present trends continue, may not be so in the future. In 1976 the American Medical Association (AMA) House of Delegates adopted the following definition: “The Emergency Physician is a physician trained to engage in: the immediate initial recognition, evaluation, care and disposition of patients in response to acute illness or injury.” In that same year the American College of Emergency Physicians (ACEP) expanded the AMA definition to include nonurgent care by adding the phrase, “To meet the needs of patients whose needs are not amenable to scheduling, the emergency department has emerged as a locus of medical care.” In 1980, ACEP added another qualifier, “Emergency medicine is practiced as patient demanded and continuously accessible care.” These early statements combine elements of what most physicians would regard as a true emergency with those considered an emergency only by the patient. Increasingly, deference was being accorded to the patient's perspective. In 1982, ACEP's board of directors adopted a policy statement entitled, “Bona Fide Emergency Defined.” More emphasis was placed on the acute medical aspect of the patient's condition while acknowledging the patient's perspective with the inclusion of the term “prudent layperson.” It read as follows: We feel a patient has made an appropriate visit to an emergency department when: An unforeseen condition of a pathophysiologic or psychological nature develops which a prudent layperson, possessing an average knowledge of health and medicine, would judge to require urgent and unscheduled medical attention most likely available, after consideration of possible alternatives, in a hospital emergency department. This would include: Any condition resulting in admission of the patient to a hospital or nursing home within 24 hours. Evaluation or repair of acute (less than 72 hours) trauma. Relief of acute or severe pain. Investigation or relief of acute infection. Protection of public health. Obstetrical crises and/or labor. Hemorrhage or threat of hemorrhage. Shock or impending shock. Investigation and management of suspected abuse or neglect of a person which, if not interrupted, could result in temporary or permanent physical or psychological harm. Congenital defects or abnormalities in a newborn infant, best managed by prompt intervention. Decompensation or threat of decompensation of vital functions such as sensorium, respiration, circulation, excretion, motility or sensory organs. Management of a patient suspected to be suffering from a mental illness and posing an apparent danger to the safety of himself, herself or others. Any sudden and/or serious symptoms which might indicate a condition which constitutes a threat to the patient's physical or psychological well-being requiring immediate medical attention to prevent possible deterioration, disability or death. In 1994, ACEP rescinded the 1982 policy and adopted the current definition: Emergency services are those healthcare services provided to evaluate and treat medical conditions of recent onset and severity that would lead a prudent layperson, possessing an average knowledge of medicine and health, to believe that urgent and/or unscheduled medical care is required.

However, patients don't know or care about such definitions. For the most part neither do emergency departments (EDs). Consequently, it has been the common policy in most EDs throughout the United States to register, evaluate, and treat any patient who presents at any time with any complaint without regard to acuity of the condition or availability of alternate sources of health care. Many health care professionals mistakenly believe that all patients must be seen by the ED physician on duty. In actuality, federal law merely requires that the patient be evaluated by a qualified health care worker and stabilized. There is no federal requirement that nonemergency medical conditions be treated. However, to a large extent this point is moot as no hospital administrator would turn away a patient with means to pay or risk refusing care to an indigent patient with all the adverse consequences that action might engender. Much of what has just been stated is rapidly changing. The last few years have witnessed a rapid transformation of the American health care system with regard to its financing as well as the manner in which health care services are organized and delivered. Over the past three decades, health care costs have consistently risen faster than general inflation. For years commercial medical insurers, the so-called third-party payers, merely raised their premiums to compensate. This worked to a point but that point has now been reached. Federal, state, and local governmental authorities do not have an unending ability or willingness to raise taxes to fund these ever-rising health care costs. Corporate America can no longer stay competitive in a market that has turned toward a global economy. The average American family can barely afford to buy a good health policy and yet risks financial ruin if one family member becomes seriously ill without coverage. This has all resulted in the formation of new third parties, which have taken away control of the health care system from its two primary constituents—the patient and the physician. The definition of emergency has been usurped by these new third party players who, without ever laying an eye or hand on a patient, are changing the rules.

URGENT OR NOT? The National Hospital Ambulatory Medical Care Survey: 1994 Emergency Department Summary (US Department of Health & Human Services–National Center of Health Statistics) estimated that there were 93.4 million ED visits in 1994. Of these, 52.8% were classified as nonurgent by hospital staff responsible for completing the surveys. However, the instructions in the survey defined an urgent visit in the following manner: “Patient requires immediate attention for acute illness or injury that threatens life or function. Delay would be harmful to the patient. Nonurgent visits are those in which the patient does not require attention immediately or within a few hours.” In great contrast to the government's results, other studies have found nonurgency percentages in the 15 to 20% range. Why such a huge difference? It all has to do with the methodology. Studies with high nonurgency percentages are retrospective and diagnosis-dependent whereas studies with low percentages are prospective and symptom-dependent. A straightforward comparison of these two methodologies would be to consider a 50-year-old man who developed left shoulder pain while shoveling snow. As he presents to the ED he is a straightforward emergent patient, at the minimum needing a rapid assessment for possible thrombolytic therapy. However, if after an appropriate (and correct) evaluation the final chart diagnosis were “musculoskeletal strain” he would be classified as nonurgent using a diagnosis-based retrospective approach! Managed Care Organizations (MCOs), not having a great deal of insight into the ED evaluation process and being highly desirous of controlling costs are increasingly focusing on the final diagnosis as the basis upon how much they will reimburse or whether they will reimburse at all. Curiously, a system has evolved whereby an emergency physician is obligated to provide care but an MCO is not obligated to pay for it. To assure equitable coverage and treatment of emergency services by health plans Rep. Ben Cardin introduced H.R. 2011 (Senate version S. 1233) in July 1995 entitled “Access to Emergency Medical Services Act of 1995.” The essence of this bill is as follows: 1. It defines an emergent medical condition as “having an onset which is sudden, that manifests itself by symptoms of sufficient severity, including pain, that a prudent layperson, who possesses an average knowledge of health and medicine, could reasonably expect the absence of immediate medical attention to result in (A) placing the person's health in serious jeopardy, (B) serious impairment to bodily functions or, (C) serious dysfunction of any bodily organ or part. Therefore, MCOs would be prohibited from using a retrospective approach in the qualification process. 2. It prohibits MCOs from requiring prior authorization (that the patient has to obtain permission to go to the ED). 3. It prohibits MCOs from withholding payments for emergency physicians' service due to lack of a prior contractual relationship. 4. It establishes a penalty of $10,000 for each violation and $1,000,000 for a pattern of repeated violations. As of this writing this bill has not been passed into law. As the blatantly unfair retrospective approach meets resistance a prospective approach is gaining popularity. EDs are just beginning to address the issue that some patients should not be treated in the ED. In a study of 176,074 adult patients presenting to one California ED over a 5-year period, 18% were defined as nonemergent,

not treated and referred elsewhere. The determination was made at triage using four criterion groups: 1. Vitals within a specified range: temperature 35 to 38.5° C (95 to 101° F); respirations 12 to 20 breaths/min; Blood pressure 90 to 160 systolic and 60 to 110 diastolic; pulse 60 to 110 beats/min (100 if age more than 60 years). 2. Absence of high-risk conditions such as severe pain, chest or abdominal pain, age less than 16 years, inability to walk, or patient volunteers a high-risk condition. 3. Focused exam by the triage nurse. 4. Presence of 1 of 50 predetermined chief complaints. The authors claim no instances of gross mistriage and only a few instances of adverse outcomes. Follow-up phone contact was made in 34% of this triaged out group revealing that 39% received care elsewhere the same day, 35% within 3 days, and 26% never sought medical care, and 1% went to another ED. Despite the apparent success of this triage system there remains the troublesome issue that a so-called nonemergent chief complaint may be an emergency in disguise. For example, what possible objective criterion define a headache as minor? Who can tell if a sore throat is going to be strep positive by exam alone? Who can gauge the electrolyte levels of a “weak and dizzy” person? In contrast to prospective ED-based determinations of nonurgency are studies reflecting the patient's perspective. In one study of 268 patients judged nonurgent by the triage nurse, 82% of these patients classified themselves as urgent by answering affirmatively to one of two questions: “At the time you decided to come to the ED, was there a threat to your life if you did not receive treatment within an hour?” and “Did you feel you needed care within a few hours to prevent the problem from becoming serious?” In a similar study of 1,190 nonemergent patients, asked the question, “Did you come to the ED now because you think that you need to see a doctor immediately, or is this just a good time for you to come see a doctor?” Eighty-nine percent responded that they needed to be seen immediately. Although emergency physicians have become accustomed to treating every person who walks through the door, MCOs are rapidly making this practice obsolete. There are some emergency physicians who agree with this approach albeit for academic rather than financial reasons. As quoted in the Washington Post one such physician stated, “I am not one of the people who thinks an ED is the safety net for society. I know there are some very vocal MDs who think that. That is not what EM is all about. The sickest can't get good care because they are competing with patients with minor problems. EDs of the future will no longer be places where the worried well, the slightly sick and the deathly ill are all treated in the same place.” Patients rights are undergoing close scrutiny by patients, professionals, and Congress (1A).

WHAT IS THE COST OF PROVIDING ED CARE? Cost is a hotly debated issue predominantly because MCOs perceive ED care as more expensive than office care. Emergency medicine represents the most unplanned aspect of our health care system. Managed care seeks to plan and organize a specialty whose basis is the care of unexpected illness and injury. Managed care is structured around principles of anticipation, control, and access. However, these attributes relate poorly to the care of emergency conditions. Emergency physicians rarely have prior knowledge of a patient, often have great difficulty obtaining a complete medical history, often are distracted by the immediate needs of multiple other patients or health care workers, and rarely get a second chance to make a correct diagnosis. By necessity this all forces a prudent emergency physician to utilize more diagnostic services, consultations, and admissions than would be necessary in a more controlled setting. In contradistinction to this, emergency medicine has the potential to be extremely cost effective. Overhead of staff, facility expenses, and equipment can be spread over 168 hours per week and a large number of patients. The well trained emergency physician can efficiently handle a wide variety of medical problems, therefore, avoiding costly referrals or redundant visits to other physicians. Additionally, a rapid diagnostic workup or intensive therapeutic intervention may obviate the need for a costly admission. The presumption that ED care is exorbitantly more expensive than equivalent care provided elsewhere is fallacious. This is because such beliefs fail to recognize or distinguish the parameters of charges, average expenses, and marginal expenses. Charges represent the bill the patient receives. Average expense is essentially the ED budget divided by its patient volume. Marginal expense is the additional expense of providing care to an additional patient beyond those basic expenses that would be incurred regardless of the appearance of that additional patient. Williams ( 1), in his doctoral dissertation on the costs of emergency services provided at six community hospitals in Michigan in 1993, found average charges of $383, average costs of $209, and marginal costs of $88 spread among a patient mix of 24,010 visits classified as 32% nonurgent, 26% semi-urgent, and 42% urgent. That charges are almost double the average costs is a consequence of decades of passing along the costs of uncompensated care to the paying patient. If all patients had health insurance charges could drop to roughly one-half of present levels. Unfortunately, when an MCO gets an ED bill for a member, the MCO is being charged for the expenses of providing uncompensated care. This represents the main reason MCOs strive to divert their members from EDs. One simple way to divert patients with minor problems from the ED was used by Kaiser Permanente in 1993 with the introduction of a $25 to $35 copayment for ED usage. Examining ED use of approximately 30,000 members after the introduction of this copayment there was an overall 14.6% decline in ED registration. Interestingly, there was no offsetting increase in the use of other Kaiser or non-Kaiser facilities. Of course, such results were obtained in a middle class, 100% employed population with readily accessible alternative sources of health care, and so the study's results might not apply to the large numbers of impoverished, medically disenfranchised patients who are accustomed to relying on the ED as their primary source of health care. A new concept in emergency medicine may favorably impact on the issue of cost effectiveness. This is the introduction of short-term observation units whereby patients who fall in the nebulous range of not a clear-cut admission nor a simple discharge can be monitored for a period of 12 to 24 hours to determine more safely what the ultimate disposition should be. Although often referred to as observation units they are, in actuality, rapid diagnostic units following a variety of symptom specific protocols. Prototypical of this approach would be observation of a person with atypical chest pain with serial CPK-MBs, serial ECGs and perhaps some form of exercise stress test. Therefore, more objectivity will be brought to a discharge decision previously overly subjective in nature. Following this approach would not only reduce expensive and unnecessary admissions, but would also have the added benefit of reducing medical liability exposure to the emergency physician.

WHAT FACTORS WILL DETERMINE FUTURE ED UTILIZATION LEVELS? According to the National Center for Health Statistics there were 38 ED visits per 100 persons in 1978 and 36 in 1994 ( Fig. 155.1). Given the 16-year interval this reflects a rather flat utilization rate. However, in 1978 there were approximately 82 million ED visits and in 1994, 94 million visits. This equates to a compound annual growth rate of 0.9%, which is roughly equal to the overall growth rate of the US population during the same period. However, according to the AHA, there were 96 million ED visits in 1994, a 1.4% decline compared to their own statistics for 1993. In addition, according to the most recently released data by the National Center for Health Statistics, there were 96.5 million ED visits in 1995 and 90.3 million in 1996—a 6.4% decline (personal communication, S. Schappert, Dec. 17, 1997).

Figure 155.1. U.S. Emergency department visits. Source: American Hospital Association.

Factors leading to increased utilization include an aging population, new diseases, our increasing ability to effect acute interventions (such as thrombolysis), growing drug and alcohol abuse, and an increase in the uninsured population stemming from multiple economic factors, among them a strong trend toward part time

employment devoid of medical benefits. Factors leading to a decreased utilization include the implementation of copayments in insurance plans, various increased efforts by MCOs to discourage or deny payment for all but the most serious cases, establishment of extensive out-of-hospital multispecialty clinics with greatly extended hours and universal health insurance with easy access to primary care providers. Of all the factors the one with the greatest near-term effect on ED volume is that of the MCO. MCOs are increasingly operating telephone triage programs aimed at directing members to alternative sources of care. Such programs generally use RNs following strict symptom specific triage protocols. One California company specializing in providing such services to MCOs charges 1/month per enrollee. MCOs may face increasing resistance to their efforts to divert patients from EDs. In 1994, California passed state law SB 1832. Under this law MCOs cannot require an enrollee to obtain telephone permission to go to an ED until after they have been seen and stabilized by ED staff. Another incipient factor decreasing ED utilization is the growing push to enroll Medicaid patients into MCOs. MCOs in turn are paid monthly for each enrollee. For example, in New Jersey in 1996 there were approximately 460,000 persons on Medicaid. The state of New Jersey pays $220 to $559 per enrollee to the MCOs. As these MCOs have a profit motive the state never did, it is assumed that they will manage enrollees' utilization of health care services more efficiently than the state. The long-term effects of this system on the quality of care remains an open issue. Osborn ( 2), reviewing the experience at Lincoln Hospital in the South Bronx, reported that 48% of the patients in managed care plans were denied care by their MCOs. The authorization telephone lines were difficult to access (sometimes only an answering machine) and none of the 21 MCOs provided a physician for telephone consultation. In one egregious case an 8-year-old girl with fever, headache, and weakness was denied emergency care by an MCO, and subsequently was found to have meningococcal meningitis by the staff who saw her nonetheless. According to the National Center for Healthcare Statistics 24.7% of ED visits in 1994 were by Medicaid patients. The implications for potential cost shifting, access to care and quality of care by enrolling this group in MCOs is enormous.

ED PHYSICIAN WORKFORCE NEEDS This topic consists of two components—how many people (physicians and physician extenders) are needed and how many board certified emergency medicine physicians are needed. A rough starting number can readily be obtained by the following method. Let A = the number of ED visits = 94 million. Let B = the number of patients seen per hour = 2. Let C = the number of clinical hours worked for one full-time equivalent position = 1,900 hours. Using these figures the number of full time equivalents (FTEs) needed would be A/(B × C) = 24,737 Of course the true number must be higher than this for a variety of reasons. First, physicians do not come in fractions. When an ED volume reaches a certain level another physician will be added to the schedule. As schedules may not be saturated there will be an overall dilutive effect. In the past, increasing coverage was done hesitantly. The underlying philosophy was essentially to let the patient wait until a slower period arrived. However, as patient satisfaction concerns are gaining in importance more will be done in the future to reduce waiting times and this includes better physician coverage. Second, there are many activities not involving direct patient care—teaching, supervising residents, quality assurance, and a host of other nonclinical activities. Some emergency physicians, generally departmental directors and contract managers, have ceased seeing patients entirely. For years there has existed a widespread belief that there is a severe shortage of emergency physicians. In reality the shortfall has been one of quality, not quantity. Strangely, and with logic that defies any rational application of common sense, the leaders of the country's medical establishment have maintained that anyone with a medical degree is qualified to practice a specialty that requires a high level of medical knowledge and a wide range of procedural skills in a setting replete with multiple life-threatening illnesses and injuries. To a great extent this attitude persists because many in academic medicine regard the ED and all that occurs there a learning opportunity—“near misses” get euphemised into “learning experiences,” and anyone who works there outside of such a learning experience is “moonlighting.” Although these attitudes have been slowly changing many hospitals that require their dermatologists to be board certified will qualify any licensed medical degree for emergency medicine employment who is current in a variety of 2-day certification courses. Beyond comprehension, some hospitals will not accept even a successfully completed 3 or 4-year residency in emergency medicine in lieu of the aforementioned courses. Despite these aberrations there is an ongoing trend by hospital administrators, MCOs, and an increasingly knowledgeable public to demand a higher standard of care in EDs than has previously been the norm. To date the only standard by which competence in emergency medicine can be assured is board certification in emergency medicine. This need for highly qualified emergency medicine physicians contrasts with the concept that all patients who present to an ED require the highest level of expertise. As health care dollars get scarcer, lower cost physician extenders will become increasingly utilized. Anesthesiologists work with Certified Nurse Anesthetists. Obstetricians work with Certified Nurse Midwives. Multiple primary care specialists have worked with physicians' assistants (PA) or nurse practitioners (NP). In New Jersey in May 1996, 21 nurses graduated from a new program qualifying them to be “registered nurse first assistants.” In this most recently created nursing specialty, they will replace the surgeons who used to be the first assistants. Such examples of physician extenders have already made their presence in the ED. In one study, published in 1996, it was estimated that 4% of all ED patient care was provided by PAs or NPs. This study's reporting period was in 1992. In 1997, the American Academy of Physicians Assistants estimated that there were 2,872 PAs practicing emergency medicine ( 3). In a 1993 study of a Virginia Level I Trauma Center, it was found that NPs handled 21% of the adult ED population in the minor emergency area (MEA) with the top five diagnoses being: (a) contusion/sprain, (b) ENT problems, (c) lacerations, (d) respiratory tract infections, (e) follow-up visits. The authors also note that after 100,000 NP/patient visits there has not been one lawsuit filed. According to data provided by the American Board of Emergency Medicine there were approximately 15,552 active diplomates as of April 1998. This number can be expected to increase by approximately 1,000 per year in the immediate future and even more after that due to the rapid expansion of residency programs (116 as of this writing). Therefore, by the year 2000 there will likely be approximately 18,000 diplomates. Given the substantial and increasing numbers of patients seen by physician extenders coupled with the efforts by MCOs to divert patients from ED care, it is likely there may exist an oversupply of boarded emergency medicine specialists in the near future. This will start as a regional maldistribution as many emergency medicine specialists shun low volume, low acuity EDs (paradoxically though, this is where they are often needed the most). In addition, if universal health insurance were enacted along with the present gatekeeper and referral patterns of MCOs there would be 165,000 surplus doctors in the United States ( 4). This would certainly have a negative effect on the demand for and reimbursement of the board certified emergency medicine physician. Offsetting these factors is the largely undetermined future annual attrition rate of emergency physicians. Careers of 40 to 50 years common in many other specialties have no equivalent track record in emergency medicine. The stresses of shiftwork and chaos easily handled in one's earlier years become increasingly difficult thereafter.

SHIFT LENGTHS Working “a shift” in emergency medicine has become synonymous with working 12 hours. It divides easily into a 24-hour day and makes it easy for scheduling. Longer shifts mean less commuting time, less shift changes (a medicolegal danger time zone) and more days off. Advantages of shorter shifts include a well-rested physician, the ability to apply principles of circadian rhythms when rotating shifts and being able to engage in personal and social activities on workdays. Historically, the demands of providing “coverage” itself have tended to supersede concerns for either physician or patient well being. Emergency physicians, as though blessed with supernatural levels of adrenergic receptors and an unending capacity to time-share their brains, are not supposed to get tired. One study of 290 emergency physicians found that only 11.3% worked exclusively 8-hour shifts ( 5). Of those who worked exclusively 12-hour shifts, 58% preferred to work shorter shifts. In another study of the then existing residency programs in emergency medicine, 76% of full-time faculty preferred to work 8-hour shifts. Younger physicians, with recent memories of their lives as residents, often consider working three or four 12-hour shifts a piece of cake. However, as they age the exigencies of emergency medicine practice make previously ignored issues problematic. It is particularly interesting to note the persistence of the discrepancy between emergency physicians' desires and practices regarding shift length. Undoubtedly, this has been a reflection of lack of consideration for physicians' and patients' needs by those in control. Fortunately, the growing professionalism of the specialty has engendered a heightened concern for this issue resulting in a gradual migration toward shorter shifts.

TRAUMA CENTER EVOLUTION During the Vietnam War, severely wounded US military servicemen were treated in the field by medically trained personnel, evacuated by specially equipped helicopters, and taken to specialized surgical hospitals. The evacuation time averaged about 1 hour—down from 2 hours in the Korean War and 10 hours in WWII. Firmly in place then was an organized system as well as could be possible given the constraints of an ongoing war. Meanwhile, back home there was no system. No laws dictated training of ambulance personnel or even medical personnel (including physicians). There were no standards for equipping ambulances. Indeed, spare hearses made good ambulances at the time, providing a convenient and profitable opportunity for funeral home owners to maximize resources and income. Patients were routinely taken to hospitals with little or no regard to the hospitals' ability to provide adequate care.

This poor state of affairs changed with the publication of a paper by the National Academy of Science entitled “Trauma, Accidental Death and Disability, the Neglected Disease of Modern Society,” which outlined the great number of preventable deaths due to trauma ( 6). Much of this death was on the nation's highways, the yearly tab often exceeding the loss of American life during the entire Vietnam Conflict (about 50,000 deaths). Shortly thereafter, the Highway Safety Act of 1966 was passed. This act required states to incorporate emergency medical services (EMS) as part of their highway safety programs. Although trauma care has undeniably improved in the intervening years there remains to this day an unresolved disorganization. In 1993 the Hospital Research and Education Trust made an exhaustive study of the state of affairs. They found only five states, Oregon, New York, Nevada, Maryland and Florida, in full compliance with all the essential components of a complete trauma system. Only 23 states had established legal authority for the creation of statewide trauma systems. The slowness with which regional trauma systems has been adopted throughout much of the United States has been due to several obstacles—financial, professional, and political. How many trauma centers does a region need? Some well-designed studies suggest one for every 1 to 2 million population. Yet individual hospitals, when left to their own devices, rarely pay attention to such studies. What criterion should be used to determine what level of facility is best for any given trauma patient? There is no consensus. When should a hypotensive trauma victim be taken to the nearest hospital over a more distant but higher level facility? The value of a rapid transport to a hospital may be lost if the destination hospital does not have the capability of effecting rapid and definitive medical care. In many circumstances, it may well be worth the extra transport time to have a patient go to a hospital staffed by highly trained emergency physicians backed up by trauma surgeons and other supporting specialists. Practices long taken as gospel may give way to scientific scrutiny. Consider the near-universal belief that trauma patients transported by EMS vehicles fare better than those transported by private vehicle. A 1996 study at a major California trauma center, comparing trauma patients, adjusted for severity of injury, found that when the Injury Severity Score (ISS) was 15 or more there was a 28.8% mortality in the EMS transported group and a 14.1% mortality in the non-EMS transported group ( 7). At a minimum, such studies should give us pause to consider that intuitively designed systems may not be what they appear. Huge expenditures in certain aspects of prehospital care may be misdirected. Likewise, hospitals may no longer be permitted to self-designate as trauma centers without state consent. Studies have shown that trauma surgeons need to operate on a consistent basis to maintain their skills. The American College of Surgeons recommends a trauma center if there are 800 to 1000 severe injuries per million population in a given region. In the future, EMS systems and trauma centers will be more integrated, rely more on scientific studies of efficacy and less on visceral reflexes. There will be a greatly expanded systemwide effort to effectively match the resources of the health care providers with the needs of the patient.

THE FUTURE People have difficulty anticipating the future when their own beliefs are in conflict with the tides of change. Consider the comments of the following notable figures: “Who the hell wants to hear actors talk?” —Harry M. Warner, Warner Brothers 1927; “Everything that can be invented has been invented”—Charles H. Duell, commissioner, US Office of Patents, 1899; “There is no reason for any individual to have a computer in their home”—Ken Olsen, President, Chairman and founder of Digital Equipment Corporation, 1977 (filed for bankruptcy protection 1991). In the nineteenth century the majority of hospitals were either public or charitable institutions. As such they were protected from lawsuits under the principle of charitable immunity. There was no legal duty for either a hospital or physician to undertake the care of any patient it did not wish to take care of. Tort theory at the time strongly embraced the distinction between nonfeasance and malfeasance; the former being an omission of an act that ought to have been performed and the latter being the performance of an act negligently. Physicians and hospitals could choose whom they might treat, even in an emergency. However, once a physician-patient relationship was established the physician was obligated to carry through and provide proper care. It was not until 1961 that it was established that “when a hospital customarily renders emergency care service, and such undertaking is relied on by a person in need of emergency care, the hospital has a duty to provide service.” Although this was a great step forward nothing was mentioned about the level of service provided. There was absolutely no duty for a physician to be present or even on call. As one judge noted (1961)—“The hospital cannot reasonably be expected to station an intern at all times in the receiving room. It therefore keeps a nurse on duty. If the nurse makes an honest decision that there is no unmistakable indication of an emergency, and that decision is not unreasonable in light of the nurse's training, how can there be any liability on the part of the hospital?” In 1975, in the case of Guerrero v. Copper Queen Hospital it was affirmed that an Arizona hospital must provide emergency care, but that it could transfer financially ineligible patients to another hospital as long as the transfer did not pose an unreasonable risk. In 1986 Congress passed the Emergency Medical Treatment and Active Labor Act (EMTALA) as part of the Consolidated Omnibus Reconciliation Act (COBRA), which further restricted hospitals from inappropriate patient transfers. From then on it was required that “the medical benefits reasonably expected from the provision of the appropriate treatment at another medical facility outweigh the increased risks to the individual from effecting the transfer.” Patients could no longer be transferred for financial reasons alone even if stable. Coincident with these changes arose a vast change in the types of medical conditions seen in EDs. No longer seeing just true emergencies, EDs took on the various roles of providing primary care to the indigent, after hours and weekend care to insured private patients, and medical babysitting services for a variety of conditions in no need of immediate care (e.g., an elective admission coming through the ED). This expanded to school physicals, immunizations, and treatment of ingrown toenails. The ED, by the early 1990s, had taken on the role of trying to provide all care to all patients at all times and all in the same place. Paralleling these changes the specialty of emergency medicine arose. Initially intended to be a specialty intended to diagnose and treat emergencies, it expanded, rather involuntarily, to be a specialty that treated everything. Absurdly, patients with widely varying degrees of acuity came to be treated in the same setting. When one patient died after an unnoticed stab wound, the director of surgical care at that institution noted, “It's like a war here. Chaos is the norm. And chaos contributes to oversight.” The previous scenarios are slowly fading. Responding to intense economic pressures, EDs across the country are redefining themselves. The concept of triage, initially meant to identify the most serious cases, will come to focus on the least serious as well. Planning will play a greater role in the entire health care system. MCOs will provide their patients detailed instructions where to go for what type of problem. They will continue to encourage telephone calls prior to going to the ED to the extent not prohibited by law. They will vigorously review ED records and decline payment for disallowed services. Hospitals, in turn, not wanting to lose the nonurgent patient will make increasing use of on-site fast track areas. Physicians will be far more likely to work in groups with extended office hours more amenable to the patients' schedules. Physician extenders, as previously noted, will provide an increasing portion of care to fast track patients. The health care system as a whole, catching up with the rest of the world, will make increasing and extensive use of computer technology so that important medical records will be available when they are needed. This will eliminate the billions of dollars wasted on redundant diagnostic services. Once access and confidentiality issues are successfully addressed, records might even be available between institutions and providers over the Internet. Rapidly advancing data storage capabilities will permit an entire medical record to be contained in the space the size of a credit card, which a person might keep just as a driver's license. As the changes discussed take effect the emergency physician of the future will see fewer but sicker patients on the average, and will rely on and use more skills. As this occurs professional status will rise to become more on par with that of other acute care specialists. Moonlighting physicians from other specialties will no longer be credentialled to work in the ED by dint of possession of a current ACLS card. EDs staffed by physicians board certified in emergency medicine will become more of a standard and less an administrator's dream. The specialty will become reinvented as originally designed. References 1. Williams RM: The costs of visits to the emergency department. N Engl J Med 1996;334:642–646. 1A. Annas GJ: Patient's rights in managed care: Exit, voice, and choice. N Engl J Med 1997;337:210–215. 2. 3. 4. 5. 6.

Osborn H: Healthcare maintenance organizations: managed care or mismanaged care? Ann Emerg Med 1996;27(2):225–228. Snapshot: physician assistants. Emergency Medicine News 1997;19:24. Weiner JP: Forcasting the effect of health reform on US physicians. Evidence from HMO staffing patterns. JAMA 1994;272:2601. Thomas H, Schwartz E, Whitehead D: Eight-versus 12 hour shifts: implications for emergency physicians. Ann Emerg Med 1994;23(5):1096–1099. National Committee of Trauma and National Committee of Shock. Accidental death and disability–The neglected disease of modern society. Washington DC: National Academy of Sciences/National Research Council, 1966. 7. Demetriades D, Chan L, Corwell E, et al: Paramedics vs private transportation of trauma patients: effect on outcome. Arch Surg 1996;131(2):133–138.

Suggested Readings American Board of Emergency Medicine. Annual report. 1995–1996. ACEP Policy Statement. Bona fide emergency defined. October 1982.

ACEP Policy Statement. Definition of an emergency service. January 1994. American College of Surgeons: Committee on Trauma. Resources for optimal care of the injured patient. Chicago: ACS, 1989. Angell M, Kassirer JP: Quality and the medical marketplace—following elephants. N Engl J Med 1996;335(12):883–885. Baier CL: Editorial on costs of visits to the emergency department. N Engl J Med 1996;335(3):209. Baker DW, Stevens CD, Brook RH: Determinants of emergency department use by ambulatory patients at an urban public hospital. Ann Emerg Med 1995;25(3):311–316. Bazzoli GJ, MacKenzie EJ: Trauma centers in the United States: identification and examination of key characteristics. J Trauma. 1995;38(1):103–110. Belkin L: “Why emergency departments are on the critical list.” NY Times, 6 October 1991. Comments of Dr. Thomas M. Scalea. Binder LS: Physician workforce reform and graduate medical education reallocation: potential impact on emergency medicine. Acad Emerg Med 1994;1(2):90–93. Birmingham Baptist Hospital v. Crews. 229 Alabama 398 (1934). Brillman JC, Doezema D, Tanberg D, et al: Triage: limitations in predicting need for emergency care and hospital admission. Ann Emerg Med 1996;27(4):493–500. Brody L: “Special Nurses Join Surgery Ranks,” The Record (New Jersey). 25 June 1996, p. A3. Brown LR: State of the world. New York: W.W. Norton & Company, 1996. Buchanan L, Powers RD: Establishing an NP-staffed minor emergency area. Nursing Management. 1996; February: 25–31. Cardin B: Access of Emergency Medical Services Act of 1995, 104th Cong., H.R. 2011. (11 July 1995). Cohen JS: Credentialling emergency physicians: Time for reappraisal. EM News 1998;20:2, 30–32. Derlet RW, Kinser D, Ray L: Prospective identification and triage of non-emergency patients out of an emergency department: a 5-year study. Ann Emerg Med 1995;25(2):215–223. Derlet RW, Hamilton B: The impact of health maintenance organization care authorization policy on an emergency department before California's new manage care law. Acad Emerg Med 1996;3:338–344. Eliastam M: Reinventing the emergency department. Ann Emerg Med 1996;27(6):793. Flashner B: “How It Might Have Been.” EM News 12:3 March 1990. Gill JM, Riley AW: Nonurgent use of hospital emergency departments: urgency from the patient's perspective. J Fam Pract 1996;42(5):491–496. Hall GJ: Physician assistants in control: ED mayhem. Am J Emerg Med 1996;14:338–339. Holliman CJ, Wuerz RC, Hirshberg AJ: Analysis of factors affecting projections for the U.S. emergency medicine physician workforce. Acad Emerg Med 1997;4:731–735. Hooker RS, McCaig L: Emergency department uses of physician assistants and nurse practitioners: a national survey. Am J Emerg Med 1996;14:245–249. Hopper S: Director of Policy Unit. TennCare. Nashville, Tennessee. (personal communication, October 1996). Issen G: Manpower requirements for emergency medicine. Office of Graduate Medical Education. U.S. Department of Health & Human Services, 1980. Kellerman AL: Clinical emergency medicine, today and tomorrow. Ann Emerg Med 1995;25(2):235–238. Kelly LJ, Birtwhistle R: Is this problem urgent? Can Fam Physician 1993;39:1345–1352. Knoop RK: Health care reform and the safety net. Ann Emerg Med 1996;27(2):234–236. Editorial. Moore EE: Trauma systems, trauma centers, and trauma surgeons: opportunity in managed competition. J Trauma 1995;39(1):1–11. Olson EJ: No room at the inn: a snapshot of an American emergency department. Stanford Law Review 1994; January: 449. Pear R: “HMO's Refusing Emergency Claims, Hospitals Assert.” New York Times. 9 July 1995. Richards B: “Telephone triage cuts costly ED visits.” Wall Street Journal 24 October 1995. Rothenberg KH: Who cares?: the evolution of the legal duty to provide emergency care. Houston Law Review 1989;26:21. Selby JV, Firemenan BH, Swain MS: Effect of copayment on use of the emergency department in a health maintenance organization. N Engl J Med 1996;334(10):635–641. Shackford SR: The evolution of modern trauma care. Surg Clin North Am 1995;75(2):147–156. Stapczynski JS: Capitation for emergency physicians. Ann Emerg Med 1996;27:501–505. Steele MT: Council of Residency Directors in EM. 1992. Newsletter. Steinbrook R: The role of the emergency department. N Engl J Med 1996;334(10):657–658. Stussman BJ: National hospital ambulatory medical care survey: 1994 E.D. summary. Washington DC: National Center for Health Care Statistics Report #275. May 17, 1996. “The Past Imperfect.” Time 15 July 1996, p. 54. “University of California Policy Denying Care Draws Criticism,” EM News 11(7) July 28 1989. U.S. Code 42:1395dd. Examination and treatment for emergent medical conditions and women in labor. Washburn L: “HMO's Targeting Medicaid Recipients.” The Bergen Record (New Jersey) 23 September 1996. “The Tightening Definition of Emergency.” The Washington Post 11 June 1996, p. 1. Weil TP: Implications for current procompetitive approaches on ED's. Am J Emerg Med 1996;14:74–78. Williams RM: Triage and emergency department services. Ann Emerg Med 1996;27(4):506–507. Editorial. Wilmington General Hospital v Manlove, 54 DE 15, 174 A2d 135 (1961). Wrenn K, Slovis CM: TennCare in the emergency department: the first 18 months. Ann Emerg Med 1996;27(2):231–233.

CHAPTER 156 THE WORK ENVIRONMENT IN EMERGENCY MEDICINE: STRESS, SHIFT WORK, AND AVOIDING BURNOUT Principles and Practice of Emergency Medicine

CHAPTER 156 THE WORK ENVIRONMENT IN EMERGENCY MEDICINE: STRESS, SHIFT WORK, AND AVOIDING BURNOUT George R. Schwartz Capsule Sensory Input Responses to the Environment The Patient and Family—People in Crisis

CAPSULE For years, physicians and nurses spoke of the emergency department as “The Pit.” This implies a seething, dangerous place set in some dank subterranean chamber. Many emergency departments (EDs) were indeed situated in badly lighted basement areas, poorly maintained, and often administratively forgotten. As medical sophistication has increased and respect for EDs and their function within a hospital has grown, newer facilities have evolved. Nonetheless, certain elements remain and are inherent in the profession; shift work, unplanned visits, stress or critical illness and death, and performance in a “fishbowl.” As physicians, nurses, and paramedical personnel devote their careers to emergency medicine, it is important to isolate some of the less desirable aspects and to attempt to lessen their impact upon those working within such an environment. If unattended, many of these correctable aspects can lead to or accelerate the burnout phenomenon often seen not only in emergency physicians and nurses, but in EMTs, paramedics, and ED secretarial and clerical workers.

SENSORY INPUT The amount of sensory stimuli present in an ED is often enormous, with people moving in every direction, telephones ringing, monitors beeping, and everywhere a feeling of “what will come next?”—all in a framework of time pressure. These stimuli not only affect the nervous system but also cause measurable physiologic effects, including peripheral vasoconstriction, hypertension, changes in bowel mobility, gastric acid and intestinal secretion, hormonal changes, and many others. In addition, there are the sights, sounds, and smells of human suffering and disease. In the ED, the staff is frequently exposed to the results of violence, mangled bodies, and death in the young. Although hospital staffs have become hardened to seeing elderly people dying, it is always difficult to avoid the severe emotional effect of seeing young people dead in the prime of their lives—or even before that, in the innocence of childhood. Certain degrees of stress and sensory input are important for function, but continued high stress leads to performance decrement, particularly when associated with sleep and circadian cycle alteration. Moreover, the 24-hour shifts at some EDs surpass the ability of most individuals to maintain efficiency. Such long shifts should be interdicted unless there is likely to be rest time, because performance decrement can affect patient care. With 24-hour work periods, there is a pattern of performance deterioration. The performance peak occurs after 6 to 10 hours and then drops off to a low point at 22 hours. Patients come to EDs unprepared, frequently upset, in crisis, worried, or desperately afraid. Frequently, they act out their emotional turmoil by directing hostility or anger at nurses or physicians. Added to the potential turmoil is the need for 24-hour coverage and consequent shift changes, as well as the new stressors of capitation, “health care reform” and “approval” requirements of managed care organizations. A situation easily manageable emotionally in the afternoon may require tremendous control at 4:00 AM, especially during the first few nights before personal patterns have readjusted at least partially. Conflicting demands from distant “gate-keepers” who gain rewards from denial of care can rapidly lead to frayed nerves. The effects of circadian cycle shifts in hospital personnel can be reduced. The greatest experience, however, comes from the military and the space program, in which studies were made of psychologic reactivity and performance at various hours. Those who change shifts frequently are in constant dysrhythmia and experience sleep disturbances, irritability, and decreased performance. Of particular importance is the decrease in frustration tolerance found in such people. In addition, with sleep alterations, the myriad diurnal or circadian rhythms, of which more than 100 are known, cannot readjust rapidly and never do in some cases, even with prolonged night work. The effects of sleep deprivation and fatigue may be severe. Attempts to enhance the ability to change circadian patterns (through diet, light adjustments, and sleep patterns) may be useful. Unfortunately, some physicians are unable to make such rapid adjustments and may be frequent users of sleep medications to aid their preparedness for night shifts. Susceptible emergency physicians occasionally develop a pattern of using stimulants to aid function and sedatives to “come down” and enhance the ability to sleep. Such “performance use” of psychoactive drugs is not an addiction in the usual sense because medication use is stopped during vacations or when job needs change. On the other extreme, addiction may become a serious problem in some emergency physicians. A survey of emergency physicians documented troubling findings ( 1). One-fourth of the more than 700 respondents felt “burned out.” More than 20% used medications, and almost 25% planned to leave the field within 5 years.

RESPONSES TO THE ENVIRONMENT For some personnel, the environment proves to be overwhelming, and after a brief period they choose other types of medical work. A phenomenon, however, has been observed in some of those who stay that, although milder, is similar to that seen in survivors of Hiroshima and soldiers from Vietnam. Lifton ( 2) called it “psychic numbing.” This phenomenon allows survival in a stressful environment, but with less compassion toward others. Medical education involves a great deal of desensitization. To work effectively, the physician and nurse must not respond too emotionally to a situation if a high level of functioning is to be preserved. A balance must be kept. The depersonalization and distance are necessary on some occasions, but the ability to shift gears psychically must be maintained. As psychic numbing proceeds, there is more concentration on technical tasks and less concern with patients and their feelings. There is more intellectualization, and human concerns become expressed in technical jargon. In the early stages of this numbing, tempers are raw and people irritable, but if it is allowed to proceed to a more advanced stage there is increased apathy and acceptance. The staff members in such units often experience changes in their lives, including less general empathy, poor sleep, more rapid automobile driving, and a feeling of hypervigilance. Although this may permit adequate function with emotional protection, the end results can be decreased morale and dehumanization of the emergency or critical care department, along with behavioral changes in some staff members. Bioengineering How can improvements be made? How can the environment be engineered to reduce the need for emotional protection? Certain aspects cannot change. People in crisis will continue to respond to their inner turmoil. Death is a reality that will not go away. The ED staff must function and, to some extent, protect itself against excessive emotional response. EDs, however, can be designed to reduce sensory stimuli. For example, soundproofing and newer types of carpeting can change sound levels significantly. Analysis of staff movement can allow development of a facility in which there is less walking and less confusion. Orderly procedures can help. Telephones need not ring (they can light or designed to make modest sounds). Pages are rarely needed. The environment should be “bioengineered” for staff and patient comfort and privacy to the extent possible. Those responsible for scheduling can do so with awareness of circadian cycles and can attempt to minimize transitions. There are some nocturnal people who

perform better on night shifts; extra compensation can be offered. Circadian-mediated disruption of functions and sleep deprivation are problems for emergency physicians. One study documented slower reaction times and longer time for intubation in a test setting ( 3). Special meetings and lunch rooms for the staff can be provided for emotional well-being. An important element is to allow expression of feelings and concerns. Staff meetings that offer an opportunity to discuss difficult problems, unexpected deaths, the management of grief, and so forth can reduce the need to block out such emotions. An actively involved social service department can assist, as can conferences with religious leaders. Conferences with psychiatrists, unless they are actively involved on a daily basis in the ED, are rarely necessary. In some instances, they may have negative effects on the staff.

THE PATIENT AND FAMILY—PEOPLE IN CRISIS When people make an appointment with their physician, they have time to prepare, even if it is a frightening experience. When an acute medical situation arises, however, be it sudden accident or illness, they arrive unprepared at an ED. Faced by sudden forces outside their control, they often have a feeling of helplessness and frustration. Waiting increases the level of tension, as does uncertainty. If death comes, it is unexpected and catastrophic for the family. The physician's traditional established relationship with the patient and family allows the physician to be a comforting person, but when the physician is someone the family doesn't know, it adds to their uncertainty. This places an additional burden on the emergency physician—the need to establish trust and rapport quickly. A great source of concern for the family is lack of knowledge about a patient's condition. When a loved one is behind closed doors, with no word from the nurse or physician, people think of the worst situation they can imagine. Similarly, patients on whom procedures such as blood tests and radiographs are being performed become fearful. Communication is essential—even if it is only to ensure that tests are still in progress. Medical staff may have a deep personal commitment to the skilled technology of medicine but must also understand its broader humanistic caring function. The ED staff must communicate to the greatest extent possible with the patient and family. Use simple, easy-to-understand words rather than long, elaborate technical explanations. The patient can be reassured, even if it seems likely that death is imminent. If the patient's condition is deteriorating rapidly, the family should be told at frequent intervals that the staff is doing its best but the situation is grave. This allows time for emotional preparation. It is important that the physician not delegate this task to others unless they cannot spare the few seconds required. If the clinical situation demands constant physician presence, a nurse can inform the family. It is a mistake to send someone with the least medical knowledge to do this. In the waiting area, families should be provided with comfortable chairs. Simple things such as the availability of warm drinks offer some comfort and a feeling of being in a caring environment. Human comfort should be the overriding concern in the design of waiting areas. Various developments have introduced ombudsmen, neighborhood health workers, and others who provide a conduit for information and who can decrease tension in the waiting areas. These workers should be employed when available, but not as a replacement for the physician's or nurse's involvement with the family. The truth is sometimes hard to confront that death is an inevitable part of life and that a patient dying despite the maximum concern and treatment by the physician and other staff does not represent failure. Part of the art of medicine, which must be used frequently in an ED, is the knowledge of how to provide comfort to the survivors. They may have great guilt if there was a delay in bringing the patient, or they may regret some small conflict they had with the person now dead and beyond apologies. The physician can do much at this time to reduce needless guilt and to offer support if their world seems to have crashed. Protocols should be established and telephone numbers posted of social service and clergy. A real danger is the delegation of the caring functions to nonmedical personnel, leaving a cadre of dehumanized technicians. Henry Ford originally began with one man seeing an automobile through all its stages. Then, for efficiency, he developed a highly specialized group of workers—but he knew the dangers and predicted that the development of specialization would lead to technicians concerned with their part, but not the whole. There is a parallel here with some aspects of medicine; although perhaps not to such an extreme extent, similar tendencies are obvious (e.g., an increased concentration on small specialty areas). In the ED, there is a continual need to look at the whole patient in the context of their family or friends. Whether the emergency is minor or major, they come seeking relief. The emergency staff is in a unique and privileged position to offer them relief and, if need be, to refer them into an appropriate system of continuing care. But “care” means just that. No organic disease exists apart from a person in distress. Patients do not consult physicians because certain organs are affected, but because they feel ill. Because of the variety of demands presently imposed on the emergency physician, we must await future developments that should reduce the number of patients presenting at EDs, which will increase the percentage of those with more serious conditions. “Fast-track” systems allow this type of sorting. This allows more time for each patient and permit the flowering of the art of the emergency physician. The specialty recognition of emergency medicine and its popularity with young physicians have resulted in enthusiastic practitioners who want “to be where the action is.” This attention and concomitant directed energy has already had great impact on improving emergency services. Perhaps the major emphasis so far has been on the “high-tech” components of the ED, as contrasted with the “high-touch” elements. Major changes for “high-touch” will result from continued attention to staff selection and educational programs as well as to allowing appropriate structural changes (e.g., inclusion of facilities for families, for psychiatric interviewing, and for staff communication). Structural changes, however, will remain of substantially less importance than the people (physicians, nurses, technicians, aides, clerks, etc.) who, through their awareness and attention, perform the “high-touch” functions. The emphasis must be on maintaining basic human caring. There must be increasing attention to the needs of particular population groups. A growing case in point relates to the suitable management of medical/surgical emergencies affecting the older population. Because the population group consisting of individuals 65 years of age and older is the most rapidly increasing segment (accounting for almost 25% of the population by 2020), accommodations for such special needs are inevitable. Early attention to such bioengineering can provide a better and more effective environment. References 1. Doan-Wiggins L: Practice satisfaction, occupational stress, and attrition of emergency physicians. Acad Emerg Med 1995;2:556–563. 2. Lifton RJ. “Home From the War, the Psychology of Survival,” Atlantic Nov. 1972, pp. 56–73. 3. Smith-Coggins R, Roserand MK, Buccino KR, et al: Rotating shiftwork schedules. Can we enhance physician adaptation to night shifts? Acad Emerg Med 1997;4:951–961.

Suggested Readings Adams OS, Chiles WD: Prolonged human performance as a function of the work-rest cycle. Aerosp Med 1963;34:132. Angeil M, Kassirer JP: Quality and the medical marketplace—following elephants. N Engl J Med 1996;35:883–885. Aschoff J: Circadian rhythms in man. Science 1965;148:1247. Bartter F, Delea CS, Halberg F: A map of blood and urinary changes related to circadian variations in adrenal cortical functions and normal subjects. Ann NY Acad Sci 1962;98:969. Beranek LL: Noise reduction. New York: McGraw-Hill Book Co., 1960. Bernard VW, Ottenberg P, Redl F: Dehumanization: a composite psychological defense in relation to modern war. In: Schwebel M, ed. Behavioral science and human survival. Palo Alto, CA: Stanford University Press, 1965. Brantigan JW: Physician fatigue—some lessons from the cockpit. Hosp Phys 1973;9:13.

Broadbent DC: Effects of noise on behavior. In: Harris CM, ed. Handbook of noise control. New York: McGraw-Hill Book Co., 1957:1–34. Bulger RJ: The quest for mercy—the forgotten ingredient in health care reform. West J Med 1997;167:362–373. Cooper GD, Adams HB, Cohen LD: Personality changes after sensory deprivation. J Nerv Ment Dis 1965;140(2):103. Corcoran DWJ: Influence of task complexity and practice on performance after loss of sleep. J Appl Psychol 1964;48:339. Czeisler CA, Moore-Ede MC, Coleman RM: Rotating shift work schedules that disrupt sleep are improved by applying circadian principles. Science 1982;217:460. Falk SA, Woods NF: Hospital noise levels and potential health hazards. N Engl J Med 1974;289(15):774. Flannery RB, Penk WR: Program evaluation of intervention approach for staff assaulted by patients. J Trauma Stress 1996;9:317–324. Gallery ME, Whitley TW, Klonis LK, et al: A study of occupational stress and depression among emergency physicians. Ann Emerg Med 1992;21:58–64. Goldberg R, Boss RW, Chan L, et al: Burnout and its correlates in emergency physicians. Acad Emerg Med 1996;3:1156–1164. Grevin F: Post-traumatic stress disorder, ego defense and empathy among urban paramedics. Psychol Rep 1996;79:483–495. Hale HB: Adrenal cortical activity associated with exposure to low frequency sounds. Am J Physiol 1952;171:732. Harrison TR: The most distressing symptoms. JAMA 1966;198(1):52. Help SS: Experience of stress in accident and emergency nurses. Accid Emerg Nurs 1997;5:48–53. Kales A: Psychophysiological studies of insomnia. Ann Intern Med 1969;71:625. Kleitman N: Sleep and wakefulness. Chicago: University of Chicago Press, 1965. LaDou J: Health effects of shift work. Occupational disease—new vistas for medicine. West J Med 1982;137:525. Levi L: Emotional Stress. New York, American Elsevier Publishing Co., 1967. Luby ED: Biochemical, psychological and behavioral responses to sleep deprivation. Ann NY Acad Sci 1962;96:71. Luce TS: Vigilance as a function of stimulus variety and response complexity. Hum Factors 1964;6:101. Monk T, ed.: Sleep, sleepiness and performance. New York: John Wiley, 1991. Rogers D: “The Doctor Himself Must Become the Treatment,” Pharos Oct. 1974, pp. 124–129. Rusnak RA, Hamilton GC, Allison EJ Jr: Autonomous departments of emergency medicine in contemporary academic medical centers. Ann Emerg Med 1991;20:680. Schwartz GR: Psychological and behavioral responses of hospital staff involved in the care of the critically ill. Crit Care Med 1974;2(1):48. Schwartz GR: Psychic numbing in the emergency department. Emerg Med Serv 1975;4(1):31. Schwartz GR, Garrison SS: Family dynamics in geriatric crises. In: Bosker G, Schwartz GR, Jones J, et al. Geriatric emergency medicine. St. Louis: Mosby Yearbook, 1990:574–578. Selye H: Stress and disease. Science 1955;122:625. Steinbrook R: The role of the emergency department. N Engl J Med 1996;334:657–658. Verhaegen P, Maasen A: Health problems in shift workers. In: Johnson LC, Tepas DI, Colquhoun WP, et al., eds. Biological rhythms, sleep and shift work. New York: SP Medical & Scientific Books, 1981:271–282. Von Gierke HE: On noise and vibration exposure critera. Arch Environ Health 1965;11:327. Weiss JJ, Silday MF, Roes B: Effect of individual and work characteristics of EMTs on vital sign changes during shiftwork. Am J Emerg Med 1996;14:640–644. Wilkins WL: Group behavior in long-term isolation. In: Appley MH, Trumbull R, eds. Psychological stress. New York: Appleton-Century-Crofts, 1966. Wilkinson RJ: The effect of lack of sleep on visual watch-keeping. Q J Exp Psychol 1960;12(1):36. Williams RH: The costs of visits to emergency departments. N Engl J Med 1996;334:642–646. Williams S, Dale J, Glucksman E, et al: Senior house officers work-related stress, psychological distress and confidence in performing clinical tasks in accident and emergency. Br Med J 1997;314:713–718. Young GP, Sklar D: Health care reform and emergency medicine. Ann Emerg Med 1995;25:66–74. Zauticke JL, Neylan VD, Hart RG: Stress in the ED clerical staff. J Emerg Med 1996;14:247–249. Zauticke JL, Fracker LD, Hart RG, et al: Denial of emergency department authorization of potentially high risk patients by managed care. J Emerg Med 1997;15:611–617.

CHAPTER 157 THE ROLE OF THE EMERGENCY DEPARTMENT DIRECTOR Principles and Practice of Emergency Medicine

CHAPTER 157 THE ROLE OF THE EMERGENCY DEPARTMENT DIRECTOR Stephen J. Dresnick Capsule Introduction Desired Attributes of a Medical Director Responsibilities of the Medical Director Quality Assurance Education Group Management Uneasy rests the head that wears the crown. (William Shakespeare, Richard II)

CAPSULE The ideal emergency department (ED) director is a composite of different professions. Just as the skilled emergency medicine practitioner is proficient in a wide variety of medical specialties, the skilled ED director must be a superb clinician, a negotiator, an educator, a manager, an innovator, a counselor, and sometimes even an accountant and an architect. It is hoped that this description will not dissuade physicians from aspiring to become ED directors. The job, although demanding, can be among the most satisfying in medicine. A thorough understanding of the responsibilities and the skills needed can enable prospects to understand the position beforehand and allow them the opportunity to be properly prepared for its responsibilities. Clear expectations will surely lead to great expectations.

INTRODUCTION Hospitals have different types of contractual arrangements with emergency physician groups. These include single-hospital groups, multiple-hospital regional groups, and large multihospital national groups. In evaluating successful EDs throughout the United States, one common denominator can be identified in each regardless of the size of the group: each contract is only as good as the medical director overseeing that contract. The number one career goal of graduates of emergency medicine residency programs is to become a director of an ED. Manpower statistics in emergency medicine indicate that there are fewer than 3000 residency graduates at this time, yet there are more than 5000 acute care hospitals with EDs. When asked why they feel qualified to be a director when they are fresh from residency programs, most graduates respond that the main reason is they are residency graduates. Although they may certainly be most knowledgeable of the latest advances in medicine, a variety of skills essential to a successful medical director are not often taught during residency. A contract for a single-hospital group represents between $500,000 and $1 million in revenue. Clinical and management skills necessary to run a moderate-sized business are the cornerstone of the necessary attributes for a medical director. Although the position is sought after and coveted by those who desire to “advance their careers,” many physicians find they are not suited to the position once they have obtained it, and return to the relative peace of patient care. The disillusionment of these physicians occurs partly because the glamour they sought does not exist and partly because they were given the position without the proper tools and training to accomplish the job successfully. To be successful as a medical director, one must make the distinction between administrative and clinical responsibilities for the individual and the group, whether it be a single-hospital or a large multihospital group. The administration of an ED requires a great deal of time. Depending on the size of the contract and the complexities of the institution, medical directors may spend anywhere from 25 to 90% of their time performing administrative duties. Even small contracts with fewer than 12,000 patient visits annually require dedicated administrative time. It is not possible to perform administrative duties while working clinically. Besides the logistical problems of this, it may lead to potentially dangerous situations in which patient care is disrupted to handle an administrative issue and the physician forgets to order the proper medication or neglects to ask about drug allergies. In this era of attention to providing “service” to patients, particularly when the contract is fee-for-service, patients should not be asked to wait while the ED director goes to a meeting. Protected administrative time is essential to the success of the contract. Out of necessity, a medical director will and should work more weekdays and fewer nights and weekends. Other members of the group must be made to understand the importance of this work to the overall success of the contract. Some single-hospital groups, in their desire for “total democracy,” rotate the position of medical director among members of the group on a yearly or even quarterly basis. This practice, while noble in intent, is generally not a good idea. It is essential that the administration and the other members of the medical staff know at all times that there is a leader of the group, one who is committed over the long haul to making the ED run smoothly. This is not to say that all members of the group should not be involved. On the contrary, all members of the group should be active participants in medical staff affairs. It is reasonable to designate certain administrative duties such as quality assurance, continuing education, and certain committee membership to other members of the group. Such activities on the part of other members of the ED physician staff are necessary also for the overall success of the contract.

DESIRED ATTRIBUTES OF A MEDICAL DIRECTOR Some say that great medical directors are born, but careful analysis reveals that the most important reason for success is proper training. Clinical Expertise First and foremost, a medical director must have excellent credentials in training and experience. The medical director must set the standard for the care given in the ED. If the director is not practicing state-of-the-art medicine, who will field the complaints when the medical director is involved? This is not to say that anyone cannot and will not make mistakes; rather, the medical director must be able to address clinical issues that arise in the ED. These issues include patient complaints and concerns raised by other members of the medical staff. Additionally, the medical director will have to oversee a quality assurance program for the ED. Recruitment of new physicians is easier if the director's clinical expertise is respected by the other members of the group. Communications Skills Although good communications skills may be difficult to teach, they are essential to a successful medical director. The key to effective communication is to be a good listener. All too often, medical directors do not take the time to listen to feedback from patients, administration, and other members of the medical staff. New medical directors, particularly those fresh from residency, occasionally lack this skill and are sometimes too eager to implement change without first getting all of the parties to “buy into” the process. As Machiavelli said, “Nothing disrupts the lives of men more than change.” A medical director must have the maturity to know when to push an issue and when to leave it for another day. Perhaps the most important aspect of good communication is the need for the medical director to interact with the medical staff. This requires more than attendance on committees. It requires a sincere effort to meet all of the members of the medical staff and to make periodic visits to their offices. A medical director should make it a point to have as many meals as possible in the doctor's dining room to establish this camaraderie with the medical staff. Attendance at social events also helps to strengthen the bond between the medical director and the staff. Planning and Implementation Skills Planning is more than coming up with an idea today and carrying it out tomorrow. Today's EDs have multimillion dollar budgets. As more hospitals realize the revenue potential of the ED, they will ask the medical director to develop new programs such as fast tracking and occupational medicine programs to enhance patient volume and revenue. A working knowledge of the hospital budgeting process and cost allocation is vital to the planning process. The hospital will look to the medical director

for the implementation of these programs, and they must develop a vast knowledge of these programs because hospitals usually do not have inhouse expertise. Management Expertise This skill is usually the most ignored when considering an individual for the position for medical director, perhaps because in the past there have been so few individuals with significant experience. For success in today's environment, this attribute is essential. The medical director must have the management skills to manage a department with revenues often exceeding a million dollars. Additionally, a typical ED has 20 to 30 staff members, including clerks, nurses, and physicians. Unifying and motivating this many people toward a common goal can be difficult. Knowledge of Administrative Issues The medical director must become knowledgeable of a variety of ED administrative issues. These include state and federal regulations such as medical screening and transfer provisions required by the COBRA law. Issues constantly present themselves that require in-depth understanding of the issues involved to resolve. Reimbursement, order writing, and preauthorization are but a few examples. Further knowledge must extend into areas involving HMOs and managed care entities and understanding concepts such as “capitation.” Only by deep physician involvement can the quality in managed care organizations be maintained and enhanced ( 1). Career Commitment Perhaps the single most important attribute is career commitment. As discussed, there simply are not many qualified medical directors with experience. It is essential that the medical director be committed not only to the practice of emergency medicine but also to the hospital and the position. Nothing jeopardizes a contract more than a medical director who takes responsibilities casually and for whom this is only a part-time position.

RESPONSIBILITIES OF THE MEDICAL DIRECTOR The list of responsibilities of a medical director is virtually endless because they are responsible for virtually every aspect of the activities of the ED. Some of the responsibilities outlined may need to be delegated to other members of the group. To avoid confusion, it is always prudent to delineate the specific responsibilities of the medical director in a job description ( Table 157.1).

Table 157.1. Medical Director Job Description

Clinical Direction The director is responsible for setting the clinical standards that will be practiced in the ED. Clinical policies must be established so that all members of the group approach problems in the same manner. Physician staffing patterns must be developed, and may include double coverage or an on-call system to handle peak times. Continuing education is essential in the modern ED. Much of the on-site teaching comes from issues that arise from the quality assurance program. Although medical directors may not teach all of these sessions, they must oversee the content. Advanced Cardiac Life Support (ACLS) continues to be sought not only by the ED staff but by members of the medical staff and nursing staff as well. It is important that the emergency physician group be the leaders of this educational effort. ED Personnel The relationship between the medical director and the nonphysician staff of the ED is complex at best. No other area of the hospital has nurses and physicians working so closely together for such extended hours. The medical director should have significant input into the staffing of the ED, including numbers, length of shifts, and specific individuals. Although this relationship may not exist at many institutions, it certainly does at the most successful ones. The ED is equivalent to other physicians' offices in that the staff is a representative and an extension of the physician staff. It is important that they convey the same caring attitude that the physician staff does. The medical director should work closely with nursing administration in ensuring that nursing policy and procedures are well delineated and adhered to because the nursing staff does, in fact, work under the direction of the physician staff. This is particularly true with the implementation of triage and discharge criteria. The medical director should also have significant input into nursing continuing education. Interdepartmental Relations The ED is the proverbial fishbowl, and incidents are known throughout the entire hospital in a matter of minutes. Because virtually every department cares for patients who may be in or even pass through the ED, most physicians feel their perspective is the one through which the department should be viewed. The director must listen to all of these viewpoints and attempt to reach a consensus on a variety of issues. This is particularly true with medical staff departments because all of the medical staff feels they were “emergency physicians.” In addition to listening, the medical director must attempt to coordinate the activities of each department to the benefit of the ED. This includes on-call schedules for the medical staff and working with the laboratory and radiology departments to ensure priority handling of ED patients. Public Relations The medical director is the “point man” for various public relations issues. As more hospitals become market-oriented with their EDs, community outreach programs become more common. The director is called upon to address community groups and even employers of large companies in an attempt to establish a relationship with these groups and the hospital. Another area of public relations is in the handling of patient complaints. This is extremely important because it not only makes patients happier about their experience but also helps to mitigate potential medicolegal problems, which may arise from an unpleasant experience in the ED. Another major target group with whom the medical director will need to interface are the members of the EMS community. Although many locals have protocols that dictate to which hospitals patients will be taken, it is clear that “borderline” patients are usually taken to hospitals with whom there is a good relationship. This relationship requires more than simply providing free meals to the paramedics. Today's paramedics wish to be treated with respect, look for constructive feedback when they bring patients into the department, and have a sincere desire to expand their knowledge. A good medical director can coordinate a program to address their needs. ED Operation A director must become familiar with all aspects of ED operation. This includes budget development, staffing formulas, space requirements, department design, and a working knowledge of potential new services. Although the director may not be administratively responsible for all of these, it is always in the best interest of the physician group to participate in all aspects of the department's operations. Although the details of the various aspects of ED operation are beyond the scope of this

text.

QUALITY ASSURANCE No area is more important in today's environment for a medical director than quality assurance (QA). The Joint Commission for the Accreditation of Healthcare Organizations has made quality assurance the number one priority for the coming years. It is essential that each ED have in place a QA program that monitors the care given by each physician on a process as well as outcome basis. Clinical standards or parameters are being developed by the American College of Emergency Physicians and these, once completed, will have to be included into the QA program. QA has as a benefit the ability to identify areas that may require additional education for the physicians or nursing staff. A successful QA program has a significant effect on the potential liability of the physician group and may even help reduce liability insurance costs.

EDUCATION The medical director should oversee an ongoing educational program for the ED physician and nursing staff. Specific topics may be identified by a QA program or by specific patients who present to the department. Regular programs should also be implemented for other members of the hospital staff to make them aware of issues that confront the ED. Although advanced cardiac life support (ACLS) and advanced trauma life support (ATLS) may not be requirements for the ED physician staff, particularly for those trained in and board certified in emergency medicine, they continue to be excellent programs, and the ED should take the lead in teaching other members of the hospital staff.

GROUP MANAGEMENT The medical director is essentially managing a multiphysician practice. A variety of issues will confront the medical director regardless of the size of the group. The director must become familiar with reimbursement guidelines and billing procedures. Even if the group is on an hourly rate, improvement in physician billing is vital in future contract negotiations. If the physicians code their own charts, the medical director must audit this process to ensure that all physicians comply with various third-party regulations and are not exposed to liability for fraud and abuse. The medical director of a single hospital group must also manage the financial affairs of the group, making sure that payroll is prepared in a timely manner, that all payroll taxes are deducted and deposited, and that all bills are paid on time. The director must also develop a budget for the group and prepare the necessary financial reports for the other members of the group. Perhaps the most troubling issue confronting medical directors is the issue of liability insurance. Many policies are offered from a wide variety of companies. Choosing an incorrect policy has short-term and long-term implications for members of the group. The medical director should be well-versed in this area to guide the other members of the group through what may sometimes be a difficult decision. Even directors of departments managed by large multihospital groups will need the input of the medical director in the areas of risk management and claims evaluation. An understanding of the tort system will enable the director to provide the appropriate counseling to other members of the group during what is a trying experience for physicians as well as their families. Medical directors should be involved in the development and negotiation of the contract. It is frequently beneficial to the group for the director to identify issues that should be included in the contract language. The director of a single hospital group has the additional burden of developing specific language and actually negotiating the contract. This process requires that a medical director possess all the skills discussed and have a detailed understanding of the contracting process. Many groups are made and lost in the outcome of contract negotiations. Skill in this area is vital to the successful renewal of the contract. References 1. Ruttner R: Must good HMOs go bad: search for checks and balances. New Engl J Med 1998;338:1635–1639.

Suggested Readings Couch JB, ed: Health care quality management for the twenty-first century. Tampa, FL: American College of Physician Executives, 1991. Frew SA: Patient transfers: how to comply with the law. Dallas TX: American College of Emergency Physicians, 1991. Goldfield N, Nash D: Physician leaders: past and future challenges. Tampa, FL: American College of Physician Executives, 1989. Inglehart JK: The national committee for quality assurance. N Engl J Med 1996;335:995–999. Janiak BD: Role of the physician director. In: Matson TA, ed. The hospital emergency department: returning to financial viability. Chicago: American Hospital Publishing, 1986. Kerr A, Mittman BS, Hays RD, et al: Quality assurance in capitated physician groups. JAMA 1996;276:1236–1239. Mayer TA: The emergency department medical director. Emerg Med Clin North Am 1987;5:29. Mayer TA: Roles and responsibilities of the emergency department medical director. In: Matson TA, ed. Hospital emergency department: returning to financial viability. Chicago: American Hospital Publishing, 1991. Meyer T: The emergency department medical director. In: Saluzzo R et al, eds. Emergency department management: principles and applications. St. Louis: CV Mosby, 1997. Shore MF, Levison H: On business and medicine. N Engl J Med 1985;313:19–21.

CHAPTER 158 TIPS FOR CONTINUOUS QUALITY IMPROVEMENT Principles and Practice of Emergency Medicine

CHAPTER 158 TIPS FOR CONTINUOUS QUALITY IMPROVEMENT Thom A. Mayer Philosophical and Practical Tenets of CQI Emphasis on Design and Redesign—Kaizen Deming's 14 Essential Points

PHILOSOPHICAL AND PRACTICAL TENETS OF CQI Continuous quality improvement (CQI) arose out of the study of traditional management approaches by Shewhart ( 1), Deming (2,3), Juran (4,5,6 and 7), and Ishikawa (8). As their values began to be applied in a practical fashion, it became clear there were key features inherent to any CQI approach regardless of the specific formulation, including: 1. 2. 3. 4. 5.

Customer focus (meet or exceed expectations). Statistical application of knowledge of variation. Focus on process (including “benchmarking,” “comparisons to leaders”). Design and redesign of process (Kaizen). A redefinition of leadership (collaborative, facilitative).

Shewhart's Contribution Use statistics to reduce variation or adjust to it (e.g., changing emergency department (ED) census in winter, use practice protocols when scientifically studied, etc.). Juran's Analysis Focus on process using: (a) supplier, (b) input, (c) action, (d) output, (e) customers. Any process can be analyzed in this manner. For example, look at the process of obtaining a radiograph in the ED. This process begins with a supplier, the emergency physician, who determines the need for a radiograph based on clinical examination. In systems that use advanced triage, the supplier may be an appropriately trained triage nurse. The supplier provides input, the radiograph request, which results in a series of actions: an ED clerk enters the order into the computer; the x-ray technician reviews the order and processes it; the patient then returns to the ED at which time the ED clerk and/or physician is informed that the radiograph is completed. It is clear this process consists of a series of subprocesses, which can also be analyzed and improved. All of the previous actions result in an output, which in this case is the radiograph, as well as the physician interpretation of that radiograph. Each of these outputs have an effect on the customers, which includes external and internal customers. Viewed in this way, the simple process of obtaining an ED radiograph constitutes a series of supplier-customer relationships, which are interdependently linked to result in a quality outcome.

EMPHASIS ON DESIGN AND REDESIGN—KAIZEN Another of the key concepts in CQI is the emphasis on design and redesign. As Donald Berwick noted, “Every process provides information by which that process can be improved” (9). In the past, quality assurance (QA), improvement, and quality is attempted by routing out “bad apples” rather than by improving processes and systems. However, quality is more than the absence of adverse events; elimination of outliers in a system may have minimal impact on mean performance. Quality exists to the extent that value is added in the course of the process itself. The design and redesign concept in continuous quality improvement works on analyzing the system in such a way that the “average performance” improves rather than placing emphasis primarily on the outliers with bad outcome. Such shifts can occur only when there is a team approach to improving customer service, statistical application of knowledge of variation, the understanding of process, and the application of design and redesign for improvement. A key concept of Kaizen is that the redesign of process is not primarily a management function, but a function of the caregivers (providers) themselves ( 10). In traditional management systems a central role of the leader is to redesign the system and exhort personnel to follow the process. In the CQI model, the process of redesign includes management, but also involves the staff members responsible for care in an essential fashion. Therefore, the distinction between “those who do” and “those who think” is fundamentally altered in the CQI system. As Berwick noted, in a CQI system the provider has two jobs, their “job” and the job of improving the process in an ongoing fashion ( 9). The redefinition of leadership in the CQI model involves a number of transitions for leaders and managers that can be difficult. Among these transitions are moving from more external models of leadership to those that are more collaborative and facilitative. Whereas leaders traditionally have been viewed as those who are instrumental in systems redesigns, the CQI model envisions the leader more as a coach, consultant, and facilitator, who assures that the providers have the appropriate tools and techniques to redesign the processes in which they participate on an ongoing basis.

DEMING'S 14 ESSENTIAL POINTS 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

Create constancy of purpose for improvement of the product and service. Adopt a new philosophy of refusing to allow defects. Cease dependence on inspection and begin to use statistical control. Require suppliers to provide statistical evidence of quality—Do not award business primarily on the basis of price, but quality. Improve service continuously and forever. Institute training and retraining of all providers. Give all employees the proper tools to do the job right. Encourage communication and productivity. Break down barriers between staff: Encourage different departments to work together. Eliminate posters and slogans. Use statistical methods to continuously improve quality and productivity. Eliminate all barriers to pride in workmanship. Provide ongoing retraining to keep pace with changes. Clearly define top management's permanent commitment to quality (3).

Criticisms of Quality Improvement Programs Despite the adoption of quality improvement principles by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and its acceptance in the healthcare industry in general, there have been criticisms leveled at continuous quality improvement. The most important criticism of continuous quality improvement is that EDs are typically structured with at least three, and often four or five reporting structures ( 11). Many EDs have a physicians structure, a nursing staff structure, a business office structure to accommodate registration, administration, as well as ancillary services (laboratory and radiograph), which report through a different mechanism. Such potentially conflicting needs can produce fragmentation in terms of the overall purpose of the ED's commitment. If there is not a clearly agreed to and delineated constancy of purpose among all of the components of the ED team, any quality improvement program will have difficulty at best and is doomed to failure at worst. Outside consultants are sometimes useful in clarifying conflict and respective roles, and allowing the varying structures to see how they may have opposing needs or methods. The reality of quality improvement is that there must be top level commitment, dedication, and, frankly, courage to assure that the senior

management of the facility remains committed to the quality improvement initiative on an ongoing basis. One of the most frequently heard complaints of CQI is that it is the latest “management style du jour” or “intellectual MTV.” The presumption in this criticism is this is simply the latest management trend, which is sure to pass away as quickly as most such fads do. However, there is substantial reason to believe that CQI as a management philosophy serves as an effective bridge between the rational/scientific management schools and human relations/social science theories of management. The acceptance of quality improvement as a model for healthcare delivery by JCAHO is an example of the likely permanence of this philosophy in the medical profession. The ten points they propose for problem solving are ( 12): 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Assign responsibility. Delineate scope of care. Identify important aspects of care. Identify indicators. Establish thresholds for evaluation. Collect and organize data. Evaluate care. Take actions to solve problems. Assess actions and document improvement. Communicate relevant information to organization-wide quality improvement program.

Finally, one of the most pervasive myths concerning quality improvement is that it simply “takes too much time” ( 13). In fact, quality improvement does require a substantial amount of commitment to relearning a new approach to management, which frees us from the more classic traditional management models. The majority of CQI programs take 3 to 5 years to pay substantial dividends, particularly because the processes themselves must be reengineered to allow for maximum profitability as a legitimate outcome of the statistical understanding of variation that quality improvement entails. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Shewhart WA: Economic control of quality of manufactured products. New York: Van Nostrand, 1931. Deming WE: Quality, productivity, and competitive position. Cambridge, MA: Massachusetts Institute of Technology Press, Center for Advanced Engineering Study, 1982. Deming WE: Out of the crisis. Cambridge, MA: Massachusetts Institute of Technology Press, Center for Advanced Engineering Study, 1989. Juran JM: Leadership for quality executive handbook. New York: The Free Press, 1989. Juran JM: The quality trilogy: a universal approach for managing for quality. Quality Progress 1986; August: 19–24. Juran JM: Juran on planning for quality. New York: The Free Press, 1988. Juran JM: Quality control handbook. New York: McGraw-Hill, 1988. Ishikawa K: What is total quality control? The Japanese way. Englewood Cliffs, NJ: Prentice Hall, 1985. Berwick DM: Continuous improvement as an ideal in healthcare. N Engl J Med 1989;320:53–56. Batalden PB, Buchanan ED: Industrial models of quality improvement. In: Goldfield N, Nash DB, eds. Providing quality care: the challenge to clinicians. Philadelphia: American College of Physicians, 1989:133–159. 11. Kovner AR: The case of the unhealthy hospital. Harvard Business Review 1991; September–October: 12–25. 12. Joint Commission on Accreditation of Healthcare Organizations. Accreditation manual for hospitals. Chicago: JCAHO, 1996. 13. Berwick DM, Godfrey AB, Roessner J: Curing healthcare: new strategies for quality improvement. San Francisco: Jossey-Bass, Inc., 1990.

Suggested Readings Ackoff RL: Creating the corporate future. New York: John Wiley and Sons, 1981. Berwick DM: Peer review in quality management: are they compatible? QRB 1990; July. 246–251. Berwick DM: Quality convictions: beyond the beginning. Presented to the Quality Improvement Network Meeting, April 21, 1993, The Healthcare Forum, San Francisco, CA. Camp RC, Tweet AG: Benchmarking applied to healthcare. Jt Comm J Qual Improv 1994;20:229–238. Camp RC: Benchmarking: the search for industry best practices that lead to superior performance. Milwaukee, WI: American Society for Quality Control, Quality Press, 1989. Drucker PF: The new productivity challenge. Harvard Business Review 1991; November–December: 69–79. Dubnicki C, Williams JB: The people's side of TQM. Healthcare Forum Journal 1992; September–October: 55–61. Fralic MF: Creating new practice models and designing new roles: reflections and recommendations. JONA 1992;22:7–20. Garvin DA: Building a learning organization. Harvard Business Review 1993; July–August 78–91. Hall G, Rosenthal J, Wade J: How to make reengineering really work. Harvard Business Review 1993; November–December: 119–131. Hammer M, Stanton SA: The reengineering revolution: a handbook. New York: Harper Collins Publishers, Inc., 1995. Hammer M, Champy J: Reengineering the organization. New York: Harper Collins Publishers, Inc., 1993. Kennedy M: Reengineering and healthcare. The quality letter for healthcare leaders. September 1994;2–10. Lathrop J: The patient focused hospital. Healthcare Forum Journal 1991; May–June: 76–78. Lowenthal JN: Reengineering the organization: a step by step approach to corporate revitalization. Milwaukee, WI: ASCQ Press, 1994. Mayer TA: Quality improvement in emergency medicine. In: Schwartz GR, Cayten CG, Mangelsen M, et al., eds. Principles and Practice of Emergency Medicine. 3rd ed. Philadelphia: Lea & Febiger, 1993. Mayer TA: Industrial models of continuous quality improvement. Emerg Med Clin North Am 1993;10:523–547. Morris D, Brandon J: Reengineering your business. New York: McGraw-Hill, Inc., 1993. Patrick P, Alba T: Healthcare benchmarking: a team approach. Quality Management in Healthcare 1994;2:38–47. Pellegrino ED, Thomasma DC: The virtues in medical practice. New York: Oxford University Press, 1993. Pellegrino ED, Thomasma DC: For the patient's good: the restoration of beneficence in healthcare. New York: Oxford University Press, 1988. Reeves M, Tory E, eds: Beyond the basics of reengineering: survival tactics for the 90's. Institute of Industrial Engineers. White Plains, NY: Quality Resources, 1994. Sahney VK, Warden GL: The role of CQI and the strategic planning process. Quality Management in Healthcare 1993;1:1–11. Senge PM: The fifth discipline: the art and practice of the learning organization. New York: Doubleday, 1990. Spendolini MJ: The benchmarking book. New York: American Management Association, 1992. Wakefield DS, Cyphert ST, Murray JF, et al: Understanding patient centered care in the context of total quality management and continuous quality improvement. 1994;20:152–161. Zimmerman D, Skalko J: Reengineering healthcare: a vision for the future. Franklin, WI: Eagle Press and Zimmerman and Associates, 1994.

J Comm J Qual Improv

CHAPTER 159 FAST-TRACK CARE AND OCCUPATIONAL MEDICINE Principles and Practice of Emergency Medicine

CHAPTER 159 FAST-TRACK CARE AND OCCUPATIONAL MEDICINE David Brooke* Capsule Advantages Disadvantages Getting Started The ED Triage System Occupational Medicine

CAPSULE The purpose of establishing a “fast track” as part of an emergency department (ED) is to give a relative degree of priority to minor cases. There are many reasons why this direction may be taken and also some difficulties to be overcome. As a busy ED develops, the point at which a fast track can be established must be identified. Then, as it grows, it is in constant need of adjustment and change.

ADVANTAGES Most EDs need some form of double coverage when the annual total of patients seen is approximately 30,000. Many EDs already have double coverage for some shifts on busy days, such as weekends, before this number is reached, but after this double coverage, some time every day is usually required. Systematic care of minor illnesses and injuries, usually known as fast track care but with other potential names ( Table 159.1) is a solution to this problem. The establishment of a fast track is not usually considered until the ED is seeing another 10,000 to 15,000 patients, for a total of 40,000 to 45,000. By this time, these EDs are usually accounting for a one-fourth to one-third of all hospital admissions, and about one in every six patients presenting to the ED requires admission. This means that a considerable number of patients are at least moderately ill and may require close attention and a workup with laboratory, x ray, scans, and so on.

Table 159.1. Potential Names for the Systematic Care of Minor Illnesses and Injuries

Therefore, the majority of patients, with such problems as ankle sprains, upper respiratory infections, earaches, and lacerations, may well have to wait for some time before the busy physician is able to attend them. If these patients can be diverted to a separate area, where they do not have to await the investigation and management of major cases, speedy management for minor illness and injury allows a more appropriate, shorter length of stay. This is obviously attractive to patients. When there is a competitive element in obtaining patients, this may be a marketing tool for the hospital. When walk-in clinics have been set up to operate in the community, many patients still prefer to go to the hospital if there is a fast-track area. It provides flexibility if their illness is more than can be managed on a fast track in that they can be directed to the main ED without all the problems of doing this from a walk-in clinic. Again, many patients do not think of themselves as having a “minor illness,” and prefer to go to a hospital ED, but readily accept being directed to the fast-track area. Another advantage is that the staff involved in a fast track, whether they are physicians, nursing staff or clerical staff, tend to focus on caring for minor cases, concentrate their equipment for these, and ultimately can become efficient in managing this focused area.

DISADVANTAGES Frequently, fast track has to be sold carefully to the medical staff because they may look on it as a threat to their own practices in dealing with similar cases. The arguments and strategies in achieving success in persuading the medical staff to accept a fast track often need careful planning and differ in each particular area. Another disadvantage is that in the hours when the fast track is open and all the minor cases are removed from the main ED, the nursing staff and emergency physicians in the main ED will be dealing almost constantly with major cases or cases taking a considerable time, without the relief of a few minor problems to manage. It must be recognized that the physicians are unable to see as many patients per hour in these circumstances. An approximate figure of 2.5 patients per hour is suggested as a maximum for emergency physicians working in a main ED where there is a fast track filtering off the minor cases. There is no question that the stress in the main ED is greater on all staff when there is no relief in the form of minor cases. However, the fast track physician may well be able to see six or even seven patients an hour, depending on how efficiently the system has been set up to work.

GETTING STARTED The chief movers in initiating a fast track are the nursing director of the department, the administrator responsible for the ED, and the medical director of the department. After juggling some initial ideas, these three must then introduce the concept to their own particular staff and then to all the support services that will be required, once it has been accepted that they will go ahead. Any development in an ED requires the cooperation and understanding of the support services, as well as the firm commitment of all staff and administration involved. Radiology It is assumed that the department has its own x-ray unit or is adjacent to the hospital radiology department, which provides services directly and as a priority to the ED. The cooperation of the radiographers is needed to collect patients from the fast track and return them with their films to the fast track, giving a degree of priority despite the fact that they are minor cases. Laboratory Most fast tracks within an ED do not need a great number of laboratory tests. An occasional blood draw may be sensible, however, along with a few cultures and sometimes a urine specimen. Most people feel that a fast track should not be clogged by patients waiting for laboratory results, so that nearly all patients needing laboratory work are usually referred to the main department.

Central Supply Suture sets may be required in some abundance, together with other sets for minor procedures, and these may differ from those in the main ED. A good relationship with central supply is needed, particularly to obtain their flexibility and quick response when large numbers of patients arrive. Alternatively “disposable” suture sets may be used. Pharmacy A separate stock of drugs needing constant replenishment is essential. The pharmacy may want some say in their control and to be assured that scheduled drugs are controlled properly. Some arrangement for rapidly available drugs for the indigent needs consideration. Security EDs are among the main areas needing support by the hospital security services, and the fast track is no exception, so that senior security staff members should be involved in the planning of the new unit. Other Support Other support will be required from hospital computer and data control and the housekeeping service to maintain cleanliness in the fast track and a constant supply of linen. With HMOs, clerical services have increased along with changing responsibilities. Occasionally, there may be a need for the social services department to assist patients on the fast track. In this area, hospital volunteers can be helpful, and it may be a good initial place to start because the patients are not severely ill and the stress level tends to be lower than in many other places in the hospital. Before getting the architects to produce their drawings, it is valuable to develop a list of the illnesses and injuries with which patients present that can be sent by the triage nurse directly to the fast track ( Table 159.2).

Table 159.2. Fast Track Criteria

Obviously, the particular setting of any ED may indicate additions to or subtractions from this particular list. One ED physician felt strongly that pelvic examinations should be managed on the fast track and another that the slit lamp should be used only in the main ED and that, therefore, all eye cases should avoid the fast track. These feelings are well worth exploration and trial. These two particular cases are mentioned because they have some effect on the design of the department. Staffing NURSING STAFF The nursing tasks required are fairly basic, and licensed practical nurses (LPNs) or nursing assistants may well be ideal for this area. The nursing director of the department is ultimately responsible for the nursing. They may feel that a registered nurse (RN) should be placed separately as overall manager of this area. The question may arise whether to stay with fixed staff on the fast track, who devote all their shifts to this area alone, or rotate the nursing staff through the fast track from the main ED, and there may be a wish to try both methods for a time. Most fast tracks end up with a fixed staff who come to know and run the fast track and do not rotate. CLERICAL SUPPORT Depending on how busy the area becomes, one or two full-time registration clerks may be needed, as well as a clerk in the department who will be responsible for the charts, phone calls, contacting radiology and occasionally the laboratory, and the myriad other clerical functions that arise during each shift. MEDICAL STAFF This would seem to be an ideal area for physician extenders. To have a physician assistant or nurse practitioner in this area for the whole time that it is open is ideal. Some hospitals and medical staff insist on a high degree of supervision of physician extenders, initially one of the double-covering physicians should release themself from the main ED on a fairly regular basis to check on the fast track patients. If this is unacceptable, a full-time physician is necessary. Board-prepared and board-certified emergency physicians tend not to get sufficient job satisfaction from working exclusively in the fast track area, although this may be ideal for older emergency physicians nearing retirement. An alternative, however, is to use family practice physicians with, for example, some upgrading of their skills regarding laceration repairs, radiology, or use of the slit lamp. With these upgraded skills, family practice physicians appear to be ideal. The combination of a family practice physician and a physician extender during the busy hours of the day provides optimal patient service. The important point about staffing is the need for flexibility and constant reevaluation. The nurses, physicians, and clerical staff who are present at the opening of a fast track may not be the right people or in correct numbers when the fast track has been operating for 1 or 2 years, has doubled in size, and, for example, is dealing with many more lacerations than originally envisioned. Appropriate patient management within a reasonable period needs frequent changes to any fast track area. Design With the exception of extremely large EDs, the vast majority of fast tracks can be run with 4 to 10 patient rooms. Figure 159.1 is an example of a fast track layout.

Figure 159.1. Example of a fast-track layout.

If an ED is seeing 45,000 patients and it is decided to open a fast track, it should be possible to filter off about one-third of the patients to the fast track area within 1 or 2 years. This one-third is usually seen within a 12-hour period, although later this may be extended to a 16-hour period daily. So the 15,000 patients making up the one-third will mean an average patient load of 41 patients a day. On some days, this may be 30 and on others it may be 50, but the average is about 4 patients an hour, and, under the usual circumstances, four rooms are enough for this track. However, an ED that is seeing 90,000 patients and has one-third filtered off to the fast track and is open for 16 hours a day, sees an average of 5.1 patients per hour. For the sake of argument, this particular hospital sees most of its patients who require pelvic examinations, and performs a considerable amount of laboratory work, on the fast track. To avoid clogging the system, this fast track may require 10 rooms for patients, so that those waiting for test results do not interfere with patients who can be managed more speedily. But even in this busy fast track, it is not impossible to operate with just four patient rooms. Although a curtain divider can be used in these rooms, it is better, from the point of patient privacy, to have individual rooms with doors that close and are relatively soundproof. The use of sheetrock is not expensive in general terms, and a lot of flexibility in these rooms is not needed. In addition, of course, the constant cleaning of curtains that act as dividers can become a nuisance. The size of each patient room need not be more than about 8¢ × 8¢. But this may depend on statutary requirements. In some states 10¢ × 10¢ is a minimum size. This allows a proper examination couch, so that the physician can examine the patient from the right-hand side; a wash basin with running water; and linen cupboards, together with other accessories. One chair for an accompanying relative fits into this space. A wall otoscope can be fitted if necessary, or the physician and physician extender can carry their own. This type of room is serviceable for most patient problems in a fast track area. In addition, one or two special rooms must be provided. Lacerations are much more easily dealt with in a bigger room, and it may be possible to place two carts in the laceration room, so that two patients can be managed at the same time. Running water and more cupboard space for the additional equipment that must be stored is obviously necessary. Eyes and ears can be managed on the fast track in one room as long as a slit lamp is provided, with two stools and an ENT chair that can be placed at various angles, so that eyes can be conveniently examined as well as ENT patients. A room 10¢ × 12¢ is ideal for this, with visual acuities performed in the hall. An eye tray with all its equipment takes up little space, but some ENT equipment may need a separate cupboard. If pelvic examinations are to be performed on the fast track, a room 10¢ × 10¢ would be more appropriate. Suitable lighting attachments, placement of the table to ensure patient privacy, and an additional curtain running across inside the main door to the room are valuable. Apart from the individual patient rooms, the hub of the fast track area is the nurses' station. A counter of reasonable length that can house a computer terminal is essential. The charts of new patients to be picked up by the physician or physician extender need placing to suit the efficient running of the department, as do trays for patients waiting, laboratory work to be ordered, orders on patients, and patients to be discharged. It may be that patient discharges may best be completed at the nurses' station, or there may be a preference for the nurses to do these in the patient rooms. The cupboard for medications should be nearby, as should a store for various dressings and ice packs for wounds. In a busy fast track, a clock is usually placed in the nurses' station, one purpose of which is entering times on the charts. Physician and physician extenders need a small room with a counter and 3 to 4 x-ray viewing boxes. A room 8¢ × 5¢ is more than adequate for two people to do all the paper work required, read the radiographs, and have a small library and other books as needed. A door that can be closed is useful but not essential. If a dictation system is available, this is an ideal area for the physician to dictate. A waiting area with 10 to 12 chairs is usually adequate and is often conveniently placed with the registration clerk at one end with the computer and the various forms required. Ideally, the waiting area is broken up into small areas of three to four chairs, so that the patient, friends, and relatives can talk to one another conveniently, and interesting wall decorations, potted plants, and artistic pottery may all make a potentially drab area more interesting and welcoming. Charges The charges must be established and agreed on with the hospital administration. A contract group of physicians and physician extenders, or those who are direct employees of the hospital, may have one bill sent out to cover the hospital charge for the nurse's time and skill, use of equipment and use of the room, and the physician charge. Even in a fee-for-service contract, the hospital administration, from a marketing point of view, may wish to have some say in the physician charges. Regarding the level of services, the physician charges usually cover problem focused (99281) or expanded problem focused (99282 and 99283). 99281 level of service is defined as a level of service pertaining to the evaluation and treatment of a condition requiring only an abbreviated history and examination. This can cover a cold, a bee sting with no obvious complications, a superficial abrasion, and other such minor problems. An expanded problem focused service (99282 and 99283) refers to the evaluation of a circumscribed acute illness or the periodic reevaluation of a problem including an interval history and examination, the review of the effectiveness of past medical management, the ordering and evaluation of appropriate diagnostic tests, the adjustment of therapeutic management as indicated, and the discussion, findings, and/or medical management. This would cover ankle sprain with radiograph, an eye examination, any condition needing laboratory work or an x ray, or a respiratory infection requiring examination of ENT and the chest. Most fast tracks use “detailed” (99284) level of service less commonly, as in a patient found to have something more serious than was supposed initially when referred to the fast track. For example, a young woman with minor chest pain might turn out to have a pneumothorax, or a blow to the lower leg of 2 or 3 days' duration might turn out to have significant cellulitis and, perhaps, need intravenous antibiotics. Most of these patients, however, are referred to the main ED under the usual circumstances. A pelvic examination usually falls into the 99284 level of service. Any patient receiving multiple laboratory tests or laboratory tests with radiographs may also receive a 99284 charge, although most fast tracks refer these to the main ED. Examples of actual charges from two busy fast track EDs, in which there is a combined fee covering the physician, the personnel, and the room, are as follows: $52.50 for intermediate$85.00 for intermediate $43.00 for a brief $30.00 for a brief $48.50 for a limited $40.00 for a limited 52.50 for intermediate $85.00 for intermediate These are suggested as guidelines only and are not proposed to induce price fixing that may infringe antitrust laws. In addition to the charges for levels of service, additional charges should be made for equipment and for specific physician procedures. For example, this would cover

the use of ice packs, elastic bandages, various dressings, and suture material from the equipment list; and then physician charges for laceration repair, the amount depending on the site and the size and covered in the procedure coding for emergency medicine. Additional examples are foreign body removal from the eye, subcutaneous tissue, ear, and nose; and the drainage of abscesses. Radiologists provide their own charge for reading the radiographs although, with some negotiation, these charges may be lower on the fast track than in the main ED. Fast Track Medications The suggested outline for medications available on a fast track managing about 25,000 patients a year is given in Table 159.3. It should be noted this fast track does not deal with women requiring pelvic examination or patients who may potentially require considerable laboratory work.

Table 159.3. Fast Track Formulary

Some fast tracks are being used as substitutes for outpatient blood transfusions, intravenous (IV) antibiotics, and the use of regular IV oncology drugs. The patients involved do not seem suitable for fast-track management because these procedures conflict with the overall concept of managing patients quickly. These patients should be treated in another part of the hospital. Medical Staff Use of Fast Track The question arises as to whether the medical staff should be permitted to use the fast track to manage their own patients. There is no reason why they should be excluded if they accept the basic concept of moving patients quickly and do not, for example, settle their patients to wait for hours while they finish their office work. With clear guidelines, a reasonable arrangement can usually be made to negotiate this with the medical staff. Minor pediatric problems, for example, can be ideally managed by pediatricians here. Dictation System This is not the place to argue the obvious merits of a dictation system, but it is worth emphasizing this system does save considerable time for fast track physicians and physician extenders and provides a clear record that can be useful to the medical staff and others. The presence of a dictation system is as important on the fast track as in the main ED. Quality Assurance A system for chart review for quality assurance of the nursing staff, physicians, and physician extenders is important. A director of nursing in the department should be responsible for setting up a regular monthly nursing review, and the department medical director should arrange a regular review of the physician and physician extender charts, picking them out at random and also looking at the management of specific clinical problems. For example, physicians working on the fast track are usually less experienced at reviewing radiographs than ED physicians, and this may need special attention.

THE ED TRIAGE SYSTEM Decisions must be made as to where the patient chart and registration are to be performed. Ideally, patients for the fast track should be identified the moment they present to the ED area, and a separate system devised for the nursing assessment and obtaining vital signs. Whether this should be done at the entrance of the main ED area or referred to nurses working in the fast track must be decided in each ED. Additionally, registration must be appropriately arranged so that, again, too much patient time is not taken up before the patients are admitted to the fast track area to await the physician or physician extender. If possible, this should be considered early in the plans for a new ED or, certainly, for the initiation of a fast track. Otherwise, there is a danger that it may be eliminated by default and all patients channeled through the regular ED triage and registration systems. Turnaround Time A reasonable goal for average time from the moment a patient walks into the ED area until discharge from fast track is less than 60 minutes. This provides a reasonable prospect for an average American to obtain management of a minor illness or injury that can be fitted into an average day without too much disruption. The whole concept of a fast track is to be consumer-oriented, and it is suggested that a goal similar to this should be set in each fast track area and regular time evaluations performed. Conclusion The time from the conception of a fast track to be added within an ED until the unit can actually open is probably a minimum of 2 years. A planning team involving all the personnel who may be involved can usefully obtain help from other fast tracks with an emphasis on looking at their errors rather than their successes. Ultimately, an understanding of the system would then allow the involvement of architects, who should not be permitted to function in a vacuum without the planning team. Then follows the budgeting process, which may be arduous in view of the increasing competition for funds in today's hospital industry. The building always takes longer than expected and must be constantly watched, particularly the many minor points in placement of, for instance, washing facilities and equipment that serves the staff and patients in a functional way. Finally, clear direction and support to assist competent nursing and medical staff are essential with the incorporation of a process, so that the staff actually working in the area can be prime movers in suggesting appropriate changes and adjustments as the fast track grows.

OCCUPATIONAL MEDICINE Introduction As emergency medicine has developed, there has been a trend toward subspecialization in areas including toxicology and EMS systems. Occupational medicine is

also an area of increased focus for emergency physicians. Occupational medicine, a natural outgrowth of the ED, is an area that is clearly underserved. The Institute of Medicine Subcommittee on the Physician Shortage in Occupational and Environmental Medicine concluded that there is a shortage of 3100 to 5500 physicians in this area ( 1,2). Although the role of a physician working in this area often varies substantially from the more rapid pace of recognition and response in the ED, many environmental conditions, when left untreated, become emergencies. For example, ongoing toxic exposure in the workplace may manifest as an attack of asthma or an acute dermatologic condition. Occupational and environmental medicine is developing because of need rather than major commitment from medical centers or academic leadership. Therefore, it resembles emergency medicine as a specialty based primarily on patient and community need. Environmental medicine incorporates most, but not all, aspects of occupational medicine and also includes understanding and treatment of the myriad physical, biologic, and chemical agents encountered inside and outside the workplace. Occupational medicine shares the need to know areas of toxicology, epidemiology, public health, and preventive medicine, but the focus tends to be more narrow, dealing with companies and professions and the particular health aspects of these facilities. For example, a physician specializing in health aspects of aviation and pilots may well be concerned with the risks of air pollution for jet engines and carbon monoxide levels in workers, but is ordinarily little concerned about the general problems of air pollution within a city. Although the need is great, obstacles in the practice of occupational medicine should be addressed. Frequently, the physician is working for an employer, and, therefore, the usual physician-patient relationship becomes physician-employer-patient. Not only does this facet alter the ability and desire of patients to reveal important but potentially harmful (in terms of employment) information such as drug or alcohol use; it places the physician in possible adversarial relationships involving workmen's compensation claims and disability evaluations. Such difficulties can be mitigated through careful planning and need not be permanent obstacles. For example, there can be assurances of confidentiality and, when adversarial situations arise, they can be referred to another physician who is independent of the employer-employee relationship. On a practical level, although specialists are needed in occupational and environmental medicine as educators, researchers, and skilled clinicians, the current financial environment mandates clinical focus on them as the only ones substantially reimbursed or funded at this time. Emergency physicians who can provide occupational medicine services can alternate them with ED practice if such practice can provide a needed hiatus when a change of pace is needed or desired (e.g., pregnancy, lifestyle needs, etc.) The current situation is dynamic as to special certifications. Only the American Board of Preventive Medicine provides specialist certification, and various boards (ABIM, ABFP, ABEM) are considering certificates of special competence ( 3). There is a movement within emergency medicine to offer such certificates in special competence. This would mean an increased focus on such concerns not only in Annals of Emergency Medicine and other journals for specialists in the field, but increased focus at national and specialty meetings. As with many changes of subspecialization, other modifications are necessary to blend a practice of occupational medicine with that of emergency medicine, including equipment needs (e.g., special hearing tests or laboratory capability to test for certain types of exposures) and intellectual needs. An example of the latter is the focus on each employer to determine specific medical needs and hazards and to tailor-make programs that can offer the most benefit, as well as to offer emergency treatment of minor injuries. The effort has already been effective in many locations. In view of the stress and “burnout” potential of working solely in the ED for more than 10 years and the higher numbers of emergency physicians planning to leave the field, it seems not only useful but helpful to retain physicians within the field and provide the change of pace often believed to be an antidote to burnout ( 4). This development in emergency medicine meets a demonstrated need for occupational and environmental physicians and offers a model for handling occupational stress within its own specialty. Detailed history forms are available as well as extensive sources for additional information ( 5). The interested reader is referred to this extensive review. * George R. Schwartz, MD provided the occupational medicine section of this chapter.

References 1. 2. 3. 4. 5.

Castorina J, Rosenstock L: Physician shortage in occupational and environmental medicine. Ann Intern Med 1990;113:983. Institute of medicine report addressing the physician shortage in occupational and environmental medicine. Washington, DC: National Academy Press, 1991. Rosenstock L, Rest KM, Benson JA Jr, et al: Occupational and environmental medicine—meeting the growing need for clinical services. N Engl J Med 1991;325:924–927. Gallery ME, Whitley TW, Klonis LK, et al: A study of occupational stress and depression among emergency physicians. Ann Emerg Med 1992;21:58–64. Newman SL: Occupational illness. N Engl J Med 1995;333:1128.

CHAPTER 160 TIPS FOR CONTRACTING WITH MANAGED CARE ORGANIZATIONS Principles and Practice of Emergency Medicine

CHAPTER 160 TIPS FOR CONTRACTING WITH MANAGED CARE ORGANIZATIONS Thom A. Mayer

I. The basic concept of the managed care organization (MCO) is to lower cost by A. Transferring risk to physicians. B. Choosing low-risk patients. C. Contracting with low-cost primary physicians and specialists. II. Initial Steps A. Meet with hospital administration to discuss overall strategy. B. Negotiate directly with MCO within basic strategy guidelines. C. Keep hospital and MCO aware of pivotal role of emergency medical service (EMS) systems in controlling costs by suitable emergency department (ED) treatment. The MCO tends to take the opposite position from the physician, i.e., to an emergency physician, the patient defines the emergency while to many MCOs, this approach is too costly. As a result they frequently require preauthorization to treat, or transfers to participation hospitals, as well as large copayments. The COBRA/EMTLA legislation requires medical screening, but the MCO can refuse to authorize payment. In any case, by creating such barriers, they create financial bonanzas, and at the least, carry a great deal of interest-bearing money (the “float”) while they negotiate their rejection of care, which can take months or years. III. Contract Tips A. Always get an experienced attorney to hammer out final details. B. Clearly define preauthorization requirements. Otherwise, you can spend fruitless hours on the telephone while your sick patient deteriorates. C. Finances need to be upfront with no hidden charges, downcoding, or penalties, and a time period for claims to be paid, with a penalty if there is excessive delay (e.g., interest charge). D. Get protection against retrospective denials of payment (after preauthorizations). E. Agree on CPT codes (usually get from AMA CPT) and provide a mechanism for settling disputes. F. Protect against insolvency (bankruptcy) of the MCO. G. Have an overall mechanism for dispute resolution. Mandatory arbitration is often required by the MCO and this effectively limits legal rights. These clauses (mandatory arbitration) can be crossed through or modified. H. Assure ability to modify fee schedules. I. Capitation agreements in the ED can be risky. (These offer a fixed price per member per month and can be disastrous if there are penalties for “over utilization” or if clinics in the area close so the ED gets excessive patient flow.) However, the promise of a fixed monthly income has encouraged this trend. It is the extreme example of the physicians assuming all the downside risks. J. Use consultants as needed. They may be expensive in the short term, but economical over the long term with the MCO. Suggested Readings American College of Emergency Physicians Board of Directors: Managed healthcare plans in emergency care. Ann Emerg Med 1988;17:97–98. American Medical Association CPT Editorial Panel: American Medical Association current procedural terminology—95. Chicago: American Medical Association, 1994. Dresnick S: Managed care systems in the emergency department. In: Schwartz GR, Cayten CG, Mayer TA, et al., eds. Principles and practice of emergency medicine. 3rd ed. Philadelphia: Lea and Febiger, 1992. Dresnick S: Emergency departments in the integrated healthcare system. Presented to the ACEP Management Academy, May 18, 1995, Boston, Massachusetts. Eiglehart JK: Physicians in the growth of managed care. N Engl J Med 1994;331:1167–1171. Foster Higgins Survey. The Wall Street Journal, 2 March 1993. Goldsmith JC, Goran MJ, Nackel JG: Managed care comes of age. Healthcare Forum Journal 1995; September–October: 14–24. Iglehart JK: The American health system: managed care. N Engl J Med 1992;327:742–747. Karpiel M: Managed care in emergency medicine: understanding the new economics and opportunities. Dallas, TX: American College of Emergency Physicians, 1995. Krohn RW: Achieving the best—and avoiding the worst—of capitation contracting. Group Practice Journal 1995;44:18–24. Mayer T, Dresnick S: Contracting with managed care. In: Saluzzo R, Mayer T, Strauss R, et al., eds. Emergency department management: principles and applications. St. Louis: Mosby, 1997:341–360. Rodwin M: Conflicts in managed care. N Engl J Med 1995;332:604–607. Shaw KN, Selbst SM: Indigent children who are denied care in the emergency department. Ann Emerg Med 1990;19:59–62. Shaw E, Stepnick L, Cowden V, et al: Capitation strategy. Washington, DC: The Advisory Board, 1994. United States General Accounting Office: Emergency departments: unevenly effected by growth and change in patient use. Gaithersburg, MD: U.S. General Accounting Office, 1993. Waldo D: Health spending through 2030: three scenarios. Medical Benefits February, 1992. Young GP, Sklar D: Healthcare reform in emergency medicine. Ann Emerg Med 1995;25:666–674.

CHAPTER 161 FINANCIAL ASPECTS OF EMERGENCY MEDICINE Principles and Practice of Emergency Medicine

CHAPTER 161 FINANCIAL ASPECTS OF EMERGENCY MEDICINE James S. Cohen Introduction Independent Contractor Verses Employee Taxes Expenses and Deductions Retirement Accounts How to Calculate Total Compensation Malpractice Insurance ED Characteristics Personal Financial Considerations Should I Use a Headhunter? What About Preparing My Own Tax Return? Read Your Contract (Before You Sign) Summary

INTRODUCTION A number of job-related factors have financial implications for the practicing emergency physician. This chapters' focus will be on which factors to consider, how to analyze them, what to be aware of and also—beware of. There may be large differences between how much a job pays, what the total compensation is worth, and, factoring in circumstances beyond direct pay and benefits, what the whole picture is worth. Afterwards, you should be able to assess the true value of any given job offer as well as be aware of many factors with financial implications that might otherwise escape notice. First address whether or not you are to be paid as an independent contractor or as an employee.

INDEPENDENT CONTRACTOR VERSES EMPLOYEE STATUS You need to be aware of your employment status predominantly because of multiple tax implications dictated by the Internal Revenue Service (IRS). The IRS strongly emphasizes the degree of control within the employer-employee relationship as its major determinant of employment status. For example, the person who cuts your lawn once per week is an independent contractor. They are responsible for the purchase, upkeep, and maintenance of the equipment; transport of the equipment to and from your property; disposing of cuttings; and hiring and supervision of assistants. They perform the work on their schedule, not yours. They control just about every aspect of the job in an effort to produce the final product—a well manicured lawn. You, the property owner, are mostly concerned with the final product and are largely uninterested in the ways and means by which it is accomplished. In fact, if the yardmen got sick they could have someone else substitute without your knowledge or permission. If, however, you are an owner of a large estate you may have need for full time help to keep the property in shape. You may own all the landscaping equipment, pay for all repairs, and provide housing. You may make out the schedule each week for the help—Monday, cut the lawn; Tuesday, trim the privet hedge around the tea garden, etc. In this latter case your control over the workers and work would result in their being considered employees. As a resident you were hired with employee status—your paycheck had a gross pay (your annual salary divided by the number of pay periods), a net pay (the actual check), and a paystub detailing all the deductions. Most of the deductions were for federal tax, state tax, perhaps city tax, Social Security, and FICA. If your employer offered a pension plan to which you chose to contribute there may also have been a deduction for that as well. At the end of the year you received a W-2, which is a summary statement of all the year's paychecks. Your employer sends this information to the IRS who in turn uses this in processing your tax return. If you are an independent contractor you theoretically work for yourself and are paid in lump sum payments for your work with no deductions of any kind. In emergency medicine typically this amounts to hours worked times pay rate. In the past it was common for emergency medicine physicians to be employed as independent contractors. Contract managers strongly preferred this for two reasons—financial and legal. Financially, they could avoid the expense and headache of providing benefits such as malpractice insurance, medical insurance, disability insurance, etc. They would also save the expense of the employer's share of Social Security and FICA as well as save the administrative expense of filing a lot of tax forms. From a legal point of view, independent contractor status makes it easier for a contract manager to terminate services without having to provide a reason, although this point will vary widely depending on the details of your particular contract. From a malpractice point of view, having you as an independent contractor might make it a little easier for a contract manager to insulate himself from liability. If you get sued, the contract manager will assert that they only provided your services and had no control over how you practiced medicine. A good lawyer, however, will destroy this defense. Despite all of this there has been a steady trend toward being hired as an employee. This trend is the result of IRS victories in the tax courts as well as the perceived threat of what major damage the IRS might do if a contract manager lost a case. Unfortunately, this has led to a particularly bad category of employment created by a few contract managers who convert their physicians from independent contractor status to employee status with no benefits at all. In this worst of all case scenarios, you will have neither an employee-sponsored pension plan or the right to set up a self-employed pension plan (KEOGH). Your ability to put away pension money will be reduced to an Individual Retirement Account (IRA), which has a much lesser benefit than the aforementioned plans. You will no longer be able to deduct a lot of expenses and will have to secure all of your benefits on your own with after-tax dollars; often at higher prices than an employer can secure. If you stay in this situation for your emergency medicine career you will be in dire straits in retirement.

TAXES As an independent contractor you are responsible for paying all taxes. You must file quarterly estimated tax statements and pay the prorated amount of what you owe to the IRS. These statements are due April 15, June 15, September 15, and January 15. These four returns are in addition to your annual return due April 15. You will likely also have to file the equivalent return for your state taxes, unless you live in the state of Alaska, Florida, Nevada, South Dakota, Texas, Washington, or Wyoming, which presently have no income tax. If you forget to pay or underpay what you owe, you will be hit with some heavy penalties and interest. At the end of the year, you will receive a 1099-Misc form from whoever paid you. This amount was also reported to the IRS as a business expense of whoever paid you. As an independent contractor the IRS considers you as an employer of yourself, the employee. Consequently, you have to pay both ends of the Social Security and FICA tax. As an employee your Social Security equaled 6.2% and your FICA equaled 1.45% of your gross pay. As an independent contractor you pay 12.4% Social Security and 2.9% FICA. In 1995, the ceiling for Social Security was $61,200. For 1996 it is $62,700. The ceiling for Social Security goes up every year. FICA has no ceiling. On a gross earned income of $150,000 you would owe $6,857 in taxes beyond what you would owe with the same income earned as an employee. In actuality you will get back some of this amount because one-half of your self-employment tax (SS + FICA) can be used as a tax deduction on form 1040 in the section entitled “Adjustments to Income.”

EXPENSES AND DEDUCTIONS As an independent contractor you must pay for a number of items that would generally be provided by an employer. The big ticket items are malpractice insurance and medical insurance. In addition, you may want to consider purchasing disability and life insurance. Malpractice insurance is totally deductible as a business expense on schedule C (Profit or Loss from Business). Approximately 30% of any medical insurance you pay is deductible on Form 1040 under the heading “self-employed health insurance deduction.” If you can get your employer to pay for health insurance it generally costs a lot less. This is because when they buy it for you they get to deduct 100% of the premiums as a business expense. In addition, most employers benefit from the lower group rates. Unfortunately, this will probably not happen as an independent contractor because if you start to get any benefits the IRS will classify you as an employee. As an independent contractor you can deduct from taxable income, on Schedule C, a variety of expenses. Typical deductions include malpractice premium, professional licence fees, conference fees, CME or profession-related travel expenses, payments to accountants and lawyers, and miscellaneous items such as expenses for medical journals, books, uniforms, and equipment. Two deductions liberally used in the past deserve a word of warning. These are travel expenses and business use of your home. If you regularly travel from home to hospital and back, this is considered commuting, not business travel, and is not deductible. However, if you travel to a locum tenens those expenses would be deductible to the extent you were not reimbursed. Business use of your home office (expenses of mortgage, property taxes, utilities, furniture) has become increasingly difficult to justify to the IRS and unless you are a contract manager with no other office or do patient follow-up at an office in your basement, you would do well to avoid this deduction. The fact that you regularly bring home charts to review or use your home office to read medical materials does not qualify. The IRS argues the expenses mentioned previously are personal in nature and you would incur them regardless of your working at home or not. Notwithstanding this you can comfortably deduct expenses directly related to your profession such as telephone calls, postage, stationery, or a computer you use predominantly for professional purposes. If you claim business use of your home (Form 8829) be prepared for an IRS audit, not just of this one item, but of your entire return. For the most part you

can also deduct expenses you incur as an employee. However, instead of getting a simple direct deduction from your gross income you must report these expenses on Schedule A “Itemized Deductions” under the heading “unreimbursed employee expenses.” To start, the IRS has a disallowance equivalent to the first 2% of adjusted gross income (this translates into $3,000 disallowed using the model income of $150,000). Second, the IRS has a formula whereby any income in excess of $114,700 reduces your allowed itemized deduction. This has the resultant effect of raising your effective marginal tax bracket.

RETIREMENT ACCOUNTS The most common type of retirement account for self-employed persons is a KEOGH account. You can contribute 20% of your net income up to a ceiling of $150,000. This works out to a maximum contribution of $30,000. You must open this account with a qualified financial institution such as a bank, a brokerage house, or a pension fund management company. Whatever you contribute will be deducted from your taxable income on your federal return and may be deductible on the state return (varies by state). You have the ability to invest in individual stocks, bonds, mutual funds, etc. You cannot directly invest in hard assets such as gold bullion or real estate, although you could invest in their financial equivalents such as stocks in gold mines or Real Estate Investment Trusts (REITs). All retirement plans share the important feature of deferral of all income and capital gains, and, therefore, these plans grow at a much greater rate than ordinary taxable accounts. For example, $1000 invested at 8% in a taxable account for a person age 35 in the 37.5% marginal bracket will grow at a 5% rate after taxes. At age 65 the account will be worth $4,321. The same money invested in a tax deferred account will grow to $10,062. Applying these typical figures to approximately 30 years of contributions can result in huge differences in ultimate retirement plan values. If you are fortunate to make a wise decision given investment in a retirement account you can sell it to lock in the gain and not have to pay a cent of taxes. In addition, in the event of bankruptcy, divorces, malpractice judgments not covered by your policy limits, and other financial disasters you may be afforded some degree of asset protection for assets held in retirement accounts. Of course, as with all retirement accounts, when you begin to withdraw you have to pay taxes at whatever rate may then be in effect. To discourage you from early withdrawals the IRS charges a 10% penalty if you take out any money from a retirement account before age 59. However, they don't want you to keep it earning tax deferred income forever so at around age 70 you must withdraw a certain minimum amount each year, which is roughly equivalent to the fraction created by dividing one by the actuarial number of years of your remaining life. These withdrawals are subject to federal, state, and local taxes. As an employee you can contribute $2,000 per year to an IRA. If you had a nonworking spouse you could contribute $2,250 up to 1996. Starting in 1997 you can contribute $4,000 even if your spouse does or does not work. An IRA account is set up and managed by you. Your employer has no control over your IRA. You have the right to contribute to an IRA as long as you have earned income as an employee. Filling out a few simple forms at a bank or brokerage house is all it takes to open an IRA. The deadline for making a contribution is April 15 of the year following the year for which you are contributing. You do need, however, to have the IRA set up by December 31 of the contribution tax year. However, you should make your contribution as early as possible (ideally, in January of each tax year) to gain the maximum benefit of tax deferred savings. If you have no other pension plan related to your income as an employee then your IRA contribution will be fully tax deductible regardless of your income. If you participate in an employer sponsored pension plan then there is a phase out range of deductibility based on your income. For single people the phase out income range is $25,000 to $35,000. This means that if you made less than $25,000 you can deduct the whole $2,000 even though you also participated in an employer sponsored pension plan. If you made more than $35,000 you can not deduct any of the $2,000. Deductibility within the range is determined by a sliding scale formula on a worksheet. The same principles apply for married persons but the phase out range is $40,000 to $50,000. Because of the tremendous value of tax deferred investing you should contribute to an IRA even though you may be denied a deduction in the current year. A $2,000 annual contribution earning 8% made from age 25 to age 65 will grow to $518,000. Your employer may also offer you a pension plan from which payroll deductions will be made. This is called a contributory plan, an example of which is a 401k plan. You will not pay any federal taxes on contributions to such a plan; state deductibility varies by plan. In 1995, the limit of your payroll deductions to such a plan was $9,240. In addition to this your employer may contribute certain amounts of your salary such as 2%, 4%, 6%, etc., depending on the plan. A lot of federal regulations that govern the rules for any given employer are based on a complex formula and, of course, the generosity of your employer. You should be aware that the noncontributory (employer) derived portion of your plan value is subject to a vesting period. The vesting period represents how long you have to wait before the money is yours for keeps. If you leave the employer before the end of the vesting period you are liable to lose everything they contributed. Given the high turnover in emergency medicine jobs, especially in the years immediately postresidency, a short vesting period (2 years or less) is highly desirable. Unlike a KEOGH or IRA in which you exert total control the types of investments you can make, employer sponsored plans are limited to certain preset choices such as money market funds (least yield and highest safety), bond funds, stock funds, etc. If you get a “hot tip” on a particular stock you will not be able to use this type retirement account to make an investment.

HOW TO CALCULATE TOTAL COMPENSATION When you are paid as an independent contractor your total compensation is merely the sum of all your checks. As an employee you need to calculate the value of your “package” where package equals salary plus benefits. You need far more detail than just asking about your salary and how many shifts you will work each month. You need to arrive at one number—the number of hours actually worked after allowances for vacation, holidays, sick days, personal days, and CME. Also, be certain that the way you do your calculations is the same as your employer. In fact, it would be a good idea to show your calculations to your employer to avoid any misunderstandings. As an example, suppose you are told that the job pays $150,000 per year based on a 40-hour week, 4 weeks vacation, 8 paid holidays (8 hours per day), 2 personal days (8 hour days), 5 sick days, 1 week CME. Your actual hours worked would be 52 × 40 = 2,080 minus 4 × 40, 8 × 8, 2 × 8, 5 × 8, 1 × 40 = 1,760. You also get malpractice insurance paid for (worth $12,000 per year), medical insurance (worth $5,000 per year), CME expenses paid worth $1,500), life and disability insurance (worth $500 per year), and an employer sponsored pension plan to which your employer will contribute 4% of your salary (worth $6,000 per year). So you have total compensation of 150K in salary and 23K in benefits equals 173K. Dividing this by your hours worked would give gross compensation of about $98 per hour. To be more accurate, you would add the value of not having to pay the employer half of Social Security/FICA. This is roughly $4 per hour bringing the total to $102 per hour. You should also get your benefits explained in detail. For example, how are sick days treated? Do you have to pay back the person who covered for you? Can you accumulate sick days and apply them to future time off? What happens if you exceed your sick day allowance? When does your disability policy kick in?

MALPRACTICE INSURANCE There are two basic types of malpractice coverage—occurrence and claims made. The former covers your actions with reference to a period of time you practice. For example, if you have an occurrence policy paid for the calendar year 1996 you would be covered for any patient you saw in 1996. You would be insured for the rest of your life for malpractice claims arising from patients seen in that one year. A claims made policy covers a period of time with respect to when a claim is filed against you regardless of when you may have treated the patient. If you have a claims made policy for 1996 and do not renew it in 1997 and subsequent years then you would be unprotected against a suit by any patient you saw in 1996. Once you start claims-made type coverage you are locked into this type of insurance because insurance coverage of your actions expires at the end of each policy period. To obviate the necessity of perpetually buying claims-made policies you can make a one time payment to purchase a tail policy. This tail policy provides retroactive coverage for those years of claims-made policies that would have otherwise expired. If you are provided claims-made malpractice insurance by an employer learn what the provisions are for tail coverage. There are four possibilities. First, there may be a prepaid tail, which covers you forever. This arrangement is almost equivalent to an occurrence type policy. Second, you may be provided tail coverage for a limited period such as 5 years. Although most claims are filed within 5 years of the date of the alleged malpractice you should recognize you will be unprotected when the coverage period expires. This is important because the statute of limitations for filing a claim, which normally would expire within 5 years, may be extended in special circumstances such as actions involving minors or the discovery rule. Minors have until their 21st birthday to file, which is one of the reasons obstetricians have such high malpractice premiums. The discovery rule focuses on the date a patient learns—“discovers”—the alleged malpractice as opposed to the date the patient was seen. For example, if you did something in your treatment to make a patient infertile but she did not learn about it until 10 years later, because she did not try to get pregnant until 10 years later, then the statute of limitations clock would start to tick at this delayed date. The third possibility is you are told that when you leave your employer they will buy you a tail policy. This is inferior to the purchase of a prepaid tail policy insofar as you are dependent on the employer's actions after you are gone. If they become insolvent and do not buy the promised coverage you are exposed. The fourth possibility is you are given no tail coverage. You should not work under this circumstance. Because just one lawsuit could knock you out financially, you should familiarize yourself with what type of coverage you have and obtain proper documentation of such.

ED CHARACTERISTICS Beyond your clinical hours worked, there are some other time factors that deserve attention. How long might you stay in the ED after the shift ends due to “cleaning up” cases best disposed of by you, making detailed signout rounds to the oncoming physicians or making teaching rounds? Will you be assigned duties completing

charts, performing chart reviews (quality assurance), teaching, preparing and giving conferences, or patient callback activities. If so, you need to know if there is protected time out of your workweek or if these duties are on top of an otherwise full schedule. If these activities are on top of a full clinical schedule will you be paid for these extra duties? Also, do not forget to factor in the value of your commuting time. This is not just the travel time but rather the span of time from when you leave home to when your shift starts. As actual commuting time increases there is an increased need to leave extra early to be sure of arriving on time. Your tolerance of a long commute will be directly proportional to how much you love your job or your home. Another often neglected factor is that if you are working solo in a place that is moderately busy you will almost certainly be doing the additional work of a fraction of a second physician. You may tolerably see 30 patients in a 12-hour shift. If the volume averages 40, many employers will not add any coverage. You will work harder, skip lunch and breaks, walk a little faster, write shorter (and worse) notes, and have less patience with patients who ramble on with their histories. The walkout rate might go up a little and when your shift ends the oncoming physician will get a longer signout. Unless you work in a democratic fee for service group you will not monetarily benefit from this extra work. In short, you are being grossly underpaid for the job. If you perceive yourself as merely selling your time and not your services then you might not see things this way. However, if you calculate your salary in terms of dollars per patient seen and not dollars per hour your perspective might change drastically. Consider what type of community the hospital serves and what other hospitals compete in that community. Is the economic base growing or shrinking? Ask if the ED is self-supporting financially or needs subsidies from the general hospital budget. Be aware that the concept of being self-supporting financially is misleading, insofar as it measures ED cash flows in isolation from the rest of the hospital budget. The ED in a typical hospital may be responsible for 20 to 30% of admissions—admissions that result in generating large amounts of revenue for the hospital. If told that the hospital (or distant contract management company) cannot afford to pay a better salary because “the ED is a moneyloser,” ask if the hospital would be better off closing the ED and having all the ED-derived admissions go elsewhere. Ask if all the ED physicians are paid the same, work the same number of hours, and share good and bad shifts equally. What are any salary differences based upon—specialty training, board status, experience, seniority, nonclinical assignments, etc. How do these factors affect you? Beware promises of major pay increases after working two or three years. If you are doing identical work as your peers you should not be penalized. Be assured that places exist that subsidize the profits of the contract managers or senior ED partners with a constant turnover of younger physicians. You may consider asking about physician turnover in the past few years—how long they were there and why they left. If you do not receive a satisfactory answer take it as a major red flag for problems. Similarly, inquire about the tenures of the current director, previous directors, and current and previous contract holders.

PERSONAL FINANCIAL CONSIDERATIONS Beyond the microeconomics of your job look at the macroeconomics of the community and state where you may live for years. The greatest single expense most Americans have is their housing. A $600,000 house in one area may cost $150,000 elsewhere. On a 30-year 8% mortgage this $450,000 difference would translate into $3,300 per month or $40,000 per year in payments. Likely, too, there would be a large difference in property taxes. A common mistake is to make as large a downpayment on a house as you can in order to lower the monthly mortgage payments. With this logic you would pay all cash if you had the money. There are two reasons this makes poor financial sense: inflation and taxes. Currently, the inflation rate in the United States is running around 3%. This means that any loan you have is paid off with a invisible coupon reading “take off 3%.” You get another coupon every year equivalent to whatever the inflation factor is that year. The coupons are also additive. Also, a mortgage payment is over 90% interest for the first several years and the home mortgage interest deduction remains the last great tax deduction. Interest paid on credit cards, personal loans, auto loans, and student loans is not deductible on your return. If you have any student loans outstanding and are buying a house what you should do is use any cash you were planning to use to reduce your mortgage payments to pay off as much of your student loan as possible. This will have the net effect of converting your student loan into a mortgage. As private school tuition costs a fortune, pay attention to the quality of the local public school systems to determine whether or not you would want to send your children there. Good measures of the quality of any school system include the percentage that graduate, percentage that go to college, and performance on standardized tests such as the SAT.

SHOULD I USE A HEADHUNTER? Think twice before using a headhunter to perform your job search activities; don't believe it when you are told there is no expense to you. In 1996, a typical fee was $20,000. That's how much less your employer has available to pay you. If you know what area of the country or state you would like to live in then get a detailed state map and obtain a publication called the AHA (American Hospital Association) Guide to the Healthcare Field. It contains a wealth of useful information on over 7000 hospitals including ED volumes, names of persons to contact and telephone numbers. It is available in most medical libraries and many hospital administrator's offices. (If you want your own copy you can order one from the AHA by calling 1-800-AHA-2626. The price is $250 for nonmembers; $95 for members [a personal membership costs $75 per year].) With a few phone calls you can set up some interviews and with a little luck even get someone else to pay for your trip. Sometimes an employer pays a signing bonus to physicians who come in such a direct fashion. Any group actively seeking a new physician will be delighted to deal with you directly. All your preliminary questions will be easily answered without the delay, uncertainty, and expense of using a telemarketer who has your name on a Rolodex. Conversely, if you come with a headhunter you will be at a distinct disadvantage compared with applicants who present themselves without a big price tag. In short, you should do the job search.

WHAT ABOUT PREPARING MY OWN TAX RETURN? One final financial topic often ignored by emergency physicians. Should I do my own tax return? Most would rather not, saying they are not interested or do not have time. The true value in doing your own return is a heightened awareness of your financial life and being able to plan in such a way as to maximize future income and reduce future taxes. The largest portion of work involved in preparing any return is the organization and accounting of many pieces of paper into various income, expense, and deduction categories. Most of this must be done by you anyway. Given that most of you will pay roughly one-third or more of your income to taxes you should give strong consideration to being able to take an active role in reducing this burden. A simple tax course at a local college or reading some books will provide you a far larger payback than doing a few extra shifts.

READ YOUR CONTRACT (BEFORE YOU SIGN) For starters remember this: If it is not in writing it does not exist. Legal scholars will be quick to note the validity of the verbal contract while they enforce it at $200 per hour. If you hear anyone say something such as “Oh, don't worry about that, it's just a standard contract,” this should serve as your first prompt to read it carefully. The first item to review is the termination provisions. These come in two flavors—with cause and without cause. If you think for a moment about it the latter doesn't seem to make sense. Why would you be terminated without a reason? There is always a reason. So, what this really means is that they don't have to tell you the reason. Not knowing the reason there is nothing you can do about it. A good example of “with cause” is messing up on a patient with a bad outcome due to gross negligence on your part. An example of “without cause” would be making a fast-track patient wait too long because you were seeing sicker patients and it turned out the patient was the wife of someone influential. This scenario was the basis of one of the best medical motif movies ever made, State of Emergency. Interestingly, a termination without cause is considered an administrative action and is not reportable to the National Practitioner Data Bank as an adverse event. In those situations where it is clear why you have been terminated you may not be able to defend yourself as some contracts have cleverly written out your right to be given a fair hearing by your medical staff peers. Basically, you are found guilty without a trial. This is also known as lack of due process. Currently, California is the only state that prohibits physicians' termination without due process. You will be given notice of from a few seconds to a few months. Unless you are able to procure work at another hospital your untimely departure will result in a major financial setback—loss of income, expenses of selling your home and relocation, upset of spouse's career, and kids changing schools, etc. This leads to the subject of restrictive covenants. Restrictive covenants refer to what you can't do in a variety of situations; the most important of which is where you can work after you leave. For example, it may be written that you can't work at any other hospital within 50 miles for a period of 2 years. Interestingly, “any other hospital” may include your own hospital. You could be in this situation if the contract management company you work for lost its contract with your hospital. Your contract might stipulate that you cannot stay on with whoever takes over the contract. You are a scarce resource and by prohibiting your recycling this contract is more likely to be renewed. If it is not renewed and the replacement contract management company wants to keep you, somebody (perhaps you) may be liable for breach of contract damages. There is some good news—restrictive covenants have been found illegal in some jurisdictions. You may be unaware of any restrictive covenants, not because you never bothered to read and understand your contract, but interestingly, because they were not in your contract but rather in the collateral contract between your hospital and your contract manager, their agreement with the hospital for “managing” you. Consequently, it behooves you to get a copy of that document. If your request is denied it may be because they don't want you to see certain items that are sensitive such as just how much money they are making off your services. Assuming you can live without that information ask to see just those portions of the contract which affect you. If your modified request meets resistance you have cause for concern. Discuss this with your lawyer. And finally, remember this: when it comes to contracts the smaller the print the more important the clause.

SUMMARY

In order for you to properly assess all the factors discussed you are going to have to ask questions of people who are not used to responding candidly. Beyond the basic questions physicians often do not ask much. This is due to a combination of ignorance, fear, and apathy. Hopefully, the contents of this text will serve to ameliorate the first and third elements in the above triad. The middle element, fear, requires additional discussion. You may be afraid to ask important questions because you will be seen as aggressive or nosy, therefore making yourself an undesirable candidate for the job. This author once asked to see a copy of a malpractice policy provided by a large contract management company and was told that no emergency physician had ever put in this type of request. It was important to evaluate the financial stability of the underwriter, the policy limits, what procedures were covered, and to be sure that the policy was an occurrence one and not claims made. It is tragic that emergency medicine physicians hold back on investigating issues as important as these for fear of standing out. Those of you who have read Dr. Keaney's book, The Rape of Emergency Medicine, know that emergency medicine has a checkered past with respect to the qualifications of some of its physicians. It was not uncommon for such physicians to take any job offer and ask little. Although the quality of emergency medicine physicians has changed drastically in the past 20 years there has been a persistence of the tendency not to ask too many probing questions. An honest ED director or contract manager should not have any compunction answering your legitimate questions. If they have difficulty, you should just emphasize that you feel these issues are important for you to be able to evaluate the job. Of course, if all emergency medicine physicians presented themselves and their profession as a unified front the solo physician would no longer stand out and contract managers would get accustomed to dealing with this new breed of experienced, well trained and empowered emergency medicine specialists. Suggested Readings Publication 17, Your Federal income taxes. [Department of the Treasury/yIRS. Available for free by calling the IRS at 1-800-829-3676, or faxing at 703-368-9694.] Publication 505, Tax withholding and estimated taxes. [Department of the Treasury/IRS. Available for free by calling the IRS at 1-800-829-3676, or faxing at 703-368-9694.] Publication 533, Self-employment tax. [Department of the Treasury/IRS. Available for free by calling the IRS at 1-800-829-3676, or faxing at 703-368-9694.] Publication 560, Retirement plans for the self-employed. [Department of the Treasury/IRS. Available for free by calling the IRS at 1-800-829-3676, or faxing at 703-368-9694.] Publication 587, Business use of your home. [Department of the Treasury/IRS. Available for free by calling the IRS at 1-800-829-3676, or faxing at 703-368-9694.] Publication 590, Individual retirement arrangements. [Department of the Treasury/IRS. Available for free by calling the IRS at 1-800-829-3676, or faxing at 703-368-9694.] Publication 917, Business use of a car. [Department of the Treasury/IRS. Available for free by calling the IRS at 1-800-829-3676, or faxing at 703-368-9694.] Publication 936, Home mortgage interest deduction. [Department of the Treasury/IRS. Available for free by calling the IRS at 1-800-829-3676, or faxing at 703-368-9694.] Bullock C: And due process for all. Emerg Med News. August 1995. Call 212-840-7760 for reprint. Tarshis S: Emergency medicine physician—employee or independent contractor? In: Risk management report. Newburgh, NY: Emergency Department Consultants vol. 2, no. 2, 1996. Call 1-800-563-6384 for reprint. Weinstein GW: The lifetime book of money management 3rd ed. Detroit, MI: Visible Ink Press, 1993. Meals RN: Termination without cause—protecting your right to work. Emergency Physicians' Monthly January 1996. Call 1-800-EPM-DOCS for reprint.

CHAPTER 162 EDUCATION IN EMERGENCY DEPARTMENTS: FOCUS ON DECISION MAKING Principles and Practice of Emergency Medicine

CHAPTER 162 EDUCATION IN EMERGENCY DEPARTMENTS: FOCUS ON DECISION MAKING Sheldon Jacobson and George R. Schwartz Introduction Training in Decision Making Use of Consultants Emergency Medical Systems and Services EMS Medical Direction Physician Stress and “Burnout”

INTRODUCTION The functioning of the entire emergency medical services (EMS) system should be incorporated into any education program for emergency medicine. This includes direct observation and, if possible, direct clinical experience in delivery of emergency care in the streets. Decision making with limited data base use must be emphasized (1,2 and 3). Designing a training program with appropriate objectives requires a clear definition of the mission of the ED. There are two polarized perceptions and another, more middle-of-the-road concept. There are those who think that emergency medicine is a critical care specialty, with blurring and integration into the function of a critical care or shock trauma unit (4). Another view that the ED functions as an extension of the primary care specialties and provides episodic primary care. There are aspects of emergency medicine that support both contentions. It is preferable to clearly delineate the primary care and critical care aspects in planning an educational program. Education in the ED should not consist simply of teaching discrete subjects to ED trainees. It is all too easy to compartmentalize the didactic material and to present the information as a series of lectures. Formal talks dedicated to these topics may actually take time from more important educational issues.

TRAINING IN DECISION MAKING The most important lessons to learn from an ED experience relate to the techniques involved in gathering a specific limited data base on the critically ill or injured patient and using this data base in patient care decision making. Hundreds of decisions are made by the emergency physician every week, and many of these are important in terms of patient outcomes. Yet this decision-making process is particularly important to emergency medicine. In the ED one does not have the same series of checks, rechecks, and consultation available to the hospitalized patient. The results of these decisions can be devastating to the patient if wrong. Practice guidelines can lead to “cost-effective” medicine but have the potential of compromising quality. This can be termed “mismanaged care” ( 4A). Laboratory Data Integral to the decision-making process is the appropriate use of laboratory data. The practitioner must learn to use such data, but with restraint. The questions being asked of the test should be appropriate to the study, and the results interpreted in the context of the known sensitivity, specificity, and predictive value of these tests. Unnecessary tests are costly and can be misleading. Using a statistical approach to patient laboratory data is dangerous because we do not have a universe of patients to treat, and on any given occasion the test may be positive or negative consequent to statistical variability and not necessarily to the presence of an active disease process. Therefore, laboratory data should be used to support our diagnostic impression and not to make the diagnosis in and of itself. A mandatory concomitant of this educational process is proximate patient follow-up. We could be making serious errors in our ED and not know until it is too late. It is essential from an education standpoint that there is follow-up of patients who are discharged from the ED. In some cases, a simple telephone call is all that is needed; in others, return to the ED is mandatory. For patients admitted to hospital, inpatient follow-up rounds are invaluable educationally and represent sound ED practice. Retrospective review of cases and auditing of charts for form and process have limited value as teaching tools. Although there are legal and informational aspects of the medical record, quality of care and quality of the record cannot be equated. Proximate outcome is the gold standard for auditing quality of ED practice ( 5,6 and 7). Criteria for good outcome must be developed. Certain outcomes are obviously indicators of poor decision making. However, there are certain areas in which the deductive analytical process may be too time-consuming and perhaps disconcerting. Therefore, in one's approach to resuscitation of the cardiac arrest or trauma victim, the major initial actions should be reflexive to ensure that the hierarchy of priorities is adhered to and are dealt with swiftly. There is little time for developing an extensive data base or, for that matter, innovative decision making. Later on, the decision-making process can be individualized to meet specific patient needs.

USE OF CONSULTANTS Part of the educational process in the ED is the training of providers to be selective in their utilization of consulting services. This relates to decision-making activities and calls heavily on knowledge of the important diagnostic entities in the consultant's purview. An emergency physician usually does not call a consultant because they do not know what to do. A consultant is usually called when the emergency physician has decided that what has to be done requires admission to the hospital or entails a procedure that they feel is necessary. Use of consultants in this manner also leads to effective patient care because the consultant is more likely to accept the data already generated and to proceed from that point rather than reevaluate the patient completely. It also leads to recognition of the emergency physician as a highly skilled decision-maker. Obviously, there are times when a consultant is called due to uncertainty. Although predominantly interested in the acutely ill patient, one does have a responsibility as part of primary care activities to look for and treat some major public health problems, and preventative care should be clearly delineated as an area in which the emergency physician can play a significant role.

EMERGENCY MEDICAL SYSTEMS AND SERVICES Disaster management and the organization and direction of prehospital care are programs that are unique to our field and require us to gain the expertise that permits us to attain leadership roles in these activities. Although we need input from pediatricians, cardiologists, and traumatologists, it is our expertise as emergency practitioners that enables us to set priorities and standards, develop treatment protocols, train paramedics and EMTs, direct prehospital care from base stations, and audit the quality of prehospital medical care. To play this dominant role in EMS systems, emergency medicine physicians must spend time with the prehospital care providers (e.g., accompanying paramedics in ambulances). It is this experience that will allow them to make realistic judgments relating to training programs for ambulance personnel, to prehospital drug treatment protocols, and to the quality of care.

EMS MEDICAL DIRECTION In Chapter 149, the importance of overall physician direction of EMS systems has been accentuated and some of the internal conflicts identified. Medical oversight becomes critical for patient well-being in a dynamic EMS environment. For example, Chapter 150 and Chapter 151 highlight field interventons likely to make a difference in survival. As part of teaching EMS to physicians there must be ongoing concern with the dynamic research in this area. EMS systems that try to regulate EMS activity based on faulty or outmoded concepts or political concerns can harm patients and expend excess funds and potentially create enormous liability risk.

PHYSICIAN STRESS AND “BURNOUT” Finally, we need to prepare emergency physicians to cope with and function under the stress inherent in EDs. Stress can manifest itself in the emergency physician in a number of forms. In its early phases, the individual may perceive what is called “functioning under pressure.” If this pressure is not recognized and dealt with

appropriately, it can lead to depression, anxiety, and physician “burnout.” It can certainly impair one's effectiveness and lead to chronic dissatisfaction with emergency medicine (8). How one goes about teaching physicians to deal with stress is difficult to set forth briefly, but it begins with recognition of stress by the physician. Once the stress is recognized, a number of actions can occur to modify the situation. In some EDs, the physician's work schedule in and of itself can lead to unacceptable stress levels. It is not uncommon for emergency physicians to work a 12-hour or, on some occasions, a 24-hour shift. A major factor in preventing burnout is adequate time off from duty. Frequent short vacations can be therapeutic and should not be thought of as a luxury. A mutually supportive staff and team approach can be useful. Short periods of quiet meditation may work for some individuals. Training in emergency medicine is undergoing substantial reevaluation particularly as the health care system changes ( 9,10 and 11). References 1. 2. 3. 4.

Albert DA: Decision theory in medicine: Milbank Mem Fund Q 1978;56:362. Gorry GA: New prospectives in the art of clinical decision making. Am J Clin Pathol 1981;75:483. Jacobson S: Decision-making in the emergency department. Comprehensive Ther 1985;11:16. Wagner DK: Critical care medicine and the emergency physician. Ann Emerg Med 1982;11:49.

4A. Jacobson S: Avoidable errors in emergency practice: Mismanaged care. J Emerg Med 1996;28:42–45. 5. 6. 7. 8. 9. 10. 11.

Ashton CM, Kuykendall DH, Johnson ML, et al: A method of developing and weighting explicit process of care criteria for quality assessment. Med Care 1994;32:755–770. Brook RH, McGlynn EA, Cleary, PD: Measuring quality of care. N Engl J Med 1996;335:966–968. Keeler EB, Rubenstein LV, Kahn KL, et al: Hospital characteristics and quality of care. JAMA 1992;268:1709–1714. Gallery ME, Whitley TW, Klonis LK, et al: A study of occupational stress and depression among emergency physicians. Ann Emerg Med 1992;21:58. Tintinalli JE: The strengths and weaknesses of undergraduate education in emergency medicine. Ann Emerg Med 1990;19:1187. Hedges JR: The role of undergraduate education in emergency medicine. Ann Emerg Med 1990;19:1187. Rosenzweig S: The other half of the curriculum. Ann Emerg Med 1991;20:591.

CHAPTER 163 COMPUTERS AND EMERGENCY MEDICINE Principles and Practice of Emergency Medicine

CHAPTER 163 COMPUTERS AND EMERGENCY MEDICINE Mark Mandell, Ashraf Nashed, John Horning Capsule Introduction Computers in Clinical Practice Integrating Information Computerizing Nursing and Physician Notes Education The Internet The Computer as a Teaching Tool Hand-Held Computers Sources of Information

CAPSULE Advances in software and hardware allow emergency physicians to use computers to access and organize patient information and medical knowledge. Emergency departments (EDs) are using computers to become more efficient and cost-effective, and to improve patient care and documentation of that care. Emergency physicians use computers to write their charts, to track patients in the department, and to obtain and share medical knowledge via the Internet.

INTRODUCTION Computers store, organize, and sort large amounts of information. It is these early functions that make computers useful to emergency physicians for the retrieval of medical reference material and information on individual patients. Advances in computer technology and software have created numerous tools for the emergency physician. Software allows the computer user to navigate through a system of pictures and menus with a mouse and cursor. This has made using the personal computer simpler and encouraged increased use.

COMPUTERS IN CLINICAL PRACTICE Most EDs already capture patient demographics and financial information into a hospital mainframe computer for logging and billing. Improvements in technology combined with economic and market forces will ensure more widespread computerization of hospitals, including the ED. Computers will influence the practice of emergency medicine. One key concept being explored is spoken voice recognition systems. When fully developed, these systems will produce enormous changes with “real-time” voice capture (200 words per minute) and less than 1% error ( 1). A number of academic medical centers are in the process of developing integrated information systems. In one system, physicians can, from the same workstation, order medications for a patient, read about the medication in a separate window, check laboratory results, do a literature search on the patient's problem, and consult a standard medical textbook. The ideal ED system would have not just patient information, but also medical references, built-in practice guidelines, alerts for deviations from guidelines, red flags for significantly abnormal laboratory tests, the ability to track messages from primary physicians, and a host of other features that would improve practice and reduce costs.

INTEGRATING INFORMATION In addition to a mainframe system, many hospitals currently have a number of computer systems that organize laboratory, x-ray, and pharmacy records. The majority of these systems, however, are separate and the information remains unlinked, for the individual patient. Among the most important issues is how to integrate all of the patient information that is already computerized and how to get the rest of the information, including physician and nursing notes, into electronic form. Once integrated, this information will comprise the electronic ED record. In electronic form, this information can be used to control costs, look at practice patterns, and share information with primary physicians and insurance companies. The paperless ED is on the horizon, but hurdles remain to the full computerization of the ED, not the least of which is the development of appropriate user-friendly software. Although most hospital information systems have been based on a large mainframe system, it seems likely, however, that ED systems will be based on networked personal computers. One of the problems with hospital mainframe systems, from the point of view of the ED, is that each hospital's system tends to be uniquely customized. As a consequence, it would be difficult to adapt a system from one ED to another ED. One aspect in the development of software for the practice of emergency medicine is the relatively small market for the products. Large software companies have spent hundreds of millions of dollars producing mass-market software such as word processors. A large proportion of the money was spent on making the software attractive and easy to use. Obviously, there will never be the potential for profits that would generate similar efforts in emergency medicine. Happily, one of the things that has happened over the last few years, besides the improvement in the capability of hardware, is the production for personal computers of developer's tools that can create attractive and friendly software at a much lower cost. Because of this development, most of the applications that are currently being developed for the ED are based on networked IBM-compatible personal computers. These systems are relatively cheap and have standard operating systems. As a result, software written for one ED can be installed in other EDs. It, therefore, becomes possible for us to learn from each other's experiences. The practice of emergency medicine utilizes information intensively. Incomplete information is a hindrance to quality care of critically ill patients. Necessary information includes demographic data, patient location and status, hospital bed availability, laboratory and x-ray results, old records, previous laboratory tests and radiographs, all of which have to be obtained and then juggled simultaneously. Most EDs still track large numbers of patient via a hand-maintained white board. Frequently, ED records are in one place, clinic records in another, laboratory results in another, and inpatients' records in a fourth location. In most institutions, these records must be hand carried to the ED, if they are even available at all. If one were to compare hospitals to airlines, an industry which is similarly information dependent, but much more fully computerized, the anachronistic aspects of hospital practices become readily apparent. The application that is currently one of the most fully developed is computerized tracking of patients in the ED, with more than one-half dozen software vendors currently selling systems (Table 163.1). When the patient arrives and is registered, the patient's name appears on a tracking screen, similar to the old-fashioned grease board, and the patient can then be followed throughout the course in the ED. Strategically placed monitors allow physicians and nurses to locate patients, to track laboratory results, and to keep track of waiting times. Most of these systems are for personal computers, and are designed to have data links to hospital mainframe information systems, therefore avoiding the necessity of double-entry of information. But most of the companies that develop these systems are small, and have sold, at the time of this writing, only a few systems. Because hospitals have a wide range of computer systems, the data links require customized software and installation.

Table 163.1. Emergency Department Software Vendors Tracking Systems

Tracking systems can serve as the hub of an integrated computer system in the ED. With the right links, tracking systems can not only locate patients and notify the charge nurse of delays in patient care, but can receive information on laboratory results, and x-ray reports. In short, the tracking system can integrate information in the ED and function as the nidus of the electronic medical record. Once installed these systems have the potential to easily generate custom reports on microcomputer, depending on the software and the links. These reports might include patient waiting times for each individual physician by diagnosis, or average laboratory costs for each physician by diagnosis. In an era of cost containment, competition, and managed care, the ability to generate organized information is the key to survival. Referring back to the airline analogy, it is hard to imagine an American airline unable to instantaneously generate information on the maintenance costs of each plane, or the profitability of each flight. EDs and hospital systems must be able to generate detailed reports on costs and practices in order to survive.

COMPUTERIZING NURSING AND PHYSICIAN NOTES The most important parts of the medical record are the nursing and physician notes and these have been the most difficult to computerize. It is possibly because of this feature that EDs have been so slow to computerize. This difficult problem has generated a number of solutions, none entirely satisfactory. The physician can type the information, can dictate the information to someone who will type it, can use voice recognition software, or can enter the information using templated screens and a mouse, touch-screen, or light-pen. While there are physicians and nurses who can type and would happily type all medical records, these happy typists constitute a distinct minority. A system designed to capture notes by professionals cannot successfully depend solely on keyboard entry, but must eventually use real-time spoken voice recognition with high accuracy. One approach that is used in many areas of the hospital is dictation by physicians to professional transcriptionists, who enter the information into a computer. In the ED, this approach is feasible but tends to have delays and high costs, with a tradeoff between the length of the delay and the cost. The quickest systems tend to have the most resources and backup personnel and the highest costs. One source estimated the cost of $1.45 for each chart, but this estimate is much too low, in our experience. It is not enough to print a dictated record on paper to get the full benefits of the electronic chart. Because most printed charts are now being produced on a computer, it is a simple enough process to output the transcribed file into an electronic record, in addition to printing the chart onto paper after transcription. Simple as it may be, it is a safe bet that the majority of transcribed charts are printed out and never placed into electronic storage, therefore losing much of the advantages of having a chart produced on a computer. Voice recognition software or automated speech recognition software has been a promising alternative for the last 10 years, but has not fulfilled its promise and even the advanced systems are slow and frustrating. With this software, the physician speaks into a microphone attached to a board installed in a personal computer. In theory, the software would flawlessly capture the physician's words and converts them into the printed word and an electronic chart (See Table 163.1). Although startup costs for hardware and software can be high, an accurate, reliable, and user-friendly system would be low in cost compared with paying professional transcriptionists. A number of departments use voice recognition systems successfully, and are strong advocates of the systems. The systems take dictation at a speed roughly comparable to a good touch typist, 60 words/minute, which is significantly slower than the rate of normal speech (200 word per minute). To use the systems with facility requires patience, practice, and persistence. Ambient noises, a not uncommon problem in most EDs, tend to produce bizarre responses. Each system can handle only one physician at a time. For a second physician to use the machine, the first user must log off to allow the second to log on, which takes at least several minutes. It is estimated that 90% of the voice recognition systems that have been purchased are not currently being used. Some observers attribute this to “resistance” on the part of physicians to the use of computer systems, but others have commented that physicians will use systems that enhance their practice of medicine. It is reasonable to expect that in a busy ED, physicians will resist a system that increases the time to produce a chart. For a system to be accepted, the benefits of the system should be readily apparent. The solution to the problem of producing electronic medical records ultimately will be improved voice recognition software on more powerful hardware. It is likely, over the next few years, that hardware and software will improve to the point where dictation to a computer becomes a highly viable option for most departments. For now, the best system for the electronic production of nursing and physicians' notes appears to be software using well-designed templates. This approach uses a series of templates for each diagnosis, with choices made via some sort of data entry device, such as the mouse, a light-pen, a touch screen, or the keyboard. Most people are somewhat familiar with the use of a mouse, but may be less familiar with a light-pen or touch screen. A light-pen is attached to the computer and the tip is placed on the monitor screen to make choices between alternatives on the screen. A touch screen is a specially designed monitor, which allows one to make the same choices on the screen using a finger. The best systems have hundreds of the most common diagnoses, with most information entered via a series of decision points or tab points, asking the user to choose the proper alternative, using the data entry equipment. Many of the current systems have settled on this approach to data entry for nurses and physicians, because it minimizes the amount of typing required. The general experience has been that these systems require patience. Naturally, anything out of the ordinary requires typing, or the use of a touch-screen keypad, which is a typewriter keyboard that appears on the screen, through which data can be entered by typing on the screen. One interesting approach has been the use of scanning to convert the handwritten, paper chart into a computerized record. This approach has been made more practical by the rapid drop in costs for computerized storage. Scanning produces pictures of the medical record, and once scanned the medical record can be stored, faxed, wired by modem, and retrieved. It obviously does not improve or change the handwriting of the medical record nor can the information on the chart, captured as a picture, be tabulated for quality assurance or financial control. As opposed to a scanned chart, an typewritten chart in electronic format can be checked by computer for completeness of information and is more likely to be complete. In selecting automation software and hardware, it is important to sit and use the software without pressure from a salesman and to use it in a way that would simulate real-life situations. It does not seem unreasonable to spend as long as 10 hours or more using software before purchasing it. Another important issue when utilizing digital patient records is that of system security. When confidential information is accessible from several computers throughout the ED and hospital over a network, specific measures must be taken to limit access. Similarly, the ability of such systems to change or amend physician or nursing notes should also be examined. Issues that frequently arise include log-on procedures, user convenience, and software compatibility.

EDUCATION Perhaps the greatest dividend of the computer age has been the improved accessibility of immense volumes of educational resources. What once took hours of research in the library can now be accomplished with a few simple keystrokes. In addition, newer methods of organizing, storing, retrieving, and displaying information

have made managing this data less tedious and more productive. Computers have largely revolutionized the availability and utility of information. Great strides have been made, primarily in the area of data storage and data access, permitting efficient utilization of digital, or computerized, references. Digital reference sources can be classified as either local or remote, although with the proliferation of networks, the distinction has begun to blur. Information on a network server may be in the next room, or across campus. Local information can be stored in a computer's hard disk memory or on a portable medium such as a floppy disk or CD-ROM disk. Remote information, stored on an off-site computer, must be accessed via a telephone line using a modem or though a data link hooked up to the local network. Remote information can be accessed on computers owned by educational, commercial, or government institutions. Much of the information is freely available, but some is only available to those with access rights. Local computer references reside either on the hard drive or on a CD-ROM disk. A single CD-ROM disk currently can hold approximately 600 MB of data, a larger capacity than many individual hard drives, which makes it an ideal medium for storing and accessing entire reference libraries. Because of this large storage capacity, CD ROM disks are suitable for storing digital photographs, audio tracks, and video segments. These various formats are already being integrated with text to create multimedia medical teaching applications and references. Such technology adds new dimensions to traditional textbook approaches to medical learning and will play a major role in medical education in the coming years. Many publishers have already placed entire textbooks, including photographs, on CD-ROM. Journals are also being stored in full text as well as in abstract form on CD-ROM archives. Most collections include search and retrieval software, which allows the user to find relevant sections or citations rapidly and print the material onto paper for later, or more convenient, reading. In addition to textbooks and journals, several references designed specifically for the computer have emerged. Many of these references offer the advantage of containing more information about a specific area than can be included in a single, usable textbook. In addition, some have refined their software to facilitate the search process so that a clinician can rapidly obtain important information while in the setting of a busy ED. Others provide reference information in the form of question and answer format and as case simulations. The advantages of on-site reference materials are generally related to the ease of access to the material. Because there is no dependence on telephone or data connections, retrieval of information is frequently more rapid and reliable. The disadvantages include high up-front costs involved in purchasing hardware and the reference software packages. In addition, to take advantage of one of the primary advantages of computerized references, the software requires frequent updating, which incurs additional cost. In general, an extensive on-site, electronic reference library is worthwhile if it is to be shared by several individuals. For the individual physician, a more versatile and affordable approach is to obtain information via an outside source such as an on-line service or remote computer. Several on-line services currently provide up-to-date medical reference materials and information via modem connections. They range from expensive, highly specialized services to the vast and largely unregulated worldwide network of computers known as the Internet. Commercial services frequently offer features such as literature searches, electronic mail, and news clipping services. Some also provide reference materials such as drug information, full text articles, continuing medical education, reprints, and discussion forums. One commonly utilized feature of these services is the ability to search medical bibliographic databases. Commercial services provide access to these databases offering various rates and packages. Cost is usually related to the amount of time connected. The most widely used database is the Medline system by the National Library of Medicine, which is offered by a number of vendors. Learning to use Medline takes some practice. It has been shown that formal training in performing a computerized literature search can result in more effective and successful searching. The actual sensitivity of a Medline search in finding relevant articles has been questioned, however. It should be noted that many journals are not included in the Medline database at all.

THE INTERNET One aspect of computing that has received a lot of attention has been the Internet, thought by some to be the nucleus of the future information highway. The Internet is not a commercial network, but rather an interconnected network of networks, in which each user pays its own connection costs. More than 3 million computers are connected to the Internet, with thousands being added every month. These include many government agencies, universities, research centers, hospitals, and commercial companies. It has become relatively simple and inexpensive to have a 56,000 baud modem dial-up connection to an Internet service provider and use the full features of the Internet. All of the large commercial on-line services have now added full Internet access to their systems, with many newly purchased personal computers being shipped with such software already included. The user can send electronic mail throughout the world, download and upload files, participate in special topic discussion groups, view information in a graphical, multimedia environment, and search the Internet using keywords. There are hundreds of valuable Internet resources relevant to the emergency physician. A list of some sites is given in Table 163.2. Following is an outline of general methods for using the Internet's features and obtaining current information on medical resources and applications. As with most computer applications, the only way to learn how to use the Internet is to actually try it out with a good manual nearby. For the novice computer user, the large commercial on-line services, such as Compuserve, America On-Line, and Prodigy, are recommended because of their user-friendly software and technical support. Many individuals with a university affiliation or appointment can obtain a dial-up connection to the Internet for free simply by asking.

Table 163.2. Interesting Medical Websites

The Internet is complex, can be difficult to use, and is filled with abstruse jargon, impenetrable to the novice computer user. There is a wide assortment of software used on the Internet known by a variety of acronyms, mostly designed by and for hackers and professional computer users. Fortunately, the World Wide Web is a graphical interface with the Internet and uses pictures and menus in an approachable form, even for a novice. Besides the World Wide Web, software used on the Internet include various E-mail programs, FTP, Telnet, and Gopher. For the emergency physician, the most useful aspects of the Internet will be electronic mail and the World Wide Web. Electronic mail (E-mail) is currently the most popular service used on the Internet. Most commercial Internet service providers include E-mail accounts and software with a subscription. Simple text messages can easily be sent via Internet E-mail. Although it is possible to send more complex messages, such as pictures, the procedure can be quite complex. A new protocol, MIME, permits the transfer of audio and video files. This protocol allows file attachments to E-mail messages and is more efficient than the standard protocol. Because it was recently released, many Internet access providers do not support MIME. In addition to messages, E-mail can be used to send manuscripts, data files, and updates to colleagues in a rapid, efficient manner. A complete patient case, including digitized radiographs, electrocardiograms (ECGs), and lab results, with the right connections and software, could conceivably be sent to a consulting or treating physician within seconds. Professional and informal correspondence has also been initiated on a global scale using mailing lists. These consist of central list server computers to which mailing list subscribers send an E-mail message. The messages are then mailed out to each subscriber. Emergency physicians can use such lists to consult their colleagues

informally on a regular basis on a variety of subjects ranging from clinical to administrative in nature. There are several electronic mailing lists, accessible to anyone with Internet E-Mail access, of interest to emergency physicians. A message on a medical topic or administration can be posted, will be read by hundreds of emergency physicians throughout the United States, and is sure to receive a response. It is not uncommon to exchange information and ideas on tough administrative or patient care problems. A hospitalized patient with an unknown poisoning in China was presented to an emergency medicine mailing list and correctly diagnosed as thallium poisoning by participants. Such sharing of ideas is perhaps the most powerful application of this communications tool. The World Wide Web, also known as the Web, WWW, and W3, has been the most rapidly growing service of the Internet, and with good reason. The WWW allows computers to access and display documents stored on computer servers throughout the world. Several text-based, and graphical-based client software browsers have been produced to display and use WWW documents. The browsers also connect to other Internet services such as FTP, Telnet, WAIS, and Gopher while remaining in the same environment. Among the most popular graphical browsers are Netscape and Internet Explorer, which are frequently available at no charge from Internet service providers or the software firms that make them. The WWW is organized as a series of homepages with a web of interconnections. A homepage (or HTML page) is a file that usually displays text with or without graphics that is automatically downloaded and displayed by the browser software to the user's computer. The hallmark of HTML pages are hypertext links, which are commands that retrieve other WWW documents, files, or services when the user selects designated or highlighted words. Simply clicking on a set of highlighted characters or images (hypertext links) results in the execution of a command. This command may be to download another HTML document or file, to make a Telnet connection to another server to the client computer, or to send an E-mail message to the administrator of a WWW server. Whether the action is taking place on the same server or on one thousands of miles away, a new host-to-server connection is initiated with each hyperlink command. If the connection is high speed, the homepage appears to function to the user as if everything were in the same location. More than 8 million people in the United States now have access to the Web's user-friendly interface to the Internet. WWW servers are being added to the network at staggering rates, resulting in the availability of a myriad of medical and nonmedical resources. The National Library of Medicine has led American efforts in organizing and creating medical resources on the WWW. Other major web sites include the World Health Organization, the Agency for Health Care Policy and Research practice guidelines, the FDA bulletin board, and The Morbidity and Mortality Weekly Report. Several major medical institutions have also created WWW servers. One of the most notable is that of the University of Iowa, which created the Virtual Hospital. It features multimedia textbooks, radiology cases, continuing medical education, and medical information for the lay public. Several sites are devoted to emergency medicine, EMS, trauma, radiology, and virtually every medical specialty. Other sites feature educational resources such as clinical photographs, electrocardiograms, radiographs, clinical cases, clinical reviews, and original articles. Many sites also offer links to other relevant websites ( Table 163.2). Each WWW server has its own address, similar to a telephone number, which is called a URL (uniform resource locator). To reach the National Library of Medicine, for instance, the following URL can be called by the browser: http://www.nlm.nih.gov/. These and other sites can be found using the many of the search services available on the WWW. Because site addresses may change on occasion, it may be necessary to search for a particular site to locate its new address. Table 163.3 lists several search services and their URLs. To use many of these “search engines,” keywords can be entered with the return of the appropriate matches. Then, a simple click with a mouse button on the hyperlink makes a connection to that web server, eliminating the need to memorize or manually re-enter long, tedious URLs.

Table 163.3. World Wide Web Search Engines

The WWW serves as the basis for the emergence of on-line, electronic publishing. Anyone with an Internet connection and Web server software can set up a WWW site and publish or display documents for the world to view. Unlike a peer-reviewed journal, however, such medical documents rarely undergo the scrutiny of medical colleagues. This has created controversy among some authorities who have expressed concern over the proliferation of non–peer-reviewed material. In addition, this material is easily examined by nonmedical persons who may not have sufficient training to appropriately evaluate the articles or information. As the WWW continues to mature, these issues will be examined further with possible solutions or more controversies. In the meantime, the Web has much to offer the medical community in terms of storing, displaying, and retrieving educational resources in a graphical-based, easy-to-use environment. Besides the WWW, there are other ways to access information on the Internet. File transfer protocol (FTP) allows a client (local) computer to send (upload) or receive (download) files to or from a server (remote) computer. A remote FTP server provides a directory so that users may browse through until they find the desired file. Most FTP directories display only the filename without any description. Any type of file may be downloaded. Current Windows-based FTP client software has made the FTP process much easier to use than the text-based systems, where users need to be familiar with several commands to make use of FTP. A great deal of free or inexpensive software is available for downloading over the Internet via FTP. Software of interest can be located using search services on the WWW or by using the Archie, Gopher, or WAIS systems. Gopher is a menu-based interface that, when accessed by a user, lists the contents of a Gopher server. Unlike FTP, listed files usually have descriptions to aid in the selection process. Gopher servers also frequently include a directory of other Gopher servers, which may be browsed to find information or files of interest. For instance, when connected to a Gopher server at one university, a menu of medicine-related Gopher servers is displayed. When another site is selected from the menu, a connection to that server is then initiated. The content of the second site's server is then displayed for additional selections. Gopher is relatively easy to use, but lacks the elegance and access to pictures of the WWW. Telnet is a method for remote log-in to another computer on the network. Similar to a direct dial-in connection to a stand-alone computer bulletin board system, Telnet allows a user to dial into their Internet provider and then, through the provider's Telnet server, connect to another computer on the Internet. As with the WWW, the address of the desired computer must be known. Using Telnet and a local Internet connection, a user can log-in to a computer thousands of miles away for the price of a local telephone call. Once logged-in to the remote computer, the display depends on what the remote server provides. Telnet is a common application on the Internet but is much less user-friendly.

THE COMPUTER AS A TEACHING TOOL Many emergency physicians are involved in the teaching of medical students, nurses, prehospital personnel, and resident physicians. The computer offers the educator an extensive collection of software tools for teaching and research. There are many choices, but we have had satisfactory experience with the software listed in Table 163.4.

Table 163.4. Useful Software

Presentations can easily be prepared using one of several software packages. Once completed, a presentation can be converted into 35-mm slides using a film recorder. As an alternative to using film, slides can be shown directly on a large computer monitor. This can result in lower overall costs as well as increased flexibility; slides can be displayed minutes after composing them. For larger audiences, computerized images can be projected using either an LCD projector or an LCD projection panel placed on a high-power overhead projector. To enhance a lecture, digitized images can be imported into computer slide presentations. Digitized medical images are available on the Internet or in commercially sold reference software. Images such as photographs, preexisting slides, and radiographs can be digitized into an image file using a scanner. This is most easily accomplished with photographs; a scanner transparency adapter is usually required to digitize a slide or radiograph. The practice of emergency medicine encompasses many clinical scenarios and procedures that can be simulated on computer. While it is difficult to truly recreate an actual situation, current computer simulations can provide sufficient clinical information to the learner in the form of text, photographs, ECGs, and radiographs to produce a somewhat realistic patient encounter. The learner must then enter diagnostic or treatment options to the computer. The clinical course of the simulated patient changes based on the treatment given. The software can then provide feedback to the learners on their performance. Simulations are useful in providing practice opportunities for several types of situations: (a) When real life practice may cause harm to patients; (b) Uncommon clinical conditions or practice environments; (c) Complex clinical conditions, which require a great deal of practice; and (d) Standardized clinical situations for purposes of evaluation. There is evidence that computer simulations may be used to reliably evaluate performance of emergency procedures. This may lead to their use in future board certification examination. There are simulation programs available for advanced cardiac life support (ACLS) arrhythmias, chest pain, abdominal pain, thoracotomy and blood gas analysis, among others. Simulations can be purchased from medical software vendors or directly from the authors. New and updated versions of these programs are frequently published.

HAND-HELD COMPUTERS Improved technology has resulted in the rapid miniaturization of computers. Notebook computers have decreased in size to as little as 3 lbs., and have the advantage of functioning like full-size computers. Hand-held computers are much smaller and can, in fact, fit into a coat pocket, making it feasible to carry them around the ED. Although these “palmtop” computers lack color and have small screens, some of the more expensive models approach the desktop in functionality. Palmtop computers can function using DOS or Windows and can be used for word processing. Documents produced can be transferred to desktop computers using cable, or infrared connections, or can be printed directly. Internet access is also possible. Typing on the small keyboard is a drawback and although efficient systems for easy touch typing have been developed, time must be invested to learn these techniques. Software is available for these computers, which covers a range of emergency medicine topics, mainly as reference material. In the ED, pharmacology databases on a pocket computer can be particularly useful. Drugs can be referenced and dosages calculated rapidly. Programs are available to calculate A-a gradients, creatinine clearances, sodium and water deficits, serum osmolarity, estimated dates of confinement, and other formulae. Palmtop computers can be used to track patients and procedures using database programs and spreadsheets. Programs exist for direct connection to hospital mainframe computers for downloading of laboratory results. These hand-held computers also have the ability to function as electronic pagers and can receive wireless electronic mail. As technology improves over the next few years, it can be expected that the hand-held computer will be as fully functional as a desktop computer and will be able to interface with the hospital and ED network via wireless connections.

SOURCES OF INFORMATION Technology possibly advances more rapidly in computing than in any other scientific field. Today's personal computer becomes obsolete within about 3 to 4 years, unable to run software that has just been produced. As a consequence, what is current today is likely to be out of date quickly. Useful sources of up-to-date general computing information include mass-market magazines available on most newsstands. There are also a number of computer magazines which specifically address computing topics of interest to physicians: MD Computing, Medical Software Reviews, and Physicians and Computers. MD Computing produces an annual issue that lists vendors and software by field, including emergency medicine. Current information can also be obtained via a search of the WWW. ACEP has a computer interest section that produces a list of software and reviews of interest to emergency physicians. Practice Guidelines Chapter 14 identifies some of the many practice guidelines developed by national organizations and consensus groups. These can now be accessed via the Internet (2). For example, the Communicable Disease Center (CDC) offers travel guidelines ( http://www.cdc.gov) while the American College of Physicians (www.acponline.org) has a site with search capability of all guidelines published in the Annals of Internal Medicine. The National Library of Medicine has attempted a clearinghouse function for guidelines. Practice protocols, guidelines, and parameters are becoming more common and, despite their detractors, are proving useful for cost savings (3). References 1. Interview with Bill Gates, Chairman of Microsoft. PBS, Charlie Rose February 1998. 2. Owens DK: Use of medical informatics to implement and develop clinical practice guidelines. West J Med 1998;168:166–175. 3. Guterman SJ, Van Rooyan MJ: Cost-effective medicine: the financial impact that practice guidelines have on outpatient hospital charges in the emergency department. J Emerg Med 1998;16:215–221.

Suggested Readings Bird D, Bowles CK, Breeze G: Using the Internet. Indianapolis: Cue Corporation, 1995. Bleich HL, Slack WV: Designing a hospital information system: a comparison of interfaced and integrated systems. MD Computing 1994;11(5):293–296. Chapman DM, Marx JA, Honigman B, et al: Emergency thoracotomy: comparison of medical student, resident, and faculty performances on written, computer and animal-model assessments. Acad Emerg Med 1994;1(4):373–381. Clayton PD, Sideli RV, Sengupta S: Open architecture and integrated information at Columba-Presbyterian Medical Center. MD Computing 1992;9(5):297–303. Cole AB, Counselman FL: Comparison of transcribed and handwritten emergency department charts in the evaluation of chest pain. Ann Emerg Med 1995;25(4):445–449.

Glowniak JV, Bushway MK: Computer networks as a medical resource, accessing and using the Internet. JAMA 1994;271(24):1934–1939. Hendrickson J, Anderson RK, Clayton PD, et al: The integrated academic information management system at Columbia-Presbyterian Medical Center. MD Computing 1992;9(1):35–42. Holbrook J: Physicians and computer use. In: Hellstern RA, ed. Managing the emergency department: a team approach. Dallas: ACEP, 1992:153–159. Holbrook J: Dictation and trancription. In: Hellstern RA, ed. Managing the emergency department: a team approach. Dallas: ACEP, 1992:161–173. Hoyt SH, Bradley V, Taylor TB: Emergency department informatics: management systems. Top Emerg Med 1996;18(1):1–87. McKinney WP, Wagner JM, Bunton G, et al: A guide to mosaic and the World Wide Web for physicians. MD Computing 1995;12(2):109–114. Taylor TB, Bradley V, Hoyt SH: Emergency department informatics: an overview. Top Emerg Med 1995;17(4):1–80. Tierney WM, Overhage JM, McDonald CJ: Towards electronic medical records that improve care. Ann Intern Med 1995;122(9):725–726. Zelingher J: Exploring the Internet. MD Computing 1995;12(2):100–108.

CHAPTER 164 MEDICOLEGAL ISSUES IN EMERGENCY MEDICINE Principles and Practice of Emergency Medicine

CHAPTER 164 MEDICOLEGAL ISSUES IN EMERGENCY MEDICINE John D. Dunn Capsule American Law Regulations Malpractice Litigation Expert Testimony Standards of Medical Care in Malpractice Litigation Medical Record Issues in the Courtroom Actuarial Analysis of ED Malpractice Claims High-Risk Clinical Entities Other Claims Studies Chest Pain Febrile Infants and Children Wounds and Lacerations Bite Wounds Fractures and Dislocations Abdominal Pain Dangerous Discharge Diagnoses Miscellaneous Causes of Malpractice Claims Legal Problems in Transfers Controversies on Cobra Enforcement Return Visit Syndrome Patients who Walk out AMA or without Care Unscheduled Admissions after ED Evaluation Violation of Confidentiality or Privacy Potential Injuries to Unknown Third Parties Medical Staff Issues Release of Records Admitting Orders On-Call Physician Response Legal Problems Related to Resuscitation Managed Care Problems Professional Liability Insurance Alternate Insurance Programs Insurance Coverage Channeling Programs Credentialing and Medical Staff Privileges Antitrust Law Contract Law Agency Law Reportable Events Consent Summary

CAPSULE Medical professional liability litigation has attracted attention because of the unpleasant nature of the confrontation that occurs in a medical malpractice case, but emergency medicine practice involves many other legal issues. Emergency department (ED) physicians, as a group, deal with the legal aspects of medical practice more than any other specialty. ED physicians are frequently involved in cases of child abuse, adult abuse, criminal investigations, patients with psychiatric conditions requiring commitment, terminal illness, consent, and other medicolegal issues. This chapter deals with general legal issues and also professional liability litigation claims against ED physicians.

AMERICAN LAW American law has many parts: regulatory/administrative law, civil law, and criminal law are the parts most important to emergency medicine. Regulatory Law The practice of medicine is highly regulated. Because 17% of the national economy, that converted to almost 1 trillion dollars in the year 1995, is devoted to health care, 40% funded by government, state and federal legislatures and agencies are intent to regulate health care. These efforts result in statutes, laws, and regulations that have enormous impact on health care providers. Statutes and laws are passed by Congress and state legislatures that give executive branches (president or governor) and their regulatory agencies power to write rules and regulations. State and federal agencies issue regulations and policies to achieve the goals of legislation. There are sometimes differences between the legislature's intent, the law that they wrote, and the way in which the regulations might be written or enforced. Disputes between regulators and the person or entity regulated are dealt with by agency administrative procedures, and, if not resolved, may be appealed to the state or federal courts for review. Civil Law Civil law is the law of the society. It includes medical malpractice and personal injury litigation, the rules that affect the success of a malpractice litigant, and the remedies available to individuals involved in malpractice litigation. Civil law also governs contracts, family relations, property, estates, and conflicts between individuals or organizations. CAVEATS State laws vary and all laws are constantly being revised; therefore, this chapter is intentionally general in its approach and national in scope. State statutes are generally similar on civil and other legal issues across the nation. Reference to particular state laws for each practice setting is essential. Federal law is national in scope, but sometimes state law supersedes federal law if it is stricter or more comprehensive or if federal law is silent. In other situations, federal law controls because state law is preempted as too strict, too restrictive, or against national interests. Legal opinions reported in the medical or lay press are often on preliminary legal issues that are on appeal. The outcome of litigation, particularly malpractice litigation, is usually based on the factual medical issues. Appellate opinions appear to reach ultimate legal conclusions when they may not. The medical issues and the facts of the case often control the outcome, and although appellate court legal dicta may appear to dramatically affect the outcome of a case, in practice they may not be so important. Read the reports of these appellate opinions with caution. They may only be opinions on preliminary motions, admissibility of evidence or inclusion of a party in the suit. Often, the actual case must still be tried.

REGULATIONS Medicare/Medicaid Conditions of Participation Participants in Medicare and Medicaid are under contract with the federal government. Agencies for the federal government, therefore, have the authority to regulate these “participants.” Medicare “Conditions of Participation” ( 1) are the federal regulations that outline how hospitals should be operated. The Healthcare Financing Administration (HCFA), which is a division of the Department of Health and Human Services, is in charge of regulation of Medicare/Medicaid participating providers. The Conditions of Participation tell the hospitals how to operate and appear to be a scaled-down version of the standards promulgated by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). These Conditions of Participation outline how the various departments of a hospital should be organized and run.

The regional offices of HCFA delegate their investigative responsibilities to local state agencies, usually departments of health, to ensure compliance with the conditions, but HCFA supervises and makes final decisions in the regional office. Accreditation from JCAHO is automatic Medicare certification, called “deemed status.” A small percentage of accredited hospitals are independently reviewed by the agencies working for HCFA to determine the adequacy of the accreditation process as performed by the JCAHO. New York does not accept accreditation and “deemed status” and conducts separate inspections to ensure hospital compliance with Medicare Conditions of Participation, but it is the only state known to do so. This trend may continue. The Medicare Conditions of Participation essentially set out standards for operation of Medicare contract hospitals. Violation of any of these conditions can be investigated on the basis of a complaint from the public or from a professional. The HCFA regional office authorizes an investigation to be conducted by the local state health department. Failure to comply with Medicare Conditions of Participation on any of the units might subject a hospital to a 23-day fast track termination for immediate and serious risk to patients' safety, or a 90-day termination, which allows for interim review and inspection to assure compliance. Only rarely do hospitals fail to bring themselves into compliance within a 90-day period. Essentially, the 90-day termination approach is intended to force hospitals to modify policy and procedure or activities in a certain area of noncompliance. Medicare violations are reviewed by HCFA regional offices, then referred to the US Department of Human Services Office of Inspector General for civil and criminal evaluation. Any activities that are in violation of civil rights statutes can be referred to the Office on Civil Rights in the Justice Department. If investigations show violations of other federal laws, appropriate referrals can be made to the Occupational Safety and Health Administration (OSHA), the Equal Employment Opportunities Commission (EEOC), or even the Environmental Protection Agency (EPA), which is in charge of enforcing laws related to waste (toxic and otherwise), underground storage tanks, clean air, clean water, and other environmental compliance issues. States and the federal government have special laws with regard to the disposal of medical waste (2). Other Medicare Rules and Regulations There are laws that have been written to control the Medicare dispersal of funds. These laws automatically include Medicaid, which is the indigent component of the federal health care payment program. There are many regulations that relate to billing, collections, balance billing, balance collections, and there are new rules that relate to self-dealing, kickbacks, Medicare fraud, and other efforts on the part of the federal government to control Medicare and Medicaid activities by providers. A classic example is the Medicare Fraud and Abuse Rules ( 3) that have to do with rules about billing and physician ownership of ancillary services and other sources of income where there is a potential for self-referral, kickbacks, or unnecessary services and billing abuses. State Law States have medical practice acts that provide for the licensure and regulation of physicians; pharmacy acts, which would control the distribution of drugs and the prescribing practices of physicians; and other health laws that affect, for example, nursing practice and the operation of hospitals or other health care institutions. Usually, there is shared responsibility for regulatory activity in a state, and many different agencies in the state might have control and authority over the practice of medicine and hospital practice. The lead agency is the Department of Health in most states. Boards of professional practice play a licensure and regulation role. State legislators and Congress have not only an interest, but the authority to affect the practice of medicine in many ways. The law provides one with the authority to practice medicine and also limits that authority. Common Law Common law is the law that comes out of litigation in the court room. Decisions of courts in cases in English and American law (with the exception of Louisiana, which follows a civil law tradition) create the common law decisions that are the basis for generally accepted principles of law. In the case of Louisiana, the net effect is the same because attention is paid to decisions on the law, and court opinions are important to the development of the law in Louisiana. Louisiana assigns priorities somewhat differently, with the Napoleonic Code taking priority over court opinions. The common law tradition is based on deference to previous decisions, called the principle of “stare decisis.” This means that prior decisions, particularly those in the same jurisdiction, will be given great, if not completely controlling, influence on a current decision. Tort Law Tort (injury) law is a part of civil law that governs matters related to the allegations of negligence by doctors. If an individual wants to file a suit against a doctor or a claim against the doctor for improper care, tort law principles apply. ELEMENTS REQUIRED FOR SUCCESSFUL LAWSUIT AGAINST A DOCTOR FOR MALPRACTICE Show that the doctor had a duty to take care of the individual. Show that duty was not properly performed because of a negligent act or omission (failure to live up to the appropriate standard of care). The plaintiff must show that the negligent act or omission was the legal or “proximate” cause of the damages claimed. The damages must be measurable and remediable under the law of the jurisdiction. An easy way to remember is the four Ds—duty, dereliction, damages, and direct relation.

MALPRACTICE LITIGATION The steps involved in a medical malpractice claim and lawsuit include the following: A Claim or Demand is Made When an incident or problem case develops, it is important to recognize that this is only the first step that might lead to a malpractice claim. The perception of improper care by the patient or family is frequently more important than the reality. The management of a claim or complaint can be the most important part of professional liability risk management. Proper response and careful evaluation of a complaint or claim and the medical information related are essential. It is important to recognize the following principles of good complaint and claims management: 1. Information should be gathered by somebody familiar with rules of the law, and the medical issues should be reviewed with a medical expert. 2. During the initial process of gathering information, no attempt should be made to resolve the claim or dispute other than to make sure that the patient receives appropriate ongoing care and assurance of a complete evaluation of the problem. 3. If there is a strong probability of litigation, the case should be labeled as a likely lawsuit to create some immunity of the investigation from discovery efforts later by the plaintiff when the suit is filed. 4. If the claim or dispute does not involve a significant injury or a significant medical dispute, it is advisable to try to evaluate it completely, allow the individual to ventilate the complaint, and attempt to achieve an amicable resolution as quickly as possible. 5. If there are significant damages and a good possibility of litigation, the insurance company should be informed so that it might protect the interests of their insured. (If one receives notice of a lawsuit, one must inform the insurer immediately.) 6. During the initial stages of the investigation of a serious incident, it is absolutely essential that a good medical expert, familiar with the medical issues and appropriate standards of care, evaluate the case objectively and fairly and make no premature judgements or promises. If attempts to resolve the complaint or claim are unsatisfactory, the plaintiff and the plaintiff's attorney may decide to file a lawsuit. If a lawsuit is filed, responses from

the defendant to the accusation are filed with the court. The statute of limitations is a special state or federal civil procedure law that limits the time in which someone can sue. For example, states have a rule that one must sue within 2 or 3 years of the time of the injury; there are some provisions for delay or extending the time when the cause of the injury could not be discovered. It is important to know the statute of limitations for a claim in your own state because it controls the exposure period. Many states have special rules for injuries to minors, extending their opportunity to sue until they become adults, or at least until they become older. Discovery After the suit is begun, “discovery” commences, involving the gathering of information. That gathering of information is formalized by legal procedures pertaining to exchanges of questions (interrogatories), the production of evidence, the requirement of medical examinations, and the taking of written sworn testimony (depositions) from witnesses and experts on the facts and the issues in the case. Trial If, during the discovery stage, resolution of the claim does not occur or a settlement cannot be made, the case proceeds to a trial. In a trial, the judge rules on the legal issues. The judge can also try the case or the trial can be to a jury. Appeal If either party is dissatisfied with the findings at the trial court level, that party can appeal such a decision to a higher appellate court in the state system or, if the case is being tried in federal court (allowed under special circumstances), the appeal is to a federal circuit. The final appeal goes to the state supreme court or for federal cases to the United States Supreme Court if these courts agree to hear the case. Acceptance of the case is discretionary, and medical malpractice cases do not reach the supreme court of the state or the United States Supreme Court unless there is an important legal dispute to resolve. Appellate courts stay away from facts and deliberate and rule on procedure, evidence, and other legal issues.

EXPERT TESTIMONY Under the federal rules of evidence, which are usually imitated by the states, experts are allowed to give testimony that would assist the trier of fact. Federal Rule of Evidence 702 allows that experts provide scientific, technical, or other specialized knowledge that will assist the trier of fact to understand the evidence or to determine a fact in issue. Experts are allowed to testify on hypothetical situations and to give opinion testimony. The information that an expert is allowed to depend upon is in Rule 703 and allows experts to rely on those types of information that are normally relied upon by experts in their field. New Rules on Expert Testimony Experts are allowed to give opinions on the ultimate issues that normally would be thought of as in the province of the jury, particularly if those opinions are based upon the expert's area of knowledge, so long as the expert is not offering a legal opinion. Federal Rule of Evidence 705 allows that an expert may testify in terms of opinion or inference, but that an expert “may in any event” be required to disclose the underlying facts or data on cross examination. The old test for admissibility of expert scientific testimony was articulated in Frye v. United States ( 4) that essentially said that anything that is generally accepted by scientists is acceptable as evidence, but in Daubert v. Merrill Dow ( 5), the rules were refined, and the Daubert court essentially said that the courts must require experts who present testimony to show the following: 1. 2. 3. 4.

Whether the theory or technique has been tested. Whether the theory or technique has been subjected to peer review, publication, and other tests of its validity. What is known of the potential error rate of the scientific technique, and whether there are standards that control the technique and its mistake rate. Whether the technique or theory has been generally accepted by the relevant scientific community.

Along with these rules, scientific testimony is subject to cross examination on reliability, the basis for the opinion, and tests on whether it tends to prejudice the jury or help the jury in its deliberations. The post-Daubert litigation requires that attorneys, courts, and experts respect the scientific rules and do more than just offer opinions. For example, in a Seventh Circuit Court opinion ( 6), which upheld a lower court rejection of a well-recognized cardiologist's testimony, Chief Judge Posner opined that a mere offering of an opinion by an expert does not prove that the testimony is genuinely based upon scientific information and does not eliminate the fact that it may be an opinion based upon unscientific speculation and not subjected to the rigid criteria required of science. Judge Posner asks, “Why should a court rely on the sort of exposition the scholar would not tolerate in his professional life?” and demanded that, in a court, an expert offer “ the same standards of intellectual rigor that are demanded in their professional work.” In this particular case, Dr. Fozzard, a well known and recognized cardiologist, offered the opinion that Nicotrol, a nicotine skin patch used for assisting people to discontinue cigarette smoking, might be the cause of an acute myocardial infarction, without basing his opinion on legitimate scientific studies. The opinion, although based on somewhat circumstantial speculation that cigarette smoke causes heart disease, ignored the fact that acute events are not chronic disease, and causation in the legal setting requires a “more likely than not” test for the testimony to be acceptable. Plaintiffs are required to prove a duty. They are required to prove that a physician defendant or other defendant fell below a standard of reasonable care, and that failure to meet the standard more likely than not caused the damages alleged. Merely getting up in court and expressing an opinion that has not been satisfactorily researched may in the future fatally flaw a plaintiff's medical malpractice case or a defendant's defense. Development requires that defendant physicians carefully study the medical and the scientific issues of any medical malpractice case and make sure that experts are not just speculating on those issues. This is particularly important, considering that the burden of proof is on the plaintiff to establish their case and has heightened the importance of close study of the medical issues of any medical malpractice case and has improved the opportunity for defendants to show that junk science and the unquestioned presentation of what amounts to mere speculation on the part of plaintiffs' experts may not meet the standards of admissibility and may be considered by the courts to be prejudicial, and misleading. Physician as Witness The physician defendant is the best witness for the defense. Rules to follow are Dress respectfully. Act respectfully. Be serious. Be prepared—read and know the records and the issues. Listen carefully and respond honestly and carefully to the question. Do not be argumentative or clever. Hold your temper. Take a break when you cannot do the above. Watch to make sure the opposing attorney is asking questions, not putting words in your mouth. Do not expand your answers—do not educate or try to convince the opposing attorney. Answer every question accurately, then you will be credible on the big questions.

STANDARDS OF MEDICAL CARE IN MALPRACTICE LITIGATION Across the country, physicians struggle with the concept of the appropriate standards of care. These standard-of-care issues are related to appropriate allocation of resources for health care, the resolution of professional liability claims and litigation, and appropriate standards to be applied to physicians in quality assurance and peer review matters. The “legal” or common-law definition of standard of care can be paraphrased as follows: A physician is required to possess and exercise that degree of skill and knowledge that is exercised by the average prudent and reasonable physician who claims the same specialization and who practices in the same or a similar locality.

When we consider the content of this statement, which basically describes the dicta or rulings of many courts in the United States on the standard of care, it is important to understand the following elements: 1. “Average prudent physician” does not mean superior physician, but means what it says. Time, energy, educational, and resource limitations sometimes do not allow superior evaluation and treatment. The question remains, what would be the average prudent approach to a particular problem? 2. The average physician is assumed to be a prudent and reasonable physician. 3. Practicing a certain specialty creates a distinct legal expectation. If you announce yourself as a specialist in neurosurgery, the public has the right to expect you to perform as the average prudent neurosurgeon would. If you claim no specialization or expertise, you are expected to perform as an average, prudent, licensed physician would perform under the circumstances, which includes appropriate use of consultants. 4. The “same or similar locality” qualifier is designed to create a generally accepted standard of care that allows differences in facilities, personnel, training, education, styles of practice, and other matters that relate to reasonable practice variance across the country. Although a national standard of care is accepted by courts, it is important to recognize that within that national standard of care are variations created by geographic and other factors in addition to the variances that exist because of medical training and custom and specialty practices. Clinical Policies in Malpractice Litigation A majority of medical specialty societies and other public service organizations write practice parameters and guidelines with the intent of promoting uniformity of practice across the country. The practice parameters that have been written are numbered by the American Medical Association at more than 1200 ( 7). Some of these are elaborate practice parameters based upon a research of the literature, and others are less authoritative. ACEP has written a number of practice parameters called clinical policies which include guidelines on the management of headache, nontraumatic chest pain in adults, febrile children under the age of 2, acute blunt trauma, acute toxic ingestions or exposures, nontraumatic acute abdominal pain, seizure not in status epilepticus, penetrating extremity trauma, and vaginal bleeding ( 8). ACEP also has a policy that provides for review and approval of policies generated by other organizations. For example, ACEP has endorsed the heart failure clinical policy from the Agency for Healthcare Policy and Research (AHCPR) and the unstable angina policy from AHCPR, both published in 1994. ACEP has also endorsed the asthma guidelines from the National Heart, Lung, and Blood Institute published in 1991. In 1996, ACEP endorsed the American College of Cardiology/American Heart Association Guidelines for the Management of Patients with Acute Myocardial Infarction, and, in 1997, ACEP assigned acceptance with some reservations to the clinical policy “Stroke: The First Hours Emergency Evaluation and Treatment” from the National Stroke Association and the guidelines regarding thrombolytic therapy for strokes from the American Academy of Neurology and the American Heart Association. As of June 1994, ACEP had a formal policy for review and endorsement of clinical policies from other organizations ( 9). AHCPR developed practice parameters through blue ribbon committees and contracts with various organizations during an approximately 3-year period, 1992–1995 (10). Eighteen Clinical Practice Guidelines have been published by AHCPR by 1996, but in 1996, the agency announced that it would no longer publish practice guidelines, but would attempt to support practice guideline writing across the country. The Maine legislature passed a law called the Maine Medical Liability Demonstration Project in April 1990 that dealt with a limited number of guidelines for practice in obstetrics-gynecology, radiology, and emergency medicine. In the case of emergency medicine guidelines, the only practice guidelines that were issued had to do with proper transfers and the management of patients with no evidence of cervical spine injury on criteria for not obtaining cervical spine radiographs (11). Since these Maine practice guidelines were published, it has been difficult to assess any real benefit for medical malpractice litigation ( 12). The rule applied in Maine is that following these practice parameters is an absolute defense for defendant in the litigation; however, in practice, minor violations of these practice guidelines or interpretative problems with the guidelines may result in no real impact on malpractice litigation. Addressing the question of practice parameter, practice guideline, and standard of care testimony and publication, some warnings are appropriate, and cautions are necessary as follows. Writers or testifiers on standard of care and practice parameters should be aware of some basic principles that will stand the test of time in the legal setting as well as in the practice setting. Those standards are: 1. 2. 3. 4. 5. 6.

Guideline and practice parameters and standard of care must be based upon a consensus. They must be based on verifiable and reliable medical research, not just what we do because we have nothing else to offer. They should be reasonable and practicable. They should be specialty specific because in many cases specialties have different approaches, skills, competence, and preference. When possible, they should be written conjointly by medical specialty societies interested in the same area. They must be updated when necessary and reviewed on a regular basis for timeliness and accuracy ( 13).

Daubert—More Stringent Rules As pointed out previously, the Daubert Supreme Court decision ( 14) has modified the old Frye (4) principles for expert testimony and has required that a new and more stringent rule be applied to expert testimony accepted in federal courts. This undoubtedly will be a trend that will affect state litigation ( 15). The goal of these legal opinions is to reduce the junk science and improperly presented scientific testimony that is either founded on inadequate or questionable research. Testimony by medical experts in medical professional liability litigation can frequently be misleading for the following reasons: 1. 2. 3. 4.

The medical profession, as a whole, aspires to success in every case, and no one is happy with a failed effort or an unsuccessful attempt. There is a generally held illusion that good doctors do not have bad results. In retrospect, one can frequently find a way in which the care could have been modified to theoretically avoid a bad outcome. Medical experts can create strict and idealistic standards when reviewing the medical records, particularly when there is a bad result ( 16,17).

Too often, testimony by expert witnesses in a courtroom has to do with normative or ideal standards of care as opposed to real standards of care. Contained within these conflicting standards is the fact that ideally the medical record is complete without any omissions and care is perfect, but the actual standard of care involves compromises on documentation as well as diagnosis and management. This is another area that requires particular attention for the defendant and the defendant's attorney in medical malpractice cases. There are clearly times when testimony presented by experts for the plaintiff discusses not the real-world practical and functional standard of care, but an idealized standard of care. For example, many times a plaintiff's expert will testify that a complete neurologic examination is required on any patient who presents with a potential neurologic problem; however, in practice and in fact, the neurologic examination in the ED varies in terms of its completeness because a complete neurologic examination is rarely done even by a neurologist, but is usually guided by the history and the individual case.

MEDICAL RECORD ISSUES IN THE COURTROOM

The legal importance of a medical record has evolved in the last 15 to 20 years to create an increasing documentation burden for physicians. Medical records are presumed by a rule of law (an exception to the hearsay rule) to be an accurate reflection of events, but the amount of information that a physician acquires to make a medical decision is awesome, even for minor cases, and not usually completely documented in the record. The opinion “if it wasn't in the record, it wasn't done” does not match reality or the limits of time and space. The record is realistically a short document that ideally says everything that occurred, but cannot. The better the documentation, however, the stronger the argument for acceptable care. The reality is that the medical record cannot hope to show all of the observations or the factors considered by the physician involved. There has been an increased emphasis on making sure that certain pertinent negatives are included in the documentation, to support the evaluation of the physician. Most medical malpractice claims against ED physicians occur when the patient was discharged from the ED and thought to have a condition that was not serious. Unfortunately, this also creates the mind-set that produces lesser documentation and a failure to document negatives that might help to support the decision to discharge the patient. In any event, ongoing studies of documentation and evaluation of ED records may show a significant problem of which the reader should be conscious. Including some pertinent negatives that help to support the decision to discharge the patient makes the medical record more of an asset in defending a malpractice claim or a lawsuit. Computer driven, transcription by computer, and hard copy medical record systems have been developed in the last 10 years to improve on ED medical documentation. The end result of these improvement programs is to improve quality assurance, risk management, and billing along with the obvious advantage of improving patient care. Computer-driven screen protocols can be used, but take the physician away from the bedside for entry unless bedside computers are available. Dictation requires a transcription booth and generates charts, which include descriptions of normals that are initiated by dictation that says normal or within normal limits. Handwritten protocol sheets at this point are less costly, on the order of $1 per record, and provide satisfactory entry of risk management and billing appropriate material. This author is familiar with the T-system from Emergency Services Consultants of Dallas, Texas. This author has no financial interest in the T-system approach, but finds it to be excellent for improving general medical documentation with a focus on new documentation requirements under the 1998 requirements from HCFA on Medicare/Medicaid documentation, but also documentation that is friendly to risk managers and quality assurance coordinators. Variations on this concept are superior, in this author's opinion, to freestyle dictation, but freestyle dictation is certainly usually better than handwritten records. The important thing to remember is that the medical record becomes the focus whenever a bad result occurs. Unfortunately, in the setting where a patient is discharged because the working impression is a nonserious illness, documentation tends to fall short of responding to all the questions that might be asked in retrospect. Quality assurance and risk management experts commonly are presented with this type of problem it is the reason why ED malpractice suits tend to be dominated by patients who are discharged, and it creates the medical record documentation conundrum that conflicts directly with the old saying about if it was not in the record, it was not done. We all know that is not true, but the problem is that it is like any deception, repeated enough and put in print enough and pretty soon a less sophisticated audience assumes it to be true. Many a defense case has been won on the quality of documentation, and many times defenses win malpractice cases in spite of omissions on documentation after all the disputes and all the witnesses are exhaustively examined; so a poor record is not a fatal flaw to defense of a case in a bad outcome, it just makes the work harder for the attorney and for the defense of a case. In malpractice litigation, the chart can be your ally and can bear witness to a thorough and thoughtful evaluation. When the chart is incomplete or was overlooked because the case was tough and the physician was distracted, the defense has to depend on other sources of information.

ACTUARIAL ANALYSIS OF ED MALPRACTICE CLAIMS Since 1980, there has been an increased interest in analysis of emergency medicine malpractice claims. The best analysis available is of closed claims for the endorsed insurance program of the American College of Emergency Physicians (ACEP), 1976 to 1984: 55 million visits, 1547 claims. There are characteristics of malpractice claims in the ED that will guide the physician in reducing malpractice risk ( 18).

HIGH-RISK CLINICAL ENTITIES The following produce more than 50% of malpractice claims dollar losses for ED physicians. 1. 2. 3. 4. 5.

Failure to diagnose chest pain (usually angina or myocardial infarction, frequently a claim that involves sudden death). Failure to properly care for wounds (includes infections or foreign bodies, tendon, nerve and vessel injuries undiscovered at the time of care). Mismanaged or missed fractures or dislocations (particularly spine and pelvic fractures). Meningitis (usually failure to diagnose in febrile infants and children). Delay or failure to diagnose abdominal pain (appendicitis, ectopic pregnancy, and other, usually surgical, conditions).

After this list of items, which create more than 50% of the dollar losses, are some other cases that frequently create malpractice claims against ED physicians, including the following: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Failure to treat alterations in mental status and central nervous system (CNS) status. (Headaches, TIAs, metabolic encephalopathies, and other CNS disorders.) Improper management of diabetes and its complications. Mental health and suicide/self-destructive behavior cases. Multiple trauma cases. Vascular disease, particularly in the elderly. Testicular torsion (delay or failure to diagnose). Management of seizure patients. Respiratory diseases with respiratory failure Airway problems (epiglottitis, croup, trauma, abscess, aspiration) Dehydration and electrolyte disturbances (particularly in the extremes of age), various causes. Ingestions, poisonings, and toxic exposures (delayed or inappropriate treatment) Sepsis, septic shock (delayed or inappropriate treatment).

All of these clinical entities presume primarily a standard of care related to diagnosis, but some claims involve inappropriate treatment. That leads us to an important conclusion regarding malpractice claims in the ED: More than 70% of all claims against ED physicians involve patients who are discharged from the ED, and, therefore, good discharge instructions and appropriate follow-up and reevaluation are essential to good risk management.

It is also important to recognize in these claims that we see a significant impact from high disability or death claims in emergency medicine professional liability claims (19). The magnitude of the claims has a major impact on the losses for ED physicians, with deaths and serious disabilities representing a significant part of malpractice claims. The Ohio Hospital Association Insurance Program did a 1985-1988 closed ED claims study that showed the following results: 1. 2. 3. 4. 5. 6. 7. 8.

Male claimants outnumbered female claimants. ED claimants tend to be younger. Older patients are under-represented in terms of ED claims. Self-pay and workmen's compensation claimants tend to be more frequent in their claims, but compensated less. The ED physician was the principal defendant in more than 60% of the ED claims. Residents tend to have more claims against them when they are on the emergency service. Frequently, ED claims involve a second physician, with most of those second physicians either the radiologist or the ED physician. Sixty percent of the ED claims involved a diagnostic error.

9. In terms of frequency, not magnitude, the following, in declining order, were the cause of claims: Missed fractures, myocardial infarctions or chest pain undiagnosed, soft tissue and wound problems, and appendicitis. 10. Forty percent of the ED claims are considered frivolous. The actual percentage of dollar losses for types of claims is not available from the Ohio report. Reviewing the reported claims that were listed, however, the missed diagnosis of chest pain had a tremendous impact in terms of dollar losses ( 20).

OTHER CLAIMS STUDIES Studies done by the Texas Medical Liability Trust (TMLT), Century American Insurance Company, the Gaultney Group of Houston, St. Paul Fire and Marine Insurance Company, and the Physician's Insurance Association of America, which is an organization of physician mutuals from across the country, all show the same trends as the ACEP study in the types of claims made against ED physicians and the financial impact of those types of claims. A recent comprehensive claims report by the Massachusetts College of Emergency Physicians Risk Management Program shows essentially no major new trends except that cases of missed MI are gaining increasing percentages of indemnity payments and the average payment for claims is trending up. In the Massachusetts program, only chest pain has a higher than 50% payment rate on claims ( 21). There are important new trends, however, that have shifted the type of claim to performance and management as opposed to purely diagnosis and identification. Delays in treatment of infections, failure to properly intervene, and failure to aggressively treat are now more common claims so that failure to diagnose cases which used to dominate malpractice against ED physicians have become less important. In some studies, mismanagement has risen to a 20 to 25% factor in terms of claims against ED physicians (22,23).

CHEST PAIN Nontraumatic chest pain in adults presents the most important malpractice problem for ED physicians. Failure to diagnose unstable angina, myocardial infarction, new-onset angina, and other catastrophic conditions, such as aortic aneurysm and pulmonary embolism, can result in a patient being discharged to later suffer sudden death or serious disability. Because most of these chest pain cases involve heart disease, the failure to diagnose cardiac disease is usually the measure of negligence and a failure to comply with the standard of care. The work of Lee Goldman, Thomas Lee, and their Chest Pain Study Group, as well as other researchers, has established some basic parameters for the accuracy of ED evaluation of chest pain ( 24,25,26,27 and 28). A multicenter Chest Pain Study Group analysis of 3000 plus adults seen with nontraumatic chest pain in both academic and nonacademic hospitals has been reported (29) and confirms a significant error rate in patients who are sent home. The Chest Pain Study Group showed that 35 of 1283 who were sent home had myocardial infarction or sudden death. This is despite the fact that the physicians seeing the patients were operating under a rigid chart protocol, including special attention to the history and the evaluation of the ECG. Of the most diagnostic help in the diagnosis of ischemic heart disease are: 1. 2. 3. 4. 5.

Central epigastric or chest and left arm pain of more than minutes. Generally severe and crushing or heavy rather than intermittent and sharp pain. Pain is associated with autonomic symptoms such as dizziness, nausea, vomiting, and diaphoresis. Pain is severe and ominous and often has a radiation factor. Physical findings may show new murmur or cardiac failure (30).

Patients with ischemic heart disease may have risk factors such as family history, diabetes, previous heart disease, high blood pressure, smoking, cocaine use, high cholesterol, and abnormal lipids ( 21,31). However, only previous heart disease is helpful for the single case. Americans, in general, are at risk for heart disease. Certain diagnostic findings on the ECG, if new, must be emphasized, including: 1. 2. 3. 4. 5.

Hyperacute T waves ST segment elevations more than 2 mm in chest leads and 1 mm in limb leads in 2 or more anatomically contiguous leads. ST segment depressions that are flattened and more than 1 mm New Q waves New conduction defects or significant axis changes ( 32,33).

Patients who are mistakenly sent home are characterized as follows: 1. 2. 3. 4. 5. 6.

They tend to be younger (under 35 years old). They have first-time pain, or atypical pain. Enzymes and ECG are normal (both are normal in the early stages of many an MI). They have pain characterized by the examiner as chest wall or pleuritic pain. For one reason or another, their history is not reliable ( 26). They may have no pain (34).

Standard-of-care analysis requires that the physician take a good history, perform a physical examination, and read the ECG correctly to successfully defend against a malpractice claim. The pressure is on to improve time to thrombolytics in patients with acute myocardial infarction. National studies and national projects are underway to promote early treatment of acute myocardial infarction with thrombolytics ( 27,35). The National Heart Attack Alert Program goal of treatment with thrombolytics within 30 minutes of arrival in the ED is based on the evidence that this has a beneficial effect on survival and morbidity ( 36,37). The January 1997 issue of Annals of Emergency Medicine was devoted to the current standard of care on workup of the patient with chest pain-suspected ischemic heart disease. Various diagnostic strategies were compared, and the basic conclusions included the following: 1. The ECG is the initial basic tool for differentiating acute injury from other possible ischemic syndromes. 2. The technetium-99 nucleotide test, both resting and stress, is the most sensitive, physiologic, and specific tool for evaluating possible ischemic heart disease. 3. There are many other tools available including stress testing on the regular Bruce protocol, echocardiographic evaluation, and thallium testing, which are helpful, but not as sensitive or specific as technetium-99. Enzyme markers for cardiac damage include myoglobin, which is sensitive, but not specific; troponin, which is not only sensitive, but specific, and available in two forms, troponin-T and troponin-I (38); CPK, which is nonspecific, but sensitive; and CPK-MB, which is sensitive and specific. Recent literature shows that troponin is valuable as a test that remains elevated longer than CPK-MB. Troponin-I is slightly more sensitive than troponin-T in some studies, but that is preliminary. Rising myoglobin in the first two hours after chest pain may be an indication of cardiac ischemia, but is not specific. CPK, CPK-MB, troponin-I, and troponin-T are all enzymes that rise after a period of time, so they may be negative in the early stages of a myocardial infarction. Troponin-I markers appear to be sensitive enough that they will identify patients with minor ischemic syndromes, non-Q wave, non-ST segment elevation injury who are at risk for future cardiac events. All this information is reviewed in the appropriate chapters in this textbook. As mentioned, the January 1997 issue of Annals of Emergency Medicine is an excellent review article on diagnostic strategies for chest pain in the ED.

New malpractice litigation in the area of treatment of myocardial infarction will deal with subtle and sometimes esoteric questions on reperfusion, potential for reduction of injury, stunned myocardium, delayed treatment, and many other issues that are not easily studied in the clinical setting, but do offer plaintiffs an opportunity to claim damages that may or may not exist. The potential for confusion, and, therefore, benefit to plaintiff claims, is created by an interest in improving response time and reducing morbidity and mortality. However, reductions in mortality of a few percentage points, when nonthrombolytic mortality is on the order of 14%, creates significant problems in terms of the burden of proof for plaintiffs if the patient survives, and the case if the patient does not survive is that a few percentage points in survival may or may not meet the burden of proof requirement of “more likely than not” in court. The Medical Record in Chest Pain Cases Chest pain patients are sometimes inappropriately sent home. When this happens, the medical record is analyzed in excruciating detail. If a physician mistakenly sends a patient home, it is important that the defendant show that it happened despite appropriate medical evaluation. The Armed Forces Institute of Pathology (AFIP) studied the problem of misdiagnosis of chest pain in the ED under the leadership of Flannery and Granville. In a survey conducted in 1988 with 50% response from the ACEP members, the respondents ranked in priority 10 items to be documented in any adult seen for nontraumatic chest pain. The items, in order of priority, were: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Past history of myocardial infarction or angina Quality of pain Time elapsed since pain began Location of pain Radiation of pain Presence of diaphoresis Presence of dyspnea Response to therapy Comparison of this pain with past anginal pain Risk factors

AFIP then compared actual performance of ED physicians in selected EDs. The performance fell below 60% compliance on individual items, with an overall performance level over the 10-item list significantly below 60% performance ( 39). This variation between ideal and actual documentation cannot be ignored in the analysis of medical malpractice claims. Medical malpractice litigation is not a charting contest, but plaintiffs would like to make it one. Trends in emergency medicine claims seen over the past few years indicate an increase in the impact of heart disease on the total dollars lost in emergency medicine malpractice claims. The author has personally reviewed more recent loss runs in which chest pain claims were more than 30% of the total dollar losses, up from 19.7% in the ACEP study period 1975 to 1984. A recent study by the Physician's Insurance Association of America on missed myocardial infarction shows the same trends that we have discussed before and suggests the same risk management strategies for physicians ( 40). WARNINGS Response to nitroglycerin, antacids, and reproduction of the pain with palpation of the chest should be viewed with caution because frequently these are misleading findings (25).

FEBRILE INFANTS AND CHILDREN Evaluation of febrile infants and children is common, but difficult and perilous. Problems include the following: 1. Children are seen against a background of common illnesses that produce fevers, and the rare serious illness may start out as a benign-looking process. 2. Although physicians generally recognize the potential risks of bacteremia, sepsis, meningitis, and pneumonia in febrile infants and children, the evaluation of the febrile infant or child is at a point in an unpredictable process. Infections can be benign or develop into life-threatening processes. The work of McCarthy at Yale (41) has taken some of the mystery out of the evaluation of febrile infants and children. Starting with a long list of observation items that clinicians might use in evaluating febrile children, McCarthy and his group have found that certain sensitive and reliable observation items establish the children with fevers who are likely to have serious illness. This approach creates an appropriate evaluation of the febrile child. The standard of care for evaluation is important in these febrile child cases. McCarthy's list of observation items is as follows: 1. 2. 3. 4. 5. 6.

Quality of cry Response to parents and examiners State of hydration General state of alertness Response to talk, smile, and social overtures Color

Many elements of the medical evaluation of patients of all ages are used almost subconsciously. Physicians may walk into a room aware of many important clinical characteristics of a patient, yet frequently fail to put any record down that shows the observations. It is important to consider that a neurologic examination can be performed in many cases without touching the patient and that, specifically in evaluating febrile infants and children, the general state of the child and the child's reaction to parents and the environment are obvious but sensitive measures of the severity of the child's illness. The brain is a sensitive barometer of a child's or infant's health and frequently the first functioning organ to be affected by serious illness; therefore, general state is one of the best measures of a child's condition. McCarthy has finalized this basic concept of clinical medicine into the Yale Observation Scale (YOS). Some basic caveats, however, must be attached to the work of McCarthy. They include the following: 1. In a child under 3 months, neurologic development limits use of the observation scale. 2. With temperatures above 40°C (104°F) or subnormal and white blood cell counts above 15,000 or below 5,000, increased risk of bacteremia is present and should alert the physician. 3. The Yale Observation Scale (YOS) ( 39) and the Young Infant Observation Scale (YIOS) ( 42,43) should be used to assist in developing the diagnostic hypothesis. There are no magic approaches to febrile infants and children. Although many medical experts have appeared in court and declared certain “rules,” the clinical evaluation is a complex and multifactored medical exercise, and no single element should control. An excellent review of concepts in pediatric bacterial meningitis is available from the October 1993 issue of Annals of Emergency Medicine by Lipton and Schafermeyer from the Carolinas Medical Center ( 44,45). Medical Record in Cases of Febrile Infants and Children The importance of documentation in evaluating febrile infants and children becomes important in the context of medical malpractice litigation. In retrospect, parents' stories of what happened are often affected by the eventual outcome of the case. Recollection of the events surrounding the evaluation is limited, and, as a result, the

medical record becomes more important. Physicians do not send home children that they consider to be lethargic and at risk for meningitis, but plaintiffs' attorneys frequently accuse physicians of doing just that. The plaintiff's attorney finds a medical expert who picks through the chart and finds a few omissions of documentation and concludes that anyone who misses certain items of documentation must be providing a negligent evaluation. These criticisms leave the impression in the minds of the jury that the defendant physician was incompetent because: 1. Good doctors do not have bad outcomes. 2. All doctors do extensive documentation, even in a busy ED. 3. A combination of omissions of documentation and a bad result is somehow prima facie evidence of malpractice. These deceptions always affect litigation on meningitis or sepsis malpractice cases. The reality is that medical practice is an imperfect art and science, and the judgment is sometimes wrong, but that is not medical malpractice. Malpractice is the failure to do a prudent evaluation, not a misjudgment after the evaluation. Studies have focused on the question of timeliness of antibiotic therapy. Median time from ED registration until antibiotics was delayed in many cases, in one study 3 hours with a total range of 30 minutes to 18 hours. Delays come for many reasons, sometimes because of CT scan and laboratory analysis ( 46,47). Studies have shown that antibiotics given even before the spinal tap and spinal fluid are available created no clinical problems ( 48,49). Therefore, early empiric treatment may be preferred. Some studies have shown that delay in treatment or a failure to treat and a delay in diagnosis have no consistent connection with outcomes ( 50). This may reasonably be related to the virulence of the organism and the health status of the patient and is not so mysterious when considered logically, but, in the heat of a meningitis malpractice case, plaintiffs benefit greatly from exaggerating the effects of delayed diagnosis. WARNINGS Response to Tylenol in the ED, absolute level of temperature, and white blood count can all be misleading because patients with severe infection can have low temperature and low white blood count and the patient's general condition is more important than the response to Tylenol or the white blood count ( 44,45). In circumstances where there is doubt and cultures have been done, but the patient will be seen as an outpatient, coverage with Ceftriaxone is an effective strategy and has had a substantial impact on ED practice ( 51,52). There is an ongoing controversy about the management of febrile infants, and the debate will continue ( 53,54). It is also important to recognize that practice and theory do not always coincide ( 55). The debate goes on, and studies show that the Rochester criteria ( 40,41) may be a reasonable alternative. With regards to the evaluation of febrile infants, it appears that the Rochester criteria, which is also called the Young Infants Observation Scale (YIOS), and the Yale Observation Scale (YOS) have become important tools in the evaluation of children and infants with fever. Controversies in the management of febrile infants include the management of a first time febrile seizure, and at this time the standard of care provides for a less aggressive approach as long as the child completely clears after the seizure. Given the current trend toward outpatient management of many illnesses, evaluation of the very young infant and outpatient management as well as the strategies for outpatient management of febrile infants and children will require continued analysis and research into how to identify children and infants with serious bacterial illness (SBI) (56).

WOUNDS AND LACERATIONS Wound cases create frequent and sometimes significant malpractice risks because all undiscovered underlying injuries or subsequent infections could potentially promote a malpractice suit. It is essential that documentation address the prime areas of complications of wounds so that the physician's medical record will be defensible. That is not to say that a record that fails to mention these items is indefensible, but it is important to create the most favorable medical record possible under the circumstances. Busy EDs and higher priority patients may prevent the physician from making all of the documentation a part of the wound/laceration medical record. Establish a routine that includes the evaluation of wounds for the presence of foreign material, irrigation and debridement, and a search for underlying injuries to nerves, tendons, bones, or blood vessels. The care of the wound should attend to potential complications and document proper precautions with good discharge instructions and follow-up. Plain radiographs show most metallic and glass foreign bodies and should be used in suspicious cases ( 56A,56B). Ultrasound and CT have been used for organic foreign bodies.

BITE WOUNDS Particular attention must be given to bite wounds, whether animal or human, because of the high risk of infection. The notorious bite wound is the human bite to the hand held in a fist position that results in deep injuries that are displaced when the hand is examined in the open position. In addition, the problem of hand infections in other types of wounds to the hand cannot be ignored as a major consideration. Management of bite wounds with close follow up and prophylactic antibiotics is advised. Closing bite wounds in some circumstances would be imprudent, and secondary closure after observation, antibiotics, irrigation, debridement, and conservative initial treatment may be the better choice. Animal bites in the extremities or in areas where esthetics are not important should be treated with a conservative approach and frequently, unless they can be cleaned and properly debrided, should be left open. Obviously, tetanus, rabies, and infectious complications must be considered. Poisonous snake bite and spider bites frequently create potential for malpractice litigation because the patient and family often arrive in the ED anxious and upset. The initial changes caused by poisonous snake bite also have a tendency to jeopardize confidence in the physician, because extreme swelling, discoloration, and pain are frequently a part of the poisonous snake bite scenario. Mild snake bites or dry snake bites should be watched carefully for a period of time to ensure against a delayed reaction. Mild to moderate reactions should initiate studies to identify coagulopathys. Remember that the coagulopathy of snake bite is not DIC and that blood component therapy replacement is appropriate. Antivenin in a patient with coagulopathy and systemic symptoms is appropriate with 5 to 10 vials for mild and more for moderate to severe reactions. Good patient education and communication are essential because of the factors mentioned above. The risk of anaphylaxis in the use of antivenin is a significant factor at this time, but, in the near future, less antigenic sheep antivenin may reduce this therapeutic problem. Black widow spider bites are important for the same reason as poisonous snake bites; they cause great anxiety and concern. In the extremes of age, they can produce morbidity and even an occasional death. Symptomatic treatment, antivenin when available, are all accepted. Calcium IV has been endorsed by some as beneficial for muscle contraction pain, but sedation, pain medication, and control of blood pressure are the keys to supportive therapy in black widow bites. Brown recluse bites produce local damage, and the initial characteristic lesion is a bulls eye with ischemia in the middle that breaks down to an indolent ulcer. Currently, there is no generally accepted effective therapy, but supportive conservative therapy of the wound site is still the standard of care. From the medicolegal point of view, the important thing is to warn the patient of the indolent and disfiguring nature of these ulcers.

FRACTURES AND DISLOCATIONS In the setting of a victim of trauma, spine fractures and pelvic fractures can be missed. Screening for possible spine fractures and pelvic fractures is a part of the systematic care of trauma patients. The unconscious patient must be assumed to have a neck fracture if the mechanism of injury is appropriate. Plain radiographs lateral of the cervical spine should always show the top of T1. There is some controversy about how many views are required to “clear” the cervical spine, but a full set of three films and consideration of CAT scan and flexion extension views may be necessary in some cases. Pelvic fractures have a high mortality rate because they are usually associated with other severe injuries and can be missed in the hurry of trying to take care of a desperately ill patient. Excellent work done by many investigators has established that a conscious, alert patient without other significant injuries to distract (for example, bilateral femoral fractures might be a distraction) can reliably tell the examining physician whether neck pain is present. If the patient does not have neck pain or tenderness, studies

show that the need for screening radiographs of the neck and concern about neck fractures is eliminated ( 57,58 and 59). Stabilization and immobilization of the neck are an important part of prehospital care. Soft collars are not acceptable, but many rigid collars and rigid fixation devices are effective in reducing flexion, extension, or lateral movement of the head and neck. Management of patients with possible neck fractures who require intubation is less controversial now. The important thing is physician experience and comfort with the procedures chosen. Oral, nasal, or surgical airways are all acceptable with in-line stabilization. There is strong evidence that oral intubation is a safe and acceptable procedure for patients even with suspect cervical spine fractures who have not yet been cleared. The other intubation procedures have some complications, including surgical and infectious as well as injury complications related to nasotracheal intubation and tracheostomy; therefore, if a physician is most familiar with oral intubation, in-line stabilization and oral intubation is the preferred method ( 60,61 and 62). In order of frequency, other missed fractures are those of ribs, hands, feet, elbows, and knees. Missed fractures of the face and skull are a significant legal risk. Certain fractures and dislocations are more likely to create permanent unexpected disability, thus being more likely to cause suits. Examples are tibial plateau, carpal and tarsal navicular, and elbow fractures.

ABDOMINAL PAIN The most important and common source of malpractice litigation in this group of patients is delay or failure to diagnose appendicitis. Surgical abdomen in the extremes of age is hard to diagnose. Ranking after appendicitis in terms of frequency in malpractice claims in patients with abdominal pain are ectopic pregnancy, biliary tract disease, vascular conditions of the abdomen (particularly abdominal aortic disease), bowel obstruction, cholecystitis, diverticulitis, peptic ulcer disease, intussusception, and other rarer catastrophic conditions. The catastrophic abdominal conditions are usually surgical, and, therefore, the threshold standard of ED care issues are related to when the surgeon should be consulted. A thorough evaluation of the patient with good chart documentation, close follow-up, and appropriate discharge instructions are critical factors. In the elderly with abdominal pain, particularly excruciating and severe abdominal and back pain, do not overlook the possibility of abdominal aortic aneurysm. The most frequent misdiagnosis under these circumstances is renal colic, with catastrophic consequences. Ischemic bowel syndrome presents with severe pain and physical findings that are puzzling. A hint in favor of ischemic bowel syndrome is unexplained acidosis and pain out of proportion to physical findings. Some general rules about abdominal pain: 1. 2. 3. 4. 5. 6.

The most common cause of abdominal pain of surgical origin is still appendicitis followed by gall bladder disease. Serial examinations are essential in order to avoid missing surgical abdomen. Many times early peritoneal signs are the only signs available, pain, point tenderness, and peritoneal irritation. The rectal examination is probably overrated in the discovery of intra-abdominal surgical conditions, but is occasionally diagnostic. 50% of the elderly who present with abdominal pain have a surgical abdomen or a significant intra-abdominal condition. Appendicitis is usually a short-term disease, but can present with variable white blood count and no fever. The more common situation is pain, fever, tachycardia, and elevated white blood count with point tenderness. 7. A flat plate without an upright is generally not a valuable radiograph. 8. Do not forget the pancreas, lipase may be more sensitive than amylase.

DANGEROUS DISCHARGE DIAGNOSES Following is a list of diagnoses frequently seen when the diagnosis was missed: 1. 2. 3. 4. 5. 6. 7. 8.

Gastroenteritis (missed meningitis, appendicitis) Functional disorder (missed PE, diabetes, sepsis, pneumonia, renal failure, MI) Rib pain/Chest wall pain/Reflux (missed heart disease, PE) Shoulder pain (ectopic heart disease, abdominal condition) Irritable bowel (diverticulitis, appendicitis, pancreatitis, CA, ulcer) Otitis media (early meningitis, pneumonia) Alcohol abuse (ulcer, GI bleed, sepsis, pneumonia) Conversion syndrome (neurological disorders undiagnosed, CNS trauma, tumor, infection, Guillain-Barré)

MISCELLANEOUS CAUSES OF MALPRACTICE CLAIMS Central Nervous System Problems Modifications of central nervous system (CNS) function caused by toxin, trauma, infection, tumor, metabolic disorders, and vascular disorders all create high risk situations for ED physicians. Any damage to the CNS can be irreversible and can produce a malpractice suit. Number one on the list of high-risk situations is the sudden severe headache that might portend the subarachnoid hemorrhage. Patients with sudden, severe, excruciating headaches at the peak of the head occurring during exertion or possibly even without any inciting activity should be evaluated carefully. CAT scans are not effective in identifying a small percentage of small bleeds and certainly are not effective in identifying the sentinel bleed, which may go before the massive rupture. MRI is a more sensitive test but can still miss subtle findings. Physical examination that shows sub-hyaloid hemorrhages in the retina along with suspicious history requires CAT scan and spinal tap if the CAT scan is negative. Although the dogma has always been that a fundoscopic exam is important in evaluation of patients with acute elevated intracranial pressure, this may be one of those myths that is useful only in the extreme circumstances of malpractice litigation. In fact, some research shows that disc changes and fundoscopic changes are delayed and inconsistent even with documented elevated intracranial pressure ( 63). Intervention in vascular problems including new treatments for transient ischemic episodes, carotid disease, and ischemic strokes are all discussed elsewhere in this textbook and create new standards of care and new management possibilities, which open up a great deal of opportunity for plaintiffs' attorneys in cases with bad outcomes. There are other trauma and infectious conditions that have produced some malpractice cases with regards to CNS injury, and they include central cord syndrome secondary to trauma with underlying spinal stenosis and also central cord related to infection and vascular problems as well as neoplasms. The central cord patient presents with proximal rather than distal weakness and mixed sensory findings. These partial cord syndromes are particularly difficult to diagnose. Guillain-Barré syndrome, an ascending motor neuropathy, can progress rapidly and initially present as, what appears to be, a functional disorder with patients claiming that they have clumsiness, weakness, and feel terrible. Since a cooperative patient is required for testing muscular strength, suspicious ED physicians frequently miss this diagnosis in its early stages. Unfortunately, within 24 hours, bulbar paralysis may develop that produces hypoventilation and can be life threatening. Epidural abscess in the age of drug abuse and IV drug users along with individuals with major immune disorders and the potential for bacteremic episodes can easily be overlooked because it may present as a mysterious neurologic syndrome in a patient with previous back problems or underlying psychiatric and personality disorders. The nightmare for an ED physician is to too quickly jump to a psychiatric diagnosis in the ED. It is easy to see how it can occur, but, frequently, it puts the ED physician unwittingly in the way of an oncoming litigation train.

Multiple Trauma Nobody is happy with the outcome on a multiple trauma case unless it goes as well as it would on television. Unfortunately, even the best of trauma care leaves some patients permanently disabled. The public relations people for major trauma centers sometimes forget to tell the public that we cannot replace devitalized CNS structures, and, for example, musculoskeletal damage may stymie the best ministrations of the best surgeons. Patients frequently survive the initial insult only to die of multisystem failure because of the massive and relentless effects of overwhelming shock discussed in other sections of this textbook. Although the management of multiple trauma cases is ideally straightforward and systematic, frequently cases are not cooperative in this matter, and patient conditions do not allow systematic and thorough evaluations in the face of catastrophic events. Most multiple trauma system protocols suggest reevaluation, reevaluation, reevaluation, reevaluation. Even then, occasionally, injuries will only reveal themselves at a later time. Advanced trauma life support is a basic course in trauma care available from the American College of Surgeons, which emphasizes the principles of basic resuscitation, repeat evaluation, and deals with proposed management strategies for patients who are the victims of major trauma. There are areas of controversy and debate in trauma care, and, as with most complex areas of medicine, there are many acceptable approaches to management. For the ED physician, coordinating appropriate consultant care and assuring general surgery management of overall care for the patient are the preferable strategy with an emphasis on constant reevaluation and repeat examination of the patient. High-risk concerns in the multiple trauma patient are as follows: 1. 2. 3. 4.

Proper brain resuscitation and protection. Airway management. Resuscitation with simultaneous evaluation. Screening x-rays to deal with the axial skeleton, the chest, and the pelvis where significant hemorrhage might occur or where life threatening conditions might develop. 5. A sophisticated approach to occult bleeding in the abdomen with an up to date awareness of diagnostic studies recommended and current surgical strategies. (See Chapter 21 for discussion of approaches to abdominal trauma.) Most important in a multiple trauma case is communication with the family and the patient. The ability of a physician to communicate at the time of a catastrophe may significantly impact the tendency of that patient or family to file a lawsuit over a grievance about the care provided, and it will also reduce the chance for disappointment and unrealized expectations for a good outcome. As many physicians have learned in their careers, it is best to thoroughly warn the patient of the limitations of our best efforts rather than to leave them with unrealistic expectations of excellent outcomes. Even the best ED physician and trauma surgeon cannot change some trauma situations. In the setting of major trauma, protecting the central nervous system is one of the major considerations in management, and the standard of care at this point includes special attention to acute spinal cord injury. Some individuals in the neurosurgical community are not convinced that methylprednisolone provides as much benefit as is suggested, but the National Acute Spinal Cord Injury Study has recently reasserted the importance of methylprednisolone for spinal cord injury ( 64). Vascular Conditions Particularly in the elderly, vascular insufficiency, embolic phenomena, and vascular compromise can be subtle, irreversible, unavoidable, untreatable, and catastrophic. Most vascular insufficiency situations produce pain out of proportion to the physical findings. Patients with other vasculopathy should be suspect for vascular causes of all sorts of complaints, and even early and aggressive intervention may not avoid permanent, irreversible disability or death. For example, ischemia of the superior mesenteric artery, even with the best care, has very high rates of mortality. Dissecting aneurysms of the thoracic aorta or the abdominal aorta are life threatening and catastrophic problems, and an index of suspicion must guide the physician. Although thoracic aortic dissections are an uncommon event, they occur in younger individuals, so the damages on a malpractice case based upon delayed diagnosis or inappropriate management can be significant. Elderly patients have diminished pulses in the extremities and compromised circulation, so the development of complete occlusion can be subtle and difficult to diagnosis. Recurrent abdominal pain due to ischemic bowel syndrome can easily be overlooked. Complications of injuries and infections occur more commonly in those patients who have vascular insufficiency, and, as a result, patients with diabetes and peripheral vascular disease should be approached with caution when they have extremity infections or injuries. A minor infection is a life-threatening situation in an ischemic limb. Testicular Torsion This urologic emergency usually presents as unilateral testicular pain in the prepubertal boy. Trauma is frequently thought to be the cause, but even minor trauma can result in testicular torsion, or the patient can incorrectly attribute the pain to trauma. Testicular torsion can come during exercise, for example swimming or running, and produces a unilateral swollen, painful, malpositioned, indurated, high-riding testicle. Doppler and nucleotide studies are helpful. The opposite testicle will show the bell-clapper deformity. The important thing is index of suspicion and analysis of the patient's history and condition with special consideration for testicular torsion. The window of opportunity for correction is narrow (up to 4 to 6 hours), and, therefore, speed of diagnosis and surgery to save the testicle is essential. A 30 to 40% negative exploration rate is acceptable to urologists. Suicide Gestures and Suicidal Ideation These cases frequently involve patients with chronic mental health problems, and management is difficult; therefore, the potential for malpractice litigation is high. Documentation regarding involuntary commitments, decisions that relate to therapy, and disposition can be critical in retrospect because these patients frequently do not have good family or professional support. This writer believes that outpatient management of many of these patients is acceptable and preferable. Standard of care analysis of suicide gestures and suicide ideation shows that outpatient mental health evaluation and management of depression and suicidal ideation is not only necessary, but preferable, since recovery from depression and avoidance of mental health hospitalization are significant factors in patient self-esteem and potential for recovery. A patient who believes he/she has been labeled mentally ill is more likely to make that a permanent identity problem. Most community mental health programs now have respite programs for emergency situations that do not provide complete security, but are assumed to be reasonable alternatives to mental health hospitalization, particularly at state hospitals for the insane. Initial evaluation should address the basic questions of whether the patient is suicidal, whether the patient has a plan for suicide, and whether the patient has previously attempted suicide. All of these things increase the risk. ED physicians can reasonably rely on community mental health programs even if those programs are staffed by nonphysician professionals, since they are a part of a system of mental health care that is custom and practice across the country. Patients with Drug and Alcohol Problems By definition, these patients have personality and mental health problems and are frequently unreliable in providing for their own care, which complicates the medicolegal environment. These patients are also litigation-prone. Use of social service agencies and support groups with careful chart documentation reduces risk. The personality disorder factor makes therapy of all kinds a treacherous effort. ED physicians are best advised to refer.

LEGAL PROBLEMS IN TRANSFERS State and federal laws, as well as some general medical principles, affect the conduct of a transfer. ACEP and the American College of Surgeons (ACS) have both developed position statements on the conduct of a transfer ( 65,66). The ACS focused on the importance of the receiving physician and the consulting physician controlling the quality of the transfer and coordinating transfer with the transferring physician. In addition, the ACS emphasizes the importance of expediting transfers, particularly in trauma cases in which patient outcome is affected by the inappropriate delays. Transfers are a high risk from a litigation point of view because patients being transferred are usually seriously injured or ill, families are upset, and there is a potential

for misunderstanding between the transferring and the receiving facilities and physicians. There is also, in a transfer situation, an opportunity for people to be critical of others caring for the patient at a previous facility. The best advice in regards to reducing these risks is to comply with the law, communicate well with both ends of the transfer, and attempt to satisfy the needs of both the transferring and the receiving physician while expediting the transfer. Sometimes, it is impossible to decide how much of a workup to do and how much stabilization to do before transferring a patient to a higher level of care. This problem should be understood on both ends, and a little bit of courtesy and consideration will reduce the risks of malpractice suits in transfer cases. The ACEP, in its transfer position statement published in 1977 and modified in 1989 ( 65) has emphasized the importance of the following: 1. The transfer of an emergency patient should be undertaken only for good medical reasons. 2. Proper evaluation, initial treatment, and stabilization are important steps before attempting a transfer. 3. A transfer should always be initiated because the care anticipated at the receiving facility will benefit the patient and the risks of transfer are outweighed by the benefits of the care that will be provided at the receiving facility. 4. Proper communication between the transferring and receiving physicians, nurses, and facilities is imperative. 5. Proper conduct of the transfer includes transfer of information on treatment at the transferring facility. 6. The transfer should be conducted with proper transport equipment, personnel, and intratransfer preventative and stabilizing care. 7. The receiving physician and the transferring physician should share the responsibility of conducting the transfer according to appropriate medical standards. During the early 1980s, several articles appeared in the medical literature criticizing the conduct and the motivations of transfers ( 67,68 and 69). These articles criticized the fact that many transfers appeared to be economically motivated. Specifically, they criticized transfers to public hospitals such as Parkland in Dallas, Cook County in Chicago, and Baptist in Memphis because the writers felt that proper communication and proper stabilization were not carried out before the transfers and that many patients suffered as a consequence of inappropriate transfer. In response to the problems of the Dallas area, the state of Texas passed the first formal state transfer law specifying that an appropriate protocol must be used for transfers ( 70). Texas law requires that a memorandum of transfer be completed and evidence of proper communication between the transferring and receiving facility be assured. The acceptance of the patient must be obtained and secured by the transferring facility under the Texas law for a transfer to be properly accepted. The Texas transfer law cited ACEP's policy (65) on transfers in the law itself as a good outline. The Texas Hospital Licensing Standards, in Chapter 11, codified all of the various regulations that controlled the conduct of transfers. In 1985, Congress considered, in hearings on the problem of transfers, amendments to the Social Security Act. Legislation was passed in the Consolidated Omnibus Budget Reconciliation Act (COBRA) of 1985, which was signed into law in 1986. Section 9121 put into federal law a requirement that hospitals and physicians follow federal regulations on transfers or be found in violation. Emergency Care and Transfer Regulations “Responsibilities of Hospitals in Emergency Cases” appeared originally in the Consolidated Omnibus Budget Reconciliation Act (COBRA) of 1985 (signed into law in 1986) and were called the COBRA 9121 amendments to the Social Security Act ( 71). Additional amendments appeared in 1989 and 1990 ( 72). Section 1867 requires the following: 1. Emergency patients who present to the ED must be seen and evaluated to determine whether they have an emergency condition or are pregnant and having contractions. (Screening requirement.) 2. If an emergency condition, defined under the law as an urgent life-, limb-, or organ-threatening condition, is determined, the hospital must either treat, or stabilize and transfer. This also applies to a woman pregnant and having contractions. (Stabilization or transfer requirement.) 3. The hospital must use its resources and provide the care that it is capable of, or arrange for transfer to another more appropriate facility, considering that the benefits of treatment at that other facility will outweigh the risks of the transfer. 4. The transfer patient must be properly stabilized according to appropriate medical standards of care. 5. The receiving facility must be ready and willing to accept a transfer patient, and information on the patient's care at the transferring hospital must be communicated and transferred with the patient. 6. If the patient refuses treatment at the transferring hospital or refuses transfer, or if the patient requests transfer against medical advice, these matters should be documented and informed consents or refusal signed, if possible, in the medical record to show that the hospital is exempted from the requirements of any state or federal transfer laws. 7. The law requires a physician's written certification that the benefits of transfer and treatment at the receiving facility outweigh the risks of transfer. If there are any knowing or even negligent violations of the provisions, as outlined, the hospital is subject to a $50,000 fine, $25,000 if the hospital is less than 100 beds. The hospital is subject to termination from the Medicare program. This means that the hospital is subject to a 23-day termination. If it cannot show a corrective action plan in place (73), within 4 days, an announcement goes in the newspaper to warn the public that the hospital is to be closed from Medicare participation because it is an immediate and serious threat to patient safety. Even if the corrective action plan is adequate on a follow-up inspection, the warning in the newspaper may not be avoided because of a limited amount of time and the need to put the announcement in at the 4-day point ( 74). Physicians involved in inappropriate transfers or violations of COBRA are subject to fines for each knowing violation, and exclusion from the Medicare/Medicaid program for up to 5 years for a gross, flagrant, or repeated violation. The law also provides for other legal remedies: 1. Anyone injured by a violation may sue the hospital for damages using state law remedies. 2. Receiving hospitals that suffer costs or damages because of an improper transfer may sue the transferring hospital. Another rule proposed and adopted in 1994 requires report of an improper transfer by the receiving hospital ( 75). The statute of limitations for EMTALA lawsuits is 2 years (time to sue from the incident date). The COBRA 1989 amendments to the law added: 5-year limit to keep records On-call lists of physicians Sign in ED guaranteeing service Informed consent paperwork Certification by the transferring physician as to risks/benefits of transfer Active labor changed to “having contractions” No delay of screening for insurance screening “Whistle-blower” protection for physicians or personnel who refuse an illegal transfer Expand “Responsible Physician” to include on-call physician Physician who refuses to come when called is in violation A physician who transfers after an on-call refusal is not in violation, but must put the name of the refusing physician on the transfer papers. An important 1989 amendment was the “reverse dumping” section (g) which requires higher capability facilities to accept appropriate requests for transfer if they have staff and resources. HCFA interprets resource availability and geographic analysis liberally in favor of the transfer, so higher capability hospitals can be found in violation easily if they refuse an appropriate request.

The 1990 amendments added: Knowing violations changed to negligent for hospitals Reduced the fine to $25,000 maximum for small hospitals (less than 100 beds) PRO review of physician cases required (HCFA may accept or reject) Knowing, willful on physicians changed to gross, flagrant, or repeated for Medicaid/Medicare exclusion ( 76) Considering that the articles on the dumping problem were quite inflammatory and even projected 250,000 dumps a year ( 67), a published study recently showed that the “crisis” created by Cook County Hospital, Parkland of Dallas ( 68), and Baptist of Memphis (69) may have been a “tempest in a teapot.” A review of all EMTALA/COBRA investigations for the first 10 years of the law showed about 750 million ED visits; in that time there were 1700+ investigations on EMTALA, fewer than 100 hospitals fined, and 6 physicians fined ( 77). The whole area of practical politics is to keep the populace alarmed (and hence clamorous to be led to safety) by menacing it with an endless series of hobgoblins, all of them imaginary. H. L. Menken

Indeed, transfers get everyone upset, but being upset and a “crisis” were never even in the same universe on the issue of transfers. For a fact, there were never 250,000 dumps a year as asserted by Ansell and Schiff (67). The Arizona group study proves it. On another “crisis,” there is a lot of concern about the increase in EMTALA claims filed by plaintiffs along with the usual malpractice claim. The federal circuits have consistently rejected the use of EMTALA as a new expanded malpractice statute. The federal circuit courts have staked out the following positions. 1. The screening requirement is for a basic nondiscriminatory screening, and the analysis will not go to accuracy of the diagnosis ( 78). 2. The hospital cannot be found in violation of the stabilization requirement unless it knew of an emergency condition and failed to stabilize ( 79). The Fourth Circuit, which includes Virginia and surrounding states, expanded the concept of EMTALA in a case cited frequently by many, called Power v. Arlington (80). In Power v. Arlington, a Fourth Circuit panel reviewing a case out of Arlington, Virginia supported the District Court decision to allow a quality assurance medical malpractice analysis of the screening exam done on a young woman who presented with what, in retrospect, appears to have been a case of early septicemia. The initial complaint was hip pain, and the patient, after a radiograph, was treated for a musculoskeletal condition. The next day, she returned to the same ED in septic shock, subsequently suffering significant and catastrophic injuries. The Fourth Circuit panel in this case allowed for a “cookbook” analysis of whether the screening examination was appropriate. For example, an expert criticizing the decision not to get a CBC was influential in the trial court's analysis of the case and was allowed in as relevant to the issue of whether an EMTALA violation occurred. Among other things, the Fourth Circuit in the Power v. Arlington case opined that a quality of care analysis/medical malpractice analysis of a case was allowed on the issue of whether an individual received a proper screening examination. Before and since, the other circuits and the Fourth Circuit have rejected this Power v. Arlington analysis, and so the Power v. Arlington case stands as the only case allowing the HCFA approach to analysis of screening to be the legal standard. All other circuits have essentially declared in one voice, “We will analyze whether the hospital complied with the EMTALA screening requirement in a limited way, and that limited analysis will be an effort to determine whether the hospital was discriminatory in its screening examination.” The Fourth Circuit in Vickers v. Nash ( 81) retreated to an earlier position articulation on the issue of screening examinations, essentially leaving Power v. Arlington without any influence even in the Fourth Circuit. At one point, the Eighth Circuit (Midwest) issued a panel decision in Summers v. Baptist Hospital of Arkedelphia ( 82) in an opinion with the following rational. Mr. Summers fell out of a tree while hunting and says that he went to the ED complaining of chest pain. In a deposition, the defendant physician admitted that he would have ordered a chest radiograph if the patient had complained about chest pain. This failure to do a chest radiograph was allowed as a basis for the EMTALA claim in court, and the Eighth Circuit reversed the trial court decision to dismiss the case. At that point, the trial court had been following the more restrictive interpretation of the screening requirement. An articulate dissent by the chief judge of the Eighth Circuit, who sat on this panel, resulted in a decision on the part of the Eighth Circuit to vacate the original Summers v. Baptist Hospital opinion and reconsider. In 1996, the Eighth Circuit came back home to the original opinion it had issued in Williams v. Birkeness (83), which was an opinion that stated essentially the general rule adopted by all the other circuits that the screening examination will only be analyzed in terms of whether it avoids discrimination and not on the adequacy of that examination. What the federal circuit courts have all said is that they will not use the EMTALA statute as a medical malpractice statute. They will only use it with the limited purpose of preventing discrimination against an individual who presents to the ED. That is diametrically opposed to the HCFA approach to the screening part of the statute, which is a quality of care quality assurance analysis of whether the screening is adequate and appropriate. Another factor here is that HCFA always has the benefit of retrospect in whether the screening examination was adequate—a bad outcome is bound to influence the opinion of a HCFA investigator. It is critical to risk management on the transfer case to communicate adequately with the receiving facility, its personnel, and the receiving physician. Nothing is more likely to produce a malpractice suit than a dissatisfied receiving facility and physician. Moreover, a decision as to timing on transfer, appropriate pretransfer workup, and intratransfer care is always something that should be coordinated with the receiving physician and facilities so that there is no potential for criticism at the end of the transfer in front of patient and family. One of the quickest ways to expose oneself to malpractice litigation is to transfer a critically ill patient without proper communication and coordination.

CONTROVERSIES ON COBRA ENFORCEMENT A number of questions have arisen over the last 10 years of COBRA enforcement, created by inconsistencies among the federal HCFA regions and unpredictable interpretation of the law. These questions are: 1. What is the screening examination? It has always been the position of ACEP that only physicians should do screening examinations; however, even from the beginning, hospitals and others, as well as HCFA, which is in charge of interpretation of the rules and regulations, have accepted the idea that nonphysicians could do screening examinations. In the Federal Register, June 22, 1994, three public commentors proposed that the regulations affirmatively state every patient regardless of ability to pay should receive a medical screening examination performed by a physician ( 84). The response from HCFA was, Even when physicians are present in the hospital, there may be circumstances that are so clearly not emergency medical conditions that other qualified medical personnel may conduct the initial screening examination. However, although it is up to the hospital to determine under what circumstances a physician is required to perform an appropriate medical screening examination, that does not mean that HHS (that means HCFA) must accept the hospital's determination of what circumstances require that the screening exam be performed by a physician.

In the interest of turf and economics, many ED physicians are saying that the only safe approach to this ambiguity is to have physicians do all screening examinations with the resultant ongoing traffic and priority problems of busy EDs. At the same time, managed care organizations in the public and private sector object to the idea that a physician should do every screening examination. In addition, a problem arises because of the language of the law that states that a screening examination is “an appropriate medical screening examination within the capability of the hospital's ED, including ancillary services routinely available to the ED, to determine whether or not an emergency medical condition within the meaning of subsection (e)(1) exists.” Given that HCFA has said that many presenting complaints are clearly not emergency medical conditions, the question then is how to interpret capability. HCFA

has interpreted capability to mean that anything, including consultation and esoteric testing, would be considered part of the screening examination. This makes no sense. The common sense interpretation of the statute as written is that the screening examination is designed to determine whether it is reasonable to think an emergency medical condition exists. Under the definitions in the law, an emergency medical condition is “a medical condition manifesting itself by acute symptoms of sufficient severity (including severe pain) such that the absence of immediate medical attention could reasonably be expected to result in (author emphasis) (a) placing the health of the individual (or with respect to a pregnant woman, the health of the woman or her unborn child) in serious jeopardy, (b) serious impairment to bodily functions, or (c) serious dysfunction of any bodily organ or part”( 85). Therefore, this writer interprets the language to say what it appears to say once the examination indicates that you could reasonably expect that there might be an emergency medical condition, treatment and stabilization obligations are triggered, and we are no longer dealing with a screening exam. Therefore, once the ancillary services of the ED are recruited for the evaluation, we have passed the threshold of “could reasonably be expect to result in,” and we are dealing with treatment, stabilization, and additional evaluation, not screening. That does not take away the paranoia that exists across the country in EDs with regards to this screening examination requirement, fed to some extent by inconsistencies between the HCFA regions on enforcement and the ongoing tension between the emergency medicine community and the managed care community on the question of inappropriate use of EDs. 2. Can an ED develop a screening examination protocol that does not include a physician examination? Clearly, an ED can, and they do. Part of the problem is that many EDs that do use nonphysicians for initial screening and evaluation of patients either refuse to report it or refuse to stand up and be counted when the question comes up. Most major EDs have to have some kind of nonphysician screening of patients and prioritization that would clearly come under the obligations as set out by EMTALA; however, the mechanisms and methods used by these hospitals are not well known and may not have been reviewed either by HCFA or the emergency medicine community in order to properly evaluate the adequacy of screening by nonphysicians. The University of California Davis has the only longitudinal comprehensive report on nonphysician screening protocols. This ED has reported extensively their experience showing that there is no significant risk involved in doing it right, and that 18% of the patients seen in their ED over a 5-year period of 176,000 visits were screened and triaged away from the ED as nonurgent and nonemergent. Resources in the ED are best devoted to critically or seriously ill patients and the nonemergent, nonurgent complaints that are referred to other clinics and away from the Cal-Davis ED after a screening examination makes good sense ( 86). Key to the program at the University of California Davis, which has been approved by HCFA out of the San Francisco office and has also passed JCAHO accreditation surveys, is a protocol on the screening examination and training for screener RNs in the system. The 17-page protocol essentially outlines the criteria for evaluation, focused examination, and nonurgent chief complaints that may qualify for triage away from the ED. All other patients are evaluated and seen by physicians after an initial nurse priority assessment. There is no question that, across the country, hospitals with less sophisticated protocols are attempting to triage patients away from the ED on an attrition basis or on an economic basis if they are in a highly managed care environment. A managed care environment does not immunize the hospital or the physicians in the ED from their obligations under EMTALA, and, therefore, a more sophisticated and regimented approach such as that used at the University of California Davis is preferable to some of the informal “triage” systems being used at many hospitals. The Cal-Davis program is a properly regimented and developed screening protocol that could be adopted across the country and could achieve the nondiscriminatory screening examination that reduces the volume of EDs by the approximately 18% reported by Derlet. However, emotions, politics, economics, and turf as well as ongoing difficulties with HCFA regional variations lead this writer to predict that the nonphysician screening controversy will continue for the foreseeable future. 3. What about requests for transfer (e.g., from HMOs) that are economically motivated? The hospital, under the obligations set out by EMTALA, is required to stabilize patients and additionally treat them if an emergency medical condition is identified. Within the staff and facilities available at the hospital for such further medical examination and such treatment as may be required to stabilize the medical condition 87). (

or the hospital must provide for a transfer to another facility based upon medical risk/benefit analysis ( 88). As mentioned previously, the federal courts have obligated the hospitals to this particular stabilization requirement only if they “know” of an emergency medical condition, but that does not address the question of patients who have an emergency medical condition that is basically stabilized and then a managed care organization requests a transfer to one of their contract hospitals. This has become even more complicated because HCFA has indicated that they would consider the hospital to be coercive if they described financial arrangements and possibilities to a patient. This particular twist means that patients, according to some HCFA regions, should not be informed of any of the economics of medical care provided or the opportunity to go to a plan hospital. There are clearly situations where an emergency medical condition is seen, evaluated, identified, and stabilized and a transfer will not risk the patient. Lateral transfers, in general, are advised against, but clearly there are situations where adults have the right to ask for a lateral transfer to a doctor of their preference, to a hospital of their preference for various reasons. A classic example would be a fracture of the femur that will require surgery and hospitalization and a patient wants to go home, which may involve a 100 or 200 mile ambulance trip. Under what circumstances would it be inappropriate also for the patient to ask for a transfer to a hospital 10 minutes away that happened to reduce out-of-pocket exposure to the medical expenses by 20 to 40%? These kinds of issues will continue to vex ED physicians, who are basically obligated to ignore economics and make sure that patient care is not compromised. There are clearly situations, however, where patients with a “right to know” have a right to demand what the economic consequences of their decisions are, and it may be that, over time, managed care, HCFA, and emergency medicine will develop a cooperative effort designed to reduce inappropriate ED utilization, hold down costs of emergency care, and arrange for appropriate triage and transfer of patients based on reasonable medical and economic evaluation. Under no circumstances would this writer pretend that there is not a strong and, in fact, vocal group of ED physicians, including leadership, who disagree with the position taken here and would reject the University of California Davis approach to medical screening exam or any discussion of appropriate economically motivated transfers; however, this problem will not go away, and it would be important for ED physicians to recognize that at times some of the arguments appear to be economic and turf arguments, which ignore the realities of reasonable medical care and economic considerations. HCFA created a task force in 1997 and included representatives from various medical and hospital organizations in order to attempt to iron out some of the problems. The early reports in late 1997, prior to a formal report, indicate that the task force was unable to change HCFA policy on some matters, but, on other matters, HCFA has become a little more flexible. General rules on HCFA investigative and regulatory approaches include the following: 1. HCFA will still do what amounts to a basic quality of care analysis on screening examinations with an expansive approach to the question of “capability.” (Circuit court opinions across the country have taken exactly the opposite approach, only requiring that hospitals do not discriminate in their screening examinations, but HCFA is a regulator, and the basic rule here is that regulators like to regulate.) 2. Discharge of a patient from the ED without definitive and complete care will raise HCFA's level of suspicion, but they may be willing to accept transfers to clearly more appropriate care, such as an ophthalmologist's office for an eye injury or an eye problem. HCFA will continue to reserve the right to retrospectively criticize any decision made by ED physicians. 3. There will be a continued tension with regards to HMO decision making and gatekeeping, and HCFA will not take a position for or against who is in authority or in control, but they will blame an ED or an ED physician if a patient was evaluated and sent out of the ED when appropriate care might have been provided by that ED. In addition, HCFA will play no role in forcing payment of fees for emergency medical screening on managed care patients or authority of the examining physician versus the gatekeeper physician on proceeding with care. 4. HCFA still stands strongly against any kind of registration procedure that might be interpreted to interfere with initial medical screening and evaluation. 5. HCFA equivocated on the issue of whether physicians should be used to review cases on questions of appropriateness of treatment. Up to this point, regional

offices have had variable approaches to the question of quality assurance reviews of screening examination and stabilization. For many years, there has been variation among the regions on whether qualified physicians were available to review records, but the 1990 amendments to the Act required state peer review organizations to review on any cases that might be referred for civil penalties. That does not mean that PRO review occurs on all investigations. Given the fact that almost all major military installations and most major EDs have to provide for nonphysician initial screening, and given that economically motivated transfers are a real world necessity, the fact that recent studies of EMTALA and court decisions on EMTALA make it less fearsome than some would assert, compromises will occur, and, hopefully, reason will prevail for the benefit of the patient and the health care system.

RETURN VISIT SYNDROME Patients who return should be seen as an opportunity to correct a problem. We distinguish the “return visit syndrome” from the patients who come to the ED repeatedly for primary care. Return visit cases involve individuals with an acute illness or injury who are seen and then return because they do not get relief from the treatment prescribed. Physicians, under these circumstances, should be careful to reevaluate completely the patient and protect against oversights. If a patient returns for a third time, it may be necessary to consider even a consultation or precautionary hospitalization or observation period to avoid misdiagnosing the patient's condition. The “third time” returnees are time-honored problem cases in many institutions.

PATIENTS WHO WALK OUT AMA OR WITHOUT CARE Effective triage helps to avoid excessive delays in treatment. EDs see a spectrum of disease, but it is important to recognize that the patient who is ambulatory one day might be on a stretcher the next day; therefore, we must be conscious of the importance of ambulatory care in the ED. Departments are not only for the care of acutely ill or dying patients, and we must provide reasonably efficient and effective ambulatory care. Pure economics demand that EDs take proper care of ambulatory patients with injuries or illnesses. Every patient who presents to the ED should receive efficient and humane care, then a proper disposition with follow-up and good discharge instructions. Cases of patients who leave against medical advice need some chart documentation. Those who leave without being seen cannot effectively sustain a malpractice claim in almost all cases unless they present with a complaint that should be a priority. Research by Robert Williams published in 1996 indicates that EDs can provide reasonably efficient and cost effective primary care ( 89). Separate from that argument, there is no way to avoid primary care responsibilities in the ED setting, and, therefore, we must avoid triage by attrition, excessive waits, and inefficient approaches to ambulatory urgent and even nonurgent care. Dr. Williams' research shows that we can provide efficient and cost effective care because fixed overhead in the ED converts into a capacity that can make the marginal cost of ambulatory care competitive with clinics.

UNSCHEDULED ADMISSIONS AFTER ED EVALUATION Unscheduled admissions to a hospital within a short time after ED evaluation increase the risk of potential malpractice litigation, and should be monitored. With increasing efforts by insurance companies as well as Medicare and Medicaid to keep patients as outpatients, patients are often seen in the ED and later admitted because there is no improvement on outpatient therapy. However, it is important to recognize that if the patient or the family is not aware of this potential, they might think inappropriate care was received and consider lawsuit. Patient and family expectations must be tempered by physicians. Patients should be encouraged to return if not better with treatment.

VIOLATION OF CONFIDENTIALITY OR PRIVACY The ED environment is not conducive to confidentiality or privacy. Histories are taken in areas where others might overhear as well as see the patient's condition. Too little is done to reduce breaches of confidentiality in the ED, but, when possible, ED personnel should be conscious of an individual's need for privacy and confidentiality. Under no circumstances should one be careless or casual about revealing information on the patient's condition. The basic rule on confidentiality of a patient's record and privacy is that those with a need to know should know, and those that do not need to know and are merely curious should be prevented from invading the privacy of the patient. All patients deserve respect and privacy, particularly at the time of a personal or family crisis. Rarely do breaches of confidentiality or privacy produce lawsuits, but good patient relations are a product of consideration of patient privacy and modesty.

POTENTIAL INJURIES TO UNKNOWN THIRD PARTIES If an impaired patient is allowed to leave the ED and the medical staff knew or should have known that they would put the general public at risk, e.g., a medical condition that would impair driving, even an unknown victim might accuse the physician or nursing staff of a failure to protect the public from a potentially harmful person. If, however, known third parties are threatened, such as by an individual who has expressed homicidal or violent intentions, that known potential victim might reasonably expect a licensed physician to take steps for protection ( 90). When the public welfare or safety is at risk, confidentiality of the patient has to be weighed against larger responsibilities. It is best to refer matters involving public safety or welfare to law enforcement and social services agencies. Use common sense and record the action taken.

MEDICAL STAFF ISSUES One of the major areas of medicolegal concern for ED physicians is the sharing of responsibility for patient care with the members of the medical staff. ED physicians cannot practice alone. Most hospitals prohibit ED physicians from having admitting privileges to avoid splitting of patient responsibilities. As a result, all seriously ill patients require cooperative effort between the ED physician and the medical staff. This author has heard others claim that ED physicians are responsible for the conduct of other physicians, even consultants asked to review a case. There are clearly circumstances where other physicians may be under the supervision of an ED physician, for example, residents or interns working in the unit; however, it is illogical and self-destructive, not to mention somewhat arrogant, for ED physicians to claim that they are responsible for the actions of their colleagues. For example, nurses work under protocols that are set out by the hospital, and, unless a physician is directly supervising and controlling the activities of a nurse, that physician is not responsible for the actions of that nurse. Nurses are independent practitioners in their own field of expertise. The same is true of neurosurgeons, general surgeons, and others working in the ED. Only in circumstances where an impaired physician, or a physician who is known to the ED physician as incompetent, attempts to do something that is inappropriate and that comes to the attention of the ED physician could there be some potential liability. Short of that, most of this talk about “we are responsible for everybody” is expansive and ambitious to a fault. ED physicians are, like most health care providers, required to be team players, and that includes a reasonable approach toward professional liability questions. That reasonable approach includes allowing other practitioners to make their own decisions and not second guessing everyone else on the team. The current environment of malpractice litigation has increased the tendency of most physicians to be too judgmental about their colleagues and too paranoid about the exposures that might occur because of other practitioners' actions. It also has encouraged the tendency to point fingers and to blame others when cases turn sour. Cases turn sour frequently because medicine is a complex business. Professionals are wise not to allow the tendency of the body politic in general to find someone to blame to poison the atmosphere in the ED or in the hospital. A little respect for one's colleagues includes giving them room and not being quick to judge or condemn without a complete review of the facts and circumstances.

RELEASE OF RECORDS Release of medical records is governed by state law, and there are many exceptions to the general rule that a physician should not release a medical record or information about a patient's care without the patient's consent. Requests for information from insurance companies, criminal investigators, state agencies, or parties to lawsuits where the patient has made the medical condition an issue might all trigger exceptions to the rules about confidentiality. Subpoenas issued from courts must be responded to, and any decision as to resisting a subpoena should be made only with competent legal counsel. Inquiry with the State Medical Association and the State Board of Medical Examiners might provide the physician with background information, but legal counsel may be required in order to avoid the pitfalls of inappropriate release of medical records. A summary of medical records with didacted material that might harm the patient or cause the patient unnecessary injury

may be appropriate in some circumstances, for example, insurance requests.

ADMITTING ORDERS If ED physicians do not have admitting privileges, how can they write admitting orders? What are bridge orders? Once the admitting physician is identified and information is relayed to that admitting physician requesting acceptance of the patient, there are many circumstances in which the ED physician might facilitate admission to the floor by writing limited admitting orders. No significant risk is involved in writing limited admitting orders, which facilitate the admission of the patient and continue care started in the ED. On many occasions, this writer has presented to ED physicians who have been told that writing admitting orders was insane. The argument goes, “Sometimes the attending physician does not come to see the patient in a timely fashion, and, therefore, you could be sued since you were the last one to see the patient.” First, ED physicians can be sued anyway, and they probably will be if their name is on the chart. Second, the responsibility for the patient can easily be transferred by phone; it does not require physical contact. Third, writing orders may initiate treatment that otherwise would be delayed to the detriment of the patient causing a lawsuit for other reasons. Fourth, in many hospitals, the initiation of practice parameters, practice guidelines, and practice pathways is intended to facilitate and expedite treatment. It has been this author's experience recently that delays in treatment for the arrival of the attending physician have caught ED physicians in the web of medical malpractice litigation and that delays in treatment out of courtesy for the attending physician did not immunize the ED physician from being named as a defendant. In contrast, with few exceptions, reasonable bridge orders, admitting orders, or treatment instructions that merely continue the management of the patient that was started in the ED add no more exposure to the case and may add to the benefits to the ED in the following ways: 1. It reduces the number of unnecessary arguments about whether the patient should be admitted—the inconvenience to the attending is reduced. 2. It does not take away from the fact that, if the patient is critical, the ED physician still has the option to demand that the attending immediately attend the patient for the benefit of the patient and for the political and social benefits to the patient and family. 3. Writing reasonable and limited admitting and bridge orders is helpful to colleagues, good for patients, and displays the ED physician's willingness to participate in the effort rather than avoid some theoretical malpractice risk. On the theory that the at-home attending physician's orders are better than the ED physician's bridge orders, some people have advocated that the ED physician merely transcribe orders or give the phone to the nurse so the attending at home can call in the orders—consider the logic when those orders are written on the basis of a report of the patient's condition by the ED physician. Would the attending not say, in retrospect, that he was relying on the report of the ED physician while writing those orders? Would that change the risk for the ED physician? Moreover, frequently these attendings are not the patient's personal physician, but merely covering for someone else, and their knowledge of the patient is no better or worse, in many cases, than the ED physician's. Additional inquiry into this hot legal topic might include the question: Should antibiotics be withheld until an attending physician can be present? Would IV fluids be withheld until the presence of the attending physician? If orders are written in the ED, should those orders continue to impact the patient's care while the patient goes to the floor, or should the orders and treatments be stopped when the patient crosses the threshold to go upstairs? Separate from that, if the ED physician is the only physician in-house, there might be matters of courtesy and patient care that require a commitment and involve a certain risk. Theoretical avoidance of malpractice risk may have a negative impact on patient care and participation of ED physicians in patient care. These discussions should not be interpreted as encouraging extraordinary and inappropriate extensions of ED physician responsibility, just an attempt to deflect some of the paranoia that motivates those who would argue against any form of bridge orders, admitting orders, or involvement in patient admissions. If more than 40% of the admissions to hospitals across the country are generated from the ED, this is no small matter and may impact patient care in EDs more than most would admit. How much does it impact the care of ED patients? Admissions invariably demand extraordinary amounts of energy and effort on the part of ED staff. What is the cost of that effort if you include delays in the ED and a failure to get the patient to the appropriate area of care in the hospital? What about admissions to the ICU, would not some bridge orders and moving the patient to another place where one-to-one nursing care is available be more appropriate? These are just a few questions that should be asked before this debate is joined. Whenever the ED physician writes orders to facilitate admission, these orders should refer the nurses to the admitting physician for additional care.

ON-CALL PHYSICIAN RESPONSE Refer to the Joint Commission on Accreditation of Healthcare Organization (JCAHO) sections on emergency services for appropriate guidelines regarding on-call responsibilities and response from on-call physicians. In a level II ED, the on-call response time should be 30 minutes with voice communication acceptable ( 91). Hospitals are responsible for establishing on-call lists ( 92,93). JCAHO is not so specific in the 1996 accreditation standards, but 30 minute voice response is still reasonable. ED physicians who transfer patients because the on-call physician will not respond are immunized from any federal liability or accusation of illegal acts as long as they transfer the patient only because of a refusal of the on-call physician to come and see the patient and if they name in the transfer papers the physician who refused to respond (94).

LEGAL PROBLEMS RELATED TO RESUSCITATION Although the best rule to follow in emergency services is to resuscitate when in doubt, under certain circumstances legal barriers are created to automatic resuscitation. When in doubt, resuscitation is still the best rule because a 5- to 10-minute delay in a resuscitation could cause permanent and irreversible damage, but in certain circumstances there are state laws and common law that would create additional considerations. Most states have passed some kind of legislation that allows individuals to give an “advance directive” to physicians if they have developed a terminal or incurable, irreversible condition ( 95). Individuals may, under circumstances in which they have an incurable or terminal condition, instruct physicians not to provide resuscitative efforts if they have a cardiac or respiratory arrest. This principle of autonomy and control over one's treatment is a well-established and accepted principle that goes back to the basic concepts of consent for treatment. Present law in the United States requires that physicians inform patients of the diagnosis, the risks of the condition, and the alternate treatments for that condition, and then obtain consent to treat ( 96). An ongoing area of concern for ethicists is advanced directives by basically healthy elderly individuals who do not want to be resuscitated if they have a cardiac arrest. Most state laws on advanced directives and living wills anticipate that the individual executing the document has some kind of terminal illness and might even have requirements that two doctors diagnose the individual as having a terminal illness. This does not address the elderly individual who is in good health, has no terminal illness, and would still wish to direct “No Resuscitation.” There are rational explanations for this, because most informed individuals know that recovery from a resuscitation to discharge from the hospital is a mixed blessing. Creation of a durable power of attorney for health care decisions may be a way to circumvent this problem, but most individuals do not consider a durable power for this kind of decision making unless they develop health problems. The simple answer is to recall that American law prohibits treatment without consent. Because individuals are authorized to consent for family members who may be incompetent or unable, much of this may be professional lawyering rather than real world difficulties. Although most of the law in this area was created by physicians and hospitals that refused to follow the instructions of family members on the fear that there might be a retrospective decision to sue the hospital or the health care provider, the courts have, in most cases, clearly upheld the right of individuals and their families to make these kinds of decisions. In the normal situation, a discussion with the family member who has the authority may be all that is required, but nervous physicians and hospitals often have complicated this area because of paranoia about the unknown family member who might sue because the provider or the hospital did not do a full court press in management of the patient's condition. Some of these risks are theoretical, but that has not changed the tendency of the health care professions to go to courts for definitive rulings. Most of the time, a considerate and empathetic discussion with the family is all that is necessary in order to get a sense of what the patient and the family believe is reasonable and complies with the patient's wishes. Because life is a terminal condition, there is a reasonable argument for advanced directives even for patients who do not have an incurable or terminal medical

problem, and advanced directives refusing resuscitation are a reasonable alternative within the current legal system. Some states have already passed special advanced directive statutes, for example in Texas and New Mexico, that specifically are designed for prehospital care providers. You can expect that, given the increasing interest in management of life decisions at the end of life, and during interminable, incurable illness, and debate in all the legislatures of the states, that more legislation will be written in the next few years pertaining to these matters.

MANAGED CARE PROBLEMS Managed care is a generic term that can apply to all kinds of health insurance claims management situations. For example, managed care is a part of the strategy of Medicaid and even third party intermediary activities related to Medicare. Refusal of payment, retroactive denials, questions on appropriateness of care, even delays on payment and difficulties with payment can produce cost savings for the insurance entities. Direct patient care rationing, access decisions, and other activities may not be a part of the typical government approach to managed care, but they are certainly a significant part of commercial insurance and HMO management strategies. In spite of the work by Williams showing that marginal care for ambulatory services in EDs is really competitive with other sources of care, HMOs and managed care organizations work hard at reducing ED utilization. This will clearly produce present day and future conflicts between emergency care providers and the payors for health insurance. Naturally, in a theoretical effort to control their costs, the managed care organizations try to refer patients away from EDs and attempt to provide urgent or emergent care in non-ED settings. When gatekeeper physicians attempt to refer patients away, it is important to recognize that the ED cannot delegate away its liability or professional responsibility to the patient. Moreover, managed care organizations have been treated in many courts as nothing more than insurance entities, and, therefore, the professional responsibility of the physician and the ED will not go away. The best advice when dealing with managed care situations is to provide appropriate care for the patient and fight with the insurance company about the payment later ( 97).

PROFESSIONAL LIABILITY INSURANCE One part of risk management is the intelligent purchase of insurance. The average cost of meritorious claims in emergency practice is well above $50,000, and many jury verdicts go in excess of a million dollars for meningitis and myocardial infarction cases; therefore, insurance must be purchased. There are various types of insurance companies, including: 1. 2. 3. 4.

Stock companies Mutual companies that are owned by the insureds Self-insurance entities such as trusts and captives Risk Retention Act insurance programs, which are either purchasing groups or domestic “captives” ( 98).

In most states, ED physicians are premium-rated equal to general surgeons or general practitioners who perform surgery, because of the frequency of claims against ED physicians and the magnitude of those claims. The financial projections from an actuarial experience show that the range of malpractice costs for ED physicians are in the order of a range of 4 to 8 dollars per ED visit. The cost increase has been more than twofold over the past 10 years in costs per visit for ED malpractice. The dollars spent on claims during the 1974 to 1983 period under the ACEP-endorsed programs was 1-2 dollars-per-visit (indemnity paid plus costs), and there was a claim about every 30,000 visits ( 99). Now claims are one per 15,000 visits and more costly.

ALTERNATE INSURANCE PROGRAMS ED physicians and emergency groups frequently have chosen specialty insurance programs for the following reasons: 1. 2. 3. 4.

Main line insurers are not always willing to create the flexible programs needed for ED groups. Premiums were thought to be excessive in the regular market. Corporate and partnership entities in the practice of emergency medicine are inclined, and able, to follow national trends of corporations toward self-insurance. Price sensitivity and a past history of inconsistent service and availability as well as fluctuating commercial prices forced ED physicians to look toward specialty resources for emergency medicine professional liability coverage.

The Risk Retention Act (98), which was a modification of an earlier federal legislation allowing manufacturers to insure themselves on products liability, created the opportunity for the formation of onshore self-insurance entities in two basic categories—purchasing groups and risk retention groups. The purchasing groups essentially try to trade purchasing power for better prices, whereas the risk retention groups are self-insurance entities that have licensure in one state and can insure only their own class of risk—such as ED physicians in all the states. Insurance companies and insurance groups formed under the Risk Retention Act are licensed in one state and admitted in other states to sell insurance, and they do not contribute to the insolvency funds of the states in which they operate. This reduces the amount of protection that a physician has if the insurance company becomes insolvent. The insurance entities created under the Risk Retention Act must be formed by those who are the intended insured. Before the Risk Retention Act, self-insured entities would start a captive offshore in a suitable domicile, Bermuda or one of the West Indies. Some of these captives are still offshore.

INSURANCE COVERAGE The types of professional liability policies sold are either: 1. Occurrence, which is absolute coverage for the period no matter when the claim is made, or 2. “Claims made,” which is effective only as long as coverage is continued consecutively with the same company and if the claim is filed within that insured period. For example, if you own a claims-made policy and terminate your coverage with the company, and you receive a claim on that period after you terminate, the insurance is no longer effective unless you buy an “extended reporting endorsement” or “tail,” which provides coverage for an extended period. Claims-made coverage does not cover on a claim made after termination, even on an incident during the insured period. In the case of occurrence coverage, coverage is for the insured period no matter when the claim is filed. Tails usually cost one and one-half to two times the last year's premium, so they are expensive, usually more than $20,000 for a mature claims made policy with 1 million/3 million coverage. Liability insurance is the most expensive overhead item for ED physicians; therefore, it must be purchased intelligently. The most flexible and effective insurance is based on the number of visits. If the insurance policy provides coverage for the facility and is based on a per visit or slot rate, insurance can be purchased for aggregate coverage for the group. The advantages of a per visit or slot rate are elimination of tail coverage for departing physicians or separate policies for part-timers. The professional liability coverage is unified rather than “piece meal,” and the costs are predictable from year to year. When the group loses the contract, a tail will be assessed to the tune of one and a half to two times the last year's premium, which can be significant. For example, an ED with 20,000 visits could easily be paying $100,000 per year on a mature policy, which means that the tail could be $150,000 to $200,000. Another problem with tails for a group is that they cannot be budgeted as an expensed item, and, therefore, reserving money for the tail creates tax consequences that are not easily circumvented and should be considered. The face sheet of the policy for insurance usually includes the amount of insurance available which is given in two numbers, the first number for each case or incident, the other for the aggregate amount available for the year. For example, a $1 million/3 million policy covers $1,000,000 for each case and a total of $3,000,000 for the year of coverage. It is the custom in the hospital industry to ask ED physicians to have that much coverage since frequently hospitals are also liable for ED claims and want the ED physician to carry enough coverage to absorb the losses.

CHANNELING PROGRAMS Large physician and hospital groups are increasingly going to “channeled” programs that insure the whole entity, including the physicians that work within the healthcare entity's activities. For example, the Harvard Foundation includes physicians, hospitals, and other patient care provider entities within the Harvard group, and a combined insurance program is developed for all the doctors, hospitals, and patient care entities. These channeled programs have definite advantages and are sometimes available through hospitals or hospital groups. It is important to recognize that there may be conflicts of interest in the defense of a malpractice case, but that the attorneys involved in providing defense for each defendant are required to work only for that defendant and not against the interests of the individual defendants. When involved in a case that has multiple defendants, it is important for ED physicians to recognize these potential conflicts in the defense and be aware of the downside risks of compromises on settlement or management of malpractice litigation in channeled programs.

CREDENTIALING AND MEDICAL STAFF PRIVILEGES Law over approximately the past 20 years has established that if physicians are to provide services, particularly in the hospital environment, the hospital is responsible for appropriately credentialing those physicians and properly monitoring the care they provide through its internal credentialing, peer review, and quality assurance programs (100). One of the reasons in the past for not giving ED physicians active staff privileges was the hospital administration's desire to be able to dismiss ED physicians at will, but proper privileging and credentialing, along with membership in the medical staff, provides the ED physician with an opportunity to participate, hold office, and protect professional interests and the interests of the ED. Most emergency service contracts waive due process medical staff protection in the case of termination of the contract. Because an exclusive franchise for emergency services is provided through the contract, this kind of automatic waiving of due process protections is a routine part of the contract. For example, exclusive radiology contract or anesthesiology contract would be similar in that losing the contract means a surrender of privileges for that particular exclusive contract. When hospitals offer exclusive franchises, they include a clause that requires termination of privileges should the contract be terminated in order to avoid a potential of competing physicians trying to practice in the same area with the new exclusive franchise group. Internal quality assurance, risk management, peer review, and disciplinary activities in most states require that the hospital comply with the Healthcare Quality Improvement Act and its companion National Data Bank reporting system (101). Health care groups and hospitals must report to the National Practitioner Data Bank, any disciplinary action, restriction of privileges, or denial of privileges which involves disciplinary action, but also report to the State Medical Practice Supervisory Board. The State Board may report to the Data Bank, but also would report to the National Federation of Medical Boards. Physician discipline and supervision is created by public and private activities of regulatory and licensure activity, including the following: 1. 2. 3. 4. 5. 6. 7. 8.

State Board Medical Examiners Drug Enforcement Administration State drug control acts Medical societies and associations Hospital credentialing Specialty societies and boards Office of the Inspector General of Department of Health and Human Services Medicare and Medicaid Peer Review organizations

This impressive list of regulatory and disciplinary authorities requires at least a little attention. Basic rules regarding these matters include the following: 1. Once a physician has a license, privileges, or membership, they cannot be removed without appropriate disciplinary action, which means the concept of procedural and substantive due process guaranteed by State and U.S. Constitutions. 2. Substantive due process is interpreted by the court as thorough and impartial. 3. Procedural due process requires basic steps, including notice of charges, opportunity to defend yourself, and the right to a fair and impartial hearing. 4. If the action involves the removal of hospital privileges, the hospital medical staff is required to follow its own bylaws and provide due process. 5. Peer review organizations (PROs), which deal with Medicare reviews, are required to follow their own regulations and procedures, but at the lower levels of discipline (less than formal sanctions), PROs are not required to follow as many rules of due process as one might imagine. For example, decisions on corrective actions and denials are somewhat unilateral. 6. Removal of membership or discipline by a medical society is also measured on the fairness and due process standard, with specific prohibitions against discipline based on advertising, participation in HMOs or managed care plans, or some other perceived anticompetitive bias that would create potential antitrust problems for the society or association. 7. Disciplinary actions against physicians must avoid the taint of economic or personal motivation that is implied in the concept of impartiality. It is important for physicians to know their rights once they have become licensed or once they have obtained privileges. New law trends require that applications for hospital privileges be treated in the same manner as disciplinary actions that remove privileges. Public and private hospitals, particularly those with sole community provider status, must now deal with new applicants fairly, and are allowed less leeway in barring physician applicants for medical staff. Private hospitals are allowed to use some arbitrary rules like requiring board certification or closing staff, if the rules are applied consistently.

ANTITRUST LAW This is a brief review of this complex area of the law, governed by the Sherman Antitrust Act ( 102) and other Federal and State laws. The basic concept involved in these laws is as follows: it is considered a violation of anti-trust law to price-fix, boycott, create a monopoly, or engage in any other activity that is plainly anticompetitive and to the detriment of the consumer. The most famous antitrust case involving peer review/disciplinary activities was the case of Patrick v. Burget ( 103) that involved a hospital staff attempt to eliminate Dr. Patrick from practice in a small town in Oregon. Patrick sued the town clinic for antitrust violations. The defendants attempted to defend themselves on the basis that their activities were protected by state involvement because the state had an interest in peer review. The state action antitrust defense was rejected by the United States Supreme Court eventually because Oregon was not that actively and closely involved in the hospital peer review process. In response to the problems that some perceived to be created by the Patrick v. Burget opinion, Representative Ron Wyden introduced a bill called the Healthcare Quality Improvement Act (86) discussed previously, which provided that, if peer reviewers followed a fair procedure, acted in the furtherance of good care, and were guided by the due process provisions of the act, they were immune from antitrust litigation and were also in a position to collect expenses for defending any other type of suit filed by a physician who was disciplined. The due process requirements of the Act are: 1. Proper notice and reasonable notification as to the anticipated disciplinary action (30 days, the nature of the alleged violations, and the potential disciplinary action). 2. An opportunity for a thorough and fair hearing and a chance to defend. 3. A fair hearing panel that did not have the taint of membership by competitors. 4. Right to legal counsel. 5. A written justification for the final recommendation or ruling. 6. All actions taken must be for the benefit of patient care and not motivated by financial, competitive, or personal considerations. National Practitioner Data Bank requires that reports of disciplinary actions and professional review actions taken by health care entities must be reported ( 104).

There are permanent Data Bank records available to inquiring health care entities. Reportable events include payments made for malpractice suits and professional liability settlements along with an explanation of the case. Disciplinary actions by State Boards also are reportable. Professional review actions by health care entities are reportable if they involve the change of privileges for more than 30 days based upon clinical competence or behavior ( 105). Hospitals are required to inquire with the National Data Bank at the time of a physician's application or reapplication for privileges. The hospital is assumed to know what was in the data bank, if that is pertinent to a lawsuit filed against a hospital suit, when it fails to inquire. The Data Bank may release information to hospitals, practitioners requesting information about their own records, state licensing boards, a health care entity that is inquiring about a candidate for employment or affiliation, and, in limited cases, an attorney who is filing suit against a physician who must first submit information that the hospital failed to request information from the data bank about the provider. Purely statistical information that does not require identification can be released for research purposes ( 106). For general Data Bank information there is a guidebook available ( 107). As one might have expected, some in Congress want to give the public access to the Data Bank. When hospitals move physicians in and out of an exclusive contract arrangement, that is not a Data Bank Medical Board reportable event. Reportable events arise only after completion of a formal disciplinary action or if a physician resigns or surrenders privileges when under threat of disciplinary action. Sometimes hospitals make reports to the Data Bank that are not the result of a final hearing or a final decision on a due process hearing. Under no circumstances should an ED physician accept a reassignment or dismissal until he or she is aware of whether the hospital plans to report the matter to the Data Bank. Final decisions from a due process hearing are the only basis for a Data Bank report other than a surrendering of privileges while under investigation or under threat of discipline ( 108).

CONTRACT LAW ED physicians work in an environment that requires contractual agreements. Contract law governs agreements between individuals or legal entities like corporations. Most ED physicians in this country work as either employees or independent contractors. An independent contractor is an individual who offers his or her services for sale, not as an employee of the individual who pays, but as an equal or at least theoretically equal party to the agreement. For a contract to exist, two parties must exchange promises for what is legally called “consideration.” Consideration is some kind of benefit, goods, or services, considered part of the exchange in a contract. Some important concepts of law: 1. Oral contracts are effective in the law, but less easy for the courts to deal with; therefore, important contracts should be written. 2. A written contract includes information on the agreement that is essential for the interpretation, including: a. Date of the contract and identity of the parties b. Term of the contract or the amount of time over which it will be effective c. The terms of the contract, which include the promises that were exchanged and the consideration involved in the contract d. Any additional restrictions on either party (These are also terms, but should be thought of as separate modifiers) e. Conditions for nullifying or terminating the contract f. Provisions for notice to either party g. An indication as to what law would apply in interpreting the contracts (e.g., the state law where the contract is entered into is normally the controlling law) ED physicians frequently enter into contracts with either hospitals or emergency services groups that hold the contracts for service to a hospital. Therefore, two contracts may be involved in the personal services provided. It is important for physicians to understand that contract law is no more than the formal legal approach to the process of bargaining. If one considers the process a bargain, the law of contracts does not seem so mysterious. The two parties who enter into the contract should understand what is expected on both sides; this requires adequate research as to the responsibilities of the two parties on both sides. For example, there are laws that pertain to the operation of a hospital and the operation of emergency services, and there are expectations of the medical staff, the nursing staff, the hospital, and the ED physician that should be thoroughly considered and researched before entering into a contract. It is often said that the effect of a contract is no more long-lasting than the good intentions of the parties, but frequently the good intentions of the parties are compromised because of a failure to prepare properly for the contract negotiations and unwritten or unspoken expectations of the parties that result in later frustrations, disappointments, and even disagreements. Generally, the four corners of a written contract are the controlling terms and conditions of the agreement. Parole evidence is evidence not in the contract that might be presented to a court to explain or clarify written sections of the contract or attempt to resolve disputes that have developed over the written contract, but courts generally do not like to consider parole evidence. It is therefore important for physicians, hospitals, and ED physician groups to be careful about the contracts they write, and to properly research and thoroughly evaluate contractual arrangements.

AGENCY LAW The ED physician may be “agent” of the hospital and possibly an agent of the group that contracts for services. If an ED physician is an employee, he or she automatically becomes an agent of the employer, but in an independent contractor situation, the agency relationship may be established by legal rulings. Many states have case law that creates an “apparent agency” of the ED physician in the ED ( 109,110). This term essentially means that the hospital is not allowed to delegate away its responsibility for the emergency services provided because the patient who presents to the ED does not really have a choice of physicians to see. The institution provides the ED physician as a part of its service. This may create “vicarious” liability for the hospital because the liabilities that are created by ED physician malpractice can then be transferred up to the “vicarious” liability of the institution. When the ED physician works as an employee, the employer-employee relationship automatically creates vicarious liability. In an effort to reduce the vicarious liability of the hospital, many EDs try to clarify for the patient the fact that the ED physician is an independent contractor and is not an employee of the hospital. If the hospital follows certain guidelines, there would be a reduction in the vicarious liability of the hospital; however, most courts are inclined to find agency liability in circumstances where exclusive contracts occur. ED physicians and emergency groups can expect that the hospital will make its best effort to separate the identity of the ED physician from the hospital. Independent Contractor Under liability law and contract law, there are some professionals who reasonably could be termed independent contractors. Independent contractors provide services that otherwise might be provided by employees because they are considered to be “equal to the contracting entity.” A classic example in the business of emergency medicine is an independent contractor physician who provides ED physician services to a hospital or to a contract company that has contracted to provide total emergency services for the department. The Internal Revenue Service has something to say about this arrangement, and, if there are certain indicia of independent contractor status, then it may be allowed as a practice and custom within emergency medicine. If the physician does not have any special benefits normally considered to be employee-type benefits and if the physician does not depend upon the contracting party for uniforms, inordinate amounts of supplies or provisions, health benefits, insurance benefits, and if that physician pays a self-employment tax and complies with all normal Internal Revenue code requirements for independent contractors, then the status of the physician as an independent contractor will probably be satisfied. Certain things that may “whittle away” that status as an independent contractor are uniforms, pension and insurance benefits packages, special employee-type benefits such as health clubs or other services available to employees, and the legal arrangements normally thought of to be characteristic of employee-employer relationships. In 1996, the IRS, in the midst of this battle about independent contractor status, has renewed its advice with regard to independent contractor status by delineating the “safe harbor” guidelines. In the case of emergency medicine, if a significant percentage of the ED physicians across the country are involved in independent contractor arrangements for a period of years, it reduces the likelihood that IRS will be able to attack and successfully destroy independent contractor arrangements.

Again, if you as an individual or if groups are attacked on independent contractor status, the advice of an attorney and appropriate resistance is advised. In 1997, a dramatic and significant policy change by HCFA may make the dispute and debate about independent contractor status a different one in the future. Regulatory changes requiring that physicians receive all of their payments directly from Medicare and Medicaid eliminated some business options for large contract groups, and most of those large contract groups decided that changing physicians to employees from independent contractor status would be the only viable option. Up to that point, HCFA had been increasingly uncooperative on issuing new numbers and on restricting the flow of payments directly to groups. ED physicians who work for large groups as independent contractors were not impacted in any significant way, but the large groups developed major cash flow problems related to the decisions of HCFA. This HCFA approach probably will not affect single hospital groups or small partnerships, but partnerships or corporations with large groups of independent contractors may be forced to make those independent contractors employees. Most decisions related to this changeover had been made by the end of 1997, so in 1998 there will be a significant shift from a majority of ED physicians being independent contractors to a larger proportion of ED physicians becoming employees.

REPORTABLE EVENTS Any suspected criminal act that involves public risk, such as gun play, violence, and injuries to persons, certainly should be reported to law enforcement. There are probably physician judgement issues raised when a patient is seen with alcohol or drug abuse even though that may be in violation of criminal statutes. When an individual is judged to be a public hazard, the rules change, for example, an individual who insists on driving in spite of alcohol or drug impairment or an individual who uses or is inclined to use violent weapons on innocent parties. The violent injury of a victim should be reported to law enforcement even if the individual says that they will not file charges, because police involvement may decrease the chance of a repeated offense. Introducing law enforcement into situations where individuals have been harmed is probably the better choice, and, even though under some particular circumstances the victims may plead that the physicians or nurses not make the report, a report may be better for the safety of that victim and a chance that something might be done to decrease the potential for a repeated offense. It also increases the chance that a perpetrator will be found, captured, and convicted when reports are made, and violent criminals often are repeat offenders. Child Abuse All states have laws requiring that medical and child care professionals report any suspected child abuse. These statutes also provide immunity for anybody who reports a possible child abuse case in good faith. Physicians who identify a child who might be the victim of physical abuse or neglect are obligated to report such an event to the local law enforcement agencies or child protective services. The reporting requirements vary from state to state, but usually the important protocol to follow is: 1. 2. 3. 4.

Evaluate the child. Make sure that the child is maintained in medical protective surroundings by any means necessary if identified as a possible victim of child abuse. Make a report to the local agency responsible for investigation. Some states require a follow-up written report, but at least make sure that written documentation is made of a verbal or phone report if the agency is informed.

Legal risks for medical professionals exist on both sides of this issue, including families who are upset at being accused of child abuse, or the state, which has the power to deal harshly with an individual who fails to report child abuse. Child abuse goes unreported, but there are also many instances of cases that could not be substantiated because of inappropriate investigative and victim interview techniques. In any event, unexplained injuries and histories that are not consistent with the nature of the child's problems, in the setting of a child who has poor development, poor socialization, and poor language development or any other signs of neglect, should lead one to report a suspected abuse or neglect. Adult Abuse This generally involves the abuse or neglect of the elderly or disabled. Certainly the difficulties of taking care of an adult who has significant disabilities, mental and/or physical, can increase the potential for abuse and neglect. This abuse can come at the hands of relatives, friends, spouses, or individuals who provide housing for dependent adults and will increase with increasing rates of dementia. As a separate phenomenon from spousal abuse, adult abuse should generally be suspected in an individual who needs the help of others and who appears to be receiving inadequate nutrition and general care, or to be suffering from injuries that are not easily explained or are explained with inconsistent histories. Report adult abuse to local law enforcement and, in some states, social service agencies. The obligation to report adult abuse is the same as for child abuse in most states. Spouse and Companion Abuse This is a well-known form of violence in the United States and is so complex because of the interdependencies that exist and complicate the relationships. Frequently, alcohol and substance abuse aggravate spouse abuse. The dynamics of marital and nonmarital dependence complicate the matter and create difficulties requiring counseling of both parties. The pathology of spouse/companion abuse is too complex to deal with in detail here, but the general suggested approach is to: 1. 2. 3. 4. 5.

Take care of the medical and psychologic needs of the victim. Try to determine whether alcohol and substance abuse are contributing factors (the patient and abuser should be referred for appropriate support). Look for the potential neglect or abuse of minors. Use spouse abuse counseling services. Recognize that it is frequently difficult to break a relationship even when abuse is involved.

Sexual Abuse of Minors Sexual abuse of male and female minors continues to be a repulsive and too common event. In the evaluation of sexual abuse, it is important to recognize that sexual abuse of children and adolescents requires careful investigation and careful interview of the victim. ED physicians usually should not do the comprehensive interview, but should provide the physical examination and general medical supervision required for the potential victims of childhood sexual abuse. Rape Rape is sexual contact without consent of one party, and comes in various degrees, all the way from unconsented touching to intercourse. Statutory rape involves an underage victim (see Chapter 58). The ED physician, in evaluating a patient who has been raped, should follow a basic protocol: 1. A history of the assault, with attention to potential for physical injuries and whether sexual penetration and/or ejaculation occurred. 2. Proper head-to-toe examination, with notes as to evidence of injury. 3. Collection of clothes, hair samples, fingernail scrapes, blood samples, and vaginal and rectal samples as well as swabs of areas where semen might be present (semen fluoresces under Woods lamp). 4. Samples for evidence should be generally done according to rape kit instructions and with the specimen containers and documentation available in the standard rape kits. 5. The medical record should include the general examination, general history, specific history of the assault, and general physical examination with specific attention to the examination for alleged sexual assault and other injuries. 6. The patient should receive proper treatment to prevent sexually transmitted diseases because perpetrators of rape are at higher risk for carrying sexually transmitted diseases. 7. The patient should be given the option of “the morning-after pill,” which is generally effective. 8. The patient should be provided with proper psychosocial support because rape creates complex syndromes of mental as well as physical symptoms and difficulties. 9. The patient should be provided with medical follow-up to ensure no pregnancy and no transmission of venereal diseases.

The evaluation and treatment of a rape victim is challenging, and male physicians are encouraged to enlist the assistance of female nurses and doctors to help make it easier for the female victim. Proper management of rape cases includes not only the criminal investigation, but the medical and psychologic needs of the patient (see Chapter 58). Chain of Evidence The chain of evidence is the sequence of custody that can be demonstrated in court to rebut any allegations of possible tampering with the evidence collected. For example, if a bullet is removed and is to be used as physical evidence in a case, the custody of that bullet from the time it was removed from the victim must be established and documented. The same is true in collection of evidence in other types of cases, but ED physicians are most familiar with the concept of chain of evidence in rape cases. In rape investigation, the collection of evidence must be done in such a way that the custody of the evidence is documented from the time of collection and the place of collection all the way to the courtroom. If there is any interruption in that chain of custody, i.e., the evidence sits on a cabinet in an unsecured place for some time, or if there is no way to know exactly how the evidence got from the doctor to the evidence room, the defense will attempt to make as much as possibly can be made of the potential for tampering with or confusing the physical evidence specimens. As a result, to tighten up a case, the prosecution must show that the physical evidence was properly collected, sealed, properly secured, and kept in proper custody from the time of collection until the time of trial when it is presented as an exhibit in evidence for the prosecution. Physicians working in the ED should be conscious of the importance of the collection of the physical evidence and a documentation of the chain of custody of that evidence. Blood Alcohol Blood alcohol and substance specimens can be collected without patient consent in many states if a serious injury or death has resulted from a suspected alcohol or drug related accident. These specimens can be collected without significant legal risk for the physician. They are collected under the order of the state, and collection of blood specimens under a state criminal statute is allowed. If the accident does not involve situations that specifically provide for involuntary collection of a specimen, and if the patient refuses to consent to collection, the physician is best advised not to collect the specimen. The conviction of the individual can be accomplished even if the specimen is not collected. If the physician, the medical staff of the hospital or the laboratory, or the nursing staff are threatened by the police for “obstruction of justice,” be aware this is not the case and that no one has to contribute to the prosecution of a case or collection of evidence, particularly when the patient is refusing such a collection. Obviously, the collection of a blood specimen does not involve any significant potential for a claim or damages, but there is generally no point in forcing a patient to allow collection of a specimen under these circumstances unless the police have the authority by statute to collect the specimen involuntarily. Contact counsel for the hospital in difficult cases. Employment also creates legal obligations for the employee to allow drug testing on a random basis or at the time of an accident. Consent of the employee at time of specimen is necessary. Refusal may mean termination, but should be controlling for the ED Physician. Reportable Communicable Diseases The reportable diseases list varies from state to state, but generally the infectious and communicable diseases that produce epidemics are the diseases of concern. Reporting sexually transmitted diseases and communicable disease follows state law. Special state laws have been written regarding the reporting and management of HIV. Because the laws differ in various states, it is important to refer to your state law for the following important items: 1. 2. 3. 4. 5. 6.

Any restrictions on testing patients without consent. Can patients be tested if they are going to expose medical personnel? Rules on informing potential sexual partners for any positive test that is received if the patient is not willing to inform the sexual partner. State law on the management of an HIV-positive patient who continues to participate in high-risk activity. Many states have developed rules on proper counseling for anybody who has a positive test for HIV. Many states have laws specifying confidentiality, how the reporting of a positive HIV test must be done, and to whom the positive test can or must be reported.

CONSENT The basic rule on consent in American law is that the patient has the right to control treatment and that, therefore, the physician has the responsibility to inform the patient of the following: 1. The working diagnosis 2. Alternative therapies 3. The risks of the diagnosis, therapies, and alternate therapies ( 96) Physicians should take the opportunity to make sure that the patient understands that medicine offers no miracles and that risks are involved in all forms of medical activity, along with the benefits that might be achieved. Offer the second opinion. When asking a patient for consent to treatment, the physician should make sure that the patient does not have any unreasonable expectations that will increase the risk of malpractice litigation, misunderstandings and hostility if a bad or unexpected result occurs. Many states have formal requirements for complying with the law regarding consent, but the basic rules are the following: 1. People should be given the opportunity to consent to treatment. 2. The general consent signed when the patient comes into the ED or hospital should pertain only to routine procedures without significant risk. 3. Follow state laws regarding formalities as to consent. For example, Texas has a complex and formal approach to consents and has a List A and List B for procedures with different requirements on the two lists. Your state laws should be reviewed. 4. In any event, the basic common law rule is that the physician should provide the patient with the information that a reasonable person would require to make a decision about appropriate care. The best defense in a consent case is to provide the patient with the most appropriate care because, ultimately, to prove a lack of informed consent case, the plaintiff must establish that they: 1. Did not receive the information 2. Would have chosen not to have the procedure if they had received the information The plaintiffs must establish and prove to a jury that a reasonable person would have refused the treatment offered. This is the reason why most consent cases are unsuccessful when appropriate care was provided. Consent for Minors and Implied Consent Under no circumstances should appropriate emergency medical care be withheld from any patient incompetent, unconscious, or a minor waiting for some kind of formal consent since an emergency condition implies consent. Most reasonable people want treatment when they have an emergency condition; therefore, providing emergency care is appropriate and should not be delayed.

Consent for treatment for minors is frequently reason for significant consternation and confusion at the registration desk in an ED; however, the concern is out of proportion to the reality. Any minor with a medical emergency is assumed to have implied consent, and proper treatment will avoid any significant problems. Obviously, complex treatment strategies require a consent, but basic emergency care can and should be provided without consent. What defense is there if basic emergency care is not provided because a family member or parent was not available to give consent? There are special rules created by statute that allow consent by minors to include, in many states, treatment for emergencies, pregnancy related conditions, alcohol and drug related problems, and treatment for infectious or communicable disease, particularly sexually transmitted disease. These laws were written with the intention of increasing the chance that minors would go for treatment on the theory that, if their parents had to give consent, they might be afraid to seek treatment.

SUMMARY Medical-legal matters are important in emergency care. Health care in the United States is a highly regulated area, and provision of care in the ED frequently involves legal issues and legal questions. The problem of medical malpractice lawsuits filed against the ED physicians continues to grow, and a majority of ED physicians can expect to be sued at least once in their career; therefore, it is important for all practicing ED physicians to be aware of their legal responsibilities. It is also important for ED physicians to analyze their malpractice risk exposure, appropriate strategies for reducing that risk, and appropriate actions to be taken when they become the defendant in a medical malpractice case. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56.

42 CFR (Code of Federal Regulations) 401. Resource Conservation and Recovery Act. 42 USC (United States Code) Section 6901 et. seq. Amended by Medical Waste Tracking Act of 1988 Subtitle J. 42 USC 1395nn. 293 F 1013 (DC Cir 1923). Daubert v Merrill Dow 113 S Ct 2786, 509 US 579 (1993). Rosen v Ciba-Geigy Corp., 95-3064 (7th Cir, March 11, 1996). Directory of Practice Parameters: Title sources and updates, updated yearly. American Medical Association. Chicago, IL (Also available on CD ROM.) Contact number 800–621–8335. ACEP clinical policies available from the American College of Emergency Physicians, Dallas, TX. Contact number (800) 798–1822. Personal communication, Rhonda Whitson, RRA Project Administrator and Staff Liaison to the ACEP Committee on Clinical Policies. Agency for Healthcare Policy and Research, Publications Clearing House. Contact number (800) 358–9295, P.O. Box 8547, Silver Spring, MD 20907. Maine Public Law 1990 Chapter 931 amended 1991 by the Maine Public Law 1991 Chapter 319 codified at Chapter 21 of Title 24 Maine Revised Statutes. Affirmative defense laws still awaiting a trial. Fam Prac News 1996;October 13:58–59. Attributes to guide the development of practice parameters. American Medical Association/Specialty Society Practice Parameters Partnership. American Medical Association. Chicago, IL For order information 800–621–8335. Supra note 5. EI duPont de Nemours & Co. v Robinson, 923 SW2d 549 (Texas 1995). (Unscientific studies of toxic effects rejected by Texas Supreme Court as failing basic rules for admissibility.) American Society of Anesthesiology Study. Caplan RA, Posner KL, Cheney FW. Effect of outcome on physician judgements of appropriateness of care. JAMA 1991;265:1957–1960. Schroeder SA, Kabcenell AI: Do bad outcomes mean substandard care? JAMA 1991;265:1995. Editorial. Dunn JD: Chest pain. Foresight. Dallas: TX, American College of Emergency Physicians, 1986. Trautline H, Lambert RL, Miller J: Malpractice in the emergency department—review of 200 cases. Ann Emerg Med 1984;13:709. Sites RL: Emergency room closed malpractice claims. Bulletin 89–99-A. Columbus, OH: Ohio Hospital Association, December 1989. Karcz A, Korn R, Burk ML, et al: Malpractice claims against emergency physicians in Massachusetts: 1975–1993. Am J Emerg Med 1996;14:341–345. Henry GL: Risk management in high-risk issues in emergency medicine. Emerg Med Clin N A 1993;11:905–922. Triaging emergency department closed claims. TMLT Reporter 1994;12:1–5. Austin, TX: Texas Medical Liability Trust. Lee TH, Cook F, Weisberg M, et al: Acute chest pain in the emergency room. Identification and examination of low risk patients. Arch Intern Med 1985;145:65. Lee TH, Rouan GW, Weisberg M, et al: Sensitivity of routine clinical criteria diagnosing myocardial infarction within 24 hours of hospitalization. Ann Intern Med 1987;106:181. Tierney WM, Fitzgerald J, McHenry R: Physician's estimates of the probability of myocardial infarction in emergency room patients with chest pain. Med Decision Making 1986;6:12. Lee TH, Cook EF, Weisberg M: Acute chest pain in the emergency department—identification and examination of low risk patients. Arch Intern Med 1985;145:65–69. Bresler MJ, Gibler WB: Acute myocardial infarction: subtleties of diagnosis in the emergency department. S Ann Emerg Med Dallas, TX: ACEP. February 1990. Lee TH, Rowan GW, Weisberg MC: Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room. Am J Cardiol 1987;60:219–224. Clovis CM, Weaver WD: State of the art management of acute myocardial infarction in the emergency department. Dallas, TX: American College of Emergency Physicians, 1995. Tierney WM, Roth BJ, Psaty B, et al: Predictors of myocardial infarction in emergency room patients. Crit Care Med 1985;13:526. Rude RE, Poole WK, Muller JE: Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based upon analysis of 3,697 patients. Am J Cardiol 1983;52:936–942. GISSI: Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;i:397–402. Fesmire FM, Wears RL: The utility of the presence or absence of chest pain in patients with suspected myocardial infarction. Am J Emerg Med 1989;7:372–377. Proceedings of the National Heart, Lung, and Blood Institute. Symposium on rapid identification and treatment of acute myocardial infarction: Issues and answers. Bethesda, MD: National Heart, Lung, and Blood Institute. U.S. Department of Health and Human Services. National Institutes of Health Publication No. 91-3035. September 1991. National Heart Attack Alert Program Coordinating Committee. Sixty minutes to treatment working group. Ann Emerg Med 1994;23:311. The emergency department: rapid identification and treatment of patients with acute myocardial infarction. Bethesda, MD: National Heart Attack Alert Program Coordinating Committee. Sixty minutes to treatment working group. U.S. Dept. of Health and Human Services Public Health Service National Institutes of Health. Publication No. 93–3278. September 1993. Hamm CW, Goldmann BU, Heeschen C, et al: Emergency triage of patients with acute chest pain by means of rapid testing for cardiac troponin-T or troponin-I. N Engl J Med 1997;337:1648–1653. Granville R: Armed Forces Institute of Pathology: personal communication of unpublished data. Crane, M: Don't get suckered into missing an MI. Med Econ 1996;August 26:46–61. McCarthy PL, Lembro RM, Baron MA, et al: Predictive value of abnormal physical examination findings in ill-appearing and well-appearing febrile children. Pediatrics 1985;16:167–171. McCarthy CA, Powell KR, Jaskiewicz JA: Outpatient management of selected infants younger than two months of age evaluated for possible sepsis. Pediatr Infect Dis J 1990;9:385–389. Dagan R, Sofers PM, et al: Ambulatory care of febrile infants younger than two months of age classified as being at low risk for having serious bacterial infections. J Pediatr 1988;112:355–360. Lipton JD, Schafermeyer RW: Evolving concepts in pediatric bacterial meningitis—Part 1: Pathophysiology and diagnosis. Ann Emerg Med 1993;22:1602–1615. Lipton JD, Schafermeyer RW: Evolving concepts in pediatric bacterial meningitis—Part 2: Current management and therapeutic research. Ann Emerg Med 1993;22:1616–1629. Bryan CS, Reynolds KL, Craut L, et al: Promptness of antibiotic therapy in acute bacterial meningitis. Ann Emerg Med 1986;15:544–547. Talan DA, Guterman J, Overturf GD, et al: Analysis of emergency department management of suspected bacterial meningitis. Ann Emerg Med 1989;18:856–862. Winkelstein JA: The influence of partial treatment with penicillin on the diagnosis of bacterial meningitis. J Pediatr 1970;77:619. Blazer S, Berant M, Alon U: Bacterial meningitis: effect of antibiotic treatment on cerebral spinal fluid. Am J Clin Pathol 1983;80:386. Marku J, Kallio T, Terhi K: The effect of recent previous visit to a physician on outcome after childhood bacterial meningitis. JAMA 1994;272:787–791. Fleisher GR, Rosenberg N, Vinci R, et al: Intermuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young febrile children at risk for occult bacteremia. J Pediatr 1994;124:504–512. Baskin MN, O'Rourke EJ, Fleisher GR: Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatr 1992;120:22–27. Baraff LJ, Bass JW, Fleisher GR, et al: Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Pediatr 1993;92:1–12 and Ann Emerg Med 1993;22:108–120. Kramer MS, Shapiro ED: Management of the young febrile child: a commentary on recent practice guidelines. Pediatr 1997;100:128–134. Green JW, Hara C, O'Connor S: Management of febrile outpatient neonates. Clin Ped 1980;20:375–380. Bonadio WA, Hennes H, Smith D, et al: Reliability of the observation variables in distinguishing infectious outcome of febrile young infants. Pediatr Infect Dis J 1993;12:111–114.

56A. Roberts J: Retained foreign bodies in ED wounds. Emerg Med News, 1997;Nov:4–6. 56B. Kaiser CW: Retained foreign bodies. J Trauma, Injury Infection, and Critical Care 1997;43:107–111. 57. 58. 59. 60. 61. 62. 63. 64.

Fischer RP: Cervical radiographic evaluation of alert patients following blunt trauma. Ann Emerg Med 1984;13:905–907. Hoffman JR, Schriger DL, Mower W, et al: Low-risk criteria for cervical spine radiography in blunt trauma. Ann Emerg Med 1992;21:1454–1460. Kaplan D: Spine problems in emergency department patients: does every patient need an x-ray? J Emerg Med 1985;2:257–263. Rhee KJ, Green W, Holcroft JW, et al: Oral intubation in the multiply injured patient: the risk of exacerbating spinal cord damage. Ann Emerg Med 1990;19:511–514. Rotondo MF, McGonigal MO, Schwab WW, et al: Urgent paralysis and intubation of trauma patients, is it safe? J Trauma 1993;34:242–246. Scannell G, Waxman K, Tourinaga G, et al: Orotracheal intubation in trauma patients with cervical fractures. Arch Surg 1993;128:903–906. Steffen H, Eifert B, Aschoff A: The diagnostic value of optic disc evaluation in acute elevated intracranial pressure. Ophthalmology 1996;103:1229–1232. Bracken MB, Shepard MJ, Holford TH, et al: Administration of methylprednisolone for 24 or 48 hours or tirilazade mesylate for 48 hours in the treatment of acute spinal cord injury. 1997;277:1597–1604. 65. ACEP Board of Directors: Principles of appropriate patient transfer. Ann Emerg Med 1990;19:337. 66. American College of Surgeons (ACS) Committee on Trauma: Interhospital transfer of patients. Bull ACS, 1990;February:13–15. 67. Ansell D, Schiff R: Patient dumping: status, implications, and policy recommendations. JAMA 1987;257:1500–1502. 67a. Schiff RL, Ansell DA, Schlosser JE, et al: Transfers to a public hospital—a prospective study of 467 patients. N Engl J Med 1986;314:552–557. 68. Reed W, Cowley K, Anderson R: Special report—The effect of a public hospital's transfer policy on patient care. N Engl J Med 1986;315:1428–1432. 69. Kellerman A, Hackman B: Emergency department patient dumping: an analysis of interhospital transfers to a regional medical center at Memphis, Tennessee. Am J Public Health 1988;78:1287. 70. Texas Revised Civil Statute 4437f, codified at The Texas Hospital Licensing Standards, Chapter XI.

JAMA

71. 42 USC 1395 dd. 72. Omnibus Budget Reconciliation Act (OBRA) 1989, Sections 6018 and 6211. Amending Social Security Act and 42 USC 1395dd at Sections 1866 and 1867. OBRA 1990, Sections 4008 and 4027 amending 42 USC 1395dd at Sections 1866 and 1867. 73. 42 CFR 489.24. 74. Public commentary and responses from HCFA as well as a complete review of COBRA is at the Fed. Register, June 22, 1994;59(119):32086–32125. 75. 42 CFR 489.24(d). 76. For a comprehensive review of COBRA or EMTALA see Patient Transfers: How to Comply with the Law by Stephen Frew, contact ACEP at (800) 798-1822, Dallas, Texas. 77. Levine RJ, Guisto JA, Meislin HW: Analysis of federally imposed penalties for violations of COBRA. Ann Emerg Med 1996;28:45–50. 78. (a) Correa v Hospital San Francisco, 69 F3d 1184 (1st Cir 1995) (b) Baber v HCA, 977 F.2d 872 (4th Cir 1992) (c) Vickers v Nash Gen. Hosp., 78 F3d 139 (4th Cir 1996) (d) Cleland v Bronson Health Care Group, 917 F2d 266 (6th Cir 1990) (e) Williams v Birkeness, 34 F3d 695 (8th Cir 1994) (f) Stevison v Enid Health Systems Inc., 920 F2d 710 (10th Cir 1990) (g) Abercrombe v Osteopathic Hospital Founder's Association, 95 F2d 676 (10th Cir 1991) (h) Urban v King, 4 F3d 523 (10th Cir 1994) (i) Repp v Anadarko, 43 F3d 519 (10th Cir 1994) (j) Holcomb v Monahan 30 F3d 116 (11th Cir 1994) (k) Gatewood v Washington Healthcare Corporation, 933 F2d 1037 (DC Cir 1991) (l) Summers v Baptist Medical Center, Arkedelphia, 91 F3d 1132 (8th Cir 1996) 79. (a) Baber v HCA, 977 F2d 872 (4th Cir 1992) (b) Green v Touro Infirmary, 992 F2d 537 (5th Cir 1993) (c) Eberhardt v City of Los Angeles, 62 F3d 1253 (9th Cir 1995) (d) Collins v DePaul Hospital, 963 F2d 303 (10th Cir 1992) (e) Urban v King, 4 F3d 523 (10th Cir 1994) (f) Holcomb v Monahan, 30 F3d 116 (11th Cir 1994) (g) Gatewood v Washington Healthcare Corporation, 933 F2d 1037 (DC Cir 1991) (h) James v Sunrise Hospital, 86 F3d 885 (9th Cir 1996) 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111.

Power v Arlington, 42 F2d 354 (4th Cir 1994). Vickers v Nash Gen. Hosp., 78 F3d 139 (4th Cir 1996). Summers v Baptist Hospital of Arkedelphia, 69 F3d 902 (8th Cir 1995), vacated and reversed enbanc Summers v Baptist Medical Center Arkedelphia, 91 F3d 1132 (8th Cir 1996). Williams v Birkeness, 34 F3d 695 (8th Cir 1994). Supra Note 63 at page 32099. 42 USC 1395dd (e) Derlet RW, Kinser D, Ray L, et al: Perspective identification and triage of non-emergency patients out of an emergency department: a five-year study. Ann Emerg Med 1995;25:215–223. 42 USC 1395dd (b)(A) 42 USC 1395dd (B) Williams RM: The costs of visits to emergency departments. N Engl J Med 1996;334:642–646. Tarasoff v Regents of the Univ. of Cal., 551 P2d 334 (CAL 1976). Accreditation Manual for Hospitals Standard, E.R. 1.4.2., JCAHO, Chicago, 1992. Accreditation Manual for Hospitals, Standard 2.4 et. seq., Joint Commission on Accreditation of Health Care Organizations, Chicago, IL 1992. Hospital obligations with respect to treatment of emergency medical conditions and indigent care. 42 USC 1395cc(a)(1). 42 USC 1395dd (C) For example—The Natural Death Act. Texas Health and Safety Code, Chapter 672. Canterbury v Spence, 464 F.2d 772 (DC Cir 1972). Wickline v California, 183 Ca. App. 3d 1175 (1986). Risk Retention Act, 15 USC Sec 3901 et. seq. Rogers and Fastow supra note 17. Darling v Charleston Community Hospital 200 NE 2d 149 (Illinois Supreme Court 1965). Healthcare Quality Improvement Act, 42 USC Section 11111, et. seq. 15 USC 1 et. seq. Patrick v Burget, 486 US 94 (1988). 42 USC Section 11133 et. seq. (Data Bank Section of the Healthcare Quality Improvement Act). Healthcare Quality Improvement Act, Reporting of Information, 42 USC 11131 et. seq. 45 CFR Section 60.11 and 61.13. National Practitioner Data Bank Guidebook. U.S. Dept. of Health and Human Services. Contact (800) 767-6732. Rockville, Md. 42 USC Section 11133(B)(i)(ii) Smith v. Baptist Memorial Hospital System, 720 SW 2d 618 (Tex. App. San Antonio 1986 ref. n.r.e.) Hanola v City of Lakewood, 426 NE 2d 1187, (1980). Occupational Safety and Health Act. 29 USC 651 et. seq.

APPENDIX A. NORMAL REFERENCE VALUES Principles and Practice of Emergency Medicine

APPENDIX A. NORMAL REFERENCE VALUES Reference Values in Hematology Reference Values for Blood, Plasma and Serum (For some procedures the reference values may vary depending upon the method used) Reference Values for Urine (For some procedures the reference values may vary depending upon the method used) Reference Values for Therapeutic Drug Monitoring Reference Values in Toxicology Reference Values for Cerebrospinal Fluid Reference Values for Gastric Analysis Gastrointestinal Absorption Tests Reference Values for Feces Reference Values for Immunologic Procedures Reference Values for Semen Analysis Oral Glucose Tolerance Test

Reference Values in Hematology

Reference Values for Blood, Plasma and Serum (For some procedures the reference values may vary depending upon the method used)

Reference Values for Urine (For some procedures the reference values may vary depending upon the method used)

Reference Values for Therapeutic Drug Monitoring

Reference Values in Toxicology

Reference Values for Cerebrospinal Fluid

Reference Values for Gastric Analysis

Gastrointestinal Absorption Tests

Reference Values for Feces

Reference Values for Immunologic Procedures

Reference Values for Semen Analysis

Oral Glucose Tolerance Test

APPENDIX B. USEFUL TABLES Principles and Practice of Emergency Medicine

APPENDIX B. USEFUL TABLES Endocrinologic and Metabolic General Infectious Diseases Neurology Obstetrics/Gynecology Pediatrics Resuscitation Vascular Emergencies

ENDOCRINOLOGIC AND METABOLIC

Table B.1. Disturbances of Acid-Base Balance

Table B.2. Types of Metabolic Acidemia

GENERAL Table B.3. Time Required for 500 mL of Blood to Pass Through Cannulas of Different Sizes Against No Resistance

Table B.4. Temperature Equivalents

Table B.5. Vital Signs by Age INFECTIOUS DISEASES

Table B.6. Antimicrobial Therapy for Sexually Transmitted Diseases

Pulmonary Complications in HIV Table B.7. Pneumonia in the HIV + Patient

Table B.8. PCP

Table B.9. M. tuberculosis

Table B.10. Bacterial Pneumonia NEUROLOGY

Table B.11. Glasgow Coma Scale

OBSTETRICS/GYNECOLOGY Table B.12. The Apgar Score PEDIATRICS

Table B.13. Pediatric Dosing and Administration Guidelines for Nebulized Albuterol in the Management of Asthma

Table B.14. Pediatric Dosing and Administration Guidelines for Selected Drugs Used in the Management of Asthma

Table B.15. Routine Immunizations RESUSCITATION

Table B.16. Cardiopulmonary Resuscitation: Drugs and ET Sizes

Table B.17. Rapid Sequence Intubation (RSI)

Table B.18. Comparison of Sedatives and Analgesics for Conscious Sedation

Table B.19. Drug Dosages for Resuscitation of Neonates, a Infants, and Children VASCULAR EMERGENCIES

Table B.20. Emergencies and Urgencies: Drugs Available

Table B.21. Intravenous Antihypertensive Drugs: Category and Dosage

Suggested Readings Bartlett JG: Medical management of HIV infection. Glenview, IL. Physicians and Scientists Publishing Co., Inc., 1996. Goodman PC: Tuberculosis and AIDS. Radiol Clin North Am 1995;33(4):707–717. Guss DA: The acquired immune deficiency syndrome: an overview for the emergency department physician, I. J Emerg Med 1993;12(3):375–384. Huang L, Stansel JD: AIDS and the lung. Med Clin North Am 1996;80(4):775–799. Kelen GD, Johnson G, DiGiovana G, et al: Profile of patients with human immunodeficiency virus infection presenting to an inner-city emergency department: preliminary report. 1990;19(9):41–47. Marco CA: HIV infection and AIDS. In: Tintinalli JE, Ruiz E, Krome RL, eds. Emergency medicine, a comprehensive study guide. 4th ed. New York: McGraw Hill 1996:701–706. Moran GJ: Managing the HIV-related medical emergency. Emerg Med 1995;April:18–30. Moran GJ, Fuchs MA, Jarvis WR, et al: Tuberculosis infection-control practices in United States emergency departments. Ann Emerg Med 1995;26(3):283–289. Moran GJ, McCabe F, Morgan MT, et al: Delayed recognition and infection control for tuberculosis patients in the emergency deparmtent. Ann Emerg Med 1995;26(3):290–295. Talan DA, Kennedy CA: The management of HIV-related illness in the emergency department. Ann Emerg Med 1990;20:1355–1365.

Ann Emerg Med

Chapter 26-2 Appendix – ECG Illustrative Tracings Principles and Practice of Emergency Medicine

Chapter 26-2 Appendix – ECG Illustrative Tracings

Figure A–1. Sinus arrest. The arrows point to the anticipated location of the sinus P wave. The last three P waves document the rate of the sinus discharge. The PP interval of the first three P waves is double the succeeding PP intervals, indicating a transient 2:1 sinus block.

Figure A–2. AV dissociation. The first three complexes are due to a junctional escape rhythm at a rate of 50 beats/min. A sinus rhythm at a rate of 65 beats/min then emerges for three complexes. The sinus rate then slows temporarily, allowing the junction to escape until the sinus rate again accelerates. The junctional complexes are slightly aberrant.

Figure A–3. First-degree AV block. The PR interval is prolonged to 0.40 seconds. The P wave (P) is partially hidden in the descending limb of the T wave.

Figure A–4. Second-degree AV block (Mobitz II). The strips are not continuous but are taken from the same patient. Strip A shows complete AV block with a junctional escape rhythm. Strip B shows a prolonged period of asystole owing to complete AV block with a single escape junctional beat (J). Strip C shows 2:1 AV block with the nonconducted P wave hidden in the T wave (arrows). The 2:1 conduction abruptly returns to 1:1 in the middle of the strip.

Figure A–5. Supraventricular tachycardia with aberration. Frequent premature atrial complexes (X) are noted. After a long cycle a premature atrial complex (P) results in a brief run of aberrant complexes. The long-short sequence and the obvious premature P wave suggest that the tachyrhythmia is supraventricular with aberration.

Figure A–6. Ventricular tachycardia. A premature ventricular complex (X) strikes on the T wave, initiating a transient burst of ventricular tachycardia.

Figure A–7. Ventricular tachycardia. Two sinus beats are followed by a fusion complex (F) leading off a run of ventricular complexes. A capture complex (C) transiently interrupts the ventricular rhythm. Cardiac arrest occurred in this patient seconds after this ECG was recorded.

Figure A–8. Premature ventricular complexes. Multiform premature ventricular complexes with variable coupling intervals are shown.

Figure A–9. Ventricular fibrillation. A premature complex of uncertain origin, possibly supraventricular, initiates a period of ventricular fibrillation.

Figure A–10. Ventricular flutter. Rapid, uniform oscillations are seen at a rate close to 300 beats/min. This rhythm either terminates spontaneously or degenerates into ventricular fibrillation.

Figure A–11. Atrial fibrillation. Carotid sinus massage (CSM) transiently slows the ventricular response, revealing the fibrillatory baseline. The ventricular rate then accelerates.

Figure A–12. Multiform atrial tachycardia. Frequent premature atrial complexes with different P wave morphology are seen.

Figure A–13. Sinus tachycardia. The sinus P wave is obscured within the descending limb of the T wave. Carotid sinus massage (CSM) transiently slows the sinus rate and exposes the P wave. The rate then increases. The strips are continuous.

Figure A–14. Atrial flutter. Carotid sinus massage (CSM) transiently increases the AV block from 2:1 to 4:1 conduction, revealing flutter waves (f).

Figure A–15. AV nodal reentry. Carotid sinus massage (CSM) abolishes the arrhythmia and results in a period of sinus suppression with a junctional (J) escape beat.

Figure A–16. Wolff-Parkinson-White syndrome. The basic rhythm is atrial fibrillation. The complexes with the narrow QRS are conducted via normal conduction pathways. The complexes marked as W begin with a marked delta wave that is due to early ventricular texcitation through a bypass tract. The grossly irregular rhythm is the clue that the rhythm is atrial fibrillation and not runs of ventricular tachycardia.

Figure A–17. Junctional tachycardia. A retrograde P wave (P) follows each QRS and distorts the ST segment.

Chapter 144 – Appendix 144A/Index of Substances Principles and Practice of Emergency Medicine

Chapter 144 – Appendix 144A/Index of Substances Common Poisons and Therapy

COMMON POISONS AND THERAPY Acetaminophen Called N-acetyl-paraaminophenol or APAP, Tylenol® and others, called paracetaminol in United Kingdom. Toxic mechanism: At therapeutic doses less than 5% metabolized by P4502E1 to a reactive, metabolite, N-acetyl-p-benzoquinoneimine (NAPQI), a strong oxidizing agent. In overdose there is not sufficient glutathione (less than 30%) available to reduce NAPQI into nontoxic mercaptate conjugate and it forms covalent bonds with intracellular proteins to produce hepatocellular centralobular necrosis and renal injury. Therapeutic dose: 10 to 15 mg/kg up to 2.6 g/24 h. Toxic dose: Acute: more than 140 mg/kg possibly 200 mg/kg in child; more than 7.5 gm adult. Chronic is caused by factors affecting the P 450 enzyme: alcoholics ingesting 3 to 4 g/d for a few days, patients with eating disorders or malnutrition, patients on enzyme inducers (e.g., anticonvulsants or isoniazid, smoking), patients with AIDS may have depleted their glutathione and require N-acetylcyteine (NAC) therapy below hepatotoxic levels. Children receiving 150 mg/kg per day for 2 to 4 days may develop liver enzyme elevations. Kinetics: Onset of action is 0.5 to 1 hour, peak plasma concentration 20 to 90 min but usually 2 to 4 hours after an overdose, duration 4 to 6 hours, Vd 0.9 L/kg. PB low less than 50% (albumin), T1/2 1 to 3 hours. Route of elimination is by hepatic metabolism (more than 90%) to an inactive nontoxic (65%) glucuronide conjugate and inactive nontoxic sulfate metabolite (30%) by two saturable pathways. A small amount (less than 5%) of the dose is converted by the P450 system to a toxic reactive metabolite NAPQI that is rapidly inactivated by conjugation with glutathione into nontoxic mercaptate conjugate. In overdose the increase in NAPQI depletes the glutathione stores. In infants and children under 6 years of age, elimination occurs to a greater degree by conjugation with sulfate which may be hepatoprotective. Factors that affect APAP metabolism increased P450 enzyme by enzyme inducers, e.g., barbiturates, phenytoin, smoking, alcohol. Decreased glutathione stores, e.g., alcohol, malnutition, HIV. Manifestations: The four phases of the intoxication's clinical course may overlap and the absence of a phase does not exclude toxicity. See Table 144A.1A. Phase I occurs 0.5 to 24 hours after ingestion and consists of malaise, diaphoresis, nausea, and vomiting. CNS depression or coma is not a feature. Only massive overdoses producing plasma levels more than 800 µg/mL produce CNS depression. Phase II occurs 24 to 48 hours after ingestion and is a period of diminished symptoms. Hepatic damage begins within 24 hours of a significant ingestion, as indicated by increases in the liver enzymes, serum bilirubin, and prothrombin time, right upper abdominal quadrant pain, and oliguria. The liver enzymes aspartate aminotransferase (AST), and alanine aminotransferase (ALT) may increase as early as 4 hours after ingestion and as late as 36 hours after ingestion. Phase III occurs 48 to 96 hours after ingestion with peak liver function abnormalities. Although the degree of elevation of the hepatic enzymes do not correlate with outcome, values more than 1000 IU/L indicate hepatotoxicity. AST values up to 30,000 IU/L have been reported. Less than 1% of patients in stage III develop fulminant hepatotoxicity. If the hepatic damage is extensive, hepatic failure develops about the fourth to fifth day (altered consciousness, hypoglycemia, and coagulation abnormalities). Jaundice does not usually become obvious before the fourth or fifth day. Phase IV occurs 4 to 14 days after ingestion with hepatic enzyme abnormalities reaching resolution. Complete hepatic recovery can occur within 3 to 6 months. If extensive liver damage has occurred, sepsis and disseminated intravascular coagulation may ensue. Death may occur at 7 to 14 days. Liver biopsy shows centrilobular necrosis. Transient renal failure may develop at 5 to 7 days after ingestion (in 25% of hepatotoxic patients). The renal damage can occur without evidence of hepatic damage. Rarely, cases of myocarditis and pancreatitis have been reported. Differential diagnosis: Other liver toxins include amatoxins, chlorinated hydrocarbons, ethanol, hepatitis, isonaizid reaction, pyrrolizidine toxins in herbs. When the ratio of AST over the ALT is more than 2 it suggests APAP is not the etiologic factor for the increase in liver enzymes. (Table 144A.1C). Management: All patients with intentional overdose should be tested for APAP blood concentrations. About 1:500 without a history of APAP ingestion have a potentially toxic plasma concentration. (1) GI decontamination: Although emesis may be useful for the initial treatment of children immediately at home (within 30 minutes) it is often avoided because it interferes with the retention of the more effective AC and administration of N-acetylcyteine (NAC). Emesis in not used in the ED for the same reasons. Gastric lavage is not necessary if activated charcoal is available. Studies have indicated that activated charcoal (AC) 1 g/kg in the first 4 hours effectively adsorbs significant amounts of APAP. MDAC has not been well studied. AC does adsorb NAC if given together but this is not clinically important. However, to avoid vomiting, separate the AC from NAC by 1 to 2 hours. Use saline sulfate cathartic because it can enhance the activity of the sulfate metabolic pathway, which can be hepatic protective. (2) N-acetylcysteine (NAC). NAC is a derivative of the amino acid cysteine, which constitutes the central portion of the glutathione molecule. NAC is metabolized by the hepatocyte to a glutathione precursor (cysteine) that provides increased available glutathione and increases nontoxic sulfation pathway which reduces and conjugates NAPQI ( Table 144A.1B). Administer NAC within the first 8 hours if a toxic amount of APAP has been ingested and give a full 17 dose maintenance course if APAP plasma concentrations 4 hours after ingestion is above the lower line (the intersecting concentrations and time coordinates) on the modified Rumack-Mathews nomogram (Fig. 144A.1). The course of therapy is completed even if subsequent APAP values fall below the toxic zone. (a) Variations in therapy: (1) In patients with chronic alcoholism or on enzyme inducers (anticonvulsants, isonazid) start treatment at 50% below the lower toxic zone on the nomogram. (2) If emesis (50% vomit) occurs within 1 hour of administration of NAC, the dose should be repeated. Use 5% NAC in sweet juice. Serve chilled in covered container with a straw. If unsuccessful, a nasogastric tube into the pylorus and slow drip may be tried. If emesis persists, may use anti-emetics, metaclopramide (Reglan) 10 to 25 mg/dose IV over 1 to 2 minutes every 6 to 8 hours (children 0.1 mg/kg maximum 0.5 mg/kg per day) or ondansetron (Zofran) as a last resort 0.15 mg/kg by intravenous infusion over 15 minutes and repeat every 4 and 8 hours, if needed (may cause anaphylaxis, increases liver enzymes). (b) Variations in dosage, duration and late treatment: (1) Some investigators recommend variable durations of NAC therapy stopping the NAC therapy if plasma APAP levels fall to nondetectable levels and the liver function tests remain normal at 24 hours (however, some liver function tests may rise as late as 36 hours). (2) It has been recommended that repeated plasma APAP concentrations be obtained 2 to 4 hours after the initial 4-hour postingestion level if this level is more than 20 µg/mL or if the patient has a history of ingesting a toxic amount (more than 140 mg/kg) because of unexpected delayed peaks of APAP. Additional APAP levels may be useful in the presence of coingestants or extended release preparations. (3) An intravenous preparation has been used in Europe and Canada for about 20 years but is not approved in the United States (investigational studies are in progress). There have been anaphylactoid reactions and deaths by the intravenous route. (4) Time of administration. NAC is most effective when administered during the first 8 to 10 hours after ingestion (there is no advantage to giving it earlier), the loss of its efficacy after this time is not complete and it should be administered. (5) Late treatment with NAC has been shown to decrease the morbidity and mortality in patients with fulminant liver failure caused by acetaminophen as well as other etiologies. NAC may be administered to patients with a history of a toxic ingestion while awaiting results of the serum APAP. NAC can also be administered in APAP ingestions more than 24 hours after ingestion with detectable serum APAP levels or elevated transaminases. The benefit from NAC requires that the treatment be continued indefinitely until the hepatic failure resolves or the patient dies. NAC administration appears justified in the presence of hepatotoxicity caused by APAP no matter what the time since the last dose. (6) Extended Relief Acetaminophen overdose has “ER” embossed on the caplet side (650 mg immediate release, 650 mg delayed release). Using a single 4-hour serum acetaminophen may underestimate the peak level of Tylenol R because it can be delayed or have a second peak. It is, therefore, recommended to obtain at least 1 additional specimen at 4 to 6 hours after the first 4-hour specimen to determine if either peak is in the toxic zone on the nomogram. If either peak is in toxic zone initiate therapy, if neither is in toxic zone and falling no therapy is required. (3) Pregnancy. It is recommended that pregnant patients with toxic blood concentrations of APAP be treated with NAC to prevent hepatotoxicity in both fetus and mother. The available data appears to indicate no teratogenicity for APAP or NAC. (4) Chronic intoxication. Repeated chronic overdose can produce hepatotoxicity. Indications for therapy with NAC include: (1) history of more than recommended dose (usually 3 to 4 g) for several days or repeated APAP overdosing at risk of hepatotoxicity, (2) history of overdose with elevated liver function tests, (3) plasma acetaminophen level inconsistent with therapeutic dose, (4) chronic administration of more than 4 g daily for 3 to 4 days especially in chronic alcoholics or if the liver function tests are abnormal. (5) Specific support care. Treat liver failure, pancreatitis, transient renal failure, liver failure. (6) Liver transplant has a definite but limited role in acute APAP overdose. A retrospective analysis determined a continuing rise in the prothrombin time (PT) (4 day peak of 180 seconds or 1.8 × the control), pH less than 7.3 (2 days after overdose) serum creatinine more than 3.3, severe hepatic encephalopathy and coagulation factor VII/V ratio more than 30 seconds suggests a poor prognosis and may be reliable indicators for considering liver transplants. (7) Extracorporeal measures are not expected to be of benefit. Laboratory: The therapeutic reference range is 10 to 20 µg/mL. For toxic levels see nomogram. Appropriate reliable methods for analysis are radioimmunoassay, high pressure liquid chromatography (HPLC), and gas chromatography (GC). Spectroscopic assays often give false elevated values. Cross reactions: salicylate, salicylamide, difunisal, methyldopa increase the APAP level. Each mg/dL increase in creatinine increases the APAP plasma level 30 µg/mL. Monitor: If potentially toxic APAP level order liver profile including bilirubin, prothrombin time, serum amylase, coagulation tests, and blood glucose. CBC, platelet count, phosphate, electrolytes, bicarbonate, ECG, and urinalysis should be obtained in toxic cases. AST level is a sensitive marker for hepatic injury. Disposition: All cases of intentional ingestion require serum APAP level because 1:500 without history will have toxic level. (a) Asymptomatic with nontoxic zone APAP levels obtained at least 4 hours after ingestion (with an additional APAP done 2 to 4 hours after the first level, if the original level was more than 20 µg/mL) may be transferred or discharged after psychiatric evaluation if intentional ingestion. (b) Patients with potential hepatotoxic concentration of APAP should receive a full course of NAC therapy (However, some clinical toxicologists discontinue NAC oral therapy when the APAP plasma level is undetectable and if there is no elevation in the liver enzymes). (c) Patients with ingestion >140 mg/kg or 7.5 g should receive therapy within the first 8 hours or until the results of the more than 4-hour postingestion plasma APAP level. (d) Therapy with NAC should be started before 8 hours after ingestion if possible, however, NAC has been proven to be beneficial even after more than 24 hours if there are laboratory signs of liver impairment and should be continued until the hepatotoxicity resolves.

Table 144A.1A. Summary of the Stages in Clinical Course of Acetaminophen Toxicity

Table 144A.1B. Protocol for N-Acetylcysteine Administration

Table 144A.1C. Clinical Features Differentiating Hepatotoxicity

Figure 144A.1. Nomogram for acetaminophen intoxication. Start N-acetylcysteine therapy if levels and time coordinates are above the lower line on the nomogram. Continue and complete therapy even if subsequent values fall below the toxic zone. The nomogram is useful only in acute, single ingestions. Serum levels drawn before 4 hours may not represent peak levels. Reproduced with permission from Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics 1975;55:871.

Alcohols (Table 144A.2A)

Table 144A.2A. Summary of Alcohols and Glycols Features

ETHANOL (GRAIN ALCOHOL)

Toxic mechanism: Ethanol has a CNS hypnotic and anesthetic effect by a variety of mechanisms including membrane fluidity and effect on the GABA system. It promotes cutaneous vasodilation (contributes to hypothermia), stimulates secretion of gastric juice (gastritis), inhibits the secretion of the antidiuretic hormone, inhibits gluconeogenesis (hypoglycemia), and influences fat metabolism (lipidemia). Toxic dose: 1 mL/kg of absolute or 100% ethanol or 200 proof (proof defines alcohol concentration in beverages) gives a blood ethanol concentration (BEC) of 100 mg/dL. Potential fatal dose is 3 g/kg for children or 6 g/kg in adults. Children frequently have hypoglycemia at BEC more than 50 mg/dL. Kinetics: Onset of action is 30 to 60 minutes after ingestion, peak action 90 minutes on empty stomach, and Vd 0.6 L/kg. The major route (>90%) of elimination is by hepatic oxidative metabolism. The first step is by the enzyme alcohol dehydrogenase (ADH) which converts ethanol to acetaldehyde. This step is by zero order kinetics at a constant rate (regardless of the level) of 12 to 20 mg/dL per hour (12 to 15 mg/dL per hour in nonalcoholic drinkers, 15 mg/d per hour in social drinkers, 30 to 50 mg/dL per hour in alcoholics, and in children 28 mg/dL per hour). At low BEC, (less than 30 mg/dL) the metabolism is by first order kinetics. In the second step of metabolism the acetaldehyde is metabolized by acetaldehyde dehydrogenase to acetic acid, and then in subsequent steps acetic acid is metabolized via the Krebs citric acid cycle to carbon dioxide and water. The enzyme steps are nicotinamide adenine dinucleotide (NAD) dependent, which interferes with gluconeogenesis. Only 2 to 10% of ETOH is excreted unchanged by the kidneys. A BEC or amount ingested can be estimated from these equations:

Manifestations: (See Table 144A.2B) Acute: Blood ethanol levels over 30 mg/dL produces euphoria; over 50, incoordination and intoxication; over 100, ataxia; over 300, stupor; and over 500, coma. Levels of 500 to 700 mg/dL may be fatal. Children frequently have hypoglycemia at BEC >50 mg/dL. Chronic alcoholic patients tolerate higher BEC, and correlation with manifestation is not valid. Rapid interview for alcoholism is the CAGE questions C- Have you felt the need to Cut down? A-Have others Annoyed you by criticism of you drinking?. G-Have you felt Guilty about your drinking? E- Have you ever had a morning Eye opening drink to steady your nerves or get rid of a hangover? Two affirmative answers indicate probable alcoholism. Management: Inquire about trauma and disulfiram use. 1. Protect from aspiration and hypoxia. Establish and maintain vital functions. May require intubation and assisted ventilation. 2. GI decontamination plays no role. 3. If comatose, administer glucose 1 mL/kg 50% glucose in adults and 2 mL/kg 25% glucose in children intravenously. Thiamine, 100 mg intravenously is administered if the patient has a history of chronic alcoholism, malnutrition or suspected eating disorders, and to prevent Wernicke-Korsakoff syndrome. Naloxone has produced a partial inconsistent response and is not recommended for known alcoholic CNS depressants. 4. General supportive care. Administer fluids to correct hydration and hypotension, correct electrolyte abnormalities and acid base imbalance. Vasopressors and plasma expanders may be necessary to correct severe hypotension. Hypomagnesemia is frequent in chronic alcoholics. In hypomagnesemia administer loading dose of 2 g magnesium sulfate 10% IV solution over 5 minutes with blood pressure and cardiac monitoring and calcium chloride 10% on hand in case of overdose. Follow with constant infusion of 6 g of 10% solution over 3 to 4 hours. Be cautious with magnesium if renal failure is present. 5. Hypothermic patients should be warmed. (See General treatment of poisoning). 6. Hemodialysis in severe cases when conventional therapy is ineffective (rarely needed). 7. Treat seizures with diazepam. “Rum fits” do not need long-term anticonvulsant therapy. 8. Treat withdrawal with hydration and large doses of chlordiazepoxide 50 to 100 mg or diazepam 2 to 10 mg intravenously. These may be repeated in 2 to 4 hours. Large doses of benzodiazepines may be required for delirium tremors. Withdrawal can occur in presence of elevated BEC and can be fatal untreated. Laboratory: BEC should be specifically requested and followed. Gas chromatography or a breathalyzer test gives rapid reliable results if no belching or vomiting, enzymatic methods do not differentiate between the alcohols, ABG, electrolytes, glucose; determine anion and osmolar gap (measure by freezing point depression not vapor pressure) and check for ketosis. (See General management.) The anion gap increases 1 mg/kg for each 4.5 mg/dL BEC. Chest radiograph is given to determine whether aspiration pneumonia is present. Renal and liver function tests and bilirubin levels should also be done. Disposition: Clinical severity (e.g., intubation, assisted ventilation, aspiration pneumonia) should determine the level of hospital care needed. Young children with significant accidental exposure to alcohol (calculated to reach a BEC of 50 mg/dL) should have BEC obtained and blood glucose levels monitored for hypoglycemia frequently for 4 hours after ingestion. Patients with acute ethanol intoxication seldom require admission unless a complication is present. However, intoxicated patients should not be discharged until fully functional (can walk, talk, and think independently), has suicide potential evaluated, has proper disposition environment, and a sober escort. Extended liability means a physician can be held liable for subsequent injuries or death in an intoxicated patient who has been allowed to sign out against medical advice (AMA). No patient can sign out AMA with an altered mental status.

Table 144A.2B. Clinical Signs in the Intolerant Ethanol Drinker

ISOPROPANOL Also called IP or rubbing alcohol, solvents, lacquer thinner. Coma has occurred in children sponged for fever with IP. Toxic mechanism: Gastric irritant. Metabolized to acetone, a CNS depressant and myocardial depressant. Inhibits gluconeogensis. Normal propyl alcohol is related to isopropanol but is more toxic. Toxic dose: 1 mL/kg of 70% produces blood isopropyl alcohol concentration (BIPC) 70 mg/dL. CNS depressant effect is twice that of ethanol. Toxic BIPC is 50 mg/dL, coma occurs at 150–200 mg/dL, potentially fatal BIPC occurs more than 250 mg/dL. Kinetics: Onset within 30 to 60 minutes and peak 1 hr postingestion, elimination is renal. Can calculate out isoproyl BIPC concentration and amount ingested using equation in ethanol kinetics and specific gravity of 0.785. Manifestations: Ethanol-like inebriation with acetone odor to breath, gastritis ocasionally with hematemesis, acetonuria, acetonemia without systemic acidosis, lethargy (50 to 100 mg/dL), CNS depression, comatose (150 to 200 mg/dL), potentially fatal in adults (240 mg/dL). Hypoglycemia and seizures may occur. Management: (1) Protect the airway with intubation if necessary, Assisted ventilation may be needed. If hypoglycemic administer glucose. Supportive treatment is similar to ethanol. (2) GI decontamination has no role. (3) Hemodialysis in life-threatening overdose (rarely needed). Consult nephrologist if BIP more than 250 mg/dL. Laboratory: Monitor isopropyl alcohol levels, acetone, glucose, and ABG. Osmolal gap increases 1 mOsm per 5.9 mg/dL of isoproyl alcohol and 1 mOsm per 5.5 mg/dL of acetone. Disposition: Ingestion of 0.5 mL/kg of 70% in children is indication for ED evaluation, monitor BIPC and glucose and observe for at least 3 hours in ED. Symptomatic patients with concentrations more than 100 mg/dL may require at least 24 hours for resolution and should be admitted. If hypoglycemic, hypotensive, or comatose admit to ICU. The absence of excess acetone in the blood (normal 0.3 to 2 mg/dL) within 30 to 60 minutes or excess acetone in the urine within 3 hours excludes the possibility of significant isopropanol exposure. METHANOL (WOOD ALCOHOL) The concentration of methanol in Sterno fuel is 4%, in windshield washer fluid 30%, and in gasoline antifreeze 100%. Toxic mechanism: Methanol is metabolized by hepatic alcohol dehydrogenase to formaldehyde and formate. Formate produces tissue hypoxia and metabolic lactic acidosis. Formate is converted by

folate-dependent enzymes to carbon dioxide. Toxic dose: 0.4 mL/kg 100% (absolute). One teaspoonful (5 mL) 100% or 1 tablespoonful (15 mL) 40% is potentially lethal for a 2-year-old child and can cause blindness in an adult. The toxic blood concentration (BMC) is more than 10 to 20 mg/dL, the potentially fatal level is over 50 mg/dL. Kinetics: Onset may be delayed: may start in 1 hour but is typically delayed 12 to 18 hours, peak BMC is in 1 hour. Consider hemodialysis if the blood methanol level is more than 25 to 50 mg/dL (some use more than 20 mg/dL as indication for ethanol and more than 50 mg/dL as indication for hemodialysis), if significant metabolic acidosis, visual or mental symptoms are present. Vd 0.6 L/kg (total body water), T1/2 is 8 hours, with ethanol blocking 30 to 35 hours, with hemodialysis 2.5 hours. Elimination is renal. Manifestations: Slow metabolism may delay onset for 12 to 18 hours in adults or longer if ethanol is ingested concomitantly or in infants up to 72 hours. May produce inebriation. Hyperemia of optic disk, violent abdominal colic, “snow vision,” blindness, and shock. Later worsening acidosis, hypoglycemia, multiorgan failure develops with death from complications of intractable acidosis and cerebral edema. Absence of anion gap, osmolal gap does not exclude methanol poisoning. The methanol produces the osmolal gap (early) and the metabolite formate produces the anion gap metabolic acidosis (later). Management: (1) Protect the airway by intubation to prevent aspiration and administer assisted ventilation as needed. Administer 100% oxygen if needed. Consult with a nephrologist because many patients need hemodialysis. (2) GI decontamination has no role. (3) Treat metabolic acidosis vigorously with sodium bicarbonate 2–3 mEq/kg intravenously up to 400 to 600 mEq may be needed in first few hours. (4) Initiate ethanol therapy to block metabolism (Formulary table) if ingested 0.4 mL/kg 100%, blood methanol level is more than 20 mg/dL, or if the patient is symptomatic or acidotic with increased anion gap or osmolar gap. Ethanol should be administered intravenously (oral is less reliable) to produce a BEC 100 to 150 mg/dL. (a) The loading dose is derived from the formula: 1 mL 100% ethanol per kg = BEC 100 mg/dL (which protects against metabolism of methanol), therefore, 10 mL of 10% ethanol intravenously is administered concomittantly with a maintenance dose of 2.0 mL/kg per hour of 10% ethanol (for an alcoholic), or 0.83 mL/kg per hour (nondrinker) or 1.4 mL/kg per hour (social drinker). (b) If hemodialysis is used administer ethanol 10% 1.5 to 2.5 mL/kg per hour to a maximum of 91 mL/h. Obtain BEC, and glucose every 2 h. ( Note: The ethanol dose has to be increased during dialysis therapy.) (5) Treat hypoglycemia with intravenous glucose. (6) A bolus of folinic acid and folic acid has been used successfully in animal investigations to enhance formate metabolism. Administer leucovorin, 1 mg/kg up to 50 mg IV every 4 hours for several days. (7) 4-methylpyrazole inhibits alcohol dehydrogenase and is being investigated for use in methanol and ethylene glycol poisoning. (8) Consider hemodialysis if the blood methanol level is greater than 25 to 50 mg/dL (some use more than 20 mg/dL as indication for ethanol and more than 50 mg/dL as indication for hemodialysis), if significant metabolic acidosis, visual, or mental symptoms are present. (9) Continue therapy both (ethanol and hemodialysis until blood methanol level is undetectable, there is no acidosis and no mental or visual disturbances. This may require 2 to 5 days. (10). Ophthalmologic consultation initially and follow-up. Laboratory: Detected on drug screens if specified. Methanol and ethanol levels, electrolytes, glucose, and ABG. Formate levels correlate more closely than BMC with severity of intoxication and should be obtained if available. If methanol levels are not available the osmolal gap × 3.2 can be used to estimate the BMC in mg/dL. (see General management). A serum bicarbonate less than 20 mEq/L has been reported as having a 20% mortality and less than 10 mEq/L a 50% mortality. Disposition: All patients ingesting methanol more than 4 mL 100% methanol should be referred to an ED. Asymptomatic patients with BMC less than 10 mg/dL on admission and continuing to fall may be discharged after 24 hours, but should be observed longer if methanol was ingested with ethanol or small children because of delayed onset. Patients treated for methanol intoxication should be discharged only after methanol is nondetectable. Ophthalmologic follow-up. (11) Other alcohols: Benzyl alcohol used as a bacteriostatic preservative in saline has produced the “gasping baby syndrome.” Neonates developed hypotension, metabolic acidosis, gasping respirations, hepatorenal failure, and death. Alkali See Caustics and Corrosives. Amitriptyline (Elavil) Peak concentration in 4 hrs. Liver metabolism to nortriptyline. The Vd is 8.3 L/kg and PB is more than 80%. The T1/2 is 9 to 25 hours. Renal excretion is 18% unchanged (see Tricyclic Antidepressants ). Amphetamines Illicit methamphetamine (“Ice”), diet pills, various trade names. Analogs: MDMA (3,4 methylenedioxymethamphetamine known as “ectasy”, “XTC”, “Adam”) MDEA (3,4-methylenedioxyamphetamine known as “Eve.) Other stimulants are phenylpropanolamine and cocaine. Toxic mechanism: Amphetamines have a direct CNS stimulant effect and a sympathetic nervous system effect by releasing catecholamines from alpha (a) and (b) adrenergic nerve terminals but inhibits their reuptake. Phenylpropanolamine stimulates only the b-adrenergic receptors. Toxic dose: Child 1 mg/kg dextroamphetamine; adult 5 mg/kg and 12 mg/kg has been reported as lethal. Kinetics: Amphetamine is a weak base with pKa 8 to 10. Onset of action is 30 minutes to 1.5 hours. Peak 2 to 4 hours. Elimination T1/2 is pH dependent, 8 to 10 hours in acid urine (pH less than 6.0) and 16 to 31 hours in alkaline urine (pH more than 7.5). Vd is 2 to 3 L/kg. Route of elimination is deamination and hydroxylkation by the liver 60% into a hydroxylated metabolite that may be responsible for psychotic effects; and by the kidney, 30 to 40% at alkaline urine pH; and 50 to 70% at acid urine pH. Manifestations: Effects are seen within 30 to 60 minutes following ingestion. Restlessness, irritation and agitation, tremors and hyperreflexia, auditory and visual hallucinations. Dilated reactive pupils, cardiac dysrhythmias (supraventricular and ventricular) tachycardia, hyperpyrexia may precede seizures, convulsions, hypertension, paranoia, violence, intracranial hemorrhage, rhabdomyolysis, myoglobinuria, psychosis and self-destructive behavior. Paranoid psychosis and cerebral vasculitis with chronic abuse. Management: (1) Control the seizures, hypertension, ventricular dysrhythmias and hyperthermia. Consult anesthesiologist for control of intractable seizures. (2) GI decontamination. Avoid induced emesis because of rapid onset of seizures. Administer activated charcoal. (3) Seizure precautions and control extreme agitation or convulsions with benzodiazepines (diazepam or lorazepam). Avoid phenothiazines, which can lower the seizure threshold. (4) Hypertension is usually transient and not treated. Treat hypertensive crisis with nitroprusside, maximum infusion rate 10 µg/kg per minute for 10 minutes follow with 0.3 to 2 mg/kg per minute (see General management). (5) Hypotension can be treated with fluids and vasopressors if needed. (6) Life-threatening tachydysrhythmias may respond to a-blocker (phentolamine 5 mg IV adults 0.1 mg/kg child IV) and b-blocker (esmolol IV). Ventricular dysrhythmias may respond to lidocaine or in a severely hemodynamically compromised patient (hypotension, shock, ischemic chest pain) immediate synchronized cardioversion. (7) Acid diuresis is not recommended. (8) Treat rhabdomyolysis and myoglobiuria with alkaline diuresis. (9) Treat hyperpyrexia with external cooling. (see General management). (10) If focal neurologic symptoms are present, consider cerebrovascular accident and obtain computed tomography scan. (11) Treat agitation, paranoid ideation and threatening behavior. General management: Observe for suicidal depression that may follow intoxication, which may require admission and 1:1 observation. (12) Extracorporeal measures are of no benefit. Laboratory: Monitor for mental status changes, dysrhythmias, hyperpyrexia, rhabdomyolysis (creatine kinase [CK], myoglobinuria, urinary output, hyperkalemia, and disseminated intravascular coagulation. The peak blood concentrations are 10 to 50 ng/mL 1 to 2 hours after ingestion of 10 to 25 mg. The toxic blood concentration is 200 ng/mL. False-positive cross reactions may occur with raniditine, phenylpropanolamine, bromphenaramine, and chlorpromazine. Disposition: Asymptomatic patients may be discharged after 6 hours with appropriate psychiatric evaluation. Mild symptoms may be monitored in the ED. If severe agitation unresponsive to medication, paranoid or suicidial ideation, threatening behavior then admit. If severe hypertension, dysrhythmias or convulsions admit to ICU. Aniline See Nitrites and Nitrates. Anticholinergic Agents Drugs and plants with anticholinergic properties include antihistamines H-1 blockers; neuroleptics (phenothiazines); tricyclic antidepressants; antiparkinsonism drugs (trihexyphenidyl, benztropine); over-the-counter sleep, cold, and hay fever medicines (methapyrilene); ophthalmic products (atropine); common plants-jimsonweed (Datura stramonium), deadly nightshade (Atropa belladonna), henbane (Hyoscyamus niger); and antispasmodic agents for the bowel (atropine derivatives). Toxic mechanism: By competive inhibition they block the action of acetylcholine on postsynaptic cholinergic receptor sites. Involves primarily the peripheral and CNS muscarinic receptors. Toxic dose: variable, toxic amounts of atropine are 0.05 mg/kg in a child and more than 2 mg in adults. Fatal amounts are 2 mg of atropine mydriatic eye drops in a 2-year-old child. The minimal estimated lethal dose of atropine more than 10 mg in adults and more than 2 mg in children. Other synthetic anticholinergic agents are less toxic and the fatal dose varies from 10 to 100 mg/kg. Kinetics: Onset of action IV is immediate with peak in 2 to 4 minutes, peak effects on salivation after IV/IM dose is 30 to 60 minutes. Onset after ingestion is 30 to 60 minutes, peak action is 1 to 3 hours and duration is 4 to 6 hours but symptoms are prolonged in overdose or with sustained release preparations. Manifestations: Anticholinergic signs-hyperpyrexia, mydriasis, flushing of skin, dry mucosa and dysphagia, tachycardia, moderate hypertension, delirium, “Lilliputian type” hallucinations, coma, and rarely convulsions. Urinary retention. Management: (1) If respiratory failure, intubation and assisted ventilation. (2) GI decontamination. Induced emesis useful at scene within 30 minutes. Activated charcoal useful in ED if bowel sounds are present. MDAC not recommended. (Note: Caution with emesis if diphenhydramine overdose because of rapid onset of action and seizures.) (3) Control seizures with benzodiazepines (diazepam or lorazepam). (4) Control ventricular dysrhythmias with lidocaine. (5) Physostigmine (Formulary table) is not routine and reserved as a last resort for life-threatening anticholinergic effects refractory to conventional treatments (uncontrollable risk for injury to self and others). It should be administered with adequate monitoring and resuscitative equipment. It may cause AV block, asystole and seizures in tricyclic antidepressant poisoning. (6) Relieve urinary retention by catheterization to avoid reabsorption. (7) Treat cardiac dysrhythmias (usually supraventricular) only if tissue perfusion is not adequate or if the patient is hypotensive. (8) Control hyperpyexia by external cooling. (9) Hemodialysis or hemoperfusion are not effective. Laboratory: ABG (if respiratory

depression) electrolytes, glucose, ECG monitoring. Natural plants are not detected on drug screen. Not routinely on drug of abuse screen. Disposition: Asymptomatic patients may be discharged after 6 hours with psychiatric clearance if needed. Symptomatic patients (altered mental state, tachycardia, hypotension, confusion, agitation) should be observed on a monitored unit until the symptoms resolve. Observe for a short time after resolution because of relapse. Anticonvulsants (Table 144A.3)

Table 144A.3. Pharmacokinetics of Common Anticonvulsants

Some of these agents are used as antipsychotic agents. Toxic Mechanisms: Phenytoin and carbamzepine inhibit sodium channels; phenobarbital, benzodiazepines and valproic acid are GABA agonists. Toxic dose: Specific anticonvulsant blood levels and the clinical manifestations indicate toxicity. In general, the ingestion of five times the therapeutic dose is expected to have the potential for toxicity. Manifestations: CNS depression, nystagmus. Management: (1) Protect the airway by intubation to prevent aspiration and administer assisted ventilation as needed. Administer 100% oxygen if needed. If hypotensive, administer fluids. (2) GI decontamination. Avoid ipecac-induced-emesis because of early onset of CNS depression and paradoxical seizures in some patients. (a) Administer AC and MDAC, it shortens the T1/2 of carbamazepine and phenobarbital, but there is no evidence it shortens the coma. (b) Alkalization of the urine with sodium bicarbonate (Formulary table) increases the elimination time of phenobarbital. (c) Naloxone (Formulary table) may improve valproic acid-induced coma but is not consistently effective. (d) Flumazenil (Formulary table) is being investigated in management of carbamazepine but is not recommended at this time. It is usually contraindicated in patients with seizures and should not be used in patients that are dependent on benzodiazepines or using benzodiazapines as an anticonvulsant, e.g., clonazepam. (3) Primidone may produce crystaluria and require higher urine flow rates. Laboratory: Monitor specific anticonvulsant blood levels. Disposition: Asymptomatic patients with blood concentrations within therapeutic range may be discharged only if the blood concentration has been showing a definite decline. If intentional overdose discharge requires prior psychiatric evaluation. Antidepressants See Tricyclic Antidepressants . Antidysrhythmic Agents Classification: Class IA disopyramide, procainamide, quinidine. Class IB lidocaine, phenytoin, tocainide, mexiletine. Class IC encainide, flecainide, propafenone. Kinetics: Rapidly absorbed from GI tract (except for disopyramide and sustained release preparations) Onset of action within 1 hour, peak effects several hours. Short T1/2 3 to 11 hours but longer for Class IC agents. Toxic dose: Acute ingestion of more than twice the usual daily dose is potentially toxic. Manifestations: GI upset, lethargy, confusion, ataxia, bradycardia, hypotension. Anticholinergic effects with disopyramide. Class IB cause agitation and seizures. Nonspecific ECG changes include bradycardia, AV block, and QRS prolongation. Class IA and IC characteristically produce ventricular tachycardia, fibrillation and polymorphorous torsades de pointes and QT interval prologation. Depressed cardiac output may lead to cardiac pulmonary edema. Management: (1) Establish and maintain the vital functions. Treat hypotension with fluids and vasopressors and if persist need monitoring of pulmonary arterial wedge pressure. Cardiac pacing and intra-aortic balloon pump counterpulsation and bypass may be necessary. (2) Dysrythmias: Ventricular tachycardia is treated with lidocaine, phenytoin and bretylium. Sodium bicarbonate for wide base QRS due to Class IA or IC agents. For torsades de pointes administer magnesium 4 g or 40 mL 10% solution intravenously over 10 to 20 minutes and overdrive pacing. (3) Hypokalemia may be protective and do not treat hypokalemia unless potassium is below 3 mEq/L. (4) Hemodialysis and hemoperfusion may enhance the elimination of disopyramide and procaine amide metabolite N-acetylprocainamide but has not been scientifically investigated. Laboratory: Monitor ECG, electrolytes (mild hypokalemia), glucose (hypoglycemia with quinidine and disopyramide). Measure serum levels to confirm overdose. Antifreeze See Alcohols (Methanol) and Ethylene Glycol. Antihistamines (H1 Receptor Antagonists) I. THE H1 BLOCKER “SEDATING” ANTIHISTAMINES Many of these agents are used in combination with other medication, e.g., acetaminophen, aspirin, codeine, dextromethorphan, ephedrine, phenylephrine, phenylpropanolamine, and pseudoephedrine. (see Table 144A.4) Toxic mechanism: possess anticholinergic actions (blockade of cholinergic muscarinic receptors), depress or stimulate the CNS, and in large overdoses have cardiac membrane-depressant effect (e.g., diphenhydramine) and a-adrenergic receptor blockade (e.g., prometazine). Toxic dose: Diphenhydramine toxic oral amount in a child is 15 mg/kg, and the potential lethal amount is 25 mg/kg. In an adult the potential lethal amount is 2.8 g. Ingestion of 3 to 5 times the usual daily dose of an antihistamine is toxic. Kinetics: (see Table 144A.4) Onset 15 to 30 minutes to 1 hour, peak in 1 to 4 hrs, PB 75 to 80%, Vd 3.3 to 6.8 L/kg, T1/2 3 to 10 hours. Elimination is 98% hepatic by N-demethylation. Manifestations: Exaggerated anticholinergic effects, jaundice (cyproheptadine), coma, seizures, dystonias (diphenhydramine), rhabdomyolysis (doxylamine). Management: (see anticholinergics ). Disposition: If patient remains asymptomatic or becomes asymptomatic within 6 hours may be discharged. If symptomatic with hallucinations, or agitation admit. If coma, seizures, or cardiac instability admit to ICU. Intentional overdose need psychiatric evaluation before discharge (see anticholinergics ).

Table 144A.4. Common H-1 Blocker Antihistamines Kinetics

II. THE NEWER “NONSEDATING” SINGLE DAILY DOSE ACTING ANTIHISTAMINES (TERFENADINE, ASTEMIZOLE) Loratidine has not had serious cardiac adverse effects reported. Toxic mechanism: They do not possess anticholinergic actions. These drugs can produce prolonged QT intervals and torsades de pointes in overdose, if impaired hepatic function, if receiving enzyme inhibitors (cimetidine, ketoconazole, or macrolide antibiotics) because the metabolism of terfenadine and astemizole is inhibited producing elevated toxic levels. Toxic dose: An overdose of 3,360 mg of terfenadine in an adult developed ventricular tachycardia and fibrillation that responded to lidocaine and defibrillation. A 1500 mg overdose produced hypotension. Cases of serious dysrhythmias have been reported with more than 200 mg of astemizole. Kinetics: Onset in 1 hour, peak effects in 4 to 6 hours, duration more than 24 hours. Highly protein bound more than 90%. Plasma T1/2 3 hours. Metabolized in GI tract and liver. Only 1% excreted unchanged, 60% in feces and 40% urine. Chemical structure of these medications prevents entry into CNS. Manifestations: Overdose produces headache, nausea, confusion and serious dysrhythmias. Management: (1) Obtain ECG and establish cardiac monitoring. Treat dysrhythmias with standard agents. Torsades de pointes is best treated with magnesium sulfate intravenously and/or countershock (Formulary table). (2) GI decontamination with AC is advised. Disposition: All children who ingest new “nonsedating” antihistamines or adults who ingest more than the therapeutic dose require close cardiac monitoring for at least 24 hours. Patients on concurrent macrolide antibiotics or ketoconazole should not continue to take these while receiving terfenadine or astemizole. Medical evaluation is required for chronic uses of this combination. Loratidine and fexofenadine have not been reported to have any interation with macrolide antibiotics or ketoconazole. Arsenic (AS) Found in pesticides (insecticides, rodenticides) pesticides, herbicides, smeltering of zinc, lead, and copper. Arsine Gas (AsH3) It is a nonirritating, odorless gas formed by AS containing ore plus acid. Toxic mechanism: Inhibits sulfhydryl group enzymes and produces multi-organ system failure, impairing mitochondrial respiration. Arsenates uncouple oxidative phosphorylation. Toxic dose: Humans are more sensitive than rodents to arsenic. The inorganic arsenites (trivalent arsenicals, e.g., arsenic trioxide) are 2 to 10 times more toxic than the arsenates (e.g., pentavalent arsenic). The arsenic trioxide toxic dose is 5 to 50 mg and the potential fatal dose is 100 to 300 mg (1 to 2 mg/kg). Sodium arsenite is nine times more toxic than arsenic trioxide. The TLV-TWA for arsenic in the workplace is 0.2 µg/m3 and for arsine gas is 0.05 ppm (Table 144A.5). Kinetics: Onset is within minutes after ingestion. Arsenates are water soluble and arsenites are lipid soluble. The soluble forms of arsenic are rapidly absorbed by inhalation and ingestion. Biotransformation to pentavalent and the reverse occur in the body. Excretion: urine, 90%. Following acute ingestion, it takes 10 days to clear a single dose; chronic ingestion takes up to 70 days. Vd 0.2 L/kg. T1/2 inorganic 10 hours, organic 30 hours. Excreted in skin, hair, nails, sweat, and urine. Manifestations: (1) Acute poisoning: GI upset (the hallmark of metal salt ingestion) often hemorrhagic gastroenteritis occurs within minutes or can be delayed several hrs if food is present. Metallic taste, garlic breath odor, dysphagia, projectile vomiting, abdominal pain, watery bloody diarrhea, psychosis, confusion, coma, convulsions and death from shock. Renal: proteinuria, aminoaciduria and acute tubular necrosis. CNS: Altered mental status in severe toxicity. Peripheral neuropathy may appear 2 to 6 days after exposure. Cardiac conduction abnormalities, prolonged QT and torsades de pointes may occur immediately or after a few days. (2) Chronic poisoning occurs 2 to 8 weeks after ingestion or ongoing exposure. Affects multiple systems with the neurologic findings greater than GI. “Glove and stocking” neuropathy. Skin (hyperkeratosis, hyperpigmentation, cancer [Bowen's disease, basal and squamous cell]), gingiv and nail lines (Mee's line), alopecia, malabsorption, hepatic damage, renal impairment, cardiac, hematologic affects, peripheral vascular damage, and lung cancer. (3) Arsine gas forms when active hydrogen comes in contact with arsenic. Can occur when heavy metals are contaminated with arsenic and come in contact with acid. Arsine inhalation intoxication is characterized by a latent period of 2 to 48 hours and a triad of abdominal pain, jaundice (due to hemolysis), and hematuria.

Table 144A.5. Comparative Acute Toxicities of Common Arsenicals

Management: (1) GI decontamination: AC is ineffective. Cathartics are not advised. Gastric lavage within 1 hr after ingestion. Consider whole bowel irrigation if arsenic is seen on radiograph. Follow with abdominal radiographs after WBI. (2) Immediately administer intravenous fluids to correct dehydration and electrolyte deficiencies. If in shock administer oxygen and transfusions and vasopressors, as needed. (3) Antidotes. (a) In severe cases, administer dimercaprol (BAL). Indications for BAL use are: unknown amount or more than 1 mg/kg of ingested arsenic trioxide or equivalent, if symptoms of arsenic intoxication, or toxic blood concentration (more than 7 µg/mL) is present. The BAL-arsenic complex is dialyzable. (b) An oral chelater such as D-penicillamine (Cupamine) or perferably dimercaptosuccinic acid (succimer, DMSA, Chemet®) may be substituted when the patient is stabilized. (Formulary table). Add succimer after GI tract is clear and can tolerate oral medication. Another derivative of BAL, oral and intravenous sodium 2,3-dimrcaptopropane-1-sulfone (DMPS) is being investigated as an antidote. (4) In chronic poisoning, D-penicillamine or succimer may be used to chelate arsenic. Duration of therapy depends on serial 24 hour urine concentration of AS and the symptoms. Can discontinue chelation when 24 hour urine less than 50 µg/24 hour. (5) Treat liver and renal impairment. Consult a nephrologist since hemodialysis is effective in acute poisoning and can be used concurrently with chelation therapy in severe cases, especially if renal failure develops. (6) Cardiac dysrhythmias should be treated with standard therapy including torsades de pointes with magnesium. (7) Arsine intoxication is treated by exchange transfusion and hemodialysis if renal failure occurs. BAL is ineffective. Laboratory: Whole blood arsenic (normal less than 3 µg/dL) is highly variable and of little use. The fatal blood arsenic is more than 9 µg/dL. Obtain a 24-hour urine arsenic (more than 50 µg/24 hours indicates excessive exposure) but persons whose diets are rich in seafood, particularly shellfish, may have transient elevation of organic arsenic (arsenobetaine) for 2 to 3 days. Hair properly prepared normally contains less than 100 mg As/100 g. Monitor CBC, electrolytes, glucose, BUN, creatinine, liver enzymes, CPK, urinalysis, abdominal and chest radiograph, ECG. Disposition: Disposition should be based on chronicity of exposure, severity of the symptoms and ability to comply with treatment and followup. Persons acutely ingesting inorganic salts or exposured to arsine gas should be admitted. Mildly symptomatic patients should be admitted for 24 hours because of danger of rapid deterioration. Asymptomatic patients may be observed for 6–8 hr before discharge with next day follow-up. Public health officials and OSHA should be informed, if indicated. Aspirin See Salicylates. Atropine See Anticholinergic Agents . Barbiturates These are used as sedatives, anesthetic agents and anticonvulsants (see Table 144A.6). Toxic mechanism: Gamma-amino butyric acid (GABA) agonists that enhance the depressant effect (increase the chloride flow to inhibit depolarization) on the CNS and depress the cardiovascular system. Toxic dose: varies. The shorter acting (SAB) are more toxic than the longer acting barbiturates (LAB). Usually doses of about 10 mg/kg LAB or 6 mg/kg SAB are the minimal toxic amount or 5 times the hypnotic dose. Ten times this dose is potentially fatal. SAB 3 to 6 g and LAB 6 to 10 g is potentially fatal. Kinetics: They are enzyme inducers. (1) SAB are highly lipid-soluble and penetrate the brain readily, have shorter elimination times and may be used to induce anesthesia. Onset 10 to 30 minutes, peak 1 to 2 hours,

last 3 to 8 hours. Vd 0.8 to 1.5 L/kg. PKa is 8. Mean T1/2 is 4 hours for ultrashort up to 35 hours for short acting. (2) LAB have longer elimination times and may be used as anticonvulsants. Onset 20 to 60 minutes, peak 1 to 6 hours but in overdose can be 10 hours, duration more than 8 to 12 hours. Vd 0.8 L/kg, p Ka phenobarbital is 7.2 and alkalinization of urine promotes its excretion. T1/2 is 80 to 120 hours. Manifestations: Initial symptoms include ataxia, slurred speech and depressed cognition, pupils may be constricted later in severe poisoning with CNS depression, hypotension (venodilation) and death by respiratory arrest. Bullous skin lesions and hypoglycemia may occur. Can precipitate an attack of acute intermittant porphyria. Chronic use can lead to tolerance, physical dependency and withdrawal.

Table 144A.6. Features of Barbiturates

Management: (1) Establish and maintain the vital functions. Intensive supportive care should dominate the management. Intubation is important to avoid aspiration of gastric contents in the comatose patient. All stuporous and comatose patients should be considered for glucose, thiamine and naloxone intravenously and admitted to the ICU. (2) GI decontamination: Avoid emesis especially in short-acting barbiturate intoxications. AC (initially with a cathartic) followed by MDAC every 2 to 4 hours has been shown to reduce the serum T1/2 of phenobarbital by 50% and may shorten the coma. However, there is no data that this alters the clinical course. (3) Fluid management. Administer fluids to correct dehydration and hypotension. Vasopressors may be necessary to correct severe hypotension and in severe poisonings a central venous line or a Swan-Ganz catheter may be needed. Attention should be given to respiratory support, temperature and pulmonary complications. (4) Alkalinization (ion trapping) is used for phenobarbital and possibly for other LAB. Sodium bicarbonate, 2 mEq/kg IV during the first hour, followed by sufficient bicarbonate (Formulary table) to keep the urinary pH at 7.5 to 8.0, enhances excretion of phenobarbital (p Ka 7.2) but not the short-acting barbiturates which have a higher pKa. Alkalinization increases the excretion 10 times and shortened T1/2 by 50% to 30 to 60 hours (normal T1/2 100 hours). The clinical utility of alkalinization has been questioned and diuresis is not advocated because of the danger of cerebral or pulmonary edema. (5) Hemodialysis (shortens T1/2 to 8 to 14 hours) and charcoal hemoperfusion (shortens T1/2 to 6 to 8 hours) are effective in both LAB and SAB. If the patient does not respond to supportive measures or if the phenobarbital plasma concentration >150 mcg/mL both hemodialysis and hemoperfusion have been effective in shortening the half-life. The use of these modalities is reserved for severely intoxicated patients. (6) Treat any bullae as a local second-degree skin burn. (7) Treatment of withdrawal: In an emergency, use pentothal or diazepam intravenously. If the patient is stable, pentobarbital is given orally and the patient examined after 1 hour for signs of intoxication (nystagmus, slurred speech, and ataxia). If none is present, the dose is repeated every 3 hours until these signs develop. This is the stabilizing dose; the patient is maintained on this dose for 72 hours and then changed to phenobarbital, 30 mg substituted for each 100 mg of pentobarbital. The phenobarbital is tapered, decreasing by 10% or 30 mg every 3 to 5 days. Laboratory: Most barbiturates are detected on routine drug screens and can be measured in most hospital laboratories. Monitor barbiturate levels, ABG, toxicology screen include acetaminophen and ethanol, glucose, electrolytes, BUN, creatinine, CPK, urine pH. Disposition: Awake and oriented patients who have ingested an overdose of SAB should be closely observed for at least 6 hours and those with an overdose of LAB for at least 12 hours. If intentional ingestion need psychiatric clearance before discharge. All stuporous patients should be admitted to ICU. Benzene See Hydrocarbons. Benzodiazepines (BZP) They are used as anxiolytics, sedatives and relaxants. Table 144A.7. Classification of BZPs by duration of action. (1) Long-acting (LA) (more than 24 hours): chlordiazepoxide (Librium), chlorazepate (Tranzene), clonazepam (Clonopin), diazepam (Valium), flurazepam (Dalmane), prazepam (Centrex), quazepam (Dormalin). (2) Short acting (SA) (10 to 24 hours): alprazolam (Xanax), lorazepam (Ativan). (3) Ultrashort (USA) (less than 10 hours): temazepam (Restoril), triazolam (Halcion), midazolam (Versed), oxazepam (Serax). Toxic mechanism: GABA agonists produce CNS depression and increase chloride flow inhibiting depolarization. BZP are addictive, develop tolerance and withdrawal. Toxic dose: (1) Long-acting BZPs in overdoses 10 to 20 times the therapeutic dose (more than 1500-mg diazepam or 2000-mg chlordiazpoxide) have been ingested without respiratory depression. (2) In contrast ultra-short acting BZPs (e.g., 5-mg triazolam) has produced respiratory apnea and coma within 1 hour and death with ingestion of as little as 10 mg. Midazelam by rapid intravenous injection has produced respiratory arrest. BZPs have an additive effect with other CNS depressants. Most patients intoxicated with BZP recover within 24 to 36 hour. In elderly the dose should be reduced 50%. Kinetics: Onset of CNS depression is usually 30 to 120 minutes, peak usually occur within 1 to 3 hours by the oral route. Vd varies 0.26 to 6 L/kg (LA 1.1 L/kg). PB 70 to 99% (LA 85 to 95%; SA 85 to 95%) (see Table 144A.7). Manifestations: Ataxia, slurred speech and CNS depression. Deep coma leading to respiratory depression suggests presence of short acting BZPs or other drugs. Severe CNS depression should initiate a search for other causes.

Table 144A.7. Benzodiazepines Dosage and Kinetics

Management: (1) GI decontamination: Emesis should be avoided. Gastric lavage and AC is advised if it was a recent ingestion. (2) Supportive treatment. (3) Flumazenil is a recently approved specific benzodiazepine receptor antagonist that blocks the inhibitory neurotransmitters. It also reverses sedative effects of BZP, zolpiderm and endogenous BZP associated with hepatic encephalopathy. It does not reverse BZP-induced hypoventilation. It should be used with caution in overdose because if BZP dependency is present it can precipitate withdrawal and seizures (Formulary table). (4) Withdrawal is treated with a long-acting benzodiazepine (e.g., diazepam 10 to 60 mg for several days followed by tapering the dose 10% daily over several weeks. Laboratory: Benzodiazepines can be detected in urine drug screens. Quantitative blood levels are not useful. BZPs usually not detected in urinary screens include alprazolam, clonazepam, flunitrazepam, lorazepam, lormetazepam, midazelam, oxazepam, temazepam, and triazolam. Benzodiazepines may not be detected if dose less than 10 mg dose, rapid elimination, different or no metabolite. Cross reactions occur with nonsteroidal anti-inflammatory drugs (atolmetin, naproxyn, etodolac, fenoprofen). Disposition: If asymptomatic observe in ED for 4 to 6 hours (except for prazepam) which peaks more than 6 hours) then can discharge after psychiatric evaluations. If mild symptoms (lethargy, drowsiness, or asleep) but respond to verbal stimuli observe until recover. If responds only to painful stimuli admit to ICU for at least 24 hours. Warn not to perform any activities that

require mental alertness for several days after exposure. Outpatient followup is required for patients with evidence of chronic abuse, dependence or psychological problems. Beta-Adrenergic Blockers (b-blockers) They are used in the treatment of hypertension, and a number of systemic and ophthalmologic disorders ( Table 144A.8). Properties of beta blockers may include (1) lipid or water solubility, (2) cardioselectivity (which is often lost in overdose), (3) intrinsic partial agonist or sympathomimetic activity, (4) quinidinelike membrane stabilizing effects, (5) alpha (acetbutolol, labetolol), and (6) beta blocking effect ( Table 144A.9). Toxic mechanism: b-blockers compete with the catecholamines for receptor sites and block receptor action in the bronchial and vascular smooth muscle and myocardium. Certain agents have additional mechanisms. (1) Cardiac membrane depressive effects (negative inotropic action) include acebutolol, alprenolol, metoprolol, pindolol, oxprenolol, propranolol and sotalol (in overdose not at therapeutic dose). In overdose cardioselectivity is lost in all b-blockers. (2) Partial beta agonist activity with hypertension and tachycardia initially. These include acebutolol, alprenolol, carteolol, pindolol, and timolol. (3) Weak alpha blockage activity include acebutolol and labetalol. The lipid soluble drugs have more CNS effects and are more lethal including acebutolol, propranolol and sotalol. b-selectivity is often lost in overdose. The most toxic is sotalol and the least toxic is atenolol. Toxic dose: Ingestions of greater than twice the recommended daily therapeutic dose is considered toxic. Ingestion of 1 mg/kg propranolol in a child (may produce hypoglycemia) or 2 to 3 times a single therapeutic daily dose (smaller amounts in cardiac patients) is toxic. Fatalities have been reported in adults with 7.5 g of metoprolol IV and atenolol 12.8 g. The relative potency using propranolol as 1 is: acebutolol 0.3, atenolol 1, labetalol 0.3, metoprolol 1, nadolol 1, pindolol 6.0, oxprenolol 1, timolol 8. Kinetics: (see Table 144A.8) Regular release propranolol's onset of action is 20 to 30 minutes, peak is 1 to 4 hours (may be delayed with coingestants and sustained release preparations) and duration is 4 to 6 hours but in overdoses may be 24 to 48 hours and longer with sustained release type. Sustained release preparations onset may be delayed 6 hours and peak 12 to 16 hours with duration 24 to 48 hours. The regular preparations longest T1/2 is nadolol (12 to 24 h) and shortest esmolol (5 to 10 minutes). PB is variable 5 to 93%. Vd 1 to 5.6 L/kg. Manifestations: Bradycardia and hypotension are the major symptoms and may lead to cardiogenic shock. Bronchospasm may occur in patients with reactive airway disease. Fat-soluble drugs have more CNS effects (respiratory depression and seizures). Partial agonists may initially produce tachycardia and hypertension. ECG changes include atrioventricular (AV) conduction delay or frank asystole. Membrane-depressant effects produce prolonged QRS and QT interval, which may result in torsades de pointes. Sotalol produces a very prolonged QT. Hypoglycemia and hyperkalemia may occur especially in children.

Table 144A.8. Beta Blockers Pharmacokinetics Properties

Table 144A.9. Pharmacologic Properties of Beta Blockers

Management: (1) Establish and maintain vital functions. Treat the bradycardia with a pacemaker if necessary. Hypotension usually does not respond to fluids and requires glucagon, and cardiac pacing. (2) GI decontamination initially with AC/cathartic. MDAC is recommended in symptomatic patients with sustained release but there is no data. Gastric lavage less than 1 hour postingestion. If gastric lavage, may use prelavage atropine (0.02 mg/kg child and 0.5 mg adult) and cardiac monitoring. Whole bowel irrigation should be considered in sustained release preparations but there are no studies and it may cause desorption of the drug from activated charcoal. (3) Cardiovascular disturbances: Obtain cardiac consultation. (a) Class IA (procainamide, quinidine) and III (bretylium) antidysrhythmia agents should not be used. (b) Bradycardia in asymptomatic hemodynamically stable patients requires no therapy. If patient is unstable (hypotension or has high degree AV block), use atropine, glucagon and pacemaker. (c) For ventricular tachycardia (VT) lidocaine or overdrive pacing. A wide QRS VT may respond to sodium bicarbonate. Torsades de pointes may respond to magnesium and overdrive pacing. Prophylactic magnesium for prolonged QT interval has been suggested but there is no data. (d) Myocardial depression and hypotension is managed by correction of dysrhythmias, Trendelenburg positioning and fluids. Monitor with central line or preferably a Swan-Ganz (pulmonary arterial wedge pressure) catheter. If low cardiac output use glucagon (Formulary table). Glucagon is the drug of choice because it works through an adenyl cyclase (bypasses catecolamine receptor) and is not affected by the b-blockers. It is given as intravenous bolus of 5 to 10 mg in adults (0.15 mg/kg) repeated in 5 minutes up to 10 mg followed by continuous infusion starting at a rate equal to minimum effective dose/hr or 1 to 5 mg/h (0.05 to 0.1 mg/kg per hour). (Use D5W as diluent not the phenol diluent in infusion therapy.) Effects seen within minutes. Glucagon can be used with other agents such as amrinone. Amrinone inhibits phosphodiesterase which metabolizes cyclic AMP and should be used with other inotropic support, 0.75 mg/kg intravenously followed by infusion 5 to 10 µg/kg/minute. Repeat bolus may be given in 30 minutes. (4) Treat hypoglycemia with intravenous glucose and hyperkalemia with calcium, bicarbonate, and glucose. (5) Control convulsions with diazepam or phenobarbital. (6) If bronchospasm is present, give b-2 nebulized bronchodilators and aminophylline if necessary. (7) Extraordinary measures such as intra-aortic balloon pump support and cardiopulmonary bypass have been used successfully. (8) Extracorporeal measures: Hemodialysis or hemoperfusion for low-volume distribution drugs that have low-protein binding and are water soluble (atenolol, metoprolol, nadolol, and sotalol) particularly with evidence of renal failure. (9) Investigational: Prenalterol, has successfully reversed bradycardia and hypotension (not available in the US), Phosphodiesterase inhibitors (theophylline or amrinone) may have synergistic effect with glucagon. Laboratory: Continuous cardiac and blood pressure monitoring. Monitor blood glucose, electrolytes, ECG, PAWP, ABG if respiratory symptoms. Toxic blood level of propranolol is more than 2 ng/mL. Disposition: Patients who ingest regular release preparations who are asymptomatic and have a normal ECG (no prolonged PR interval) may be discharged in 6 hours. Sustained release ingestions, particularly in children should be observed for 24 hours. Symptomatic patients should be observed with cardiac monitoring for 24 hours. If seizures, abnormal rhythm or vital signs admit to ICU. Bleach Common household bleach is 4 to 6% sodium hypochlorite with pH 10.5 to 11.4. Commercial types are 10 to 20%. Other bleaches may contain hydrogen peroxide, sodium perborate, sodium carbonate and oxalic acid which are more caustic (See caustics) Calcium hypochlorite a mildew remover is a caustic. Swimming pool disinfectants may contain up to 20% hypochlorite and are more caustic. Toxic Mechanism: caustic action. Manifestations: Ingestion of household strength 5.6% hypochlorite bleach produces mild irritation not corrosion; commercial strength bleach 10 to 20% may produce difficulty in swallowing, pain in mouth, throat, chest, or abdomen. The mixing of chlorine bleach with acids (toilet bowl cleaner and rust removers) result in chlorine gas liberation and inhalation (see chlorine gas) or with household ammonia or urine standing in toilets) resulting in chloramine gas. Minimal exposure to chloramine gas causes irritation of mucous membranes, eyes, and

upper respiratory tract; prolonged or excessive exposure results in pneumonitis and adult respiratory distress syndrome. Management: (1) Decontamination—If ingested avoid GI decontamination procedures. Dilute with small amounts of water or milk. If ocular exposure immediately rinse by gentle irrigation with water for at least 15 minutes, followed by fluorescein dye stain to detect any damage. If dermal exposure remove clothes and rinse skin thoroughly for at least 15 minutes. (2) Esophagoscopy is generally not indicated for household bleach ingestion except if unusually large amounts have been ingested. If the patient is symptomatic with dysphagia, has persistent pain, persistent vomiting or hematemesis consider endoscopic examination. (3) Inhalation: Remove from contaminated area. If a household inhalation exposure occurs with coughing and respiratory distress that fails to respond to fresh air within a few minutes to an hour, the patient should be evaluated by a physician for respiratory therapy (100% oxygen, humidification, aerosol b-agonist bronchodilators if wheezing, intubation and positive end expiratory pressure therapy). Pulmonary edema rarely occurs. Chloramine may have a delayed onset. Pulmonary function can be monitored short-term with continuous pulse oximetry, chest radiograph and ABG. Nebulized sodium bicarbonate 4 mL of 3.75% may provide relief from chlorine inhalation, but has not been scientifically investigated. Do not use epinephrine because inhaled chlorine compounds lowers the threshold for dysrhythmias. If symptoms persist obtain a chest radiograph for pneumonitis and adult respiratory distress syndrome. Laboratory: Inhalation: Pulmonary function, pulse oximeter, chest radiograph, and serial ABG. Blood electrolytes. Disposition: If asymptomatic after small ingestion of household bleach do not need to be sent to ED. If become asymptomatic 4 hrs after treatment may be discharged. Progressive or moderate to severe symptoms should be admitted. Inhalation exposure to chlorine or chloramine gas that clears up in a few minutes to less than 1 hour in the outdoor air does not require visit to ED. Patients should be instructed to call back or return if symptoms return. Boric Acid Borax cleaners contain 21.5% boron by dry weight. 1 teaspoonful 100% boric acid powder = 2.9 to 4.4 grams. Toxic mechanism: General cellular poison. Toxic dose: The fatal dose is higher than the quoted 20 grams for adults and 5 grams in children. Symptoms of toxicity occur at blood levels of 20 to 150 µg/mL, and may be fatal at 1600 µg/mL. Chronic intoxication has been reported after topical application of boric acid for diaper dermatitis. Kinetics: Vd 0.17 to 0.50 L/kg. Elimination T1/2 12 to 27 hours. Peak CNS concentration 3 hours. Elimination is renal. Manifestations: Acute gastroenteritis with blue-green vomitus and feces. CNS stimulation and in severe cases seizures and coma. Renal failure may develop. An erythematous rash develops in 3 to 5 days postingestion and desquamates; “boiled lobster” appearance. Management: (1) Initial management and GI decontamination (see Table 144A.10). Syrup of ipecac should be administered immediately if more than 200 mg/kg boric acid is ingested. AC adsorbs boric acid poorly. (2) Treat seizures with diazepam. Seizure precautions. (3) Hemodialysis if renal failure occurs. Monitor renal function. Laboratory: Electrolytes if severe vomiting, CBC, glucose. Disposition: Asymptomatic patients may be discharged after 6 to 8 hours observation. Symptomatic patients should be admitted and observed until asymptomatic.

Table 144A.10. Management of Boric Acid Ingestion

Botulism See Food-Borne Illness. Brake Fluid See Ethylene Glycol. Calcium Channel Blockers (CCB) Used in treatment of effort angina, supraventricular tachycardia, and hypertension (see Table 144A.11). Toxic mechanism: CCB reduce influx of calcium through the slow channels in membranes of the myocardium, the AV nodes and vascular smooth muscles. Result in peripheral, systemic and coronary vasodilation, impaired cardiac conduction, slowed cardiac electrical impulses and depression of cardiac contractility. Toxic dose: Any amount greater than the maximum daily dose is potentially toxic or 5 times the usual therapuetic dose. Kinetics: nset of action of regular release preparations is 60 to 120 minutes for verapamil (20 minutes nifedipine, 15 minutes diltiazem) after ingestion, peak effect 2 to 4 hours for verapamil (60 to 90 minutes nifedipine, 30 to 60 minutes diltiazem) however it may be delayed for 6 to 8 hours and verapamil has active metabolites. Duration lasts up to 36 hours. Sustained release onset 4 hours but may have a delayed onset, peak effect is 12 to 24 hours, but can develop concretions and prolonged toxicity. Elimination hepatic, T1/2 varies 3 to 7 hours. Vd 3 to 7 L/kg. Manifestations: Hypotension, bradycardia, Conduction disturbances (30 min to 5 hrs) postingestion and prolonged PR interval is an early and constant finding. All degrees of blocks may occur and may be delayed 12 to 16 hours. Lactic acidosis may be present. Hypocalcemia is rarely present. Hyperglycemia may be present because of calcium-dependent insulin release. Mental status changes, headaches, seizures, hemiparesis and CNS depression. CCB precipitate respiratory failure in Duchenne muscular dystrophy.

Table 144A.11. Kinetics and Other Actions of the Calcium Channel Blockers

Management: (1) Establish and maintain vital functions. Continuous ECG and blood pressure monitoring. Most important a pacemaker should be available and hemodynamic monitoring considered. (2) GI decontamination AC is recommended and MDAC may be useful, however, there is no data on effectiveness. Continue AC for 48 to 72 hours. If sustained release preparation, consider whole-bowel irrigation but its effectiveness has not been investigated and it may separate the CCB from the AC. (3) If patient is symptomatic, obtain cardiac consult because may need a pacemaker and hemodynamic monitoring. (4) If heart block, atropine is rarely effective and isoproterenol may produce vasodilation. Consider the use of external cutaneous pacemaker early. (5) Treat hypotension and bradycardia with

positioning, fluids, and calcium gluconate or chloride (Formulary table) 0.2 mL/kg 10% solution up to 10 mL intravenously over 5 minutes. The dose may be repeated 4 times and calcium levels should be monitored. Calcium may reverse depressed myocardial contractility but does not reverse nodal depression or vasodilation. Calcium response lasts 15 minutes and may require continuous calcium infusion 0.2 mL/kg per hour up to maximum of 10 mL/hr while monitoring for dysrhythmias and hypotension. (6) If calcium fails, use sodium bicarbonate if wide QRS, or glucagon (positive inotropic and chronotropic effect), or both (Formulary table). Amrinone (inotropic agent) may reverse CCB, effective dose 0.75 mg to 2 mg/kg (0.15 to 0.4 mL/kg) IV bolus followed by infusion 5–10 µg/kg/minute. Ventricular pacing may be required in the severely intoxicated patient. (7) Hypotension: Fluids, norepinephrine and epinephrine may be required for hypotension. Amrinone and glucagon have been tried alone and in combination. Dobutamine and dopamine are often ineffective. (8) Patients receiving digitalis run the risk of digitalis toxicity and should be carefully monitored since CCB increase digitalis levels. (9) Extracorporeal measures (e.g., hemodialysis and charcoal hemoperfusion) are generally not considered to be useful. (10) Extraordinary measures such as intra-aortic balloon pump and cardiopulmonary bypass have been used. (11) Hyperglycemia does not require insulin therapy. Laboratory: Specific drug levels, blood sugar, electrolytes, calcium, ABG, creatinine, BUN, hemodynamic monitoring, and ECG. Disposition: Observe and monitor asymptomatic patients for 6 to 8 hrs with regular release tablets and for 24 hours with sustained release. Symptomatic patients should be admitted to the ICU. If concomitant use of CCB and b-blockers should be admitted and monitored. Camphor Ingredient found in external analgesic rubs including Vicks Vaporub 4.8% (21 mL = 1 g camphor), Campho-Phenique 10.85% (9.2 mL = 1 g camphor). Camphorated oil >20% (5 mL = 1 g camphor) and mothballs have been banned. Toxic mechanism: CNS stimulant. Toxic dose: 10 to 30 mg/kg may cause GI irritation, more than 30 mg/kg may produce toxicity and more than 60 mg/kg or 1 g in a 1-year-old child or 5 g in adults causes serious toxicity. One teaspoonful of camphorated oil is potentially lethal in infants. Kinetics: Readily absorbed through the skin, mucous membranes, respiratory and GI tract. Passes placenta and may produce fetotoxicity. Absorption from the GI tract is enhanced by fatty substances and alcohol. PB is 61%. Vd is 2 to 4 L/kg. Its onset of action is 5 to 20 minutes with peak effect within 90 minutes but may be delayed 6 hours. Route of elimination by hydroxylation and conjugation in liver to the glucuronide form, which is excreted in urine. Pulmonary excretion causes a distinctive odor on the breath. Manifestations: Odor on breath. Nausea, vomiting, and burning epigastric pain. Seizures may occur suddenly and without warning within 5 to 20 minutes after ingestion. Apnea and visual disturbances may occur. Management: (1) Establish and maintain the vital functions. Control seizures with intravenous diazepam, refractory seizures may require additional anticonvulsants, neuromuscular blockers and general anesthesia (see General management). (2) GI decontamination: AC within 2 hours postingestion. Avoid giving oils or alcohol. (3) Treat apnea with respiratory support. (4) Extracorporeal elimination (hemodialysis and hemoperfusion): Anecdotally charcoal hemoperfusion has been successful but is rarely needed. Laboratory: ABG, electrolytes, blood glucose in multiple seizures. Monitor symptomatic patients for hematologic, renal and hepatic complications. Camphor plasma concentration are not readily available and do not correlate with symptoms. Asymptomatic at levels of 1.5 µg/mL and seizures at about 19.5 µg/mL. Mothball test: Camphor mothballs float in salt and plain water, naphthalene sinks in plain water and paradichlorobenzene sinks in both. Disposition: Patients who remain asymptomatic for 6 hours may be discharged after psychiatric evaluation (if intentional) with instructions to return if symptoms occur. Medical evaluation and monitoring for symptoms should be considered for ingestions more than 30 mg/kg in a child or 3 g in adults. If symptoms of intoxication (CNS depression or seizures) or aspiration are present the patient should be admitted to ICU. Carbamazepine (Tegretol, CBZ) CBZ is a benzodiazepine derivative that is structurally related to the phenytoin and tricyclic antidepressants. Generic substitution is not recommended. Toxic mechanism: Anticholinergic, inhibits sodium channels. Toxic dose: more than 30 to 50 mg/kg has produced serious toxicity, and apnea has occured at 10 to 20 grams (29 to 60 µg/mL). Life-threatening ingestions have occured at 6 to 10 grams in adults and 2 grams in children. Kinetics: CBZ is slowly absorbed from the GI tract (anticholinergic activity). Peak usually in 4 to 8 hours but may be delayed more than 24 hours fter massive ingestions in adults, 1 to 8 hours in children, Vd 1.4 L/kg, PB is 75%. Its epoxide metabolite is active. CBZ has an enterohepatic recirculation. T1/2 in adults is about 36 hours in nonusers after single dose. It is a powerful enzyme inducer. It may take days for plasma CBZ to fall and toxicity to resolve. Manifestations: are related to anticholinergic effects, GI effects, ataxia, nystagmus, intention tremor, CNS depression and apnea 1 to 12 hours after ingestion. It causes seizures in patients with seizure disorders. It rarely causes cardiac conduction disturbances. It causes hyponatremia and hypocalcemia. Apnea develop at plasma CBZ more than 40 µg/mL in adults and more than 27.6 µg/mL in children. Management: (1) Establish and maintain vital functions. If comatose intubation to protect the airway, if hypoventilation (clinical or elevated Pa O 2) or apnea, assisted ventilation. If comatose, respiratory depression or if CBZ serum levels more than 27.6 µg/mL in children or >40 µg/mL in adults admit to ICU. Control convulsions with benzodiazepines. (2) GI decontamination. AC initially and MDAC every 4 hours is effective in reducing CBZ half-life. AC and CBZ may form concretions. Whole bowel irrigation may be considered in massive ingestion. (3) Avoid drugs with potential toxic interactions especially erythromycin and its derivatives. (4) Flumazenil, a benzodiazepine antagonist has been used to treat acute CBZ overdose, but additional investigation is needed. (5) Extracorporeal elimination: Charcoal hemoperfusion is highly effective (status epilepticus, cardiotoxicity, deterioration or serum CBZ more than 150 µg/mL or more) although it is rarely needed. Plasmapheresis has been used. Hemodialysis and diuresis are ineffective. (6) Monitor: CNS depression, cardiac status with cardiac monitoring and ECG. Obtain CBZ blood levels every 4 to 6 hours to exclude delayed absorption or concretions and determine downward trend. Laboratory: The therapeutic plasma concentration is 4 to 12 µg/mL (25 to 50 umol/L) follow CBZ levels to assure downward trend. Measure ABG if respiratory depression. Disposition Asymptomatic patients should be observed a minimum of 6 to 8 hours (slow and erratic absorption) after overdose ingestion. Do not discharge if rising CBZ, neurologic symptoms, or CBZ more than 20 µg/mL. If CBZ level more than 27.6 µg/mL in a child or greater 40 µg/mL may develop apnea and should be in ICU. Carbon Monoxide (CO) This is an odorless gas produced from incomplete combustion; it is found also as an in vivo metabolic breakdown product of methylene chloride (paint removers). The natural metabolism of the body produces small amounts of carboxyhemoglobin (COHb) less than 2%. Toxic mechanism: CO affinity for hemoglobin is 240 times greater than oxygen, shifts the oxygen dissociation curve to the left and impairs hemoglobin release of oxygen to tissues, and inhibits cytochrome oxidase system. Toxic dose and Manifestations: (Table 144A.12). Contrary to popular belief, the skin rarely shows a cherry-red color in the living patient. Sequele correlate with the level of consciouness at presentation. Up to 30% of exposed persons develop varying degrees of sequele 1 to 3 weeks after exposure. ECG abnormalities may be noted. Creatinine kinase is often elevated and myoglobinuria has occured. Kinetics: CO is rapidly absorbed through the lungs. The rate of absorption is directly related to alveolar ventilation. Elimination occurs through the lungs. The T1/2 of COHb in room air (21% oxygen) is 5 to 6 hours; in 100% oxygen, 90 minutes; in hyperbaric oxygen at 3 atm oxygen, 20 to 30 minutes. Fetal hemoglobin has a greater affinity for CO than adult hemoglobin and may falsely elevate the COHb as much as 4%. The nomogram pictured in Figure 144A.2 may help to decide whether serious CO intoxication is likely to have occurred.

Table 144A.12. CO Exposure and Possible Manifestations

Figure 144A.2. Nomogram for calculating carboxyhemoglobin concentration at time of exposure. The time since exposure is given on two scales to allow for the effects of previous oxygen administration on the half-life of carboxyhemoglobin (left-hand scale assumes a half-life of 3 hours). Note: The nomogram assumes a half-life of carboxyhemoglobin of 4 hours in a subject breathing room air. Most patients have not received supplementary oxygen before admission, and at best this will have been administered by means of a face mask, giving a maximum fractional inspired oxygen concentration of 50 to 60% with little effect on carboxyhemoglobin elimination. The scale on the left side of the time column makes allowances for prior oxygen supplements by assuming a short half-life of 3 hours. The nomogram may help decide quickly whether serious carbon monoxide intoxication is likely to have occurred and may help select patients at high risk for early management in the intensive care unit. The nomogram may be an oversimplification because patients usually are not resuscitated with constant concentrations of oxygen, and many patients may hyperventilate, thus changing elimination characteristics. (Redrawn from Clark CJ, Campbell D, Reid WH. Blood carboxyhemoglobin and cyanide levels in fire survivors. Lancet 1981;1:1332–1335.)

Management: (1) Adequately protected rescuer should remove the patient from contaminated area. Establish vital functions. (2) The mainstay of treatment is to administer 100% oxygen via a non-rebreathing mask with an oxygen reservoir or endotracheal tube. Give 100% oxygen to all patients until the COHb level is 2% or less. Assisted ventilation may be necessary. (3) Monitor ABG and COHb. Determine COHb level at time of exposure by using nomogram. Obtain an ECG. ( Note: A near-normal COHb level does not exclude significant CO poisoning.) (4) The exposed pregnant woman should be kept in 100% oxygen for several hours after the COHb level is almost zero because COHb concentrates in the fetus and oxygen is needed five times longer to ensure elimination of CO from fetal circulation. Monitor the fetus. CO or hypoxia are teratogenic. (5) Treat hypotension (see General management). (6) Metabolic acidosis should not be treated. Only if pH is below 7.1 after correction of hypoxia and adequate ventilation, give sodium bicarbonate to correct acidosis. Acidosis shifts the oxygen dissociation curve to the right and facilitates oxygen delivery to the tissues. (7) The use of the hyperbaric oxygen (HBO) chamber. The decision must be made on the basis of the location of the hyperbaric chamber and its ability to handle other acute emergencies that may coexist as well as the guideline for hyperbaric oxygen therapy listed below. The standard of care for persons exposed to CO has yet to be determined: (a) If the initial COHb is >25%. Depending on availability, some say severe poisoning COHb >40% and >25% if seizures, dysrythmias, or delayed onset sequele. 1 (b) Initial COHb >15% in a child, a patient with cardiovascular disease. 1 (c) The pregnant female: COHb >10% in a pregnant female or maternal neurologic signs or signs of fetal distress regardless of COHb level. 1 (d) Ischemic chest pain or ECG abnormalities. 1 (e) Abnormal neuropsychiatric examination. 1 Testing should include whenever possible the following: General orientation, memory testing—address, phone number, date of birth, cognitive testing—serial 7's, digit span, forward and backward spelling of three letter and four letter words. (f) Delayed onset neuropsychiatric symptoms. (g) Symptoms persist despite 100% oxygen therapy.1 (h) Abnormal chest radiograph. 1 (i) A history of unconsciousness. (9) Treat seizures with intravenous diazepam. (10) Treat cerebral edema. Laboratory: ABG may show metabolic acidosis and normal oxygen tension but reduced oxygen saturation, as measured by a co-oximeter. Monitor: If significant poisoning monitor the ABG, electrolytes, blood glucose, serum creatine kinase and cardiac enzymes, renal function tests, and liver function tests. Draw a urinalysis and test for myoglobinuria. Chest radiograph if smoke inhalation (may be initially normal) or considered for hyperbaric chamber. ECG monitoring especially if more than 40 years, cardiac history, moderate to severe symptoms. Determine blood ethanol level and toxicology studies based on circumstances. Monitor COHb during and at end of therapy. Pulse oximeter measures two wave lengths and overestimate oxyhemoglobin saturation. The true oxygen saturation is determined by blood gas analysis which measures the oxygen bound to hemoglobin. The co-oximeter measures four wave lengths and separates out COHb and the other hemoglobin binding agents from oxyhemoglobin. Disposition: All patients with loss of consciousness, with seizures, evidence of myocardial ischemia, COHb more than 25% regardless of symptoms, pregnant women, young infants and children should be admitted and considered for HBO. Some investigators use a screening neuropsychiatric examination for admission if no symptoms. Follow-up neuropsychiatric examination in 3 weeks on all treated patients. Patients with mild symptoms who become asymptomatic after oxygen therapy with COHb less than 10%, have a normal examination, normal ABG, may be discharged after psychiatric evaluation, if necessary. Discharge with instructions to return immediately if symptoms recur and document this on chart. Carbon Tetrachloride See Hydrocarbons. Caustics and Corrosives The US Consumer Product Safety Commission Labeling Recommendations on containers: caution—weak irritant, warning—strong irritant, danger—corrosive. Common acids include hydrochloric acid, sulfuric acid (battery acid), carbolic acid (phenol), nitric acid, oxalic acid, hydrofluoric acid, and aqua regia (mixture of hydrochloric and nitric acids). These are used as cleaning agents. Common alkali include sodium or potassium hydroxide (lye), sodium hypochlorite (Chlorox [bleach]), sodium carbonate (nonphosphate detergents), potassium permanganate, ammonia, electric dishwashing agents, cement, and flat disk batteries ( Table 144A.13). The substance must be identified.

Table 144A.13. Classification of Caustics by Potential for Injury

Toxic mechanism: Caustics cause chemical burns. Significant injury is more likely at pH less than 2 or more than 12, prolonged contact time, large volume. Acids produce mucosal coagulation necrosis, produces an eschar and may be systemically absorbed but they usually do not penetrate deeply (exception: hydrofluoric acid). Injury to the gastric mucosa is more likely although specific sites of injury for acids and alkali are not clearly defined. Alkalis produce liquifaction necrosis and saponification and penetrate deeply. The esophageal mucosa is more likely to be damaged. Oropharyngeal and esophageal damage by solids is more frequent than by liquids. Liquids are more likely to produce superficial, circumferential burns and gastric damage. Toxic dose: The adult potential fatal dose of concentrated acid or alkali is 5 mL. The absence of oral burns does not exclude the possibility of esophageal burns. Manifestations: General: stridor, dysphagia, drooling, oropharyngeal, retrosternal, and epigastric pain, ocular and oral burns. Alkali burns are yellow, soapy, frothy lesions. Acid burns are gray white, later eschar. Abdominal tenderness and guarding can occur. Management: (A) Ingestion, ocular, and dermal management. (1) Prehospital first aid: ingestion—wash out crystals or adherent material in mouth, dilute with milk or water immediately with small amounts—30 mL in children or 100 mL in adults. Contraindications to oral dilution are an inability to swallow, signs of respiratory

distress, obtundation, shock. Neutralization is contraindicated. Dermal and ocular involvement irrigate with copious water. Irrigation should be carried out immediately and consultation with an ophthalmologist and burn specialist should be obtained. (2) GI decontamination procedures are contraindicated. Check pH of substance, ocular and salivary pH. In acid ingestion, however, some authorities advocate small nasogastric tube and aspiration in the early postingestion phase (less than 30 min). Patient should receive only intravenous fluids following dilution until endoscopic consultation is obtained. (3) Endoscopy is valuable to predict early hemorrhage or perforation and late risk of stricture. The indications for endoscopy are controversial. Some authorities recommend all patients, regardless of symptoms, who ingest caustics undergo endoscopy but other authorities are selective using vomiting, stridor and drooling, and oral or facial lesions as criteria. Consult endoscopist on all symptomatic patients. Endoscopy is indicated for all symptomatic patients, or if intentional ingestion. The timing of endoscopy is controversial but it is usually done at 12 to 48 hours postingestion. However with newer fibroptic endoscopes may be done earlier. (4) Steroids are controversial but are used mainly in second degree circumferential burns. If used, they should be started within 48 hours and continued for 3 weeks. (5) Antibiotics are not useful prophylactically. (6) A barium swallow done early does not yield useful information. It may be useful at 10 days to 3 weeks to assess severity of damage. (7) Investigative therapy includes agents to inhibit collagen formation and intraluminal stents. (8) Late surgical procedures and esophageal and gastric outlet dilation may be needed if evidence of stricture. Bougienage of esophagus has produced brain abscess. Interposition of the colon may be necessary if dilation fails to provide an adequate-sized esophagus. (B) Inhalation management requires immediate removal from the environment, and clinical, radiographic, and ABG evaluation when appropriate. Oxygen, aerosol bronchodilators, intubation and respiratory support may be required. Laboratory: If acid ingestion determine acid-base balance, and electrolytes. If pulmonary symptoms, ABGs and pulse oximetry. Disposition: Asymptomatic adults and older children who remain asymptomatic for several hours may be discharged. Infants and small children should be admitted and observed for normal feeding, excessive crying, sleeping and excessive drooling (drooling is difficult to evaluate). Admit all symptomatic patients. Admit to intensive care if there is a potential for severe symptoms or airway compromise. After endoscopy if no injury or mucosal irritation. They may be discharged when they can tolerate oral feedings. Intentional exposures require psychiatric evaluation. Chloral Hydrate Toxic dose 100 mg/kg or more than 2 g. Fatal doses are usually 5 to 10 g. Onset 30 to 60 minutes, duration 4 to 8 hours. Vd 0.75 L/kg, PB 35 to 45%. Metabolized to trichlorethanol (active) then to trichloroacetic acid (inactive). See Sedative Hypnotics. Chlordane See Organochlorine Insecticides. Chlordiazepoxide (Librium) See Benzodiazepines. Chlorine Gas (Table 144A.14)

Table 144A.14. Classification of Toxic Inhalants (Gases)

Chlorine gas is a yellow greenish gas with an irritating odor used in bleach, in manufacture of plastics, and for water purification. Exposure usually results from transportation mishaps, industrial accidents, chemistry experiments, the mixing of household cleaners with bleach containing hypochlorite, and accidental release around swimming pools. Its density is greater than that of air, and an odor is detected at concentrations of 0.04 to 0.2 ppm. Toxic mechanism: Chlorine acts as an oxidizing agent and also reacts with tissue water to form hypochlorous and hydrochloric acids and generate free oxygen radicals. Toxic dose: The workplace TLV-TWA is 0.5 ppm for 8 hours but mild mucous membrane irritation occurs in some workers; 25 ppm is immediately dangerous to life or health (IDLH) and produces moderate symptoms of choking, severe cough and chest pain; 60 ppm produces pulmonary edema; 400 ppm for 30 minutes is lethal; and 1000 ppm is fatal in a few minutes. Manifestations: Mild symptoms include irritation of mouth, throat, nose and eyes. Moderate symptoms in addition include severe cough, wheezing, chest pain, hoarseness, and a few rales in lungs; severe symptoms also include productive cough, dyspnea, cyanosis, rales heard thoughout chest, pneumonitis, pulmonary edema, hypoxemia, metabolic acidosis, and bronchiolitis obliterans. Management: (1) Protect rescue personnel with breathing apparatus. Remove the patient from contaminated environment and stabilize vital functions (endotracheal intubation, assisted ventilation with PEEP if necessary), (2) Decontamination procedures: For conjunctival irritation, use copious water irrigation and fluorescein stain for corneal damage. For dermal burns, copious water irrigation and conventional treatment of burns. (3) There are anecdotal reports of response to nebulized 3.75% sodium bicarbonate 4 mL. (Prepared by diluting 2 mL of 7.5% IV sodium bicarbonate with 2 mL saline), but this has not been scientifically investigated. (4) If symptoms persist beyond the period of exposure, treat with humidified 100% oxygen, nebulized b-agonist bronchodilators for wheezing, and theophylline. Epinephrine should not be used because chlorine lowers the threshold for catecholamine-induced dysrhythmias. In severe cases assisted ventilation may be needed. Noncardiac pulmonary edema is treated with PEEP; furosemide (Lasix) may be used. Laboratory: Chest radiograph (may not reflect damage for 24 hours), carboxyhemoglobin (if exposed to fire, smoke, or unknown gas), ABG, pulmonary function tests, and cardiac monitor for dysrhythmias. Disposition: There is usually no delayed toxicity with exposure to highly water soluble gases. These patients need only to be observed for the duration of their symptoms. Gases with low water solubility have the potential to produce delayed noncardiogenic pulmonary edema. Admit all low water solubility exposures with any symptoms for 24 hours duration and arrange follow up because of risk of delayed bronchiolitis obliterans. Hypersensitivity pneumonitis generally resolves within 12–24 hours after removing from antigen. Clonidine (Catapres) An antihypertensive, sometimes used in opiate and nicotine withdrawal. Toxic mechanism: It has a central a-2 adrenergic (reduces sympathetic outflow), and opioid agonist activity. High doses stimulate peripheral adrenergic receptors, leading to a transient increase in blood pressure. Toxic dose in children 0.025 mg/kg, adult 4 to 5 mg. Kinetics: Onset of action within 30 to 60 minutes, peak in 3 to 5 hours and duration of 8 hours but in overdose may last up to 96 hours. Elimination is hepatic. Manifestations [resembles opioid overdose]: (1) CNS depression: drowsiness, lethargy, stupor, coma, hypotonia, hypothermia (in 50% of overdose cases), and miosis. Apnea and seizures may occur within 8 hours postingestion in significant poisonings. (2) Cardiovascular effect occurs within 1 to 3 hours postingestion and consist of bradycardia and hypotension. A transient initial hypertension may occur. AV block occurs with severe poisonings. Management: (1) ECG and blood pressure monitoring. Be prepared for intubation and assisted ventilation. (2) GI decontamination with charcoal/cathartic. (3) Caution: Naloxone may reverse toxicity, however it has been reported to produce hypertension in some children and is not a consistent antidote. Large doses are required. (4) CNS disturbances: Treat coma with intubation and assisted ventilation. Treat convulsions with diazepam. (5) Cardiovascular disturbances: (a) treat bradycardia with hemodynamic instability with atropine and pacemaker; (b) hypotension with positioning, fluids and vasopressors (dopamine or norepinephrine); (c) transient hypertension rarely requires therapy, treat hypertensive crisis with intravenous nitroprusside. Phentolamine 5 mg/kg per day oral in 4 divided doses or 0.1 mg/kg IV may be used to treat rebound hypertension after clonidine withdrawal. (6) Tolazoline advocated in the PDR is ineffective. (7) Extracorporeal procedures (hemodialysis and hemoperfusion) are ineffective. Laboratory: Monitor ECG, ABG (if respiratory symptoms), electrolytes, BUN, creatinine (if significant vomiting). Blood glucose (if altered mental status). Disposition: All children ingesting clonidine should be referred for medical evaluation. The symptoms will usually be present within 4 hours. Patients should have cardiac and blood pressure monitoring for at least 6 hours. Symptomatic patients require intensive care. Most symptoms abate by 24 hours. Asymptomatic patients may be discharged

with appropriate psychiatric or social follow-up. Chlorpromazine (Thorazine) See Phenothiazines. Clinitest Tablets See Caustics and Corrosives. Cocaine (Benzoylmethylecgonine) Cocaine is the most potent naturally occurring stimulant. It is derived from the leaves of Erythroxylon coca and Truxillo coca. A “body packer” refers to the ingestion of small packages of contraband by the criminal for concealment in the GI tract or other areas for illicit transport. The “body stuffer” refers to ingestion of substances for the purpose of hiding evidence. Toxic mechanism: Directly stimulates CNS presynaptic sympathetic release of dopamine, norepinephrine, serotonin, and acetylcholine, while it blocks the presynaptic re-uptake of norepinephrine, epinephrine, and dopamine. Blocks sodium channels along neuronal membranes. Increases platelet aggregation. Long-term use depletes the CNS of dopamine. Toxic dose: Psychoactive effects occur at 50 to 95 mg and cardiac and CNS effects at 1 mg/kg. The potential fatal dose is 1200 mg intranasal, but death has occurred with 20 mg parenterally. Kinetics: (Table 144A.15). Cocaine is well absorbed by nasal, oral, and pulmonary routes. Cocaine T1/2 45 to 75 minutes. It is metabolized by plasma and liver cholinesterase to inactive metabolites ecgonine methyl ester and benzoyecgonine T1/2 7 to 9 hours). Plasma pseudocholinesterase is congenitally deficient in 3% of population, and decreased in fetuses, young infants, the elderly, in pregnancy, and in liver disease. These individuals may be at increased risk for life-threatening toxicity. PB 8.7%, Vd 1.2 to 1.9 L/kg, 10% is excreted unchanged. Duration of cocaine is 2 to 3 hours. Cocaine and ethanol undergoes liver synthesis to cocaethylene, metabolite with a T1/2 three times longer than cocaine. Cocaethylene may account for some of cocaine's cardiotoxicity and is more lethal than cocaine or ethanol alone. Manifestations: (1) CNS: euphoria, hyperactivity, agitation, convulsions, intracranial hemorrhage; (2) EENT: mydriasis, septal perforation; (3) CV: cardiac dysrhythmias, hypertension and hypotension (severe overdose), chest pain is frequent but only 5.8% have true myocardial ischemia and infarction; (4) Hyperthermia (vasoconstriction, increased metabolism); (5) GI: ischemic bowel perforation if ingested; (6) rhabdomyolysis, myoglobinuria, and renal failure; (7) premature labor and abruptio placenta. (8) In prolonged toxicity suspect body cavity packing.

Table 144A.15. Cocaine Kenetics by Different Routes

Management: (1) Supportive care. Blood pressure, cardiac, and thermal monitoring. Benzodiazepines (diazepam) are the choice for treatment of cocaine toxicity 10 mg up to 30 mg IV at 2.5 mg/min and 0.2 to 0.5 mg/kg up to 10 mg for a child. (2) GI decontamination with AC. MDAC may adsorb cocaine leakage from body stuffers or body packers. Whole bowel irrigation has been used in body packers and stuffers (if the contraband is in a firm container as crack vials). (3) In body packers and stuffers secure venous access, and have drugs readily available for treating life-threatening manifestations until contraband is passed in the stool. Endoscopy may be used to remove hard plastic crack vials. Surgical consult and removal may be indicated if material does not pass the pylorus, in a symptomatic body packer, or in intestinal obstruction. Polyethylene glycol solution (PEG) may desorb the cocaine from AC. (4) Cardiovascular disturbances: (a) Diazepam (Formulary table) for general toxicity including cardiac dysrthymias. (b) Most cases of hypertension and tachycardia are transient and can be managed without drugs or by careful titration of diazepam. Nitroprusside may be used for hypertensive crisis. (c) Myocardial ischemia oxygen, vascular access, benzodiazepines, and nitroglycerin. Aspirin is not used because of danger of intracranial hemorrhage. Thrombolysis is not routinely recommended. (d) Calcium antagonists and phentolamine are second line drugs for myocardial ischemia. (e) Dysrhythmias are usually supraventricular (SV) and do not require specific management. Unstable SV dysrhythmias may be treated by correcting the ischemia with phentolamine. Adenosine appears ineffective. Cardioversion should be considered for unstable dysrhythmias. Lidocaine is controversial for ventricular tachycardia. Wide complex QRS tachycardia may be treated with sodium bicarbonate 2 mEq/kg as a bolus. Beta adrenergic blockers are not recommended. (5) Treat anxiety, agitation and convulsions with diazepam. If diazepam fails to control seizures use neuromuscular blockers and monitor EEG for nonmotor seizures. If focality or lateralization of seizures obtain a CT scan of head. (6) Hyperthermia: Administer external cooling and cool humidified 100% oxygen. Neuromuscular paralysis to control seizures will reduce temperature. Dantrolene and antipyretics are not recommended. (7) Suicide precautions and if patient is pregnant, monitor the fetus. Laboratory: ECG, ABG and oxygen saturation for hypoxia and acidosis, electrolytes, blood glucose, BUN, creatinine, creatine kinase and cardiac fraction if chest pain, liver profile, rhabdomyolysis and urine for myoglobin, urine for cocaine and metabolites and other substances of abuse, abdominal radiograph or ultrasound for body-packers. Computerized tomography of the head may be needed in some cases. If the urine sample was collected more than 12 hours after cocaine intake, it will contain little or no cocaine. If cocaine is found the patient has used cocaine within the past 12 hours. Cocaine's metabolite benzoylecgonine may be detected within 4 hours after a single nasal insufflation and for for 48 to 114 hours. Intravenous drug users should have HIV and hepatitis virus testing. Herbal teas, lidocaine, droperidol may give false-positives by some laboratory methods. Disposition: Patients with mild intoxication or brief seizure who become asymptomatic may be discharged after 6 hours with appropriate psychosocial follow-up. If cardiac or cerebral ischemia manifestations monitor in ICU. Body packers and stuffers require ICU care until passage of contraband. Codeine See Opioids. Corrosives See Caustics and Corrosives. Cyanide (CN) Classes of cyanide and derivatives: (1) Hydrogen cyanide (HCN) and simple salts in large doses act to produce death in 15 minutes. (2) Halogenated cyanide, such as cyanogen chloride, produce irritant and vesicant gases that may cause pulmonary edema. (3) Nitriles, such as acrylonitrile and acetonitrile (artificial nail removers) are metabolized in the liver to produce cyanide. (4) Residential fires with combustion of silk, wool, polyvinyl chloride plastics, and polyurethane may produce cyanide. (5) Cyanides are used as fumigants (hydrogen cyanide), in synthetic rubber (acrylonitrile), in fertilizers (cyanamide), in metal refining (salts), and in the home in some silver and furniture polishes. (6) Cyanogenic glycosides are in the seeds of fruit stones (as amygdalin which in the presence of b-glucosidase forms hydrocyanic acid. The seeds are harmful only if the capsule is broken. Cyanide is present in cassava, an African vegetable whose chronic consumption produces ataxic, optic atrophy and deafness. Nitroprusside the antihypertensive contains five cyanide groups. Toxic mechanism: CN blocks cellular electron transport mechanism and cellular respiration by inhibiting mitochondrial ferricytochrome oxidase system and other enzymes. This results in cellular hypoxia and lactic acidosis. Toxic dose: The ingestion of 1 mg/kg or 50 mg of hydrogen cyanide (HCN) can produce death within 15 minutes. The lethal dose of potassium cyanide is 200 mg. Five to 10 mL of 84% acetonitrile is lethal. The volatile HCN permissible exposure limit (PEL) is 10 ppm, 300 ppm is fatal in minutes. Ferriferrocyanide (Prussian blue) has low toxicity more than 50 g is toxic in adults. Kinetics: Cyanide is rapidly absorbed by all routes. In stomach it forms hydrocyanic acid. PB 60%, Vd 1.5 L/kg. Cyanide is detoxified by metabolism in the liver via the mitochondrial endogenous thiosulfate-rhodanese pathway which catalyzers the transfer of sulfur donor to cyanide forming the less

toxic irreversible thiocyanate that is excreted in the urine. Cyanide elimination T1/2 from the blood is 1.2 hours. Cyanide is also detoxified by reacting with hydroxocobalamin (vitamin B-12a) to form cyanocobalamin (vitamin B-12). Amygdalin, a cyanogenic glycoside, is hydrolyzed in the intestine in a relative alkaline media to mandelonitrile and glucose under the mediation of b-glucosidase. Mandelonitrile then dissociates into benzaldehyde and free cyanide. Manifestations: HCN has the distinctive odor of bitter almonds and can produce death within minutes after inhalation. Flushing, hypertension, headache, hyperpnea, seizures, stupor, cardiac dysrhythmias, pulmonary edema, lactic acidemia, decreased arterial venous oxygen difference and bright red venous blood can occur. Cyanosis is absent or appears late. Various ECG abnormalities may be present. Table 144A.16 presents a variable correlation between blood cyanide levels and manifestations.

Table 144.16. Blood Cyanide Concentration and Manifestations

Management: (1) Immediately administer 100% oxygen and continue during and after the administration of the antidote. If inhaled, remove patient from contaminated atmosphere. Attendants should not administer mouth-to-mouth resuscitation. Protect rescuers and attendants. (2) Cyanide antidote kit (Formulary table) The clinician must decide whether to use any or all components of the kit. Some investigators suggest sodium thiosulfate alone be given immediately in fire victims and if the patient remains critical with coma, seizures, cardiac dysrhythmias, acidemia and hypotension (cyanide manifestations) administer sodium nitrite. Others suggest 100% oxygen and amyl nitrite if conscious and sodium nitrite if unconscious or fails to improve in 5 minutes. The mechanism of action is to form methemoglobinemia (Methb) which has a higher affinity for cyanide than the cytochrome oxidase forming cyanomethemoglobinemia. The cyanide is transferred from methemoglobinemia by rhodanese to thiosulfate forming relatively nontoxic thiocyanate which is excreted in the urine. THE PROCEDURE FOR USING THE ANTIDOTE KIT Step 1: Amyl nitrite is only a temporizing measure and it can be omitted if venous access is established. Amyl nitrite forms only 2 to 5% Methb. Administer 100% oxygen and amyl nitrite inhalant from crushable perles for 30 seconds of every minute. Use new perle every 3 minutes. Step 2: This is not necessary in nitroprusside or acetonitrile poisonings. Administer sodium nitrite slowly intravenously. The goal is to produce an optimum peak Methb level of 20 to 30% at 35 to 70 minutes after administration. In adults 10 mL of 3% solution of sodium nitrite, child 0.33 mL/kg of 3% is diluted to 100 mL 0.9% saline and administered slowly intravenously. Do not administer more rapidly than 5 mL/min. Give as a slow infusion if blood pressure falls. Step 3: Administer sodium thiosulfate. This provides a sulfur atom that can be converted by the rhodanese-catalyzed enzyme reaction (thiosulfate sulfur transferase) to convert cyanide into the relatively nontoxic sodium thiocyanate, which is excreted by the kidney. Sodium thiosulfate is useful alone in smoke inhalation, in nitroprusside toxicity and acetonitrile toxicity. In adults administration of 12.5 grams of sodium thiosulfate (50 mL of 25% solution, child 1.65 mL/kg of 25%) intravenously over 10 to 20 minutes. If severe symptoms recur, repeat antidotes in 30 minutes as one-half of the initial dose. Children dosage regime must be carefully followed administering 0.33 mL/kg sodium nitrite followed by 1.65 mL/kg of sodium thiosulfate (see Formulary table). One hour after antidotes are administered the Methb level should be obtained and should not exceed 20%. Methylene blue should not be used to reverse excessive Methb. (3) GI decontamination by gastric lavage. AC is used but is not very effective (1 g binds only 35 mg of cyanide). (4) Treat seizures with intravenous diazepam. (5) Correct acidosis with sodium bicarbonate if it does not rapidly resolve with therapy. (6) Other antidotes. In France, hydroxocobalamin (vitamin B-12a) has proven effective but must be given immediately after exposure in large doses. The dose recommended is 4 g (50 mg/kg) or 50 times the amount of cyanide exposure has been recommended, with 8 g sodium thiosulfate. Laboratory: Obtain and monitor ABGs, oxygen saturation, blood lactate (takes one-half hour and lactate more than 10 mEq/L), blood cyanide (may take 4 to 6 hours), hemoglobin, blood glucose, and electrolytes. If smoke inhalation is the possible source of cyanide exposure, obtain carboxyhemoglobin (COHb) and methemoglobin (MetHb) concentrations. They can be measured on co-oximeter or on heparinized arterial blood. Disposition: Asymptomatic patients should be observed for a minimum of 6 hours. Patients who ingest nitrile compounds must be observed for 24 hours. Patients requiring antidote administration should be admitted to the ICU. DDT and Derivatives See Organochlorine Insecticides. Desipramine (Norpramin, Pertofrane) See tricyclic antidepressants . Diazepam (Valium) See Benzodiazepines. Digitalis Preparations Cardiac glycosides are found in medication and plants. Cardiac glycosides found in plants include Grecian foxglove (Digitalis lanata), which contains digoxin, dogbane (Apocynum cannabinum) which contains stophanthidin, European mistletoe ( Viscum album), purple foxglove (Digitalis purpura which contains digoxin and digitoxin), hispidus seeds (S hispidus), lily of the valley ( Convallaria majoralis, which contains convallatoxin and red squill), oleander ( Nerium oleander which contain oleandrin [2 fatalities reported] and digitalium), sea onion or squill ( Uriginea maritima and indica), Stropontus kombe, wall flower (Cheiranthus cheiri), yellow oleander (Thevtia nerifoli and peruviana) which contains thevetin, and Bufo species toad skin. More than 1 to 3 mg of cardiac glycosides may be found in a few leaves of oleander or foxglove. Toxic mechanism: Cardiac glycosides inhibit the enzyme sodium/potassium-adenosine triphosphate (ATP) in cells leading to intracellular potassium loss (increased extracellular potassium) and increased intracellular sodium producing phase 4 depolarization, increased automaticity (ventricular dysrhythmias) and ectopia and tachydysrhythmias. There is also increased intracellular calcium and contractility. Pacemaker cells are inhibited, refractory period is prolonged leading to AV blocks and vagal tone is increased leading to bradycardia and AV node blocks. Toxic dose: An oral dose of 0.07 mg/kg will produce a serum concentration of 0.6 to 2.0 ng/mL. An acute single ingestion of less than 2 mg digoxin in a healthy child or 4 mg in a healthy adult rarely results in serious poisoning. After an acute ingestion overdose the blood concentration is not reflective of tissue concentration for 6 to 8 hours. Serious overdose ingestion of digoxin are more than 4 mg (0.2 mg/kg) in a child and more than 10 mg in an adult. The fatal dose of digoxin is over 10 to 20 mg in healthy adults. Clinical toxicity is usually associated with digoxin levels of over 3 to 5 ng/mL. Kinetics: (Table 144A.17). Digoxin onset 1.5 to 6 hours, peak levels 2 to 3 hours and time to peak effect 4 to 6 hours (IV onset 5 to 30 min, time to peak is immediate and time to peak effect 1.5 to 3 hours. Elimination is 60 to 80% renal. The therapeutic concentration is 0.8 to 2.0 ng/mL. Vd is 5 to 6 L/kg. Cardiac plasma ratio is 30:1. Elimination T1/2 is 1 to 40 hours. Interactions: Patients with cardiac disease, hypokalemia, hypercalcemia, hypomagnesemia, renal impairment, quinidine, calcium channel blockers, and b-blockers are at risk. Manifestations: May be delayed 9 to 18 hrs. (1) GI: nausea, vomiting, are always present in acute ingestion and may occur in chronic ingestion, (2) CV: “digitalis effect” is EKG scooped ST segments and PR prolongation, in overdose any dysrhythmia or block is possible but none are characteristic. Bradycardia occur in overdose with healthy hearts, tachycardia with existing heart disease. Ventricular tachycardia is only seen in severe poisoning. (3) CNS: headaches, visual disturbances, colored-halo vision. (4) Hyperkalemia prior to Fab fragment antibody therapy was a predictor of prognosis. If serum potassium was less than 5.0 mEq/L all survived, if 5 to 5.5, 50% survival and if more than 5.5 all died. Hyperkalemia is generally associated with digoxin levels more than 10 ng/mL. (5) Hypokalemia is commonly seen with chronic intoxication. Patients with normal levels may have toxicity in the presence of hypokalemia. (6) Chronic intoxication was more likely to produce scotoma, color perception disturbances, yellow vision, halos, delerium, hallucinations or psychosis, tachycardia and hypokalemia.

Table 144A.17. Toxicity and Kinetics of Common Digitalis Preparations

Management: (1) GI decontamination. Caution about vagal stimulation. Do not induce emesis or use gastric lavage. Administer AC. If a nasogastric tube is required pretreatment with atropine to avoid vagal effect. MDAC may interrupt enterohepatic recirculation and absorb active metabolites. Have an external cutaneous pacemaker available. (2) Treat hemodynamically unstable ventricular dysrhythmias with digoxin-specific antibody fragments (Fab, Digibind®) 40-mg binds 0.6 mg digoxin or each mg binds 0.015 mg digoxin (see Formulary table). Fab and potassium lowering drugs should not be used concomittantly because they may produce life-threatening hypokalemia.

Can give Fab fragments as a bolus if critical, but less wastage if administered slowly over 30 minutes. Empiric dose 10 vials in adults. Indications: (a) if cardiac arrest or shock is imminent or rapid progression of clinical findings; (b) if the digoxin dose is more than 10 mg in an adult, more than 4 mg (more than 0.2 mg/kg) in a child; (c) if the serum potassium more than 5.0 mEq/L; (d) serum digoxin toxicity (more than 10 ng/mL in adults or more than 5 ng/mL in children) 8 hours postacute ingestion. The administration is based on the symptoms not solely on the digoxin level; (e) hemodynamically unstable life-threatening dysrhythmias; (f) bradycardia or second or third-degree blocks unresponsive to atropine. Fab has also been useful in digitoxin and oleander poisoning. Contact Poison Control Center for calculation of Fab dose or use package insert. Antidysrhythmic agents and pacemaker should be used only when Fab therapy fails. Complications are mainly from withdrawal of digoxin and worsening heart failure, hypokalemia, and allergic reactions, which are rare. Digitalis administered after Fab therapy is bound and inactivated for 5 to 7 days. (3) For ventricular tachydysrhythmias correct electrolyte disturbances, administer lidocaine or possibly phenytoin. For malignant ventricular dysrhythmias, such as torsades de pointes administer magnesium sulfate, 20 mL 20% IV given slowly over 20 minutes. Ventricular overdrive pacing has also been used. Magnesium should be used with caution in renal impairment and never used in bradydysrhythmia. Do not use antidysrhythmics Ia, Ic, II, IV and agents which increase conduction time, e.g., procainamide, bretyllium, diltiazem, and beta blockers. (4) Cardioversion should be used with caution in digitalis toxicity (lower setting 5 to 10 joules and pretreat with lidocaine if possible) because it may precipitate ventricular fibrillation or asystole. (5) Treat bradycardia and second-degree and third-degree AV block with atropine. If patient is unresponsive, use Fab (Digibind, Formulary table). A pacemaker should be seriously considered. Avoid isoproterenol, which causes dysrhythmias. (6) Potassium disturbances. Treat hyperkalemia (more than 5.0 mEq/L) with Fab. Never use calcium. Treatment prior to Fab with insulin/glucose and sodium bicarbonate may produce severe hypokalemia which will worsen digoxin toxicity. Treat hypokalemia less than 4 mEq/L and ventricular dysrhythmias and if AV block is present with potassium less than 3.0 mEq/L. (7) Extracorporeal procedures are ineffective. Hemodialysis is treatment of choice for severe or refractory hyperkalemia. Laboratory: Monitor ECG, electrolytes (low potassium, low magnesium, high calcium and sodium increase digitalis toxicity), digitalis levels (after Fab, use free digoxin), BUN, creatinine. Draw digoxin levels 8 hours postingestion because earlier values may not reflect tissue distribution. Be aware an endogenous digoxin-like substance cross-reacts with most common immunoassays (not with high pressure liquid chromatography), values as high as 4.1 ng/mL, have been reported in newborns, chronic renal failure abnormal immunoglobulins, and third trimester of pregnancy. The bound digoxin blood concentrations rise after use of Fab, but the free (unbound) digoxin level falls. Disposition: (a) Patients with life threatening conduction delays or automaticity related to digitalis toxicity need FAB in the emergency department, require a 12-lead ECG, continuous cardiac monitoring, intensive care and frequent electrolyte determinations. (b) Patients with elevated potassium more than 5.5 mEq/L and conduction delays or automaticity require FAB in the ED a 12-lead ECG, continuous cardiac monitoring and frequent determinations of electrolytes. (c) Asymptomatic adults who have ingested more than 3 mg (2 times TDD) or in a child, over 0.15 mg/kg, should have a 12-lead ECG, be monitored for 24 hours in an intensive care unit, and have a documented lowering digoxin level before discontinuing monitoring. Diphenhydramine (Benadryl) Toxic dose 15 mg/kg, fatal dose 25 mg/kg in child, and the fatal amount in adult is 2.8 grams. Peak in 1 to 4 hours. Vd 3.3 to 6.8 L/kg. T1/2 4 hours. See Anticholinergic Agents. Diuretics The types of diuretics include (1) osmotic, (2) carbonic anhydrase inhibitors, (3) loop, (4) thiazide, (5) potassium sparing, and (6) organomercurial. Toxic mechanism: Fluid and electrolyte loss. Toxic dose: Not defined but 5 times the therapeutic daily dose of any agent may require evaluation. Manifestations: GI upset and weakness with thiazides. Coma was reported in two children following 15 of chlorthalidone. Hyperglycemia was reported to have been produced by thiazides. Hypokalemia and hypernatremia may be present. Fluid and electrolyte balance are unlikely after acute ingestion. Management: (1) GI decontamination: not necessary unless massive ingestions. (2) Relace fluid and electrolyte loss. Laboratory: Monitor electrolytes and fluid balance. Doxepin (Sinequan, Adapin) See Tricyclic Antidepressants . Ethchlorvynol (Placidyl) See Sedative Hypnotics. Ethyl Alcohol See Alcohols. Ethylene Glycol (EG) Is found in solvents, windshield deicer, antifreeze (95%), air-conditioning units, solvent, and hydraulic brake fluids. EG is a sweet tasting colorless, water soluble liquid with a sweet aromatic aroma. Toxic mechanism: EG is oxidized by alcohol dehydrogenase (ADH) to glycolaldehyde then metabolized to glycolic acid (decreased serum bicarbonate, metabolic acidosis and anion gap), and glyoxylic acid. Glyoxylic acid is metabolized to oxalic acid, via pyridoxine-dependent pathways to glycine, benzoic acid, and hippuric acid and via thiamine and magnesium-dependent pathways to alpha hydroxy-ketoadipic acid. Metabolites produce profound acidosis, hypocalcemia, and deposition of oxalate crystals in tissues and renal damage. Toxic dose: Death has occurred after a 60 mL ingestion of 95% ethylene glycol; fatal dose in adult 1.4 mL/kg of 100% solution. The ingestion of 0.1 mL/kg 100% EG can result in a serum ethylene glycol concentration (SEGC) of 20 mg/dL a level that requires ethanol therapy. Ingestion of 3.0 mL 100% solution in a 10 kg child or 30 mL of 100% EG in adult weighing 80 kg produces SEGC 50 mg/dL (8.1 mmol/L), a

concentration that requires hemodialysis. The lethal blood level of EG is about 200 mg/dL. Kinetics: Rapidly absorbed from GI tract. Onset 30 minutes to 12 hours, peak level 2 hours. Absorption dermal, inhalation, and ingestion. T1/2 without ethanol 3 to 8 hours, with ethanol 17 hours, with hemodialysis 2.5 hours. Vd 0.65 to 0.8L/kg. Renal clearance 3.2 mL/kg per minute. About 20 to 50% is excreted unchanged in the urine. Equations used to calculate SEGC and amount ingested. Estimation of serum ethylene glycol concentration (SEGC) Calculation of SEGC: 0.12 mL/kg of 100% = SEGC 10 mg/dL Equation to estimate SEGC

Manifestations: Phase I: Onset is 30 minutes (but may be delayed 12 hours) after ingestion but with ethanol may be delayed even longer. The patient acts inebriated (SEGC 50 to 100 mg/dL), ataxia, hypocalcemia, calcium oxalate crystals in urine (4 to 8 hours) but are not always present, coma, and cerebral edema. Early osmolal gap is present later a metabolic acidosis with an anion gap develops. Metabolites produce symptoms 4 to 12 hours following ingestion. Phase II: After 12 to 36 hours postingestion, cardiopulmonary deterioration. Phase III: 2 to 3 days post-ingestion, renal tubular necrosis predominates (oliguria, anuria, hematuria, proteinuria) and pulmonary edema. Phase IV: Neurological sequel occurs 6–10 days after ingestion. It includes facial diplegia, hearing loss, bilateral visual disturbances, elevated CSF pressure with or without elevated protein and pleocytosis, vomiting, hyperreflexia, dysphagia, and ataxia. Management: (1) Establish and maintain the vital functions. Protect the airway and use assisted ventilation, if necessary. (2) GI decontamination has limited role perhaps only gastric lavage within 30 to 60 minutes. (3) Obtain baseline serum electrolytes and calcium, glucose, ABGs, ethanol, ethylene glycol, glycolate (if available) and methanol concentrations. Determine measured serum osmolality and compare to calculated osmolality. (4) If seizures occur exclude hypocalcemia and treat with intravenous diazepam. If hypocalcemic seizures treat with 10 to 20 mL 10% calcium gluconate (0.2 to 0.3 mL/kg children) or 5 to 10 mL 10% calcium chloride (0.1 to 0.2 mL/kg children) slowly intravenously and repeat as needed. (Formulary table) (5) Correct metabolic acidosis with intravenous sodium bicarbonate. (6) Initiate ethanol therapy to block metabolism (Formulary table) if the blood ethylene glycol level is more than 20 mg/dL (EG levels are difficult to obtain), or if the patient is symptomatic or acidotic with increased anion gap or osmolar gap (regardless of SEGC). Ethanol should be administered intravenously (orally is less reliable) to produce a blood ethanol concentration of 100 to 150 mg/dL. The loading dose is derived from the formula: 1 mL ethanol 100%/kg = blood ethanol concentration of 100 mg/dL (protects against metabolism of EG), therefore, 10 mL of 10% ethanol intravenously is administered concomitantly with a maintenance dose of 2.0 mL/kg per hour of 10% ethanol for an alcoholic, or 0.83 mL/kg per hour (nondrinker) or 1.4 mL/kg per hour (social drinker). If hemodialysis is used administer ethanol 10% 1.5 to 2.5 mL/kg per hour to a maximum of 91 mL/hr. (7) Obtain an early nephrology consult. Early hemodialysis is indicated if the ingestion was large; if the blood ethylene glycol level is more than 50 mg/dL; if severe acid-base or electrolyte abnormalities occur despite conventional therapy; or if renal failure occurs. Hemodialysis reduces the EG T1/2 from 17 h on ethanol therapy to 3 hours. (8) Adjunct therapy: Thiamine (100 mg/d) and pyridoxine (50 mg four times daily) have been recommended for 48 hours but have not been extensively studied. (9) Continue therapy (ethanol and hemodialysis) until the plasma ethylene glycol level is below 10 mg/dL, the acidosis has cleared, the creatinine level is normal, and urinary output is adequate. (10) Therapy with 4-methylpyrazole, which blocks ADH without causing inebriation is being investigated. Laboratory: Complete blood count, electrolytes, urinalysis (look for oxalate [“envelope”] and monohydrate [“hemp seed”] crystals), and arterial blood gases. The oral mucosa and urine fluoresce if ethylene glycol is present. Obtain ethylene glycol and ethanol levels, plasma osmolarity (use freezing point depression method). Calcium, creatinine, and blood urea nitrogen studies. If possible obtain glycolate level. An ethylene glycol level of 20 mg/dL is usually toxic (levels are difficult to obtain). Fluorescence: The oral mucosa and urine (do not put in glass tube) will fluoresce under Wood's light if antifreeze ethylene glycol is present. Propylene glycol, a vehicle in many liquid and IV medications (phenytoin, diazepam), may produce spurious ethylene glycol levels. Disposition: All patient ingesting EG should be referred to ED. Asymptomatic patients with SEGC less than 10 mg/dL 2 hours after admission may be discharged after psychiatric evaluation. If cannot obtain SEGC, follow the patient for 12 hours monitoring osmolal gap, acid base parameters and electrolytes to exclude development of metabolic acidosis with an anion gap. OTHER GLYCOLS Propylene glycols are found in deicers, antifreeze, and diluents of vitamins, drugs and as vehicles for intravenous injectibles. They are metabolized to lactate and pyruvate in large quantities and can cause anion gap metabolic acidosis. It may be responsible for the hypotension with phenytoin and diazepam and for dermal sulfadiazine toxicity. Glycol ethers are found in brake fluids, solvents, industrial coating and glass cleaners. They may be partially metabolized to ethylene glycol and produce similar toxicity in massive overdose. Flurazepam (Dalmane) Onset 15 to 20 minutes, peak effect 3 to 6 hours, duration 7 to 8 hours, Vd 3.4 L/kg, PB 97%. Metabolized to active metabolite N-desalkylflurazepam. T1/2 adults 40 to 114 hours, metabolite 47 to 100 hours. See Benzodiazepines. Fluoxetine (Prozac) Fluoxetine is one of a group called selective serotonin reuptake inhibitors (SSRI) ( Table 144A.18A, Table 144A.18B). Toxic mechanism: Selectively inhibits the neuron reuptake of serotonin (5-hydroxytryptamine or 5-HT) at the CNS presynaptic ganglia causing increased concentration of serotonin at the synaptic cleft. Toxic dose: More than 3.5 mg/kg in children. Adult fatal amount 6 g. Kinetics: Peak plasma concentrations is within 6 to 8 hours and may be moderately delayed by food consumption up to 6 to 12 hours. Peak for demethylated active metabolite, norfluoxetine, is about 72 hours with a prolonged T1/2 4 days (2 to 7 days). PB 95% Vd 20 to 42 L/kg. Its demethylated active metabolite, norfluoxetine has a T1/2 of 7 to 15 days. Elimination is 80% renal with 11% parent drug, 7% norfluoxetine. It has minimal effects on noradrenergic and dopaminergic neurons. Manifestations: GI upset. No seizures reported. Minimal risk of cardiovascular or neurologic complications. Serotonin syndrome (confusion, agitation, myoclonus, seizures, with or without hyperthermia) occur in patients ingesting SSRI within 5 weeks after taking monoamine oxidase inhibitors (MAOI)

Table 144A.18A. Selective Serotonin Reuptake Inhibitors (SSRI)

Table 144A.18B. Kinetics Selective Serotonin Reuptake Inhibitors

Management: (1) GI decontamination: administer AC. (2) Obtain ECG to exclude tricyclic antidepressant. (3) Serotonin syndrome is treated with benzodiazepines, hydration, cooling if hyperthermic, and neuromuscular blockade for refractory hyperthermia, seizures and muscular activity. Disposition: If remains asymptomatic on cardiac monitor for 6 hrs may give medical clearance. Glutethimide (Doriden) Lipophilic compound metabolized to many active metabolites. “Loads” are the combination with codiene. Manifestations: Range from sudden apnea, prolonged coma to seizures. It has anticholinergic properties, dilated pupils and tachycardia. Kinetics: Onset is 20 minutes. Peak 40 minutes, PB 50%, Vd 2.7 L/kg, T1/2 5 to 22 hours; in overdose may exceed 100 hours due to hypotension and impaired hepatic perfusion. Elimination is by hepatic metabolism into active metabolite, 4-hydroxy-2-ethyl-2 phenylglutarimide (4-HG). The parent drug and metabolite have extensive enterohepatic recirculation. Only 2% excreted by the kidney unchanged. Duration of action is 48 hours. Hallucinogens These chemicals cause distortion of perception, not the appearance of images. Hallucinations are false perceptions that do not actually occur, delusions are false ideas and illusions are false interpretations without loss of consciousness. CHEMICAL CLASSIFICATION OF HALLUCINOGENS 1. Indole alkaloid derivatives (tryptamines)—involves serotonin. Psilocin is 2/200 the potency of LSD (dimethyl-4-hydroxytryptamine) and psilocybin (dimethyl-4-phosphoryl tryptamine) from Psilocybe mushroom (“magic mushroom of Mexico”), DDT (Dimethyltryptamine), DPT (dipropyltryptamine) from cohoba snuff or synthetic Bufotenine (5-hydroxy-N, N-dimethyltryptamine) from Bufo abvarius (Colorado River Toad) and vulgaris secretions and skin. 2. Ergot compounds (ergolines)— D-Lysergic acid diethylamide (LSD) from ergot fungus, Claviceps purpura, or syntheticly produced. Toxic dose: 35 µg. Street doses are typically 50 to 300 µg. Kinetics: Peak effect in 1 to 2 hours. Duration, 12 to 24 hours. T1/2, 3 hours. Route of elimination, hepatic. Morning glory seeds (Riuea corymbosa or Ipomoea) have one-tenth the potency of LSD. 3. Piperidine derivatives—anticholinergic or adrenergic response. Belladonna alkaloids (anticholinergic)—deadly nightshade ( Atropa belladonna); Henbane (Hyoscyanus niger); Jimson weed (Datura stramonium), mandrake (Mandragora officinarium); matrimony vine (Lycium halimifolum). Adrenergic-cocaine from erythroxylon coca (snow, coke, crack) 4. Phenylethylamine derivatives (phenylalkylamines) (amphetaminelike structure) Mescaline 1/4000 as potent as LSD. It comes from peyote cactus or synthetic amphetamine involve adrenergic response. Mescaline/peyote (trimethoxyphenylethylamine, or the toxic principle of Lophophora williamsli). Toxic dose: More than 5 mg/kg. Each button of mescaline contains 45 mg (4 to 12 produce symptoms). Kinetics: Mescaline is well absorbed from GI tract. Vd 2 to 3 L/kg. Hepatic metabolism, peak effect, 4 to 6 hours. Duration: 14 hours. Some designer drugs (synthetic analogues of controlled substances) include a. MDA (3,4 methylene dioxy amphetamine) an amphetamine derivative, produces a mild LSD-like reaction lasting 6 to 10 hours (“love pill”). b. MMDA (3-methyoxy-4, 5 methylene dioxy amphetamine) from nutmeg and amphetamine derivative. c. MDMA (3,4-methylene dioxy meth-amphetamine, “Adam,” “XTC,” “ecstacy,” or “rave”) amphetamine derivative. d. MDEA or MDE (3,4 methylene-dioxy n-ethyl amphetamine, “Eve”) PMA (para-methyoxyamphetamine). e. STP/DOM (2,5 dimethoxy-4-methylamphetamine) from synthetic chemicals acts like LSD but lasts 72 hours or longer. f. TMA-2 (2,4,5 trimethoxyamphetamine). 5. Cannabinols—marijuana, hashish (delta 9 tetrahydro-cannabinol). Marijuana ( Cannabis sativa) (A9-tetrahydrocannabinol, THC). One joint equals 500 mg of marijuana; when the plant is smoked 50% is destroyed. Toxicokinetics: Time of onset, 2 to 3 minutes (smoked). Duration 2 to 3 hours. T1/2 is 28 to 47 hours (shorter for chronic user). (Note: 1% of the metabolite can be detected in urine up to 2 weeks after use) Manifestations: Visual illusions, sensory perceptual distortions, depersonalization, and derealization. 6. Arylhexylamines—phencyclidine and congeners, ketamine phencyclidine synthetic (Angel dust, Loveboat, Lovely, Hog, Crystal, Peace Weed, Super grass). Ketamine is a dissociation anesthesia. 7. Opioids—Fentanyl analogs include a-methylfentanyl (China White), meperidine analogues include 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP) and 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), which is converted into a toxic metabolite that is destroyed by dopamininergic neurons in substantia nigra creating a parkinsonismlike syndrome (“The Frozen Addict Syndrome”). 8. Plants and Mushrooms a. Mushrooms—psilocybin/psilicon (Psilcybe); muscaria ( Clitocybe dealbata and iludens, Inocybe); ibotenic acid/muscinol ( Amanita muscaria and pathernina). Psilocybin is similar in effect to LSD but short acting. Peak effect 90 minutes. Duration 5 to 6 hours. b. Other plants—Catnip (Nepta cataria); Kavakava (Piper methysticum); Juniper (Juniperus macropoda); Mate (Ilex paraguayensis); Periwinkle (Cathararhus rosus); Yohimbine (Corynathe yohimbine); Nutmeg (Myristica fragans). Toxic dose: 5 to 15 g (1 to 3 nutmegs). Peak effect 3 to 6 hours. Duration up to 60 hours. 9. Inhalants. Nitrites (amyl and isobutyl nitrite)—act immediately; aromatic hydrocarbon in airplane model glues, plastic cements (benzene, toluene, xylene) (See Hydrocarbons) nitrous oxide and halogenated hydrocarbons. Has produced sudden sniffing death. As many as 20% of high school seniors have experimented with volatile substances at least once. Toxic mechanisms: involves adrenergic, dopaminergic and serotonergic neurons in the CNS and the neurotransmitters dopamine, serotonin, histamine, and acetylcholine (usually 5-HT2 agonists) Kinetics: (Table 144A.19A,Table 144A.19B). Manifestations: Trip lasts 4 to 12 hours, it can be pleasant or alarming. (1) Adrenergic effects of tachycardia, dysrhythmias, tachypnea, and usually moderate hypertension. (2) Behavioral psychologic effects of disorientation, depersonalization and derealization, panic reaction, toxic psychosis (catatonia, paranoia, suicidal, and homicidal), synesthesia (seeing sound, smelling color), and impaired judgement. (3) Autonomic effects of dry or moist skin, variable bowel sounds, mydriasis reactive or nonreactive, hyperthermia and “flashbacks” or recurrances for up to 18 months. Laboratory: Monitor in moderate and severe toxic patients: CBC (leucocytosis), Urinalysis, ECG, electrolytes (hyponatremia), glucose (hyperglycemia), creatinine and BUN, creatine kinase, PT and PTT (elevated), test urine for myoglobinuria, arterial blood gases, chest roentgenogram. Inhalants may require carboxyhemoglobin, and examination of the urine for hippuric acid.

Table 144A.19A. Hallucinogenic Drugs Pharmacology and Pharmacokinetics

Table 144A.19B. Common Inhalants and Their Toxicity

Management: (1) GI decontamination has no role once the symptoms are present. (2) Prevent physical injury by calming techniques in a quiet room with dim lights (sensory isolation) and reassurance. (3) Minimum use of physical restraints is advised since they may result in rhabdomyolysis, myoglobinuria and acute renal failure. (4) Benzodiazepines are useful in acute panic reaction and haloperidol may be indicated for acute psychosis. (5) Naloxone can be used to reverse the CNS and respiratory depression of fentanyl analogs. (6) Bromocryptine or benzotropine for symptomatic relief of parkinsonismlike syndrome. Disposition: Patients presenting with mild symptoms can be observed in a quiet environment with a friend or relative until asymptomatic and then discharged with a reliable friend or relative. If persistent hallucinations or a psychosis, but with stable vital signs and no evidence of trauma or other complications, may be referred for psychiatric evaluation and treatment. If unstable vital signs, seizures, or coma admit to intensive care. Drug abusers should be referred for rehabilitation and counseling. Intentional administration requires psychiatric evaluation, drug counselling and rehabilitation before discharge. Haloperidol (Haldol) See Phenothiazines and other major neurolepties. Heroin See Opioids. Hydrocarbons The lower the viscosity and surface tension or the greater the volatility the greater risk of aspiration (see Table 144A.20A). All of these can lower the threshold of the myocardium to dysrhythmias produced by endogenous and exogenous catecholamines. Petroleum distillates produce an aspiration pneumonitis by aspiration into lung and result in chemical pneumonitis. Aromatic hydrocarbons produce CNS depression. Halogenated hydrocarbons produce CNS depression and have metabolites that can damage the liver and kidneys.

Table 144A.20A. Volatility and Viscosity of Hydrocarbons

1. Petroleum distillates (PD) are aliphatic hydrocarbons with greater than 4 carbon chains (more than C4). Carbon chains C1–C4 are gases such as methane and butane. The longer the chain the more viscosity. They represent a pulmonary aspiration risk because of their low viscosity (30 to 60 SSU) and tendency to spread over a large surface area. However they are poorly absorbed from the GI tract. Gasoline (petroleum spirit); kerosene (coal oil, kerosene, jet aviation fuel No. 1, charcoal lighter fluid); petroleum naphtha (cigarette lighter fluid, ligroin, racing fuel); petroleum ether (benzine); turpentine (pine oil, oil of turpentine); and mineral spirits (Stoddard solvent, white spirits, varsol, mineral turpentine, petroleum spirit). Wood distillates are turpentine (alicyclic hydrocarbon) and pine oil. Toxic dose: A few drops into the airway will produce a severe chemical pneumonitis. There is almost no absorption of these products from the GI tract with exception of turpentine. Manifestations: Materials aspirated during the process of ingestion produce the chemical pneumonitis. Hypoxia associated with aspiration is the cause of CNS depression, not absorption. It is un likely that a child accidentally or an adult during siphoning of gasoline would ingest a sufficient quantity to warrant the induction of emesis. 2. Aromatic hydrocarbons are six carbon ringed structures. Toxic dose: Benzene, a solvent used in manufacturing dyes, phenol, and nitrobenzene, has a TLV-TWA of 10 ppm by inhalation according to the OSHA but (1 ppm NIOSH). Ingested toxic dose is 15 mL in adult. Chronic exposure may cause leukemia. Inhalation of 200 ppm is fatal in 5 minutes. Toluene, has an OSHA TLV-TWA of 200 ppm by inhalation. The ingested toxic dose in adults is 50 mL. Styrene OSHA TLV-TWA 100 ppm by inhalation. Xylene, used in the manufacture of perfumes, OSHA TLV-TWA of 100 ppm by inhalation. The adult ingested toxic dose is 50 mL. Manifestations: Asphyxiation, CNS stimulation at low doses and depression and coma at high doses, defatting dermatitis, and aspiration pneumonitis. Other organ systems involved include kidneys (renal tubular acidosis), hematopoietic system (benzenebone marrow depression), skeletal muscles (rhabdomyolysis) and psychosis. A bite into a tube of household plastic cement by a young child can be observed at home. 3. Halogenated hydrocarbons are aliphatic hydrocarbons with one or more halogen substitutions (Cl, Br, Fl, or I). They are highly volatile and abused as inhalants and well absorbed from GI tract (Table 144A.20B). Manifestations: Halogens may lower the threshold for cardiac dysrhythmias, produce hepatorenal toxicity,

and CNS depression. Dichloromethane (methylene chloride) may be converted into carbon monoxide in the body. Dichloroethylene concentrates in the fetus (pregnant women should not be exposed) and causes a disulfiram (Antabuse) reaction (“degreaser's flush”) when associated with ingestion of ethanol. The indication for gastric emptying is based on the toxicity of the specific agent.

Table 144A.20B. Common Examples of Aliphatic Halogenated Hydrocarbons (48,49,50b)

4. Dangerous additives. Dangerous additives to the hydrocarbons, Mnemonic CHAMP include C-camphor (demothing agent), H-halogenated hydrocarbons, A-aromatic hydrocarbons, M-Metals (heavy) and P-pesticides may warrant gastric emptying with a small bore nasogastric lavage tube. 5. Heavy hydrocarbons. These have high viscosity, low volatility, and minimal GI absorption, so gastric decontamination is not warranted. Examples are asphalt (tar), machine oil, motor oil (lubricating oil, engine oil), diesel oil (engine fuel, home heating oil), petrolatum liquid (mineral oil, suntan oils), petrolatum jelly (Vaseline), paraffin wax, transmission oil, cutting oil, and greases and glues. 6. Products treated as hydrocarbons. Essential oils (e.g., turpentine, pine oil are alicyclic hydrocarbons). Mineral seal oil (e.g., signal oil), found in some furniture polishes, is a low viscosity and low volatility oil that never warrants emesis; it can produce severe pneumonia if aspirated. It has minimal absorption. Management: Dermal decontamination. Removal from the environment in inhalation (Table 144A.20C). (1) Asymptomatic patients who ingested small amounts may be observed at home by reliable caretakers with frequent telephone contact for at least 6 hours. (2) GI decontamination is not advised in hydrocarbon ingestion that usually do not cause systemic toxicity (petroleum distillates, heavy hydrocarbons, mineral seal oil). In hydrocarbons that cause systemic toxicity pass a small bore nasogastric tube and perform lavage if appropriate time has not elapsed (absorption is complete with aromatic and halogenated hydrocarbons in 1 to 2 hours) and spontaneous vomiting has not occurred. Gastric lavage in patients with altered mental status should have their airway protected because of concern over uncontrolled vomiting and the low viscosity of these substances allowing the material to creep the lavage tube into the airway. Some toxicologists advocate ipecac-induced emesis under medical supervision instead of gastric lavage. Charcoal is generally ineffective and may produce vomiting. It may be useful to adsorb toxic additives or co-ingestants. (3) In the asymptomatic patient observe several hours for development of signs of aspiration and respiratory distress. A chest radiograph for aspiration should be positive within 6 hrs. Pulse oximetry measurements should be done. Admit symptomatic patients, patients with a positive chest radiograph and intentional ingestions until psychiatric evaluation. (4) In the symptomatic patient offer supportive respiratory care, maintain the airway, assisted ventilation, supplemental oxygen with monitoring of pulse oximetry, ABG, chest radiograph, ECG and admit to ICU. (a) If bronchospasm may be treated with nebulized b-adrenergic agonist and intravenous aminophylline if necessary. Avoid epinephrine because of susceptibility to dysrhythmias. (b) If cyanosis is present that does not respond to oxygen and the arterial PaO is normal, suspect methemoglobinemia that may require therapy with methylene blue. (c) Corticosteroids and prophylactic antimicrobial agents have not been shown to be beneficial. (Fever or leukocytosis may be produced by the chemical pneumonitis itself.) (d) It is not necessary to treat pneumatoceles because they usually resolve. (e) Most infiltrations resolve spontaneously in 1 week except for lipoid pneumonia, which may last up to 6 weeks. (f) Dysrhythmias may require a- and b-adrenergic antagonists or cardioversion. (5) There is no role for enhanced elimination procedures. (6) Methylene chloride is metabolized in vivo in several hrs to carbon monoxide. Place on 100% oxygen, monitor serial COHb levels, ECG, pulse oximetry. (7) Halogenated hydrocarbons are hepatorenal toxins therefore monitor hepatorenal function. N-acetylcysteine therapy may be useful if evidence of hepatic damage. Laboratory: Monitor ECG continuously, arterial blood gases, liver, pulmonary, and renal function; serum electrolytes, serial chest radiographs. Disposition: Asymptomatic patients with small ingestions of petroleum distillates can be managed at home. Symptomatic patients with abnormal chest radiograph, oxygen saturation or ABG should be admitted. In general delay the chest radiograph for 2 to 4 hours. If chest radiograph is initially normal and symptoms persist repeat in 2 to 6 hours. If chest radiograph becomes abnormal admit. If patient becomes asymptomatic has normal oxygenation and normal repeat radiograph they can be discharged.

Table 144A.20C. Initial Management of Hydrocarbon Ingestion

Hydrogen sulfide (H2S) This is a highly toxic, water-soluble, colorless, flammable gas, which is heavier than air. It has the putrid odor of “rotten eggs” at low concentrations, at high concentrations causes olfactory sensory paralysis, which could result in insidious exposures, serious toxicity, and death. H 2S is a byproduct of organic decomposition encountered in livestock wastes, manure storage, sewers, holds of fishing vessels, subterranean emissions (e.g., caves), volcaneos, hot sulfur springs, burning of wool, hair, and hides. Minor amounts are produced in GI tract. Industrial exposure occurs as a byproduct of a number of industrial processes, e.g., tanning, vulcanization of rubber. In hospitals it is released from cast room drains containing calcium sulfide. Toxic dose: Levels 0.1% (1000 ppm) cause death in few minutes, 10 to 100 ppm (0.001% to 0.01%) produce unpleasant odor of “rotten eggs” and irritation. The odor is detected at 0.02 ppm. Toxic mechanism: H2S inhibits electron transport in the cytochrome oxidase system producing cellular hypoxia. Manifestions: Irritation of eye and upper respiratory tract occurs before systemic symptoms. Headache, nystagmus, nausea, vomiting, dyspnea, pulmonary edema, coma and convulsions. Cardiac dysrhythmias and shock may occur. Deaths often occur at the site of exposure. A metabolic lactic acidosis with increased anion gap occurs ( Table 144A.20D).

Table 144A.20D. Characteristic Manifestations With Concentration of H2S Exposure

Management: (1) Remove from site of exposure. Establish airway and give assisted ventilation when necessary. Administer 100% oxygen by nonrebreather mask or through endotracheal tube. Eye, skin, and GI decontamination is usually not necessary. (2) The Cyanide kit. The sodium thiosulfate portion of kit should not be used. Nitrites of the Cyanide Kit may be administered within the first few minutes to remove the sulfide ion. Sulfide reacts with methemoglobin to form sulfhemoglobin which is rapidly metabolized as the body regenerates hemoglobin. Because the body does this naturally nitrites are only of value early. Dosage schedule is similar to that used to treat cyanide intoxication. (Formulary table) Methylene blue should be available to reverse excessive methemoglobinemia (Methb). (3) Hyperbaric oxygen has been reported to be effective in a few cases. Laboratory: Thiocyanate, a detectable metabolite of H 2S can be measured on a non-emergent basis as confirmation. Monitor: Cardiac monitor, methemoglobin levels if nitrites are used, ABGs, pulse oximeter, electrolytes, blood glucose, creatine kinase (rhabdomyolysis), urine for myoglobin. Radiograph of the chest. Lead acetate paper can detect H 2S in the air. Disposition: If skin and eye irritation only, the patient may be treated and discharged home for followup by ophthalmologist. Patients who have been unconscious, or have neurologic signs, respiratory or cardiac signs should be admitted monitored and observed in an ICU. Imipramine (Tofranil) See Tricyclic Antidepressants . Iron There are over 100 iron OTC preparations. The iron content of some preparations appears in Table 144A.21A. Toxic mechanism: The elemental (free) iron is toxic not the salt. Locally iron is corrosive. Excessive free iron in the blood is directly toxic to the vasculature and leads to the release of vasoactive substances serotonin and histamine. Ferritin produces vasodilation. In overdose iron deposits injure mitochondria and cause lipid peroxidation in liver (fatty degeneration and necrosis) and kidneys (renal tubular necrosis) and in the myocardium. Calculation of elemental iron: The tablets ingested times mg of iron salt/tablet times the percent elemental iron divided by the weight (kg) = mg/kg elemental iron ingested. Toxic dose: A range of 20 to 60 mg/kg elemental iron is mild to moderately toxic. Severe toxicity is >60 mg/kg. The potential fatal dose is 180 mg/kg ( Table 144A.21B). Kinetics: Absorption occurs chiefly in the small intestine (duodenum and jejunum) usually in the ferrous (+2) state into the mucosal cells, where it is oxidized to ferric (+3) state and bound to ferritin. Iron is slowly released from ferritin into the plasma to become bound to transferrin and transported to tissues for hemoglobin (70%), myoglobin (5%) and cytochrome. About 25% is stored in the liver and spleen. Usually only 10% is absorbed but in overdose larger amounts of iron are absorbed because of direct corrosion (no mucosal barrier) and diffusion. For elimination there is no mechanism except blood loss (more in menses), bile, and sweat. These eliminate 1 to 2 mg/d. Manifestations: Patients who remain asymptomatic for 6 hours rarely develop serious intoxication. The continuum of iron intoxication follows a biphasic course: Phase I: (1 to 6 hours postingestion) GI mucosal injury possibly with hematemesis and bloody diarrhea, abdominal cramps, fever, hyperglycemia, and leukocytosis. Vomiting can occur within 30 minutes to 1 hour after ingestion and is persistent. Enteric coated tablets may pass through the stomach without causing GI upset. Acidosis and shock can occur within 6 to 12 hours. Latent Phase II: (2 to 24 hours) patient appears improved then goes into shock. Phase III: Cardiovascular collapse and severe metabolic acidosis develops. Phase IV: (2 to 4 days) Hepatic injury associated with jaundice, elevated liver enzymes, prolonged prothrombin time. Proteinuria and hematuria. Pulmonary edema and desseminated intravascular coagulation can occur. Yersinia enterocolica sepsis can occur. Phase V: (4 to 6 weeks) Sequelae of pyloric outlet or intestinal stricture may cause obstruction or anemia secondary to blood loss

Table 144A.21A. Iron Content of Some Preparations

Table 144A.21B. Severity Based on The Amount Ingested

Management: (1) GI decontamination. Emesis should be induced immediately in ingestions of elemental iron more than 40 mg/kg who present under 1 hour. However vomiting may confuse the clinical picture and most children have already vomited. Gastric lavage is useful in a child who has ingested a liquid preparation. It may be used in an adult but most tablets are too big for the tube. Treatments that are Not recommended include sodium bicarbonate, oral deferoxamine, diluted Fleet's enema solution and AC (ineffective). (2) Abdominal radiograph to determine the success of decontamination or if significant amounts of residual radiopaque material are present. If iron is still present consider WBI with polyethylene glycol solution (Formulary table and General management). In extreme cases removal by endoscopy or surgery because coalesced tablets have produced hemorrhagic infarction in the bowel and perforation peritonitis. (3) Deferoxamine (DFOM). About 100 mg DFOM binds only 8.5 to 9.35 mg of free iron in serum in transit. The DFOM infusion should not exceed 15 µg/kg per hour but faster rates have been administered in extreme cases of iron poisoning (more than 1000 µg/dL). The iron-DFOM complex is hemodialyzible if renal failure. (a) Indications for chelation therapy with deferoxamine are serum iron (SI) levels over more than 500 µg/dL or significant systemic signs of intoxication independent of SI level. Chelation should be performed within 12 to 18 hours to be effective. Start the infusion slowly and gradually increase to avoid hypotension. Successful chelation results in color change in the urine from a positive “vin rose” to normal color. (b) Adult respiratory distress syndrome has developed in patients with high dosing for several days, therefore, avoid prolonged infusions over 24 hours. (c) End point of treatment is until patient is asymptomatic and the urine clears if it was “positive vin rose color.” (d) Diagnostic chelation test—deferoxamine 90 mg/kg in children or 2 g in adults intramuscularly is not reliable however it is important to obtain a baseline urine sample for comparison. (4) Supportive therapy: Intravenous bicarbonate can be needed to correct the metabolic acidosis. Hypotension may need volume expansion and vasopressors. Coagulation abnormalities may require blood products and vitamin K. (5) Pregnant patients are treated similar to any other iron poisoning. Laboratory: Produces anion gap metabolic acidosis. Monitor for GI bleeding. SI correlate with the clinical course. SI levels taken at 2 to 6 hours that are less than 350 µg/dL predict an asymptomatic course; levels of 350 to 500 µg/dL are associated with mild gastrointestinal symptoms (rarely serious); more than 500 µg/dL suggest the possibility of serious Phase III manifestations. Obtain serum iron (SI) before administering deferoxamine because it interferes with analysis. The total iron-binding capacity (TIBC) is not a necessary study. A SI at 8 to 12 hours is useful to exclude delayed absorption from a bezoar or sustained-release preparation. A retrospective study indicated that leucocytosis more than 15,000 and blood glucose levels more than 150 mg/dL, radiopaque material present on abdominal radiograph, vomiting, and diarrhea

predict SI more than 300 µg/dL, but patients with WBC less than 15,000 and glucose less than 150 mg/dL can be poisoned. Monitor: Complete blood counts, blood glucose, serum iron, stools, and vomitus for occult blood; electrolytes; acid-base balance; urinalysis and urinary output; liver function tests; blood urea nitrogen; and creatinine. Obtain type and match of blood in severe cases. Abdominal radiographs: Adult iron preparations are often visualized however chewable and liquid preparations are rarely seen. The longer the time since ingestion the less likely iron is to be visualized. Other radiopaque substances are discussed in general laboratory tests. A “negative” radiograph does not exclude iron poisoning. Follow-up may be necessary for sequelae. Patients who develop fever or toxic symptoms following iron overdose should have blood and stool cultures checked for Yersinia enterocolitica. Disposition: Observe the asymptomatic or minimal symptoms (vomiting, diarrhea and abdominal cramps) for persistence, progression of symptoms or development of toxicity signs (GI hemorrhage, acidosis, shock, altered mental state). If no or minimal symptoms (only 1 or 2 episodes of vomiting or diarrhea) or no signs of toxicity develop within 6 hours, patient can be discharged. Treat if clinical symptoms persist or progress, estimation of elemental iron ingestion is very high, metabolic acidosis, or SI more than 500 µg/dL. For patients with SI more than 1000 µg/dL consult toxicologists, gastroenterology, hematology and surgeons, Patients with moderate or severe toxicity should be in ICU. Isoniazid (INH, Nydrazid) This is a derivative of vitamin B 3 (nicotinamide). This is an antituberculosis drug. Toxic Mechanism: INH produces pyridoxine deficiency by doubling the excretion of pyridoxine (vitamin B 6 and by inhibiting pyridoxal 5-phosphate (active form of pyridoxine) from acting with L-glutamic acid decarboxylase to form GABA the major neurotransmitter resulting in seizures or coma. INH blocks the conversion of lactate to pyruvate resulting in lactic acidosis and contributing to the metabolic acidosis. Toxic dose: INH: A dose of 15 mg/kg can lower the seizure threshold; 35 to 40 mg/kg (or 1.5 g in adults) produces spontaneous convulsions; severe toxicity occurs at 80 mg/kg (6 g in adults); 200 mg/kg is an obligatory convulsant. The malnourished, previous seizure disorder, alcoholics and slow acetylators are more susceptible to INH toxicity. Kinetics: Absorption from intestine is rapid, onset is 30–120 minutes with a peak in 1 to 2 hours (clinical symptoms may start within 30 minutes). Vd 0.6 L/kg minimal protein bound. Elimination by liver acetylation to hepatotoxic metabolite, acetylisoniazed then hydrolyzed to isonicotinic acid. Slow acetylators (2 to 4 hours) may develop peripheral neuropathy (50% of blacks and whites) and fast acetylators (0.7 to 2 hours) may develop hepatitis (90% of Asians and a majority of patients with diabetes) on chronic use. Excreted unchanged 10 to 40%. In overdose serum T1/2 is 1 to 4 hours. Interaction: INH also inhibits the metabolism of phenytoin, diazepam, phenobarbital, carbamazepine and prednisone. These drugs may need their dose decreased and these medications may also produce a double interaction interfering with metabolism of INH. Manifestations: Within 30 minutes nausea, vomiting, slurred speech, dizziness, visual disturbances, ataxia. Within 30 to 120 minutes the major signs develop: refractory convulsions (90% have one or more seizures), coma, resistant severe anion gap metabolic lactic acidosis (secondary to hypoxia, convulsions, and metabolic blocks). The clinical triad of refractory seizures, metabolic acidosis and coma occurs at more than 200 mg/kg. Management: (1) Control seizures with large doses of pyridoxine, 1 g for each gram of isoniazid ingested (Formulary table). If the dose ingested is unknown, give at least 5 g or 70 mg/kg of pyridoxine intravenously. Pyridoxine is administered in 50 mL D5W or 0.9% saline over 5 minutes intravenously. Do not administer in the same bottle as sodium bicarbonate. Repeat IV pyridoxine every 5 to 20 minutes until seizures are controlled. It should be given in combination with diazepam but at different sites. Diazepam works synergistically to control the seizures. After the seizures are controlled administer the remainder of the pyridoxine calculated dose or total dose of 5 g as an infusion drip over 1 to 2 hours. Total doses up to 375 mg/kg have been safely administered and there is a report of up to 52 g having been safely administered. However two patients that received 2 g/kg (132 and 183 g) of pyridoxine for gyromitra (false moral) mushroom poisoning for 3 days had a crippling sensory neuropathy that persisted. The maximum dose recommended is 70 mg/kg. Pyridoxine should be strongly considered in large overdoses in asymptomatic patients and some clinicians administered pyridoxine prophylactically if over 80 mg/kg of INH is ingested. Do not use phenobarbital (may increase INH metabolism to toxic metabolites) and phenytoin (interferes with INH metabolism and is not effective). (2) In comatose patients pyridoxine may result in rapid regaining of consciousness. (3) Correction of the acidosis may spontaneously occur with pyridoxine correction of the seizures. (4) GI decontamination. After patient is stabilized, or if asymptomatic, gastric lavage may be performed soon after ingestion (with protection of the airway, if necessary). AC may be administered. (5) Hemodialysis is rarely needed but may be used as an adjunct for uncontrollable acidosis and seizures. Hemoperfusion has not been adequately evaluated. Diuresis is ineffective. Laboratory: Produces anion gap metabolic acidosis. Isoniazid therapeutic levels 5–8 mcg/mL and acute toxic levels are more than 20 µg/mL. Monitor the blood glucose (often hyperglycemia), electrolytes (often hyperkalemia), bicarbonate (acidosis), arterial blood gases (acidosis), liver function tests (elevations occur with chronic exposure), blood urea nitrogen (BUN), and creatinine. If convulsions persist obtain an electroencephalogram (EEG). Monitor the temperature closely (often hyperpyrexia). Disposition: Asymptomatic or mildly symptomatic may be observed in ED for 6 hrs (onset of symptoms within 3 hours). Intentional ingestion require psychiatric evaluation. Patients with moderate or severe symptoms should be admitted to ICU. Isopropyl Alcohol See Alcohols. Kerosene See Hydrocarbons. Lead Lead is an environmental toxin. Acute lead intoxication is rare, and usually occurs by inhalation of lead resulting in severe intoxication and often death. It may be produced by burning lead batteries or using a heat gun to remove lead paint. It also occurs from exposure to high concentrations of organic lead, (e.g., tetraethyl lead). Chronic lead poisoning occurs most often in children 6 months to 6 years of age who are exposed in their environment and in adults in certain occupations. In United States children aged 1 to 5 years with VBPb more than 10 µg/dL decreased from 88.2% in a 1976–1980 survey to 8.9% in 1988–1991 survey due to measures to reduce lead in the environment. However, an estimated 1.7 million children between 1 to 5 years have blood lead (BPb) levels more than 10 µg/dL and more than 1 million workers in over 100 different occupations are exposed to lead ( Table 144A.22A). Chronic per lead poisoning toxic dose: The daily intake of more than 5 µg/kg per day in children or more than 150 µg/d in adults can give a positive lead balance. In 1991, CDC recommended routine screening for children. The CDC recommended a venous blood lead (VBPb) or a capillary blood lead (CBPb) on all children. In children a VBPb more than 10 µg/dL was determined by the CDC to be a threshold of concern (it was 25 µg/dL in 1985). The average VBPb in US is 4 µg/dL. In occupational exposure a VBPb more than 40 µg/dL is indicative of increased lead absorption in adults. Toxic mechanism: Lead affects the sulfhydryl enzyme systems of the proteins, the immature CNS, the enzymes of heme synthesis, vitamin D conversion, the kidneys, the bone and growth. Lead alters the tertiary structure of cell protein denaturing them and causing death. Risk factors are mouthing behavior of infants and children and excessive oral behavior (pica), living in inner city, poorly maintained home, poor nutrition, (e.g., low calcium and iron). The CDC questionnaire was recommended at every pediatric visit ( Table 144A.22B). If any answers to CDC questionnaire are “positive” obtain a blood screening test for lead. However to be more accurate identifying lead exposure studies have suggested the questionnaire will have to be modified for each individual community because it has had poor sensitivity 40% and specificity 60% as it stands. Sources of lead: (Table 144A.22C) (1) The number one source is deteriorating lead based paint which forms leaded dust. Lead concentrations in indoor paint were not reduced to safer (0.06%) levels until 1978. Lead can also be produced by improper interior or exterior home renovation (scraping or demolition). (2) The use of leaded gasoline (limited in 1973) resulted in the residue from leaded motor vehicle emissions. Lead persists in the soil near major highways and from the deteriorating homes and buildings. Vegetables grown in contaminated soil may contain lead. (3) Oil refineries, lead-processing smelters. (4) Food Cans produced in Mexico contain lead solder (95% do not in United States). (5) Water in lead pipes (until 1950) and lead solder (until 1986) deliver lead containing drinking water (calcium deposits however may offer some protection). Water at consumer's tap should be less than 15 ppb. ( Table 144A.22D). (6) Occupational exposure: (Table 144A.22A) OSHA standards require the employers to provide showering facilities and clothes changing for personnel working with lead, however businesses with less than 25 employees are exempt from regulation. OSHA lead standard of 1978 set a limit of 60 µg/dL of occupational exposure to lead. At a blood lead level of 60, a worker should be removed from lead exposure and not allowed back until lead level was below 40. Many authorities feel this level should be lower. The lead residue on the clothes of the workers may represent a hazard to the family ( Table 144A.22A). (7) Leaded pots to make molds “kusmusha” tea. (8) Hobbies (Table 144A.22E): stained-glass windows, making lead fish sinkers or curtain weights especially if ingested and retained, imported pottery with ceramic glaze can leach large amounts of lead into acids (e.g., citrus fruit juices). (9) Traditional folk remedies ( Table 144A.22F)—Azarcon (Mexico) to treat upset stomach. (10) Substance abuse: The synthesis of amphetamines includes lead acetate which may not be removed before using. Lead poisoning from sniffing organic lead gasoline has been reported. Kinetics: Absorption of lead is 10 to 15% of the ingested dose in adults; in children up to 40% is absorbed especially with iron deficiency anemia. Inhalation absorption is rapid and complete. Volume distribution in blood (0.9% of total body burden), 95% is in red blood cells, T1/2, 35 to 40 days; in soft tissue T1/2 45 days and in bone (99% of the lead), T1/2 28 years. The major elimination route is the stool 80 to 90%, renal 10% (80 µg/d) and hair, nails, sweat and saliva. Organic lead is metabolized in the liver to inorganic lead; 9% is excreted in the urine per day. Lead passes through placenta to fetus and is in breast milk. Manifestations: (Table 144A.22G). Adverse health effects include (1) Hematologic: Lead inhibits d-aminolevulinic acid dehydratase (early in the synthesis of heme and has been associated with CNS symptoms) and ferrochelatase (transfers iron to ferritin for incorporation of iron into protoporphyrin to produce heme) and anemia is a late finding. Decreased heme synthesis starts at more than 40 µg/dL. Basophilic stippling occurs in 20% of severe lead poisoning. (2) Neurologic: segmental demyelination, peripheral neuropathy usually motor type (wrist and ankle drop) occurs in workers, VBPb more than 70 µg/dL (usually more than 100

mcg/dL), produces encephalopathy in children (symptom mnemonic “PAINT”: P—persistent forceful vomiting and papilloedema; A—ataxia; I—intermittent stupor and lucidity; N—neurologic coma and refractory convulsions; T—tired and lethargic). Decreased cognitive abilities have been reported with VBPb more than 10 µg/dL, behavior problems, decreased attention span and learning abilities. IQ scores may begin to decrease at 15 µg/dL. In adults peripheral neuropathies and “lead gum lines” at dental border of the gingiva occur. Encephalopathy is rare in adults. (3) Renal nephropathy due to damaged capillaries and glomerulus at VBPb more than 80 µg/dL but recent studies show renal damage and hypertension with low VBPb levels. Lead reduces excretion of uric acid and high level exposure associated with hyperuricemia and “saturnine gout” (Fanconi's syndrome aminoaciduria and renal tubular acidosis), and tubular fibrosis. A linear association between hypertension and 30 µg/dL has been reported. (4) Reproductive: Maternal spontaneous abortion, transient delay in development (catch up age 5 to 6 years), decreased sperm count and abnormal sperm morphology. Lead is transmitted across the placenta in 75 to 100% of maternal blood levels and is teratogenic. (5) Metabolic: Decreased cytochrome P450 (alters metabolism of medication and endogenously produced substances), decreased activation of cortisol, decreased growth by interference of vitamin conversion (25-hydroxyvitamin D to 1,25 hydroxyvitamin D) at VBPb 20 to 30 µg/dL. (6) Other Abnormalities of thyroid, cardiac and hepatic function occur in adults. Abdominal colic is seen more than 50 µg/dL in children.

Table 144A.22A. Occupations Associated with Lead Exposure

Table 144A.22B. CDC Questionnaire Priority Groups for Lead Screening

Table 144A.22C. Product Pb Content (%) by Dry Weight

Table 144A.22D. Agency Regulations and Recommendations Lead Content

Table 144A.22E. Hobbies Associated with Lead Exposure

Table 144A.22F. Some “Traditional” Folk Remedies or Cosmetics that Contain Lead a

Table 144A.22G. Summary Lead-Induced Health Effects in Adults and Children

Management: Basis of treatment is removal of the source. Cases of poisoning in children should be reported to local department of health and cases of occupational poisoning should be reported to OSHA. Control the exposure by identification and abatement of source, improving housekeeping by wet mop and high phosphate solution, allowing the water to run 2 minutes cold before using as drinking water, planting shrubbery in contaminated soil to keep children away. (1) GI decontamination. Lead does not bind to AC. Do not delay chelation therapy for complete GI decontamination in severe cases. Whole bowel irrigation has been used prior to treatment. Some authorities recommend abdominal radiograph followed by gastrointestinal decontamination if necessary before switching to oral therapy. (2) Supportive care, including measures to deal with refractory seizures (continue antidotal therapy, diazepam and may need neuromuscular blockers), with the hepatic and renal failure and intravascular hemolysis. Treat seizures with diazepam followed by neuromuscular blockers if needed. (3) Chelation therapy for children more than 45 µg/dL and adults more than 80 µg/dL or at lower levels with a “positive” lead mobilization test (LMT) ( Table 144A.22H) (a) Dimercaprol (BAL, British Antilewsite) is a peanut oil based dithiol (two sulfhydryl molecules) which combine with one atom of lead to form a heterocyclic stable ring complex. It is usually reserved for VBPb more than 70 µg/dL, and chelates red blood cell-bound lead enhancing its elimination through the urine and bile. It crosses the blood brain barrier. About 50% of patients have adverse reactions including bad metallic taste in mouth, pain at the injection site, sterile abscesses, and fever. (b) Edetate calcium disodium (ethylene diaminetetraacetic acid or CaNa2EDTA Versenate) is a water soluble chelator given intramuscularly (with 0.5% procaine) or intravenously. The calcium in the compound is displaced by divalent and trivalent heavy metals forming a soluble complex, which is stable at physiologic pH (but not at acid pH) and enhances its clearance in the urine. It usually is administered intravenously especially in severe cases. It must not be administered until adequate urine flow is established. It may re-distribute lead to the brain, therefore, start BAL first at VBPb more than 55 µg/dL in children and more than 100 µg/dL in adults. Phlebitis occurs at concentration more than 0.5 mg/mL. Alkalinization of the urine may be helpful. (Formulary table) CaNa 2EDTA should not be confused with sodium EDTA (disodium edetate) which is used to treat hypercalcemia, inadvertent use may produce severe hypocalcemia. (c) Succimer (dimercaptosuccinic acid, DMSA, Chemet R) derivative of BAL, is an oral agent approved by the FDA in 1991 for chelation in children with VBPb more than 45 µg/dL. The recommended dose is 10 mg/kg every 8 hours for 5 days, then every 12 hours for 14 days (Formulary table). DMSA is under investigation to determine its role in children with VBPb less than 45 µg/dL. Although not approved for adults it has been used in the same dosage. Monitor for toxicity by CBC, liver transaminases, and urinalysis. (d) D-penicillamine, 20 to 40 mg/kg per day not to exceed 1 g/d. It is an oral chelator used to enhance the urinary elimination of lead, it is not FDA approved and has a 10% adverse reaction rate. Succimer is preferred. D-penicillamine is used in adults with minimal symptoms but high VBPb levels. (e) If VBPb more than 70 µg/dL or clinical symptoms suggesting encephalopathy in children. This is a potential life threatening emergency. Treatment should be accomplished in a medical center with a pediatric intensive care unit by a multidisciplinary team including critical care specialist, toxicologist, neurologist, and neurosurgeon with careful monitoring of neurological, fluid status and intracranial pressure if necessary. These patients need close monitoring for hemodynamic instability. (1) Adequate hydration should be maintained to ensure renal excretion of lead. Monitor fluids, renal, hepatic function, and electrolytes. (2) While waiting for adequate urine flow, therapy should be initiated with intramuscular dimercaprol (BAL) only (25 mg/kg per day divided into 6 doses). (3) Four hours later a combination of the second dose of BAL intramuscularly with a intravenous infusion CaNa 2EDTA 50 mg/kg per day as a single dose infused over several hours or as a continuous infusion. The double therapy is continued until VBPb is less than 40 µg/dL. (4) Therapy is continued for 72 hours and followed by two alternatives. Either parenteral therapy with two drugs (CaNa 2EDTA and BAL) for 5 days or continue therapy with CaNa 2EDTA alone if good response and VBPb less than 40 µg/dL. If cannot get VBP report back continue therapy with BAL and EDTA for 5 days. In patients with lead encephalopathy parenteral chelation should be continued with both drugs until clinically stable before changing therapy. (5) Mannitol and dexamethasone can reduce the cerebral edema, but the removal of the lead is essential and their role in lead encephalopathy is not clear. Avoid surgical decompression to reduce cerebral edema. (6) If BAL and CaNa 2EDTA are used together, a minimum of 2 days with no treatment should elapse before considering another 5 day course of therapy. Repeat 5 day course with CaNa 2EDTA alone if blood lead remains more than 40 µg/dL or in combination with BAL if more than 70 µg/dL. If a third course is required unless there are compelling reasons, wait at least 5 to 7 days before administering. Continue chelation therapy at all costs. (7) Following chelation therapy, a period of equilibration of 10–14 days should be allowed and a repeat VBPb concentrations should be obtained. If stable enough for oral intake, oral succimer 30 mg/kg per day in three divided doses for 5 days followed 20 mg/kg/day in two divided doses for 14 days has been suggested but there is limited data. Continue therapy until VBPb less than 20 µg/dL in children or less than 40 µg/dL in adults. (8) Chelators combined with lead are hemodialyzable, if renal failure. Laboratory: (1) The Lead mobilization test is used to determine the chelatable pool of lead. It is the administration of 25 mg/kg children or 1 g in adults as a single dose deeply intramuscularly with 0.5% procaine diluted 1:1 or as an infusion. Empty the bladder and collect the urine for 24 hours (3 days if renal impairment). A modified 8 hour collection may be done. If the ratio in micrograms of lead excreted in the urine to the mg of CaNa 2EDTA administered is more than 0.6 it represents an increased lead body burden, and therapeutic chelation may be indicated. However, many consider this test of little importance in making the decision to chelate. The use of x-ray fluorescence of bone as an alternative to determine the lead burden is being tested. (2) Evaluate CBC, serum ferritin; VBPb levels, erythrocyte protoporphyrin (more than 35 µg/dL indicates lead poisoning as well iron deficiency and other causes), electrolytes, serum calcium and phosphorous, urinalysis, BUN and creatinine. Abdominal and long bone radiographs are not routine but may be useful in certain circumstances to identify radiopaque material in bowel and “lead lines” in proximal tibia (occur after prolonged exposure in association with VBPb more than 50 µg/dL). Serial VBPb measurements are done on day 3, 5, during treatment and 7 days after chelation therapy then every 1 to 2 weeks for 8 weeks then every month for 6 months. Stop intravenous infusion at least 1 hour before obtaining blood lead. (3) Neuropsychological tests are difficult to perform in young children but should be considered at the end of treatment to determine auditory dysfunction. Disposition. All patients with more than 70 µg/dL, or who are symptomatic should be admitted. If a child is hospitalized, all lead hazards must be removed before allowing the child to return. The source must be eliminated by environmental and occupational investigations. The local health department should be involved in dealing with children that are lead poisoned and OSHA with occupations lead poisoning. Consultation with poison control center and/or experienced toxicologist is necessary when chelating patients. Follow-up VBPb concentrations should be obtained within 1 to 2 weeks and followed every 2 weeks for 8 weeks then monthly for 6 months if the patient required chelation therapy. All patients with VBPb more than 10 µg/dL should be followed at least every 3 months until 2 VBPb is 10 µg/dL or 3 less than 15 µg/dL (Table 144A.22I).

Table 144A.22H. Pharmacologic Chelation Therapy of Lead Poisoning

Table 144A.22I. Example of a Lead Program for Children

Lindane See Organochlorine Insecticides. Lithium (Li, EskalithR, Lithane) Lithium is an A1 alkali metal whose primary use is in the treatment of bipolar (manic-depressive) disorders. Most cases of intoxication have occurred as chronic therapeutic overdoses. One gram of lithium carbonate contains 189 g of Li. Toxic mechanism: The brain is the target organ although the mechanism is unclear. Li increases dopamine, norepinephrine function and GABA neurotransmission (antimanic). It increases synthesis of serotonin at presynaptic neurons (antidepressive). It may enhance acetylcholine functions and it may act as a substitute for cellular cations (sodium and potassium) in the body. Toxic dose: Each 300 mg dose of Li increases the serum Li level by 0.2 to 0.4 mEq/L. The toxic dose is determined by clinical manifestations and serum levels, although intoxication has occurred with levels in the therapeutic range. The therapeutic serum concentration in acute mania is 0.6 to 1.2 mEq/L, and for maintenance 0.5 to 0.8 mEq/L. Li levels are usually obtained 12 hours after the last dose. Kinetics: GI absorption is rapid, and peaks in 2 to 4 hours following regular release preparations and may be delayed 6 to 12 hours following sustained release preparations. Onset of toxicity occurs 1 to 4 hours after acute overdose. Vd is similar to body water 0.5 to 0.9 L/kg. Li is not protein bound. The T1/2 after a single dose is 9 to 13 hours, at steady state it may be 30 to 58 hours. The renal handling of Li is similar to sodium; it is glomerular filtered and significantly reabsorbed (80%) by the proximal renal tubule. Over 90% is excreted by the kidney unchanged; 30 to 60% within 6 to 12 hours. Alkalinization of the urine increased Li clearance. Reabsorption of Li is enhanced in the presence of hyponatremia, dehydration, renal hypoperfusion and diuretic use. The breast milk level is 50% of the maternal serum level and may be toxic to the nursling. Risk factors that predispose to Li toxicity are febrile illness, sodium depletion, concomitant drugs (thiazide and spironolactone diuretics), impaired renal function, advanced age, and fluid loss in vomiting and diarrheal illness. Common drug interactions with nonsteroidal antiinflammatory drugs (NSAIDs, e.g., ibuprofen), angiotensin converting enzyme inhibitors (ACE inhibitors—captopril), antipsychotic drugs, specific serotonin reuptake inhibitors (SSRI, e.g., fluoxatine). Manifestations: Must distinguish between side effects and acute, chronic and acute on chronic intoxications. Chronic is the most dangerous. (1) Li side effects include fine tremor, GI upset, hypothyroidism, polyuria and frank diabetes insipidius (DI), dermatologic manifestations, cardiac conduction deficits. It is teratogenic. (2) The toxic effects are classified in Table 144A.23. Acute poisoning may be asymptomatic with high blood levels due to the time necessary for lithium to distribute to the tissues. The onset may first occur 1 to 4 hours after acute overdose. The first sign of rising Li level may be diarrhea, nausea and vomiting. It may take as long as 3–5 days for serious symptoms to develop. Little toxicity may occur from acute lithium ingestions with levels up to 10 mEq/L. Twenty 300-mg tablets ingestion may produce serious intoxication. Significant toxicity is manifested by neurological findings of weakness, fasciculations, twitching, impaired mental state, myoclonus, hyperreflexia, rigidity, coma, and convulsions (limbs are held in hyperextension). Cardiovascular manifestations are ventricular dysrhythmias, hypotension, flat T or inverted T waves, AV block, and prolonged QT interval. Laboratory findings include leucocytosis, hyperglycemia, glycosuria. Chronic intoxication is associated with manifestations at lower levels. Thyroid dysfunction and diabetes insipidius may be present ( Table 144A.23).

Table 144A.23. Classification of Severity of Lithium Poisoning Chronic Lithium Manifestations at Different Blood Concentrations

Management: (1) Establish and maintain vital function. Treat seizures, hypotension, and dysrhythmias. Restore normothermia. (2) Evaluation. Examine for hyperreflexia signs, hydration status, renal function (BUN, creatinine). Inquire about diuretic use. If on chronic therapy discontinue the lithium. Obtain serial serum Li levels in 2 hours for acute ingestion and 6 to 12 hours for chronic toxicity. Li levels should be monitored every 4 hours until peak especially in sustained release preparations. Monitor electrolytes, and ECG, vital signs, serial neurologic examinations including mental status. Obtain Nephrology consultation for elevated Li levels (more than 3 mEq/L), significant ingestion and neurologic signs especially altered mental state. (3) Fluid and electrolyte therapy. An intravenous line should be established and hydration initiated. Determine serum sodium level before fluid administration because of existing hypernatremia from DI. Restore fluid and electrolyte balance, particularly sodium. Although current evidence supports initial saline infusion as enhancing excretion of lithium, once euvolemia, normal output and normal sodium is established there is little advantage to aggressive saline diuresis. (4) GI decontamination. Gastric lavage is useful only early after acute ingestion because of rapid absorption and is not necessary after chronic intoxication. AC is ineffective. In slow-release preparations, WBI may be useful but is unproven. Sodium polystyrene sulfonate (Kayexalate), 15 to 50 g orally every 4 to 6 hours, may be useful in massive overdoses, but is difficult to administer and still unproven. (5) Hemodialysis (peritoneal dialysis has no role in this setting) is the most efficient method of removing Li from the vascular compartment and it is the treatment of choice

for severe intoxication. Long runs should be used until the lithium level is less than 1 mEq/L because of extensive re-equilibration rebound. Monitor Li levels every 4 hours after dialysis. Dialysis may have to be repeated. Expect a time lag in neurologic recovery. Permanent neurologic sequelae (e.g., encephalopathy) can result from Li intoxication. (6) Monitor ECG. Refractory dysrhythmias may be treated with magnesium sulfate and sodium bicarbonate as indicated. Avoid thiazide and spironolactone diuretics, which increase lithium levels. Laboratory: Lithium level determinations should be serially performed every 4 hours until the peak is reached. Although they do not always correlate with the manifestations at low levels, they are predictive in severe intoxications. Levels more than 4.0 mEq/L with chronic intoxication are usually severely toxic, whereas Li levels more than 8 mEq/L following acute overdose may be asymptomatic. Other tests to be monitored are complete blood count (lithium causes leukocytosis), renal function, thyroid (chronic), ECG, and electrolytes. Disposition. An acute Li overdose cannot be medically cleared on the basis of a single Li level unless it is zero at 12 hours after the ingestion. Patients should be admitted if they have any neurologic manifestations (altered mental status, stiffness or tremor). Patients should be admitted to the ICU if dehydrated, have renal impairment, a high or rising Li level. Lomotil (Diphenoxylate and Atropine) See Opioids/Anticholinergic Agents . LSD (Lysergic Acid Diethylamide) See Hallucinogens. Marijuana See Hallucinogens. Meperidine (Demoral) See Opioids. Meprobamate (Equanil, Miltown) See Sedative Hypnotics. Mercury (Hg) Mercury is used in electrical equipment, thermometers, sphygmomanometers, other measuring equipment, dental amalgam, paints, gold mining, and ore extractions. It is still available as stool specimen fixatives, and antiseptics. It is classified into: (1) Elemental, which vaporizes at room temperature (TLV-TWA 0.05 mg/m 3) and causes toxicity by inhalation absorption (80%) but not by ingestion (0.1%) of Hg from thermometers, sphygmomanometers, and dental amalgams. Volatile at room temperature. (2) Inorganic salts which cause toxicity by corrosive action as well as GI, dermal and pulmonary absorption found in topical medicines, cathartics (calomel), stool preservatives, and catalytic agents. (3) Organic is absorbed by GI, dermal and inhalation and produce toxicity by chronic exposure found in paints, fungicides, foods, medicines, cosmetic agents. Toxic mechanism: Mercury is a cumulative and renal tubular toxin. Mercury binds to the sulfhydryl groups of enzymes, produces cellular toxicity and multiple organ failure. Inorganic mercury also inhibits the enzyme responsible for catecholamine metabolism. It is a corrosive and a direct neural toxin. Toxic dose: As little as 0.2 g of inorganic mercuric chloride has resulted in the death of a child. In adults 1 to 4 g is often fatal, although the minimal lethal dose is estimated to be 400 to 500 mg. Mercury antiseptics thimerosal (Merthiolate) and merbromin (Mercurochrome) are not well absorbed from the GI tract or dermal route and rarely produces acute toxicity. The acute single fatal dose by ingestion of these agents is 4 times the fatal dose of the mercury salts. Toxic levels more than 4 µg/dL in blood and 20 µg/L in urine should be considered abnormal. Kinetics: (Table 144A.24) Elemental mercury is not absorbed from GI tract and is eliminated in feces. It is absorbed by inhalation 100%, onset of action within few hours, T1/2 40 to 60 days. Inorganic salts 15% absorbed from GI tract, onset of corrosive action within few minutes, T1/2 is 40 days. Organic mercury is completely absorbed from the GI tract, onset of symptoms from methyl mercury may occur eeks to months after exposure. T1/2 52 to 70 days. Manifestations: Elemental mercury inhalation of the vapors from spilled mercury can produce respiratory symptoms and progress to encephalopathy. Chronic exposure to elemental and inorganic mercury can produce acrodynia in infants (“painful limbs” with swelling and redness of the feet (“pink disease”). In adults neuropsychiatric emotional disturbances (irritability, insomnia, labile affect, memory loss), cerebellar incoordination, tremors abolished by deep sleep (“erethism” or “Mad Hatter's disease”) and renal failure. The triad of gingivitis with loose teeth, discolored gums, stomatitis, and salivation may be noted. Chronic mercury poisoning is a cumulative toxin producing multiple organ failure. Inorganic mercury produces GI corrosive effects, shock, and renal failure. Organic methylmercury produces neuroencephalopathy consisting of the triad of ataxia, dysarthria, and constriction of visual fields (“tunnel vision”) known as “Minamata disease.” Minamata disease may include peripheral neuropathy, ataxia, convulsions, and coma. Mercury passes through the placenta and into breast milk.

Table 144A.24. Types of Mercury and Mercury Poisonings

Management: (1) To clean up spilled mercury dust on powdered sulfur or finely divided granulated zinc to absorb the mercury. These materials may discolor carpets. In small spills clean up as much as possible with a whisk broom. Discard the whisk broom after the procedure is completed. Vacuuming should only be done by a specialized industrial mercury vacuum cleaner (not a home vacuum cleaner). If a large spill check the ambient air (less than 1 µg/m 3) (2) Inhalation of elemental mercury—remove from exposure administer respiratory support as needed. (3) Ingestion of mercury salts may need aggressive fluid resuscitation, central venous pressure monitoring and bladder catheterization for appropriate fluid therapy. GI decontamination in ingestion of mercuric salts administer egg white, milk, N-acetylcysteine to bind and reduce salt to mercurous ion (less toxic and unproven). Activated charcoal does adsorb mercuric chloride and may be used. GI decontamination is not recommended for elemental or chronic mercury intoxication. (4) Chelating agents: (a) Intramuscular dimercaprol (BAL), a derivative of BAL, enhances mercury excretion through the bile as well as the urine and is the choice chelator if GI symptoms exist and unable to tolerate oral medication (Formulary table). Use of BAL in organic methyl mercury intoxication increases the brain mercury and appears to be contraindicated: penicillamine and its analogue should be used (decreases mercury in brain). (b) An oral chelator, 2, 3-dimercaptosuccinic acid (DMSA, Succimer, Chemet) 10 mg/kg every 8 hours for 5 days, appears less toxic and more specific therapy when patient can tolerate oral medication. (c) Another derivative of BAL, Sodium 2, 3-Dimercaptopropane-1-Sulfone (DMPS) is being investigated. It may be useful in chronic toxicity. (d) An alternative oral chelator is D-penicillamine and N-acetyl- D, L-penicillamine (Formulary table). Neither of the oral chelating agents have been approved by the FDA (lack of effectiveness data) for the treatment of mercury poisoning but they may be indicated in asymptomatic patients with elevated body burden. (5) Therapy is supportive including fluid and vasopressor therapy of shock from GI symptoms, antihypertensive therapy, management of renal failure. Monitor fluid and electrolyte levels, renal function, hemoglobin levels. Obtain blood and urine mercury levels (consult the laboratory for proper collection technique and containers). (6) Hemodialysis is not routine unless there is renal failure. It is being investigated in conjunction with chelation therapy early (within 24 hours of ingestion) in the symptomatic patient. Consult a nephrologist. (7) Surgical excision of local injection sites has been recommended. Laboratory: (1) Normally blood levels are less than 4 µg/dL and urine levels less than 20 µg/L in 90% of the adult population. Blood levels are not always reliable. Exposed asymptomatic industrial workers' urine levels are 150 to 200 µg/L. (2) In asymptomatic patients with urine levels less than 300 µg/L, a chelating challenge with BAL or penicillamine may bring a significant increase in mercury that may aid in establishing the diagnosis. (3) Methyl mercury is excreted mainly through the feces, so urine mercury would not be a reliable measurement. (4) Mercury is also excreted in the sweat and saliva. The parotid fluid level is approximately two-thirds

that of the blood. Because the hair is porous, it may absorb mercury from the atmosphere; however, hair concentrations more than 400 to 500 µg/g are likely to be associated with neurologic symptoms. (5) Radiographs of the abdomen for ingestion and chest radiographs for injections of mercury may be helpful in showing radiopaque material. Disposition: Elemental mercury ingestion is usually nontoxic. Symptomatic patients from inhaled elemental mercury, inorganic mercury, or organic mercury should be admitted to ICU. Organic mercury disinfectant ingestions are nontoxic unless massive amounts are ingested. Methadone See Opioids. Methanol See Alcohols. Methaqualone See Sedative Hypnotics. Methemoglobinemia (Methb) See nitrites. Methemoglobin results from the conversion (oxidation) of hemoglobin ferrous iron (Fe + 2) to the ferric (Fe + 3) state which is incapable of binding oxygen. The physiologic methemoglobin content of the blood is 1 to 2%. Sources: Methemoglobinemia has been reported in infants from diaper ointments containing tetracaine, with ingestion of naphthalene moth balls, high nitrate contamination of well water, benzocaine oral gel for teething, diapers labelled with aniline dye. Workers in munitions industry are at risk. Toxic mechanism: The primary role of hemoglobin, tissue oxygenation, is interrupted. The disruption occurs by two mechanisms, ferric iron of hemoglobin is unable to bind oxygen reducing tissue oxygen delivery and the ferric form binds to the ferrous form decreasing the oxygen affinity of the ferrous hemoglobin. This causes a reduced oxygen carrying capacity, oxygen saturation and shifts the oxygen-hemoglobin dissociation curve to the left binding the oxygen. Methyprylon (Noludar) See Sedative Hypnotics. Monoamine Oxidase Inhibitors (MAOI) These are used in the treatment of endogenous depression. Classification: (1) Hydrazine derivatives: phenelzine sulfate (Nardil), isocarboxazid (Marplan) (irreversible). (2) Nonhydrazine that are structurally related to amphetamines: tranylcypromine (Parnate) (irreversible). (3) Others are: Selegiline (Deprenyl, Eldepryl) which specifically inhibits monoamine oxidase B and is used as an adjunct to treat Parkinson's Disease. It has fewer interactions. However, most selectivity is lost in overdose. Not yet available in US are reversible MAOI's brofamine, cimoxatone, moclobenamide (Aurorix). Toxic mechanism: MAO enzymes, in adrenergic nerve terminals, are responsible for the oxidative deamination of endogenous and exogenous biogenic amines neurotransmitters (dopamine, norepinephrine, epinephrine and 5-hydroxytryptophan). MAO-A (liver intestinal wall, brain) metabolizes biogenic amine neurotransmitters and tyramine in food. MAO-B (liver, intestine, platelets) metabolizes b-phenylethylamines, phenylethylanolamines and benzylamine. Many substrates are metabolized by both. MAO inhibitors act to inhibit MAO and other enzymes such as dopamine-B-oxidase until a new enzyme is synthesized (usually 14 days or longer). The toxicity results from the accumulation, potentiation and prolongation of the neurotransmitters action followed by profound hypotension and cardiovascular collapse. Toxic dose: Death has occurred after a single dose of tranylcypromine 170 mg in an adult. Toxicity begins at 2 to 3 mg/kg and fatalities from 4 to 6 mg/kg. Kinetics: Hydrazines peak 1 to 2 hours; elimination route is by hepatic acetylation metabolism and are excreted in the urine as inactive metabolites. Nonhydrazine, tranylcypromine, onset of symptoms with overdose 6 to 24 hours after ingestion, peak concentration in 1 to 4 hours, peak activity in overdose occurs in 8 to 12 hours and duration 72 hours but rarely lasts weeks. Peak MAOI inhibition in 5 to 10 days. Vd is large 1.5 to 3.7 L/kg. T1/2 1.5 to 3 hours; it is eliminated by hepatic metabolism to active amphetamine metabolites. The duration in overdose is 48 to 96 hours. Interactions: (Table 144A.25). (1) Food interactions occur because of inhibition of MAO-A in the intestine (deamination of tyramine) and the undegraded tyramine releases catecholamines. Onset is within 30 to 90 minutes. Tyramine acts as a false neurotransmitter and causes the release of catecholamines resulting in headache and hypertension for several hours. Complications such as intracranial hemorrhage may occur. Mneumomic for tyramine foods: “Two basic” T—tricyclics, W—wine, O—opioids, B—beer, A—avocados, S—Sympathomimetics, I—Isoniazid, C—Cheese, caviar, chocolate, chicken liver. (2) Indirect acting sympathomimetics cause the release of catecholamines from presynaptic vesicles and give exaggerated response including headache, hypertension, diaphoresis, and tremor for 4 to 6 hours. (3) Serotoninergic agents opioids (especially meperidine), tricyclic antidepressants and selected serotonin reuptake inhibitors (SSRI) should be discontinued 5 weeks before starting MAOI. (4) Nonspecific interactions—interfere with metabolism of sedative hypnotics, anticholinergics, oral hypoglycemics to produce symptoms and prolonged action. Manifestations: (1) Acute ingestion overdose: (a) Phase I—Adrenergic crisis delayed onset (time for inhibition of MAO) for 6 to 12 hours and may not reach peak until 24 hours. Starts as hyperthermia, tachycardia, tachypnea, dysarthria, transient hypertension, hyperreflexia and CNS stimulation. (b) Phase II Neuromuscular excitation and sympathetic hyperactivity with increased temperature more than 40°C (104°F), agitation, hyperactivity, confusion, fasciculations, twitching, tremor, masseter spasm, muscle rigidity, acidosis and electrolyte abnormalities. Seizures and dystonic reactions may occur. Mydriatic pupils, some nonreactive with “ping-pong gaze.” (c) Phase III—CNS depression and cardiovascular collapse, in severe overdose, as the catecholamines are depleted. Symptoms resolve within 5 days but may last 2 weeks. (d) Phase IV—Secondary complications from rhabdomyolysis, cardiac dysrhythmias, multi-organ failure and coagulopathies may occur. (2) Biogenic-Interactions (not overdose; Table 144A.25). Occur 30 to 90 minutes after the ingestion of interacting drug or food while on chronic MAOI therapy and up to 5 weeks after discontinuing specific serotonin reuptake inhibitor (SSRI) therapy and starting MAOI. (a) Severe headache associated with severe hypertension (malignant hypertension syndrome). (b) Hyperthermia (Malignant hyperthermia), seizures, altered mental status, encephalopathy. (c) Serotonin syndromes are due to increase in serotonin synthesis ( L-tryptophan), and prevention of reuptake by certain opioids and SSRI. They have a abrupt onset of an altered mental state and confusion, agitation, muscle rigidity with or without hyperthermia or hypertension, diaphoresis, shivering, followed by vascular collapse. The secondary complications of these syndromes is similar to overdose. (3) Chronic toxicity includes tremors, hyperhidrosis, agitation, hallucinations, confusion and seizures. Confused with withdrawal syndromes.

Table 144A.25. Monoamine Oxidase Inhibitor Interactions

Management: Overdose: (1) GI decontamination early emesis, gastric lavage and AC or AC alone. (2) If admitted to hospital, for those well enough to eat order a MAOI diet. (3) Extreme agitation and seizures can be controlled with benzodiazepines and barbiturates. Neuromuscular blocker may be used if necessary. (4) If hypertension use short-acting antihypertensive agents nitroprusside and benzodiazepines. Caution do not use longer acting agents because is often followed by severe hypotension. (5) Hypotension should be managed by fluid and vasopressors. Vasopressor therapy should be administered with caution and at lower doses than usual because of exaggerated pharmacologic response. Norepinephrine is preferred to dopamine, which requires release of intracellular amines. (6) Cardiac

dysrhythmias are treated with standard therapy. (7) For severe hyperthermia and muscle rigidity administer dantrolene (Formulary table) a nonspecific skeletal relaxing agent, which inhibits the release of calcium from the sarcoplasm. It does not reverse the rigidity or psychomotor retardation resulting from the central dopamine blockade, 2.5 mg/kg oral or intravenous every 6 hours, external cooling (fan, ice packs, wet sheets) and supportive therapy, correct acidosis and electrolyte disturbances. Benzodiazepine can be used for sedation. Antipyretics are ineffective in toxicologically-induced temperature elevations. (8) Seizures and agitation should be controlled with benzodiazepines and/or barbiturates. Phenytoin is ineffective. Neuromuscular blockers may be needed in severe cases of hyperthermia and rigidity. (9) Treat rhabdomyolysis and myoglobinuria with fluid diuresis, and alkalinization. (10) Enhanced elimination measures are of no proven value. Interactions: (1) Oral nifedipine, or to phentolamine, a parenteral alpha blocking agent in a dose of 3 to 5 mg intravenously may be useful in adults. (2) Serotonin syndrome may be treated with cyproheptadine, a serotonin receptor blocker and beta blockers. (3) Malignant hypertension is treated with nitroprusside. (4) Malignant hyperthermia is treated with dantrolene (see above) and supportive measures. (Formulary table). Use a Benzodiazepine for sedation. Laboratory: Monitor ECG, cardiac monitoring, CPK, ABG, pulse oximeter, electrolytes, blood glucose, acid-base balance. Disposition: All patients ingesting more than 2 mg/kg should be admitted to the hospital for extended observation in ICU and monitoring for 24 hours because the life-threatening manifestations may be delayed. Patients with drug or dietary interactions which are mild may not require admission if symptoms subside within 4 to 6 hours. Muscle Relaxants See Table 144A.26 These medications act on the higher centers or spinal neurons to inhibit transmission. Toxic dose: Baclofen is a lipophilic derivative of gamma amino butyric acid (GABA) that acts on GABA receptors. Toxicity in adults has been reported at doses of 150 mg and death over 1250 mg. Orphenadrine is a anticholinergic agent that closely resembles diphenhydramine. It may produce seizures and cardiac arrest. Its lethal dose is 2 to 3 g with a high mortality. Chlorphenesin produces CNS depression at high doses. Carisoprodol toxicity in adults occurred more than 8 g; 3.5 g produced death in a 4-year-old child who vomited and aspirated with combined meprobamate and carisoprodol level of 51 µg/dL. Cyclobenzaprine is structurally similar to amitriptyline, however, cardiac toxicity rarely occurs. Its action is mainly central anticholinergic and sedative. It is metabolized in the liver. The toxic dose in a child is 20 mg and 600 mg in an adult. Only one report of possible serious cardiac toxicity. Kinetics: Onset of action is usually 30 to 60 minutes postingestion, although the onset of toxicity with baclofen was delayed 8 hours. Peak plasma concentrations are usually between 1 to 2 hours post-ingestion and duration of action 4 to 8 hours. Plasma T1/2 is usually 1 to 4 hours with some exceptions. Half-lives may increase many fold with overdose. Baclofen peak effects and plasma levels occur at 2 to 3 hours. As dose increases the rate and extent of absorption decreases. PB 30%, about 15% is metabolized in the liver via deamination. T1/2 is 2 to 6 hours but may be up to 36 hours in overdose. About 70 to 80% is excreted in the urine unchanged or as its metabolites, remainder in the feces. Orphenadrine peak plasmas levels are obtained within 2 to 4 hours after intial dose. Metabolized to N-dimethylorphenadrine. PB 20%, elimination T1/2 15 to 20 hours. Both baclofen and cyclobenzaprine have enterohepatic recirculation. Chlorzoazone peak serum levels are observed 2 hours after ingestion. Manifestations: (1) CNS—The most constant manifestation is depression, but some compounds (baclofen, orphenadrine and dantrolene) produce seizures. Confusion, hallucinations, agitation, hypotonia, or hypertonia, visual disturbances, cerebellar effects of vertigo, nystagmus, and ataxia may be present. (2) GI—gastroenteritis. (3) CV effects may occur with cyclobenzaprine and orphenadrine which has negative inotropic effect. Hypotension may be present. (4) Anticholinergic effects may be present with orphenadrine. (5) Orphenadrine is the most toxic and has a rapid onset of toxic symptoms within 20 to 30 minutes postingestion. Coma develops rapidly with nonreactive mydriasis, hyperreflexia, and seizures may be present. (6) Baclofen a CNS depressant produces hyporeflexia, muscular hypotonia, significant salivation, drowsiness, visual disorders, seizures, respiratory depression and coma. It increases the serum glucose and liver enzymes. It has produced a withdrawal syndrome (after chronic use) consisting of seizures, hallucinations, paranoid ideation, and mania. (7) Cyclobenzaprine produces drowsiness, syncope, hallucinations, seizures and coma. It may produce tachycardia and dysrhythmias. It can cause an increase or decrease in body temperature.

Table 144A.26. Muscle Relaxants

Management: (1) Establish and maintain vital functions. If children ingest more than 5 mg/kg or adult more than 100 mg of baclofen admit to ICU. The manufacturer of cyclobenzaprine recommends observation and evaluation if more than 20 mg (2 tablets) are ingested or more than 100 mg in adults. Monitoring should be continued for 5 days in symptomatic overdose because of the long T1/2 1.5 to 3 days. (2) GI decontamination. Emesis should be avoided. In emergency departments gastric lavage within the first hour may be used, in obtunded or comatose patients after airway protection is established. AC cathartic is administered initially and MDAC without a cathartic may be given in cases of enterohepatic recirculation (baclofen and cyclobenzaprine). Diminished or absent bowel motility preclude the administration of AC. (3) CNS depression is treated with airway protection, assisted ventilation and general support. (4) Cardiovascular disturbances from cyclobenzaprine are treated similar to tricyclic antidepressants using sodium bicarbonate for wide QRS tachycardias. (5) Hypotension is managed with positioning, fluids, and vasopressors. (6) There is no data on clinical effectiveness of diuresis, hemodialysis or hemoperfusion but carisoprodol may be dialyzable. (7) Antidote: A specific antagonist phaclofen for baclofen is being investigated in animals. Physostigmine (Formula table) may be used with caution to treat only very severe anticholinergic symptoms of orphenadrine and cyclobenzaprine. Exclude tricyclic antidepressant ingestion by ECG. Administer it slowly with monitoring. Have atropine and resuscitative equipment available. Laboratory: Monitor vital functions and ECG especially with cyclobenzaprine and orphenadrine, liver function tests, white blood cell count, blood glucose, serum electrolytes, and renal function. Blood concentrations: Therapeutic range for Orphenadrine is reported 0 to 0.85 µg/mL (toxicity at 2 µg/mL and lethal at 4 to 8 µg/mL); therapeutic range of Baclofen is 0.08–0.4 µg/mL; therapeutic range of cyclobenzaprine is 0.01 to 0.04 µg/mL and it is confused by some laboratory tests with tricyclic antidepressants, and chlorozone with aprobarbital. Carisoprodol 350 mg therapeutic dose produces levels at 1 hour of 2.1 mg/L and decline to 0.24 mg/L at 6 hours. Two deaths occurred with 36 mg/L at 4 hours and 110 mg/L. Disposition: Admit to ICU if toxic dose. Psychiatric consultation when stable before discharge. Nitrites (NO2) and Nitrates (NO3) Classification: (1) Organic nitrates used for angina pectoris are listed in Table 144A.27A. (2) Inorganic nitrates have more toxicologic importance in natural foods and contaminated well water. The most common cause of methemoglobinemia (Methb) in infants in the United States is ingestion of well contaminated water with nitrates. A nitrate folk remedy called “Sweet spirit of nitre” has caused fatalities. (3) Other sources of nitrates/nitrites are: chemical laboratories, nitrous gases used in arc welding; and the abuse of volatile nitrites. Toxic mechanism: Nitrates are potent oxidizing agents converting ferrous iron (Fe+2) in deoxyhemoglobin to ferric iron (Fe+3) resulting in methemoglobinemia, which cannot transport circulating oxygen. They also produce vasodilation. In overdose they result in venous pooling, reduced cardiac output and hypotension. These hemodynamic changes may also result in increased intracranial pressure. Toxic dose: The EPA regulations require nitrate content of potable water to be below 45 mg/L (45 ppm) and the nitrite content below 10 mg/L (10 ppm). About 1 mg/kg of nitrate is required to produce methemoglobin of 10%. The normal methemoglobin in humans is 0.5 to 2% of total hemoglobin. Potential fatal doses: Nitrite, 1 g nitrate, 10 g; nitrobenzene, 2 mL; nitroglycerin, 0.2 g and aniline dye (pure), 5 to 30 g. Ingestion of 10 to 15 mL isobutyl nitrite 40% in a room deodorizer has been fatal in a child and produced methemoglobinemia in an adult. Less than 25 nitroglycerin sublingual 0.6-mg tablets ingested orally probably will not result in toxicity based on bioavailability of oral nitroglycerin, which is 1% and gives plasma concentration of 4.5 ng/mL in 10-kg child and 0.649 ng/mL in a 70-kg adult. Kinetics: Time to onset of action of nitroglycerin sublingual is 1 to 3 minutes, with a time to peak action of 3 to 15 minutes and a duration of 20 to 30 minutes. Other routes have a slower onset (2 to 5 minutes) and longer duration of action (1.5 to 6 hours). Nitrites are potent oxidizing agents converting ferrous to ferric iron, which cannot carry oxygen. Normally humans have 0.7% of methemoglobin, which is converted by methemoglobin reductase into oxygen-carrying hemoglobin. Liver detoxification by dinitration is the route of elimination. Manifestations: depends on the level of methemoglobinemia (Methb) ( Table 144A.27b). (1) Methemoglobinemia: At 10%, “chocolate cyanosis” occurs; at 10 to 20%, headache, dizziness, and tachypnea occur; and at 50%, mental alterations are present and coma and convulsions may occur. Severe hypoxia may produce pulmonary edema and encephalopathy. Levels more than 50% produce metabolic acidosis and ECG changes; cardiovascular collapse occurs at levels of 70%. Methb can occur without cyanosis in anemic patients. (2) Vasodilation: Headache, flushing, and sweating are due to the vasodilatory effect; hypotension,

tachycardia, and syncope may also occur.

Table 144A.27A. Organic Nitrites for Angina Pectoris

Table 144A.27B. Manifestations and the Level of Methemoglobinemia a

Management: (1) Dermal decontamination, if indicated. Aniline dyes may be removed with 5% acetic acid (vinegar). (2) Gastrointestinal decontamination if ingested. (3) Hypotension can be treated by the Trendelenburg Position and fluid challenge. Vasoconstrictors (dopamine or norepinephrine) are rarely needed. (4) Once exposure to the offending substance is terminated methb returns to normal with 36 hours. (5) For methemoglobinemia: (a) Methylene blue (MB) (Formulary table) a reducing agent, is indicated for methb levels more than 20 to 30%, dyspnea, metabolic acidosis (lactic acidosis), or an altered mental state. Cyanosis occurs at 15% and is not an indication for MB by itself. Do not administer to mild cases of methb or patients with glucose-6-phosphate deficiency (G6PD deficiency). MB reduces the T1/2 of methemoglobin from 15 to 20 hours to less than 60 minutes by reducing the ferric (Fe+3) iron of methemoglobin to ferrous (Fe+2) iron of hemoglobin. A dramatic response is noted within 15 minutes. If patient remains symptomatic after 15 to 30 minutes repeat dose. Do not administer more than 7 mg/kg in first 2 to 3 hours because MB becomes an oxidizing agent. Methylene blue needs intact red blood cells to function, therefore, is not effective in chlorate methb (hemolysis) and should not be given if G6PD deficiency (13% African-American males and both sexes Mediterranean ancestry). Obtain a methb level 1 hour after MB administration and follow serial methb levels for recurrence of methemoglobinemia in cases where the agent (e.g., dapsone) is not readily eliminated from the body. A constant infusion 1 mg/kg per hour has been used in prolonged cases. Oxygen, 100%, is indicated during and after MB therapy. (b) Hyperbaric oxygen or exchange transfusions should be considered in symptomatic patients if MB is not effective, e.g., in chlorate intoxication (hemolysis) or in glucose-6-phosphate dehydrogenase deficiency (G6PD). (5) Treat hemolytic anemia with transfusions and maintain adequate urinary output. (6) Consult a hematologist for the enzymatic causes of MB failure (after recovery) of activity of G6PD, activity of NADH cytochrome-b 2 reductase deficiency. Laboratory: Methb levels by co-oximeter, ABG (show normal PaO2), hemoglobin, hematocrit, glucose, electrolytes. Bedside tests: Arterial blood has a fudge “chocolate-brown” appearance and fails to turn red on exposure to oxygen but 1:1000 dilution of the patient's blood will revert to pink color when exposed to one crystal of potassium cyanide. The chocolate-brown color indicates methemoglobin more than 10%. The use of a nitrite dipstick (used to detect bacteria in the urine) will detect nitrite in the serum of patients intoxicated with butyl nitrite. Methb levels and oxygen saturation should be measured by co-oximeter (wave length 635 nm), not by pulse oximetry. Look for serum-free hemoglobin and Heinz bodies on peripheral smear to detect hemolysis. Disposition: Admit symptomatic patients with hypotension, dyspnea, hemolysis or altered mental state. Asymptomatic healthy patients with methemoglobin levels less than 20% with normal hemoglobin (no evidence of hemolysis) may be considered for discharge if methb is declining, patients remain asymptomatic for 6 hours, if not intentional and reliable follow-up is available. Admit all children and elderly. Longer observation periods may be necessary if ingestion involves long acting nitrites such as isosorbide dinitrite. Consult hematologist if methb was unresponsive to MB (after recovery) for enzyme deficiencies (e.g., G6PD), and for any patient who develops sudden methb after ingestion of therapeutic doses of a drug. All patients who received MB therapy should be observed for recurrence of symptoms. Notify local public health and occupational authorities if poisoning is secondary to environmental or occupational exposure. Counsel patients regarding sources of exposure. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) NSAIDs are used as analgesics, antirheumatic agents, and antipyretics ( Table 144A.28) Classification: There are two major classes excluding salicylates and acetaminophen: (1) carboxylic acids (e.g., fenprofen, ketorolac, ibuprofen, indomethacin, mefenamic acid, naproxen) and (2) enolic acids (pyrazolones and oxicams). Toxic mechanism: NSAIDs act by interference with the fatty acid enzyme cyclooxygenase and inhibits prostaglandin (PG) synthesis. PG are needed for gastric mucosal barrier (GI symptoms and bleeding), thromboxane in platelets (bleeding), and vasodilation of renal vessels (renal failure). NSAIDs also have naturetic effect (salt and water retention), interfere with glucose metabolism, the Krebs cycle, and liver aminotransferases. Toxic dose: Adult single ingestion of 5 times the therapeutic dose are toxic or a single ingestions greater than the maximum daily amount. An ingestion of 2 times the therapeutic adult dose in children can be toxic. Ingestion of ibuprofen less than 200 mg/kg is usually asymptomatic, more than 200 mg/kg can be toxic and more than 400 mg/kg can produce serious toxicity (apnea, coma and seizures). In adults ingestions more than 6 g ibuprofen are at risk. NSAIDs overdose usually do not result in serious toxicity except for Fenamic acid group of carboxylic acids, e.g., mefenamic acid, which produce seizures (2.5 mg produced seizures in a 12-year-old child) and the enolic acid pyrazolones (phenylbutazone caused cardiac toxicity and death in a 1-year-old child with 2 g and in alcoholic adult with 2.5 g. Ketorolac (Toradol), the first parenteral NSIAD, has caused 80 fatalities often associated with renal failure. It is currently banned in five countries (Netherlands, Greece, Portugal, Germany, and France). Recently, a postoperative patient developed renal failure after a single dose of 60 mg intramuscularly. Kinetics: Data is specified in Table 144A.29A. In general NSAIDs are lipid soluble, weak acids with pKa of 3.5 to 5.2, absorbed rapidly from the GI tract. Peak blood concentration varies but in general occurs in 1 to 2 hours. PB more than 90%, Vd 0.1 to 1.0 L/kg. Elimination is usually by hepatic oxidation or hydroxylation then conjugation. The exception is Sulindac which is converted into an active sulfide form. Indomethacin, sulindac, phenylbutazone, and piroxicam undergo enterohepatic recirculation. Phenylbutazone exhibits dose dependent (Michaelis-Menten) elimination. The serum T1/2 varies. Those with T1/2 less than 6 hrs include diclofenac, etodolac, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, indomethacin, ketoprofen, mefenamic acid, meclofenamate, tiaprofenic acid, and tolmetin, the shortest less than 1 hour. Those with T1/2 more than 6 hrs include: apazone, diflunisal, fenbufen, nabumetone, naproxen, oxaprozin, oxyphenylbutazone, phenylbutazone, the longest more than 50 hours, piroxicam, salicylate, sulindac (sulfide) active metabolite, tenoxicam. Excretion unchanged is usually 1 to 15% but 30% of indomethacin is excreted unchanged. Interactions: High protein binding NSAID can displace other highly bound medications from their protein binding sites and increase their toxicity (warfarin type anticoagulants, beta-blockers, hydantoins, salicylates, sulfonylureas, and sulfonamides). The decreased renal function of NSAID (especially indomethacin) has caused aminoglycoside, cyclosporine, digoxin, lithium, and methotrexate blood levels to rise to potentially toxic levels. NSAIDs can have a fatal interaction with methotrexate. Clinically significant interactions may occur because of NSAID prostaglandin inhibition of the antihypertensive effects of angiotensin converting enzyme inhibitors (ACEI), beta-blockers, furosemide, thiazides. Manifestations: Most manifestations with NSAID occur before 6 hours and are mainly GI (nausea, vomiting, abdominal pain), and less frequently renal and in some cases neurological (drowsiness, tinnitus, headache, lethargy, apnea, and seizures). GI bleeding rarely occurs due to acute single overdose (it occurs in 1 to 2% of adults taking NSAIDs over 3 months). Hemorrhagic disturbances can occur and contribute to GI bleeding. Ibuprofen toxicity is usually mild but apnea can occurs more than 400 mg/kg. The NSAIDs interfere with PGE 2 and PGI2, which maintain renal perfusion, salt and water excretion. Renal damage may occur in overdose especially with fenprofen. Mefenamic acid seizures can occur up to 12 hrs after overdose. Coma rarely occurs with caroxylic acid group. Both respiratory

alkalosis and anion gap metabolic acidosis have been reported after large overdoses. Enolic acids can produces much more serious intoxications and coma, metabolic acidosis and renal failure occur more frequently and at lower overdoses. A red discoloration of the urine may occur with phenylbutazone's metabolite rubazonic acid. Chronic use adverse effects can complicate acute on chronic intoxications including GI bleeding, fatty liver and hepatitis, and variety of rashes have been reported in patients with connective tissue disorders.

Table 144A.28. Classification of Nonsteroidal Anti-inflammatory Drugs

Table 144A.29A. Dosage and Kinetics of NSAIDs

Management: (1) Refer to a medical care facility if: (a) ibuprofen ingestion in amounts more than 200 mg/kg or 2 times the adult therapeutic dose of NSAID in children or 5 times the adult therapeutic dose or more than the adult maximum daily dose in adults (Table 144A.29B). (b) any amount above the therapeutic dose of fenamic acid group of carboxycylic acids (metacloprofen), meclofenamic acid (Meclomen), mefenamic acid (Ponstel), and enolic acids pyrazolones (phenylbutazone), and oxicams. (c) if the ingestion is intentional or the amount is unreliable evaluate medically and psychologically. (2) GI decontamination is by gastric lavage within 1 hr postingestion and oral AC. AC is reported to be effective with indomethacin, mefenamic acid, piroxican, and phenylbutazone. MDAC has decreased the elimination T1/2 of phenylbutazone but there is no data on the other NSAIDs. Emesis is not recommended because with fenamic acids and ibuprofen more than 400 mg/kg ingestion can produce convulsions and vomiting, losing one of the early markers of toxicity. (3) Test vomitus and stools for blood, although GI bleeding in acute overdose is rare. If GI bleeding administer misoprostol, oral prostaglandin 200 µg four times a day, consider endoscopic examination, and transfusions may be required. (4) Treat apnea with an endotracheal airway and respiratory support. (5) Administer fluids, treat potassium derangements and metabolic acidosis, as needed. (6) Treat seizures with diazepam. They are usually brief. (7) Hypotension is managed with Trendelenburg position, fluids, rarely are vasopressor needed. (8) Hemodialysis is of no proven benefit. Hemoperfusion has been used in phenylbutazone and can reduce the serum T1/2 and clearance but has not been tested in others. Laboratory: Obtain glucose, electrolytes, ABG, renal and liver function tests, and hematologic profile if significant ingestion (more than 6 g in adult or more than 200 mg/kg). False-positive Coombs' tests have been reported. Disposition: Ibuprofen less than 200 mg/kg can be observed at home. Observation for 6 hours in a ED after decontamination procedures. Ingestion of femanic acids (e.g., mefenamic acid) or encolic acids (e.g., pyrazolones) monitor for 12 hours and if symptomatic admit to ICU for cardiac monitor and seizure precautions. Patients with coma, respiratory depression, renal failure or seizures admit to ICU. A CBC, renal and liver function tests should be repeated 24 to 48 hours in significantly symptomatic patients especially in enolic acids overdose.

Table 144A.29B. Summary Initial Management of NSAID Ibuprofen Overdose

Nortriptyline (Aventyl, Pamelor) See Tricyclic Antidepressants . Opioids (Narcotic Opiates) In addition to usual forms, opioids also come in transdermal patches. Opioids are used for analgesia, as antitussives, antidiarrheal agents and are illicit agents (heroin, opium) used in substance abuses in Table 144A.30A. They are classified as natural, semisynthetic and synthetic. (1) Opiates refer to natural products of the opium poppy including morphine, codeine (methylmorphine), heroin (diacetylmorphine), and paregoric (camphorated tincture of opium). (2) Semisynthetic analogs are congeners of morphine, produced by changes in the extracts from the poppy plant or congeners of morphine including dextromethorphan (Delsyn), hydrocodone (Hycodan, Vicodin), hydromorphone (Dilaudid), oxycodone (Percodan, Percocet), and oxymorphone (Numorphan). (3) Synthetic analogs are congeners of meperidine, methadone, and fentanyl. (a) Meperidine analogs are phenanthrene derivatives including diphenoxylate (Lomotil), loperamide (Imodium), meperidine (Demerol). (b) Methadone analogs are diphenylperidine derivatives including methadone (Dolophine) and propoxyphene napsylate (Darvon) (c) Fentanyl congeners include fentanyl (Sublimaze), alpha methyl fentanyl (“China White”) and 3-methyl fentanyl (“China white”). (4) Antagonist-agonist opioids include butorphanol (Statal), nalbuphine (Nubain), nalorphine (Alline), and pentazocine (Talwin). (5) Pure antagonist opioids include nalmefene (Revex), naloxone (Narcan), and naltrexone (Trexan). Toxic mechanism: Four main opioid receptors have been identified mu, kappa, delta, sigma ( Table 144A.30B). Mu is considered the most important for central analgesia. Kappa and delta are predominant in spinal analgesia. The sigma receptors mediate dysphoria. However studies on receptors will continue to result in reclassification. Sigma receptors are no longer considered primary receptors. Opioids overdose should be observed for CNS and respiratory depression and

hypotension. Pulmonary edema is a potentially lethal complication of mainlining (intravenous use). Toxic dose: Oral morphine has one-sixth the potency of parenteral, the peak effect is later and duration is longer. For therapeutic and toxic doses ( Table 144A.30C). Children oral doses that have produced respiratory depression include diphenoxylate 7.5 mg (3 tablets), codeine 5 mg/kg, meperidine 75 mg, morphine 10 mg, methadone 10 mg and propoxyphene 11 mg/kg. Adult doses causing respiratory depression include buprenorphen 0.8 mg oral, codeine 200 mg oral, dihydrocodeine 150 mg oral, diphenoxylate 300 mg oral, fentanyl 0.125 mg IM, heroin 15 mg oral and 3 mg IM, hydrocodone 100 mg oral, hydromorphone 6 mg oral, loperamide 360 mg oral, meperidine 250 mg oral, methadone 200 mg oral morphine 70 mg oral and 10 mg IM, opium powder 700 mg oral, oxycodone 18 mg oral, camphorated tincture of opium (Paregoric) 7 mL oral, pentazocine 120 mg oral, propoxyphene HC1 600 mg oral, and propoxyphene napsylate 900 mg oral. Kinetics: (Table 144A.30C) oral onset of analgesic effect is 10 to 15 minutes, peak 1 hour and duration is 4 to 5 hours but with sustained release preparations duration is 8 to 12 hours. Opioids are 90% metabolized in the liver by hepatic conjugation and 90% excreted in the urine as inactive compounds. Large Vd 1 to 4 L/kg, PB is 35 to 75%. The typical plasma T1/2 of opiates is 2 to 5 hours but of methadone is 24 to 36 hours. Morphine metabolites include morphine-3-glucuronide (M-3-G) which is inactive, and morphine-6-glucuronide (M-6-G) and normorphine which are active. Meperidine is rapidly hydrolyzed by tissue esterases into the active metabolite, normeperidine, which has twice the convulsant activity of meperidine. Heroin (diacetylmorphine) is deacetylated within minutes to 6-monacetylmorphine (6-MAM) and morphine. The 6-MAM metabolite is diagnostic since it does not come from any other opioid or poppy seeds. Propoxyphene (Darvon) has rapid onset and death has occurred within 15 to 30 minutes after massive overdose. Propoxyphene is metabolized to norpropoxyphene, an active metabolite with convulsive, cardiac dysrhythmic and heart block properties. Diphenoxylate is metabolized into diphenoxylic acid, which is 5 times more active as a respiratory depressant than diphenoxylate.

Table 144A.30A. Classification of Opioids

Table 144A.30B. Opioid Receptors

Table 144A.30C. Equivalency, Kinetics and Potentially Fatal Dose

Manifestations: (1) Initially intoxication produces miosis, dull face, confusion, drowsiness, partial ptosis or “nodding” (head dropping toward chest then bobbing up). All opiate agonists can progress to produce the classic triad of miotic pupils, respiratory and CNS depression and flaccid coma. (2) Dilated pupils do not exclude opioid poisoning. Some exceptions to opioid miosis include fentanyl, meperidine, and Lomotil (rarely), also hypoglycemia, hypoxia, postictal state, or a co-ingestant may produce mydriasis. (3) Increased muscle tone may be produced by meperidine and fentanyl. (4) Seizures are rare in opioid intoxication except with meperidine, propoxyphene, and dextromethorphan. Hallucinations and agitation may occur. (5) Pruritus and urticaria are common due to histamine release of some opioids involving the mu receptor. (6) Noncardiac pulmonary edema (bilateral hilar infiltrates on radiograph) and copious frothy sputum, rhonchi, rales and wheezing can develop especially with intravenous abuse. (7) Aspiration may be the cause of the chest findings but do not resolve within 48 hours. (8) Tolerance develops and physical dependence result in “flulike” abstinence symptoms, with piloerection (“gooseflesh”), back pain (“kicking the habit”), and mydriasis. (9) A heart murmur in an intravenous addict should suggest endocarditis. (10) Some specifics about opioids include: (a) Fentanyl is 100 times more potent than morphine and can cause muscle rigidity. (b) Meperidine can produce seizures, and mydriasis, (c) Propoxyphene can cause seizures, cardiac dysrhythmias and delayed onset of cardiac membranous depressant effects. Management: (1) Supportive care, particularly an endotracheal tube and assisted ventilation. Endotracheal intubation may be avoided and temporary ventilation provided by bag-valve-mask with 100% oxygen while waiting for response to naloxone. Place on cardiac monitor, establish intravenous access and obtain specimens for ABG, glucose, electrolytes, BUN and creatinine. Obtain blood for later CBC, coagulation profile, liver function, and toxicology screen, and urinalysis. (2) GI decontamination, if ingestion, gastric lavage (if less than 1 hour) and activated charcoal because opioids delay gastric emptying, but this is of no benefit if overdose is by injection. Convulsions occur rapidly with propoxyphene (Darvon) meperidine and codeine overdose, and rapid CNS depression are indications not to use an emetic. (3) Naloxone (Narcan) (Formulary table). (a) If the patient is a suspected abuser or addict, it is advisable to apply 4-point restraints before naloxone administration. The initial dose in an addict is a low 0.1 mg and double the dose with each bolus until response or withdrawal. (b) If not a suspected addict 2-mg naloxone can be given as the initial bolus and increased by increments of 2 mg every 2 to 5 minutes up to 10 mg if there is no response. Naloxone must be titrated against the clinical response and precipitation of withdrawal in narcotic addicts. (c) If vascular access cannot be established naloxone may be administered into the endotracheal tube, sublingual and intramuscularly. (d) It is essential to determine if there is a response to naloxone (mydriasis, improvement in ventilation) since it is a diagnostic and therapeutic test. A partial response requires careful search for injury or another illness and rapid sequence intubation at that time with succinylcholine. Repeat doses of naloxone as often as necessary, because the effects of many opioids in overdose can last much longer than naloxone (methadone lasts 24 to 48 hours), whereas the action of naloxone lasts only 30 minutes to 1 hour. Larger doses may be needed for buprenorphine, codeine, designer drugs, dextromethorphan, diphenoxylate, methadone, pentazocine, and propoxyphene. (e) A continuous naloxone drip may be appropriate in certain overdoses using the response dose every hour. One-half of the response dose may need to be repeated in 15 to 20 minutes after starting the infusion. Methadone may require a naloxone infusion for 24 to 48

hours. (4) Nalmefeme (Revex), an FDA approved long acting (4 to 8 hours) pure opioid antagonist is being investigated but its role in acute intoxication is unclear at this time. It may have a role in place of naloxone infusion but could produce prolonged withdrawal symptoms. (5) Noncardiac Pulmonary edema does not respond to naloxone, and patient needs intubation and assisted ventilation and PEEP. Fluids should be given cautiously in opioid overdose because these agents stimulate antidiuretic hormone effect and noncardiac pulmonary edema is frequent. (6) If the patient is comatose, give 50% glucose (3 to 4% of comatose opioid overdose patients have hypoglycemia) and thiamine prior to naloxone. (7) If the patient has seizures unresponsive to naloxone administer diazepam and examine for other causes both metabolic (hypoglycemia, electrolyte disturbances) and structural. (8) Hypotension is rare and should direct a search for another etiology. (9) If the patient is agitated, exclude hypoxia before considering withdrawal. (10) Complications to consider include urinary retention, constipation, rhabdomyolysis, myoglobinuria, and hypoglycemia. (11) Opioid withdrawal. Observe patients for withdrawal (nausea, vomiting, cramps, diarrhea, dilated pupils, rhinorrhea, piloerection). If these occur, stop naloxone. It is useful to use an opioid withdrawal score as a baseline. The signs and symptoms of withdrawal are diarrhea, dilated pupils, gooseflesh, hyperactive bowel sounds, hypertension, insomnia, lacrimation, muscle cramps, restlessness, tachycardia, and yawning. Each sign or symptom is given 0, 1, or 2 points, depending on the severity. A score of 1 to 5 is mild; 6 to 10, moderate; and 11 to 15, severe. Seizures are unusual (exclude other causes) with withdrawal and indicate severe withdrawal regardless of the rest of the score. Opioid withdrawal from heroin starts in 6–8 hrs, from methadone 24 to 72 hours. Management of withdrawal: Methadone orally can be used, 5 to 20 mg every 12 hours later it is decreased by 5 mg every 12 hours. When 10 mg is reached, may add Lomotil. Patients cannot be sent home on methadone since the FDA restricts the use of methadone to FDA-regulated programs. Clonidine (Catapres), 0.1 to 0.2 mg every 4 to 6 hours, can be used with informed consent (not FDA approved). Monitor the BP every 2 hours. Laboratory: If naloxone has been administered before blood or urine was collected, the laboratory should be informed to avoid false identification of naloxone as the intoxicating “opioid.” For acute overdose obtain levels of ABGs, blood glucose, and electrolytes; chest radiographs; and ECG. Blood opioid levels confirm diagnosis but are not useful for making a therapeutic decision. For drug abusers, consider testing for hepatitis B, syphilis, and human immunodeficiency virus (HIV) antibody (HIV testing usually requires consent). Disposition: If a patient requires naloxone, which has shorter half-life (30 to 60 minutes) than most opioids careful observation for relapse or the development of pulmonary edema is required in an ICU (with cardiac, respiratory and suicide precautions, if needed) until symptom free for at least 12 hours. Intravenous overdose complications would be expected to be present within 20 minutes and a recent recommendation has been made for discharge of asymptomatic patients after 4 symptom-free hours. Adults with oral overdose (delayed onset of toxicity), regardless of symptoms, require 6 hours observation before discharge. Children with oral opioid overdose should be admitted to hospital for 24 hour observation, especially with Lomotil. Patients requiring repeated doses of naloxone or an infusion, or who develop pulmonary edema require ICU admission for 24 hours and cannot be discharged from ICU until symptom-free for 12 hours. Appropriate psychiatric and social work for intentional and pediatric poisonings should be arranged. Restraints may have to be used should the patient attempt to sign out AMA until psychiatric evaluation. The role of nalmefene in altering these recommendations is unclear at this time. Organophosphates (OPI) and Carbamates Cholinergic intoxication sources are mushrooms, medications and insecticides. They also include the dreaded “G” nerve war weapons Tubun (GA), Sarin (GB), Soman (GB), and VX. (For examples see Table 144A.31A, Table 144A.31B and Table 144A.31C). Toxic Mechanism: Acetylcholinesterase (RBC cholinesterase) is present at the terminal endings of all postganglionic parasympathetic nerves, both parasympathetic and sympathetic ganglia, myoneural junction and in erythrocytes. Plasma pseudocholinesterase is formed in the serum and liver. About 3% of people have a genetic deficiency of pseudocholinesterase. The cholinesterase enzymes hydrolyze acetylcholine, terminating its action. Organophosphates phosphorylate the active site on cholinesterase causing irreversible inhibition of enzymes directly by the parent compound (e.g., tetraethylpyophosphate) or indirectly by a toxic metabolite (e.g., parathion or malathion). Carbamates (esters of carbonic acid) cause reversible carbamylation of the active site of the enzymes. Pralidoxime, the enzyme regenerator, may not be necessary in the management of some carbamate intoxication (e.g., carbaryl), but atropine is required. The major differences of the carbamates (from OPIs) include: (1) the toxicity is less and duration shorter; (2) they rarely produce overt CNS effects because of poor CNS penetration; (3) the cholinesterase returns to normal rapidly, so blood cholinesterase values are not useful in confirming the diagnosis. When a critical amount of cholinesterase is inhibited, acetylcholine accumulates causing transient stimulation of conduction but soon paralyzes conduction through cholinergic synapses and sympathetic terminals (muscarinic effect), the somatic nerves, the autonomic ganglionic synapses (nicotinic effect) and CNS synapses. Toxic dose: Parathion's minimum lethal dose is 2 mg (0.1 mg/kg) in children and minimal lethal dose is 10 to 20 mg (mean lethal dose 300 mg or 4 mg/kg) in adults. The lethal dose of malathion is 1,375 mg/kg (1000 times less toxic than parathion) and of diazinon is 25 g and these are unlikely to cause death. Kinetics: Absorption is by all routes. The onset of acute ingestion toxicity occurs as early as 3 hours, usually before 12 hours and always before 24 hours. Agents are absorbed by the dermal route or are lipid soluble (e.g., fenthion, “-thione” group), which may delay onset for more than 24 hours. Inhalation toxicity occur immediately. Massive ingestion can produce intoxication within minutes. The thions (e.g., parathion, malathion) undergo hepatic desulfonation and microsomal oxidative metabolism to their more toxic oxygen metabolites “-oxons” (e.g., paroxon, malaoxon). Others are metabolized to weakly active compounds through hepatic hydrolysis and other pathways. The T1/2 of malathion is 2.89 hours and parathion is 2.1 days. The metabolites are eliminated in the urine and the presence of p-nitrophenol may serve as a clue to some exposures up to 48 hours after exposure. Manifestations: A garlic odor of the breath, gastric contents, or container; diaphoresis, excessive salivation, miosis, and muscle twitching are helpful clues. (1) Early, a cholinergic (muscarinic) crisis develops and consists of parasympathetic nervous system activity or DUMBELS—diarrhea and cramps, urination, miosis (mydriasis occurs in 20%), bronchospasm, excess secretion, lacrimation, and seizures. Bradycardia, pulmonary edema, and hypotension may be present. (2) Later, sympathetic and nicotine effects occur consisting of MATCH—muscle weakness and fasciculation (eyelid twitching is often present), adrenal stimulation and hyperglycemia, tachycardia, cramps in muscles, hypertension. Finally paralysis of the skeletal muscles occurs. (3) CNS effects are headache, blurred vision, anxiety, confusion, emotional lability, ataxia, toxic psychosis, vertigo, convulsions, coma and respiratory depression. Cranial nerve palsies have been noted. Delayed hallucination may occur. (4) Delayed respiratory paralysis, neurologic, and neurobehavioral disorders have been described following certain OPIs. The “Intermediate syndrome” is paralysis of proximal and respiratory muscles developing 24 to 96 hours after the successful treated OPI poisoning. A delayed distal polyneuropathy has been described with certain OPI (e.g., tori-ortho-cresyl phosphate [TOCP], bromoleptophos, methomidophous).

Table 144A.31A. Examples of Common Organophosphate Insecticides (OPI)

Table 144A.31B. Common Cholinergic Medications and Pharmacokinetics

Table 144A.31C. Common Examples of Carbamates 1 Pesticides

Management: (Table 144A.31D) (1) Establish and maintain vital functions. Cardiac and oxygen saturation monitoring. Decontamination of the skin, hair, eyes, and removing clothing. Careful protection of health care personnel is essential (gloves, gowns, or hazardous material suits). Suction secretions until atropinization drying is achieved. Intubation and assisted ventilation may be needed. (2) GI decontamination if recent ingestion with gastric lavage and AC. No induced emesis. (3) Atropine sulfate (Formulary Table), is both a diagnostic and a therapeutic agent. Use preservative free atropine (no benzyl alcohol). If patient is symptomatic (bradycardia or bronchorrhea) administer a test dose 0.02 mg/kg in a child or 1 mg in an adult. If the patient exhibits the signs of atropinization (tachycardia, dry secretions, and dilated pupils) the diagnosis of OPI poisoning should be questioned. If no signs of atropinization administer atropine in sufficient amounts to dry the secretions and clear the lungs. Dilation of the pupils is not a sign of sufficient atropine. Atropine is administered every 5 to 10 minutes intravenously, at increasing increments, if necessary, Beneficial effects are seen within 1 to 4 minutes and maximum effect in 8 minutes. Maintain maximum dose for 12 to 24 hours, then taper the dose and observe for relapse. Poisoning especially with lipophilic agents (e.g., fenthion, chlorfenthion) may require weeks of atropine therapy. The use of a continuous infusion 8 mg in 100 mL infused at rate of 0.02 to 0.08 mg/kg per hour (0.25 to 1.0 mL/kg per hour) with additional 1 to 5 mg boluses as needed to dry the secretions. The average dose of atropine required in the first 24 hours is 40 mg but 1000 mg has been required in some patients. Atropine works only against the muscarinic effects not the nicotinic (muscle weakness) and is only partially effective on CNS effects (seizures and coma). (4) Pralidoxime chloride (2-PAM) is required after atropinization (Formulary table) and acts to reactivate the phosphorylated cholinesterase (ACHase) by binding the phosphate moiety on the esteritic site and displacing it. It should be given early (less than 24 hours) before “aging” of phosphate bond produces irreversible binding. However recent reports indicate 2-PAM is beneficial several days after the poisoning. Improvement is seen within 10 to 40 minutes. Its use may require reduction in the dose of atropine since it has both antinicotinic and antimuscarinic effects. In carbamate toxicity the rapid resolution often does not require 2-PAM, however, if the caustive agent is unknown it should be administered. The initial dose is 1 to 2 g in 250 mL 0.89% saline over 30 minutes in adults (20–40 mg/kg in children). Cardiac and blood pressure monitoring (for hypertension) are advised during and for several hours after the procedure. (5) Contraindicated drugs: Do not use morphine, aminophylline, barbiturates, opioids, phenothiazine, reserpine-like drugs, parasympathomimetics or succinylcholine. (6) Pulmonary edema may require respiratory support with PEEP. (7) Seizures may respond to atropine and 2-PAM but is not consistent and may require anticonvulsants. (8) Cardiac dysrhythmias may require antidysrhythmic therapy if hemodynamically unstable. (9) Extracorporeal procedures are of no proven value. Laboratory: Draw blood for red blood cell cholinesterase determination before giving pralidoxime. Levels, are usually more than 90% depressed for severe symptoms. A postexposure rise of 10 to 15% determined at least 10 to 14 days without exposure is important in confirming the diagnosis. Monitor chest radiograph, blood glucose, ABG, pulse oximetry, ECG, blood coagulation status, liver function, and the urine for the metabolite alkyl phosphate p-nitrophenol. Disposition: Any patient with more than a trivial exposure should be observed for 24 hours. Asymptomatic patients with normal examination after 6 to 8 hours of observation may be discharged. Symptomatic patients should be admitted to a monitored bed in the ICU. If ingested OPI, observe patient until the passage of charcoal stool. Observation of milder cases of carbamate poisoning, even those requiring atropine, for 6 to 8 hours symptom-free may be sufficient to exclude significant toxicity. Discharged patients require counseling and if intentional, psychiatric clearance. If workplace exposure notify OSHA and local health department. It is not medically advisable to administer atropine, scopolamine patches or pralidoxime prophylactically to workers exposed to organophosphate pesticides.

Table 144A.31D. Summary of Initial Treatment of OPI Intoxications

Paraquat and Diquat These are nonselective dipyridyl herbicides. Paraquat is a quaternary ammonia herbicide rapidly inactivated in the soil by binding to clay particles. Used in 130 countries it has caused more than 700 deaths since 1965. Mortality is more than 50%. ( Table 144A.32A). Toxic mechanism: Paraquat interferes with the enzymes, superoxide dimutase, and glutathione reductase, responsible for reducing these radicals. Paraquat is believed to stimulate prostaglandin synthesis, which breaks down the phospholipids in the cell membranes. Molecular oxygen is reduced to form free “superoxide” oxygen radicals. The production of oxygen radicals and interference with nicotinamide-adenine dinucleotide phosphate (NADP) and NADPH (reduced form) metabolism results in generation of hydrogen peroxide, hydroxyl groups and single oxygen. These react with alveolar cell components and membranes by lipid peroxidation and thiol oxidation producing pneumatocyte cellular injury in the lung. Paraquat 20% has a local caustic action and produces GI injury (1% preparations used for home and garden are not caustic). The mechanism of toxicity of diquat is believed to be similar but it involves the kidneys. Toxic dose: Paraquat nonindustrial preparations (e.g., Ortho 0.2%) are unlikely to cause serious intoxications. Ingestion of 10 mL of commercial preparations (e.g., Gramoxone 20%) will produce fatal pulmonary fibrosis. Ingestion 8 µg/mL. There is a high risk of auditory and ocular toxicity when the plasma concentration more than 10 µg/mL, 65% of patients will have cardiotoxicity when the concentration is >14 µg/mL and concentrations >16 µg/mL has been associated with fatalities. Monitor vital functions, electrolytes, serum glucose, liver/renal function tests, CBC and platelet count and ECG monitoring. A 12-lead ECG should be obtained. Obtain a Chest radiograph, ABGs if depressed level of consciousness or serious dysrhythmias. If there are signs of disseminated intravascular coagulation (DIC) monitor platelets, split fibrin degradation products and fibrinogen. Disposition: Hospitalize all patients with ingestion of a toxic amount of toxic plasma concentration. Intensive care monitoring and cardiac consult is required in any symptomatic patient with an overdose since ventricular pacing may be needed. Patients that remain asymptomatic for 6 hrs post ingestion with normal ECG can be discharged. Quinine Cinchona alkaloid used as antimalaria and questionable skeletal muscle relaxant. Toxic mechanism: It also has direct photoreceptor and ganglionic cell toxic effect on the retina. In large amounts it can produce significant cardiotoxicity. Toxic dose: The toxic dose in adults 2.5 to 4.0 g and the fatal average lethal amounts is 8 g although survival has been reported with 31 g. The toxic dose is children 15 mg/kg and fatal dose is 1 g. In adults amounts greater than 4 g in 24 hours will produce amblyopia which is reversible when discontinued. Kinetics: The onset is 1 to 2 hours. Peak plasma concentration is within 1 to 3 hours, the Vd is 1.8 L/kg, the elimination T1/2 is 4 to 6 hours and in overdose may be over 24 hours. PB is 70% and crosses the placenta. It is metabolized in the liver to an inactive metabolite. Less than 25% of the drug is excreted unchanged in the urine. Manifestations: (1) The onset of symptoms begin in 1 to 3 hours. GI symptoms are often the initial effects. Significant overdose causes profound hypotension due to vasodilation, myocardial depression, and disturbances in cardiac rhythm and conduction as the major life threatening effects. Confusion, dementia, and psychosis may occur. Death may ensue within a few hours. In large overdoses toxic effects of quinine and quinidine

may be indistinguishable. Quinine is more likely to produce oculotoxicity and Quinidine is more likely to result in cardiotoxicity. Thrombocytopenia occurs with chronic poisoning. (2) Cinchonism may also be seen with quinidine intoxication. It was originally described as tinnitus, vertigo, headache, deafness, and visual disturbances but now is considered a wider diversity of symptoms that includes visual disturbances (occur within 15 minutes to 10 hours or later), syncope, confusion, delirium, ataxia, choreoathetosis, mutism, seizures and generalized weakness. (3) Ophthalmologic disturbances—The ocular manifestations may be delayed for hours to days. Pallor of the optic disc, retinal artery spasm, and arteriolar constriction may be seen. A cherry red spot, retinal macular edema, and fixed dilated pupils have been reported. Central vision usually returns but the visual fields may remain permanently constricted. Visual loss lasts from 24 hours to weeks and may be permanent. (4) Cardiovascular effects may not be present with mild or moderate quinine intoxications. Myocardial depression, dysrhythmias, disturbances in conduction, and hypotension can occur in severe cases. The ECG changes may consist of prolongation of PR (although the PR is usually normal), widening of the QRS, prolongation of the Q-T intervals and torsades de pointes. (5) Dermatologic effects—A variety of skin rashes and flushing are noted. (6) Hematologic effects—Hemolysis in G6PD deficient patients may occur. Hypoprothrombinemia and fatal thrombocytopenia has been reported. DIC has been reported in three women using quinine for leg cramps. (7) Metabolic—Hypokalemia and metabolic acidosis have been noted. (8) Renal failure has been reported. Management: Immediately establish vascular access. (1) Establish and maintain vital functions. Obtain a 12-lead ECG as soon as possible. Treat hypotension with Trendelenburg positioning, intravenous fluids and vasopressors, if necessary. Cautiously monitor the fluids because of compromised inotropic action of the heart. Provide continuous cardiac monitoring for dysrhythmias and if unstable, hemodynamic monitoring. Obtain an immediate cardiac consultation. Electrophysiologic support of the heart should be readily available. (2) GI decontamination with immediate gastric lavage in asymptomatic patients. Administer AC/cathartic initially and follow with MDAC, which have been shown to alter the T1/2 but its effect on clinical course is not clear. Avoid emesis because of rapid onset of seizures and coma. (3) Obtain daily ophthalmologic and otologic consultation for several days. (4) Treat convulsions with diazepam. Blood pressure, cardiac and respiratory monitoring is necessary during IV anticonvulsant administration. (5) Cardiovascular effects: Dysrhythmias and blocks: Avoid class IA antidysrhythmic agents, beta blockers, and bretylium. Lidocaine may be used. (a) Alkalinization with hypertonic sodium bicarbonate has been recommended for patients who are hemodynamically unstable or with rhythm disturbances with prolonged QRS complex. Use hypertonic sodium bicarbonate 1 to 2 mEq/kg bolus every 5 to 10 minutes (makes sodium available for the fast sodium channel, maintains pH 7.5, and lowers the potassium level). Monitor the serum sodium and potassium. (b) If the patient is unresponsive hemodynamically, or exhibits unstable AV blocks, it is an indication for insertion of a pacemaker. The indications for temporary cardiac pacing are: QRS more than 0.2 seconds, Mobitz type II AV block, complete AV dissociation, and torsade de pointes. Significantly impaired conduction or high-degree AV block unresponsive to sodium bicarbonate therapy, complete AV dissociation, and torsade de pointes are indications for insertion of a cardiac pacemaker. (c) Ventricular dysrhythmias unresponsive to lidocaine with hypotension are an indication for cardioversion. (d) Treat torsades de pointes with magnesium sulfate (Formulary table) Atrial and ventricular overdrive pacing to shorten the QT interval may be needed. Monitor serum magnesium levels. (e) Hypotension may require Trendelenburg positioning, intravenous fluids, vasopressors (norepinephrine) and hemodynamic monitoring. An intra-aortic balloon pump has been successful in one case. (6) Glucagon may be useful for its chronotropic and inotropic actions, but it has not been scientifically evaluated. (Formulary table). (7) Acid diuresis has not been shown to be clinically useful. (8) Extracorporeal measures have not been reported useful. (9) Amblyopia management: Stellate ganglion block, retrobulbar injections of vasodilators, anterior chamber paracentesis are all ineffective and not recommended since the cause is a direct toxic action not arterial spasm. Permanent visual defects occur in 5 to 27%. Laboratory: The therapeutic plasma levels of quinine are about 5 to 7 µg/mL, tinnitus may begin at levels more than 5 µg/mL, cinchonism develops at levels of more than 8 µg/mL, visual impairment more than 10 µg/mL, cardiotoxicity occurs more than 16 µg/mL, and in 87% of patients with levels more than 20 µg/mL blindness. Monitor vital functions, electrolytes, serum glucose, liver/renal function tests, CBC and platelet count and ECG monitoring. A 12-lead ECG should be obtained. Obtain a chest radiograph, arterial blood gases if depressed level of consciousness or serious dysrhythmias. If signs of DIC monitor platelets, split fibrin degradation products and fibrinogen. Disposition: Hospitalize all patients with ingestion of a toxic amount or toxic plasma concentration. Intensive care monitoring and cardiac consult is required in any symptomatic patient with a severe overdose since ventricular pacing may be needed. Patients that remain asymptomatic for 6 hours postingestion with normal ECG can be discharged. Salicylates (Acetylsalicylic acid, ASA) salicylic acid (SA) These are used in relief of mild to moderate pain, as an antipyretic and as preventive of myocardial infarction. Toxic mechanism: The primary toxic effects of salicylate include: (1) excess salicylate directly stimulates the medullary chemoreceptor trigger zone and respiratory center (nausea and vomiting and hyperventilation) and further increases the P CO2 production, which stimulates the respiratory center (hyperventilation) resulting in respiratory alkalosis and compensatory metabolic acidosis (bicarbonate, sodium and potassium are lost in compensation for the alkalemia, alkalemia also results in decreased ionized calcium); (2) uncoupling of mitochondrial oxidative phosphorylation results in increasing the metabolic rate, oxygen consumption and heat production; (3) inhibition of the Kreb's cycle enzymes results in disturbances in carbohydrate and lipid metabolism producing a ketoacidosis, metabolic acidosis, and an anion gap; (4) inhibition of platelet aggregation (by ASA but not other salicylates), prolongation of the prothrombin time and interference with coagulation factors (GI bleeding); and (5) damages hepatocyte and increases plasma enzyme activity. Toxic dose: (Table 144A.35A) Acute intoxication occurs in adults from amounts usually more than 10 grams (thirty 325-mg adult aspirins), and in children over 150 mg/kg (two 81-mg tablets/kg or one-half 325-mg tablet/kg). Acute salicylate plasma concentration (SPC) over 300 µg/mL (30 mg/dL) are associated with toxicity. Chronic intoxication, because of cumulative kinetics occurs when more than 100 mg/kg over 24 hours have been administered for more than 2 to 3 days. Methyl salicylate 98 to 99% (oil of wintergreen, is the most toxic salicylate product and is usually found in topical preparations such as Ben-Gay. One milliliter of oil of wintergreen equals 1.4 g of salicylate and one 5-mL teaspoonful equals 7.5 g of salicylate (21.7 adult aspirins [325-mg each]) or 35 0 mg/kg of salicylate for a 20 kg 5-year-old child. Fatalities have been noted with 4 mL of 98% in a child and in 30 mL in adults. Kinetics: ASA has a pKa of 3.5 and SA 3.0). ASA is absorbed from stomach and small bowel. Dermal absorption can also occur. Onset of action is significant in 30 minutes. Methylsalicylate and effervescent tablets are absorbed more rapidly and may produce symptoms earlier than regular tablet forms. Detectable plasma salicylate serum concentrations occur within 15 to 30 minutes and peak level occurs in 30 minutes to 2 hours (15 to 20 mg/dL) but may be delayed 6 to 12 hours in overdose with enteric coated, sustained-release preparations or concretions. Serum levels with large doses may continue to rise because of inhibition effect on gastric emptying. Duration of therapeutic of action is 4–6 hours but this is markedly prolonged in overdose. Half-life for ASA is 20 minutes (rapid hydrolysis by esterases in GI mucosa, plasma, liver and RBCs) and SA is 3 to 6 hours (at therapeutic doses) to 12 to 36 hours (at overdoses). The Vd is 0.15 to 0.2 L/kg for ASA and 0.13 L/kg for SA. This Vd increases up to 0.35 L/kg or more as serum salicylate levels increase, protein binding decreases (increases free salicylate), acidosis develops. Protein binding (PB) is up to 99% for SA at physiologic pH at SPC of 100 µg/mL (10 mg/dL) and falls to 70% or less at SPC of 40 mg/dL. PB is mainly to albumin. Elimination includes Michaelis-Menton hepatic metabolism by glycine conjugation to salicyluric acid (75% saturable), glucuronyl transferase to salicyl phenol glucuronide (10% saturable) and salicyl aryl glucuronide (5% saturable), nonsaturable by hydrolysis to gentisic acid (1%), and 10% excreted unchanged. In kidneys SA undergoes glomerular filtration (nonionized) and tubular secretion in proximal tubules (ionized) and passive reabsorption in the distal tubules (nonionized). Renal excretion is enhanced by alkaline urine which converts salicylate into ionized nondiffusible form. Manifestations: Ingestion of concentrated topical salicylic acid preparations (Compound W) can cause caustic injury to the GI tract ( Table 144A.35a). Acute ingestion SPC less than 35 mg/dL no symptoms. (1) Mild manifestations (SPC 35 to 70 mg/dL) are similar to cinchonism overdose of quinine. Tinnitus (may occur at therapeutic doses) and deafness can occur in patients with previous normal hearing at salicylate plasma concentration (SPC) 20 to 30 mg/dL (200 to 300 µg/mL). Nausea and vomiting is usually present within 3 to 8 hours after ingestion of single overdose. Vomiting may occur immediately due to direct gastric irritation. Hyperventilation occurs with increases in both rate (tachypnea) and depth (hyperpnea an increase in tidal volume) at SPC of 350 µg/mL (35 mg/dL) which may be subtle results in decreased P CO2 and respiratory alkalosis. Some patients have vertigo, headache, deafness, and mental confusion or lethargy. Diaphoresis is prominent. (2) Moderate manifestations (SPC 35 to 70 mg/dL) occur at 12 to 24 hours and produce more serious metabolic disturbances resulting in respiratory alkalosis (20%), and sometimes a metabolic acidosis (20%) and mild dehydration. In children under 4 years of age the initial respiratory alkalosis will usually change to predominantly metabolic or mixed metabolic acidosis and respiratory alkalosis within a few hours, and almost all children under 1 year present with metabolic acidosis, because they have little respiratory reserve. Metabolic acidosis increases the severity of the salicylate intoxication. In older children and adults it is often a respiratory alkalosis with increased anion gap metabolic acidosis (lactate and organic acids). Metabolic disturbances may have been increased or decreased glucose, hypokalemia, increased BUN, creatinine, and lactate. Thrombocytopenia and leucocytosis may be present. Confusion, disorientation, hallucinations, mild hypotension, and convulsions may occur. (3) Severe intoxication (SPC 70 to 100 mg/dL) develop 24 hours after acute overdose. In addition to the findings of mild and moderate poisoning, have prominent central nervous system (CNS) manifestations both seizures and coma at SPC >800 µg/mL (80 mg/dL). Altered consciousness is the most important sign of severe intoxication. Metabolic disturbances include metabolic acidemia and aciduria. (increase in non-ionized salicylate which permits it to transverse into the brain. These levels of salicylate may produce pulmonary edema in the elderly. (4) Death (SPC more than 100 mg/dL) is caused by CNS failure or cardiovascular collapse. (5) Chronic salicylism (SPC no correlation) is more serious than acute intoxication and the SPC does not correlate with the manifestations. The diagnosis is often delayed because it is unrecognized. The victims are often young children and the elderly adults. A SPC within the therapeutic range does not exclude chronic salicylism because it may have already distributed to the tissues. The mortality is as high as 25% ( Table 144A.35B). Chronic salicylism is associated with exaggerated CNS findings (lethargy, confusion, drowsiness, slurred speech, hallucinations, delirium, dementia, memory loss, papilloedema, bizarre behavior, agitation, encephalopathy, seizures, coma), hemorrhagic manifestations, renal failure, pulmonary and cerebral edema, especially in the elderly. Metabolic picture is often hypoglycemia and mixed acid-base derangements. A chronic serum salicylate level more than 60 mg/dL accompanied by metabolic acidosis is very serious. In children chronic salicylate poisoning may mimic Reyes syndrome.

Table 144A.35A. Amount of Aspirin Ingested: Deposition and Manifestations

Table 144A.35B. Effects of Chronic and Acute Salicylate Toxicity

Management: Treatment is started based on clinical and metabolic findings not on SPC. ( Table 144A.35C) (1) Establish and maintain vital functions. Intubation and assisted hyperventilation. Establish urinary output with infusion of fluids (catheterize bladder) and continuously monitoring the urine pH (essential to alkali treatment). If semiconscious or comatose, immediately test for glucose, administer naloxone and thiamine in standard doses. In addition cardiac monitor, pulse oximeter, urinalysis and pH (catheterize bladder), chest radiograph, urgent ABGs, blood glucose (hypoglycemia is more frequent in the young child and chronic intoxications), electrolytes (hyponatremia and hypokalemia frequent), calcium (ionized), magnesium, renal, liver profiles, and coagulation profiles and serial SPCs (because of delayed absorption). A toxicology screen for excluding co-ingestants. Test vomitus and stool for occult blood. Bismuth and magnesium salicylate preparations may be radiopaque. Do not wait for 6-hour salicylate level to start treatment of symptomatic patients. If hemodialysis may be required, suggest immediate consult with nephrologist. (2) GI decontamination. Gastric lavage and activated charcoal may be useful if more than or equal to 150 mg/kg or 10 g ingested is useful up to 12 hours postingestion because factors that delay absorption (food, enteric-coated tablets, other drugs); pylorospasm may delay emptying; and concretions may form. “Its never too late to aspirate (the stomach) with salicylate.” MDAC should be administered every 4 hours until stools are black. Concretions may be removed by lavage, WBI, endoscopy, or gastrostomy. (3) Fluids and electrolytes. (A) Shock (hemodynamically unstable). If clinical signs of shock, establish perfusion and vascular volume. Therapy is initiated with 0.89% saline 20 mL/kg in children or 1000 mL in adults, repeat if clinically indicated until correction of shock. Establish perfusion and urine flow of 2 mL/kg per hour. Plasma or albumin may be required at doses of 10 to 15 mL/kg. This is often administered within 20 to 30 minutes. Furosemide may be added to establish urinary flow. (B) Dehydration in hemodynamically stable patients. Fluid resuscitation. All moderate and severe intoxications require hydration and alkalinization. Caution: Fluids and bicarbonate are potentially dangerous in patients at high risk for pulmonary and cerebral edema such as chronic salicylism. Do not allow the blood pH to exceed 7.55 because alkalemia shifts the oxygen dissociation curve to the left, alkalosis decreases ionized calcium and can produce tetany, potassium moves intracellularly and convulsions may occur. If tetany develops discontinue the bicarbonate therapy and administer calcium gluconate. (1) Adult patients with clear physical signs (hyperventilation, acidosis, dehydration) and laboratory findings of salicylism but no evidence of cerebral or pulmonary edema should receive a bolus 1 to 2 mEq/kg of sodium bicarbonate followed by an infusion of 1 L D5W containing 133 mEq (3 ampuls of 44.6 mEq each) of sodium bicarbonate (NaHCO 3) to each liter. Children in this category should receive a bolus of 1 to 2 mEq/kg followed by 1 to 2 mEq/kg of NaHCO 3 in 20 mL/kg D5W over 30 to 60 minutes. (2) The rate and amount of the initial infusion is 2 to 3 times the maintenance or 200 mL/h in adults or 5 to 8 mL/kg per hour in children to produce a urinary output of at least 2 mL/kg per hour and a urine pH more than 7.5 to achieve maximum salicylate ion trapping and excretion. Most authorities feel a diuresis is not as important as the alkalinization. Total fluid loss in salicylism ranges from 2.5 to 5 L/m 2 per day but carefully monitor for fluid overload because of inappropriate secretion of the antidiuretic hormone (SIADH), cerebral edema, and pulmonary edema. (3) In patients with mild intoxication with subtle physical signs and subtle laboratory findings (not acidotic and urine pH more than 6) administer D5 in 0.45% saline at maintenance with 25 mEq/L sodium bicarbonate to replace ongoing renal losses. (B) Sodium bicarbonate is administered to alkalinize the urine to pH 7.5 to 8.0. Indications include symptoms, acidosis and elevated salicylate level more than 30 mg/dL within 18 hours of acute overdose. Contraindications include cerebral or pulmonary edema, oliguric renal failure, and blood pH more than 7.55. (1) If acidotic additional bicarbonate may be required. If pH less than 7.15, administer 1 to 2 mEq/kg NaHCO 3 every 1 to 2 hours to keep urine pH more than 7.5 to 8.0. Avoid a blood pH below 7.40. (2) Large amounts of bicarbonate may be given to patients with severe salicylism and respiratory alkalemia with blood pH 7.45 to 7.50 without necessarily increasing the blood pH. Patients' with salicylism often have a significant base deficit in spite of the elevated serum pH. However the blood pH and sodium must be carefully monitored. (3) Alkalinization of the urine in children may be a difficult problem because of the organic acid production and hypokalemia. (4) The duration of alkalinization and the fluid therapy should be continued until the patient is asymptomatic for several hours. (C) Potassium is added 30 to 40 mEq/L to the infusion when patient voids and renal flow has been established. In some cases potassium may be needed in excess of 40 mEq/L when alkalinizing salicylate intoxicated patients. When the serum potassium is below 4.0 mEq/L add 10 to 20 mEq/L over the first hour. If hypokalemia less than 3 mEq/L and flat T waves and “U” waves administer 0.25 to 0.5 mEq/kg up to 10 mEq/h via peripheral vein or 20 mEq/h for 2 hours via a central vein and under ECG monitoring. Recheck potassium after each dose. A paradoxical urine acidosis (acid urine with normal or elevated blood pH) occurs and usually indicates potassium may be needed not additional alkali. Potassium reabsorption occurs at the expense of the hydrogen ion therefore it may be impossible to alkalinize the urine until the potassium deficit is corrected. (D) Convulsions: Treat with diazepam, but exclude hypoglycemia, hypocalcemia and cerebral edema or hemorrhage with CT scan. If tetany, give 0.1 to 0.2 mL/kg 10% calcium gluconate. (E) Pulmonary edema management: fluid restriction, osmotic diuresis, and PEEP. (F) Cerebral edema management: fluid restriction, hyperventilation, mannitol, furosemide, dexamethasone should be considered. (G) Administer Vitamin K-1 parenterally to correct an increased prothrombin time (PT) and coagulation abnormalities especially in chronic salicylism. However, if active bleeding administer fresh plasma and platelets as needed. (H) Hyperpyrexia is managed by external cooling measures (cooling blankets and sponging) not antipyretics. (I) Extracorporeal measures. Hemodialysis is the choice method, because although hemoperfusion is useful it does not correct the acid-base, electrolyte and fluid disturbances. The indications for hemodialysis include: (1) Acute poisoning with SPC more than 100 to 120 mg/dL with severe acidosis 6 hours after starting appropriate therapy. (2) Chronic poisoning with severe toxicity or underlying cardiopulmonary disease with SPC more than 40 to 60 mg/dL accompanied by acidosis, confusion, lethargy especially in elderly and debilitated. (3) Impairment of vital organs of elimination (liver or kidneys) of intoxicant, CHF, coagulopathy, cerebral or pulmonary edema. (4) Clinical deterioration in spite of supportive care and urinary alkalinization, i.e., persistent unresponsive coma and seizures. (5) Severe persistent acid-base or electrolyte disturbances despite appropriate corrective measures. (J) Complications of treatment include excessive alkalemia fluid overload, hypoglycemia, hypokalemia, hypernatremia, cerebral, and pulmonary edema.

Table 144A.35C. Algorithm of Management of Salicylate Management

Laboratory: (A) Continuous monitoring of the urine output, urine pH and sp gr. Every 1 to 2 hours: SPC, glucose (transient hyperglycemia occurs and in small children hypoglycemia), electrolytes including ionized calcium, magnesium and phosphorous, anion gap, ABGs including blood pH, pulse oximeter, and urine pH. Daily—BUN, creatinine, liver function tests, prothrombin time. Ferric chloride (FeCl 2) test (2 to 3 drops of 10% FeCl 2 plus 1–mL urine turns purple if salicylates are present. This is nonspecific that gives a positive test for ketones. Boiling the urine removes the ketones) (B) The salicylate plasma concentration (SPC). The Done nomogram has been used as a predictor of the expected severity following acute single ingestion. The Done nomogram is not useful in chronic intoxications; in methyl salicylate, phenyl salicylate, or homomethyl salicylate intoxications. The blood sample for a SPC for use in the Done nomogram should be obtained 6 hours or more after ingestion. Immediate treatment should be started based on clinical, metabolic findings and not on the SPC. SPC may be quite high in the first 6 to 18 hours after an acute overdose without major clinical or metabolic manifestations. Diflunisal will give falsely high salicylate plasma concentrations. Disposition: Patients that are asymptomatic should be monitored for a minimum of 6 hours and those who remain asymptomatic with SPC less than 35 mg/dL may be discharged following psychiatric consultation, if indicated. Patients with acute ingestion and SPC less than 60 mg/dL and mild symptoms may be able to be treated in the emergency department. Patients with SPC below the toxic range should be retested if a potentially toxic dose is ingested or if there are clinical or metabolic manifestations. Patients with enteric coated tablets or massive overdose where there may be suspicion of concretion should be monitored longer. All infants and young children and those with moderate salicylism may be admitted for careful monitoring for deterioration. Severe salicylism requires admission to ICU. Persistent vigorous treatment of salicylate overdose is essential because recovery has occurred despite decerebrate rigidity. Chronic salicylate intoxicated patients accompanied by a level more than more than 40 mg/dL, acidosis and altered mental state should be admitted to ICU ( Table 144A.35C). Sedative Hypnotics, Nonbarbiturate and Nonbenzodiazepines (Table 144A.36)

Table 144A.36. Toxicity and Kinetics of Nonbarbiturates Nonbenzodiazopine Sedative-Hypnotics

This category includes chloral hydrate (Aquachloral, Noctec and others), ethchlorvynol (Placidyl), glutethimide (Doriden), meprobamate (Equinal, Miltown), methaqualone (“Quaaludes, Ludes, love drug”), methyprylon (Nodular). Methaqualone was made a schedule I drug in 1982. Toxic mechanism: Direct CNS Depressants by differing mechanisms. Most of these agents react with the GABA receptor complex or the other neurotransmitters. Toxicity is increased if taken with other CNS depressants and ethanol. These agents cause tolerance to develop, and dependency and withdrawal symptoms including convulsions. Toxic dose: The therapeutic doses in table are the hypnotic amounts. Approximately 3 to 5 times the hypnotic dose is the toxic dose. Coma dose is estimated at 10 times the hypnotic dose and more than 10 times the listed hypnotic dose is potentially life-threatening amount. Kinetics: The majority of these agents are lipophilic, have rapid GI absorption, large volume distribution, and long elimination half lives that may be significantly increased in overdose. Their route of elimination is primarily hepatic and they may induce hepatic enzyme elevation. These agents should not be used in patients with porphyria. (e.g., ethchlorvynol, meprobamate, methyprylon). Manifestations: All these agents may produce coma, respiratory depression, psychologic and physiologic withdrawal, hypotension, and hypothermia (except glutethimide, which may produce hyperthermia). CNS: depression with drowsiness, ataxia, nystagmus, vertigo, dysarthria, progressing to usually a flaccid type coma with fluctuations in levels of consciousness. Hypothermia accompanies the CNS depression. Some of these agents have anticholinergic actions, e.g., glutethimide. Ingestion of other CNS depressants act synergistically, i.e., ethanol. CV: Respiratory arrest and aspiration pneumonia. Depress cardiac contractility and produce hypotension. Pulmonary edema is a major complication. GI: Decrease gastric motility, some agents have anticholinergic effects (glutethimide). Concretions develop with some agents (meprobamate, glutethimide) and prolong the effects of the medication. Dermatology: Bulla may develop on the skin. (e.g., ethchlorvynol) Abstinence syndrome: Tolerance and dependency develop and abstinence produces severe effects including symptoms similar to delirium tremors and seizures. The clinician must consider withdrawal which may develop in the course of management. Management: (1) Establish and maintain vital functions with intubation and ventilator therapy, and if necessary with continuous positive airway pressure (CPAP) for adult respiratory distress syndrome. Establish intravenous access. (2) GI decontamination. In general vomitus induction carries the risk of aspiration. Gastric lavage with airway control up to several hours postingestion may be beneficial. Administer AC. (3) Hypotension requires careful management with fluids because of the danger of pulmonary edema. The early use of vasopressors may have to be considered because of the danger of fluid overload. (4) Extracorporeal measures such as charcoal hemoperfusion or hemodialysis should be considered in patients who are severely intoxicated, or fail to respond to good supportive care and whose intoxication is life-threatening. Specific Managements: (1) Chloral hydrate (CH): The distinguishing features include a “pear-like odor” an ability to produce dysrhythmias, a caustic effect, and its late hepatotoxicity. Ethanol potentiates by inducing the formation of toxic metabolite, trichlorethanol. The management includes cautions GI decontamination if ingested over 50 mg/kg or 2000 mg in adults. Avoid emesis because of caustic action and rapid onset of action within 30 to 60 minutes. Because of the corrosive effects cautions GI decontamination by lavage. A small flexible lavage tube may be inserted cautiously when liquid preparations have been ingested. Avoid gastric lavage if drooling or dysphagia and consider endoscopy. Administer activated charcoal although there is no scientific data on efficacy. Avoid the use of epinephrine and catecholamines that may produce dysrhythmias. Propranolol, 0.1 mg/kg in 1-mg increments, appears to be more effective than lidocaine for ventricular dysrhythmias. Charcoal hemoperfusion may effectively remove chloral hydrate and its metabolite in patients who fail to respond and have potentially fatal plasma levels (250 µg/mL or higher). Hemodialysis may be ineffective because of lipid solubility. (2) Ethchlorvynol: (introduced in 1950s and still in use today) is a tertiary alcohol. Its distinguishing features include the vinyl-shower curtain odor, pink color to gastric contents, hypotension, tachycardia, prolonged toxicity and tendency to produce pulmonary edema. The management includes GI decontamination up to several hours postingestion but avoid emesis. Charcoal hemoperfusion is preferred when other measures fail in a life-threatening situation (ingestion of over 10 grams or 100 mg/kg, with serum levels of over 100 µg/mL in the first 12 hours or 70 µg/mL after 12 hours in patients with prolonged life-threatening coma). Institute external rewarming if temperature is below 32°C (89.6°F). (3) Glutethimide: introduced in 1954, is lipophilic. Its features include anticholinergic effects, sudden apnea, and prolonged coma and convulsions. A combination of glutethimide and codeine (Tylenol #4 called “loads” is used as a substitute for heroin. The management includes GI decontamination up to 6 to 12 hours postingestion. AVOID emesis because of rapid onset coma and apnea, especially if suspicion of “loads.” The drug has poor solubility in aqueous lavage solutions therefore use AC/cathartic if bowel sounds are present. MDAC is recommended. Concretions may develop. If altered mental status consider “loads” and administer naloxone. Hypotension may be better treated with

vasopressors rather than fluids because of the danger of pulmonary edema. Extracorporeal methods (hemoperfusion and hemodialysis) are considered ineffective because of extensive Vd and are not routinely recommended. Charcoal hemoperfusion may be considered in life-threatening protracted coma that has not responded to intensive supportive therapy in patients who have ingested >10 grams and have a plasma level of more than 30 µg/mL. Treat hyperthermia with external cooling. Treat increased intracranial pressure with hyperventilation and mannitol. (4) Meprobamate: an anxiolytic agent of 1955 still in use today, it is a myocardial depressant that can progress to pulmonary edema with excess fluids. It's features includes prolonged cyclic coma, and ability to form concretions. Institute aggressive GI decontamination. If alert and asymptomatic, induce emesis within minutes after ingestion (e.g., at home). This is followed by gastric lavage and AC/cathartic in emergency department up to 12 hours postingestion followed by MDAC. Persistently elevated plasma concentrations and prolonged coma may indicate the presence of a concretion. Consider contrast media examination of the GI tract if present. If concretions are found they require dissolution by breaking up, whole bowel irrigation, endoscopic or rarely surgical removal. Fluid resuscitation should be used with caution in treating hypotension because meprobamate depresses cardiac function. Positive inotrophic agents (dobutamine) may be necessary to maintain adequate perfusion without the risk of excess fluid and pulmonary edema. Charcoal hemoperfusion, hemodialysis and continuous arteriovenous hemoperfusion have been used successfully in life-threatening intoxication. They should be considered if failure to respond to intensive supportive therapy, prolonged coma with life-threatening complications (e.g., hypotension), ingestion of over 30 g or blood concentrations greater than 100 µg/mL. Although there is no controlled studies based on the low protein binding (minimal), and small volume distribution (0.75 L/kg) they are expected to be able to remove significant amounts. (5) Methaqualone: is a drug of the 1970s made a schedule I drug in 1982. Its features include sedation and hypotension with hypertonicity (hyperreflexia, clonus, fasciculations) and convulsions. Bleeding may occur because of thrombocytopenia, prolonged prothrombin time and transient elevation of the liver enzymes. The management includes GI decontamination up to 12 hours postingestion. Ipecac-induced emesis in the first few minutes at home in the alert, asymptomatic patient and/or gastric lavage with airway protection in the comatose patient followed by AC/cathartic. Convulsions are managed with anticonvulsants. Extensive bleeding may require platelet transfusion, vitamin K 1, and fresh blood transfusions. Monitor the platelet count and prothrombin time, monitor ECG. Some have advocated charcoal hemoperfusion at blood levels greater than 40 µg/mL but is not proven. Fatalities are rare. (6) Methyprylon: introduced in 1950s, is a piperidinedione derivative. Its features include mioitic pupils, hyperactive reflexes and convulsions. Management includes GI decontamination with induced emesis in the alert asymptomatic patient within minutes and/or gastric lavage with airway protection if comatose. AC/cathartic should be administered and repeated every 4 hours. Hypotension may require vasopressors of the alpha-adrenergic variety (e.g., norepinephrine. The hypotension usually does not respond to position or fluids alone. This is a hemodialyzable drug, but dialysis usually is not necessary. Fatalities are rare. Laboratory: Monitor CBC, electrolytes, blood glucose, ethanol, BUN, creatinine, ABG if comatose, chest radiograph (aspiration). The plasma concentrations are usually not important in clinical decision making, however, they may help to confirm the clinical impression and diagnosis. Disposition: Although the time of peak absorption frequently occurs within 6 hours with these agents, patients should be admitted and observed for at least 24 hours because of the potential of concretions or delayed absorption in overdose. Strychnine Strychnine is a bitter colorless, odorless, white powder, which is the principal alkaloid from the dry seeds of the Strychnos nuxvomica, a tree native to India. It is primarily available as a rodenticide only to licensed exterminators and used in treatment of nonketotic hyperglycemia. It was used historically in tonics and laxatives. It was also used as an adulterant of “street drugs” for its bitter taste, particularly opioids, and cocaine. Toxic mechanism: Antagonizes glycine, the postsynaptic inhibitory neurotransmitter. It blocks glycine's uptake at the spinal cord, brain stem, and higher brain receptor sites which results in neuronal hyperexcitability and simultaneous contraction of flexor and extensor skeletal muscle groups. Toxic dose: The approximate toxic amount is 5 to 10 mg or less than 1 mg/kg. The potentially fatal amount is as little as 15 to 30 mg in adults, or 1 to 2 mg/kg. Serum strychnine concentrations range from 0.5 to 90 µg/mL in fatal exposures. Any dose of strychnine is considered life-threatening. Kinetics: Strychnine has rapid GI and nasal mucosal absorption. Dermal and mucosal absorption has been reported. Oral onset is 5 to 60 minutes after ingestion and as early as 5 minutes after inhalation or parenteral routes. Vd is 13 L/kg and low PB. The T1/2 in one overdose case that survived was 10 hours. The route of elimination is by hepatic microsomal oxidation by the P450 enzyme to unknown metabolites. It has been found in the urine up to 48 hours after a 700-mg dose. Only 5 to 20% is excreted unchanged. Manifestations: Hyperacusis is often the first sign. Any external visual, auditory or tactile stimuli may precipitate muscle contraction. (1) Mild cases: Muscle stiffness and painful cramps precede generalized muscle contractions. Face stiffness and grimace (trismus and “risus sardonicus” or the sardonic grin). Muscle contractions are triggered by any stimuli. (2) Moderate cases: extensor muscle thrusts and opisthotonos. (3) Severe cases: Tetanic convulsions with opisthotonos and jaw tightly clenched, last 13 seconds to 2 minutes and occurs at 10 to 15 minutes intervals. The muscle contractions resemble tonic phase of convulsions but consciousness is maintained. Patients seldom survive more than 5 to 10 convulsions. The patient usually remains fully conscious during the seizures. (4) The metabolic consequences include lactic acidosis, hyperthermia, elevated creatinine kinase, rhabdomyolysis and myoglobinuria, renal failure, hepatic necrosis, and hypoxia terminally. (5) The mentation remains normal until hypoxia supervenes which is an important differential. Death is caused by respiratory arrest or secondary to hyperthermia and can occur within 1 to 3 hours postingestion. (6) Differential of rigidity includes black widow spider bite, malignant neuroleptic syndrome, serotonin syndrome, tetany and tetanus. Tetanus prevents glycine release from nerve endings. It has a slow onset, history of lack of immunization, and history of injury. Management: (1) Maintain airway and ventilation for respiratory depression. Control muscle contractions with diazepam intravenously and avoid stimulation. In severe cases use neuromuscular blocking agents to produce complete muscle paralysis. Treat hyperthermia. (2) Emesis is contraindicated. Gastric aspiration and lavage may be used only after the contractions are well controlled. AC should be given with a cathartic as soon as possible after contractions controlled and repeated every 4 hours. MDAC has not been studied. (3) After contractions are controlled monitor hyperkalemia, metabolic acidosis, CPK for rhabdomyolysis, the urine for myoglobinuria (myoglobinuria present administer fluids and alkalinize). Laboratory: Strychnine blood concentration is not helpful in management. Toxic concentration is 1.6 mg/L at 4 hours, fatal concentration range is 0.5 to 6.1 mg/L. Monitor after contractions are well controlled: arterial blood gases, oximetry, serum lactate, electrolytes, blood glucose, urinalysis, blood calcium, creatine kinase liver function tests, renal function tests, examine urine for myoglobinuria. Disposition: Patients with suspected exposures should be observed for at least 6 hours. Any symptomatic patient (hyperreflexia, rigidity, hypertension, tachycardia) should be admitted to an ICU. Symptoms subside within 6 hours but hyperreflexia, stiffness and muscle soreness may last 7 days. Tear Gas (lacrimators) Types commonly used are: (1) CS (orthochlorobenzylidene malonitrile) CS is the most widely used lacrimator. It is a white, crystalline, water insoluble powder with a pepperlike odor. It is 10 times more potent than CN or CR as an irritant but produces less systemic toxicity. (2) CN (chloroacetophenone 1%). Mace is 1% chloroacetophenone in kerosene, trichlorethane and freon. It is slower acting and less potent than CS. CN is fine white crystals at room temperature with the odor of apple blossoms. Five deaths have been reported when used in confined space. (3) CR (Dibenzo-1,4-oxazepine) CR is a pale yellow solid. It is slower acting and less potent than CS. (4) Chloropicrin (trichloronitromethane, choking gas) is an oily colorless or yellow liquid with a pungent odor. (5) Capsaicin (1%) is extracted from the Capsaicin fruits (cayenne pepper). Toxic mechanism: CS and CR reacts with the sulfhydryl (SH) group enzymes. Pain is produced by chemical action on the cutaneous nerve and ocular nerve endings. CN inhibits the sensory nerve SH group enzymes. Chloropicrin is an alkylating agent that combines with the SH groups. It has a halogen group and therefore may undergo a photochemical transformation to phosgene. Toxic dose: CS concentrations of 0.0045 mg/L will give respiratory symptoms and 0.85 mg/L for 10 minutes can produce fatalities. It has been estimated that a 250-g grenade of CS in 20 square meter shelter for 1 hour would produce fatal pulmonary injury in 50%. The lethal dose of 50% of healthy adults is 25,000 to 150,000 mg/m 3 per minute. CN: ACGIH TLV 0.05 ppm, IDLH 100 mg/m3. Irritation occurs near TLV and are adequate warning properties. CR: is less potent than CS. Kinetics: Symptoms peak in few minutes and usually abate in 1 to 2 hours. CS: is rapidly hydrolyzed with a half-life of 15 minutes. However, some types of CS may persist for much longer periods of time. For instance, CS1 remains active for 5 days and CS2 remains active for 45 days in the presence of water. CN: does not persist in the environment. CR: is slower acting than CS. Manifestations: Mucosa of the nose and eyes: Ocular symptoms include burning and blephospasm which usually lasts 5 to 10 minutes, lacrimation lasts 10–30 minutes and eyelid edema lasts 1 hour. Erythema of the conjunctiva lasts 1 hour unless there has been intense rubbing. Occasionally symptoms last for 24 hours. Nasal symptoms are burning and rhinorrhea. Inhalation may cause coughing and mild dyspnea. The inhalation of large amounts may cause retching and vomiting if secretions are swallowed. On rare occasions inhalation of large amounts in confined spaces has produced pneumonitis requiring prolonged hospitalization and fatal pulmonary edema with onset 3 hours postexposure. Dermal: Contact with the moisture on the skin causes burning sensations. If used in hot humid climates these agents may cause first and second degree skin burns. The skin lesions heal very slowly. Systemic manifestations may be delayed. They occur when used in high concentrations in closed spaces. There are reports of rare cases of hepatitis and nephritis in those exposed to very high concentrations. Management: (1) Establish and maintain vital functions by properly protected personnel. Establish airway, administer 100% humidified oxygen and if necessary, assisted ventilation. Bronchodilators may be used if bronchospasm is present. If dyspnea or bronchospasm persist over 1 to 2 hours obtain chest radiographs arterial blood gases and spirometry. (2) Protect medical personnel with gowns, goggles, gloves and masks. These agents are solids and may linger on clothing and in hair causing continued exposure. Therefore, remove contaminated clothes immediately, seal in plastic bags, label and handle as hazardous material. (3) Decontaminate skin, hair and nails with 10% sodium bicarbonate. If burning persists apply soaks of 1:40 aluminum acetate (Burow's solution). Skin lesions are treated as burns. Do not use military towelettes containing chloramine and phenol. (4) Ocular care: Irrigate with saline or water for at least 15 minutes. Fluorescein stain of the cornea and ophthalmologic consultation is indicated if ocular symptoms persist. Anesthesia ointment and eye patching may be needed. Laboratory: In cases of high exposure or ingestion consider obtaining a blood cyanide concentration. Disposition: Symptoms peak in few minutes and usually abate in 1 to 2 hours. All persons exposed to high

concentrations in confined space should be observed for several days because of delayed pulmonary edema. Theophylline Theophylline is a methylxanthine alkaloid similar to caffeine and theobromine. It is used in the treatment of asthma, pulmonary edema, chronic obstructive pulmonary disease and neonatal apnea. Toxic mechanism: Although phosphodiesterase inhibition of the breakdown of cyclic adenosine monophosphate (cyclic AMP) was considered to be the primary mechanism of theophylline effects, it is now unclear. Adenosine receptor antagonism is the favored theory. Theophylline causes the following effects in overdose: stimulates the CNS respiratory and emetic centers; reduces the seizure threshold; positive inotropic and chronotropic effects; acts as a diuretic which lowers potassium; relaxes smooth muscle; increases serum catecholamines and prolongs their effects; increases striated muscle contractility including enhanced contraction of the muscles of the diaphragm; causes peripheral vasodilation, but cerebral vasoconstriction; increases gastric secretions and increases GI mobility; increases lipolysis, glycogenolysis, and gluconeogenesis which increase blood glucose. Toxic dose: Loading dose is 5.6 mg/kg, maintenance 0.2 to 0.8 mg/kg. Acute, single dose more than 10 mg/kg yields mild toxicity. Greater than 20 mg/kg, moderate manifestations and fatalities occur at more than 8 mg/kg in children, or with 100 mg intravenously rapidly. A single dose of 1 mg/kg produces a theophylline plasma concentration (TPC) of approximately 2 µg/mL. Therapeutic range usually is 10 to 20 µg/mL (Table 144A.37A). Theophylline plasma concentration (TPC)

Kinetics: pKa is 9.5. Absorption from stomach and upper small intestine is complete and rapid with onset 30 to 60 minutes. Peak TPC levels occur within 1 to 2 hours after ingestion of liquid preparations; 2 to 4 hours after regular tablets; and 7 to 24 hours after slow-release (SR) formulations. Vd 0.3 to 0.7 L/Kg, PB 40 to 60% mainly to albumin and low albumin increases free active theophylline. Overdose increases the half-life. Elimination: Hepatic metabolism, 90% by demethylation and oxidation to active metabolite 2-methyl xanthine. Half-life varies 3.5 hours average in a child and 8 to 9 hours in an adult (range from 3 to 9 hours). T1/2 is shorter in smokers or if taking enzyme inducers, e.g., phenytoin. Longer in neonates and young infants (produce caffeine as active metabolite), liver impairment, congestive heart failure, enzyme inhibitors e.g. erythromycin and viral illness ( Table 144A.37B). Only 8 to 10% is excreted unchanged in the urine. Interactions: Many factors increase TPC. See Table 37B: Factors that increase Theophylline plasma Concentration include smoking, newborns, viral illness, influenza vaccination, erythromycin, allopurinol, oral contraceptives, cimetidine, hydrocortisone, and ciprofloxacin. Factors that decrease TPC include phenobarbital, phenytoin, carbamazepine, and primidone. Manifestations: Acute toxicity generally correlates with blood levels; chronic toxicity does not ( Table 144A.37A). (1) Clinical: GI (vomiting, ocasionally hematemesis), CNS stimulation (restless, agitation, muscle tremors, tonic-clonic protracted seizures, coma is rare), cardiovascular (cardiac dysrhythmias at TPC more than 35 µg/mL in patients more than 40 years of age or more than 50 µg/mL in patients less than 40 years of age), transient hypertension at low mild overdoses but hypotension in significant intoxications. The seizures are protracted, repetitive and resistent to anticonvulsants. They may occur 12 to 24 hours postingestion without GI manifestations in slow-release preparations. Rhabdomyolysis and renal failure are occasionally seen. Children tolerate higher serum levels, e.g., more than 100 µg/mL. Cardiac dysrhythmias and seizures occur at higher TPCs, e.g., 80 to 100 µg/mL. Mortality may be as high as 50% when seizures secondary to theophylline intoxication occur. (2) Metabolic: Dehydration, leucocytosis, metabolic acidosis, respiratory alkalosis, rhabdomyolysis, increased serum amylase, hyperglycemia, elevation of amylase, elevation of uric acid, hypocalcemia, hypomagnesemia, hypophosphatemia, and hypokalemia. Hypermagnesemia if magnesium-containing cathartics are used. (3) Chronic intoxication, defined as multiple doses of theophylline over 24 hours is more serious and difficult to treat. It is often due to changes in clearance or overmedication. Acute on chronic intoxication usually follows pattern of acute intoxication. Cardiac dysrhythmias and seizures may occur at TPC 40 to 60 µg/mL (Table 144A.37C). (4) Differences in SR preparations from regular preparations. SR preparations have few or no GI symptoms with large ingestions; peak concentration times may be delayed up to 12 to 24 hours postingestion; and onset of seizures may occur 10 to 12 hours postingestion.

Table 144A.37A. Theophylline Blood Concentrations and Acute Toxicity

Table 144A.37B. Factors that Increase Theophylline Plasma Concentration

Table 144A.37C. Summary of Differences of Acute from Chronic Intoxications

Management: (1) Establish and maintain the vital functions. If coma, convulsions, or vomiting exists, intubate immediately. Any patient with TPC more than 30 µg/mL should be admitted to a monitored bed with seizure and suicide precautions if needed. (2) GI decontamination in acute overdose. Do not induce emesis. (a) Gastric lavage up to 4 hours with regular preparations and up to 12 hours with SR preparations. Test aspirate or vomitus for occult blood. (b) Give AC 1 to 2 g/kg to all patients with TPC more than 30 µg/mL and MDAC 0.5 g/kg every 2 to 4 hours with a cathartic initially (sodium sulfate 25 mg/kg up to 30 g) and daily until TPC are less than 20 mg/mL. Charcoal may be indicated up to 24 hours following ingestion. AC shortens the T1/2 about 50%. (c) WBI, 2 liters of polyethylene-electrolyte solution oral or via nasogastric tube is recommended for special cases including massive overdose, possible concretions, a large amount of SR preparations, intractable vomiting, or severe toxicity with rising TPC despite MDAC. (d) If intractable vomiting occurs administer the antiemetic metoclopramide intravenously over 15 minutes in infants and children 0.1 mg/kg per dose maximum 0.5 mg/kg over 24 hours, in adults 0.15 mg/kg over 5 minutes repeat every 20 minutes to total of 1 mg/kg. Droperidol, 2.5 mg intravenously or 0.05 to 0.1 mg per kg per dose every 6 to 8 hours if needed. Both drugs may cause extrapyramidal symptoms. Ondansetron, 0.15 mg/kg over 15 minutes every 4 hours as needed for a total of 3 doses. It is used as a last resort because it inhibits metabolism of theophylline. (3) Monitor ECG, obtain TPC every 2 to 4 hours until they remain in the therapeutic range. (4) Control seizures, monitor airway, blood pressure, pulse oximeter, and ECG. (a) Benzodiazepines. Lorazepam 0.05 to 0.10 mg/kg intravenous bolus maximum 4 mg repeat as needed; diazepam 0.25 to 0.40 mg/kg intravenous bolus maximum 20 mg. (b) Barbiturates. Phenobarbital 15 mg/kg loading dose at rate of