5 Minute Anesthesia Consult (2013).pdf

The 5-Minute Anesthesia Consult

CHIEF EDITORIAL ASSISTANT Matthew C. Gertsch, MD Resident Physician Department of Anesthesia, Critical Care and Pain Medicine Harvard Medical School Massachusetts General Hospital Boston, Massachusetts EDITORIAL ASSISTANTS J. Scott Bluth Medical Student University of Texas Medical School at Houston Houston, Texas Mark R. Bombulie Medical Student University of Texas Medical School at Houston Houston, Texas Kelly A. Bruno Medical Student The University of North Carolina, School of Medicine Chapel Hill, North Carolina N. Matthew Decker, BS Medical Student Loyola University Chicago Stritch School of Medicine Maywood, Illinois David Frey, DO Resident Physician Department of Anesthesiology and Pain Medicine University of Washington Medical School University of Washington Medical Center Seattle, Washington Megan Dale Henley Medical Student The University of North Carolina, School of Medicine Chapel Hill, North Carolina Thomas J. Hopkins, MD, MMCi Resident Physician

Department of Anesthesiology Duke University School of Medicine Duke University Medical Center Durham, North Carolina Rachel M. Little, MPH Medical Student The University of North Carolina, School of Medicine Chapel Hill, North Carolina Carolyn Mohr, MD Resident Physician Department of Anesthesiology University of Colorado School of Medicine Anschutz Medical Campus Denver, Colorado Olutoyosi Ogunkua, MD Resident Physician Department of Anesthesiology and Pain Management University of Texas Southwestern School of Medicine University of Texas Southwestern Medical Center at Dallas Dallas, Texas Michael J. Oleyar, DO Resident Physician Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Blake W. Perkins Medical Student University of Illinois College of Medicine Peoria, Illinois Matthew M. Peterson Medical Student Tulane University School of Medicine New Orleans, Louisiana Lauren Mai Pieczynski, MD Resident Physician Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania

Philadelphia, Pennsylvaniaz Adam M. Stuart Medical Student Virginia Commonwealth University School of Medicine Richmond, Virginia Lindsay Veit, MD Resident Physician Department of Anesthesiology Rush Medical College Rush University Medical Center Chicago, Illinois CONSULTANT EDITOR Anita Gupta

The 5-Minute Anesthesia Consult Editor Nina Singh-Radcliff, MD

Section Editor Alan J. Kover, MD, PharmD Clinical Assistant Professor Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Associate Editors Kris E. Radcliff, MD Assistant Professor of Orthopedic Surgery and Neurological Surgery Thomas Jefferson University The Rothman Institute Philadelphia, Pennsylvania Emily J. Baird, MD, PhD Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Julie Scott Taylor, MD, MSc Clinical Assistant Professor Department of Anesthesiology Stanford University Palo Alto, California

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Printed in China (or US)? Library of Congress Cataloging-in-Publication Data Singh-Radcliff, Nina.

The 5-minute anesthesia consult / [edited by] Nina Singh-Radcliff. p.; cm. - (5-minute consult)

Includes bibliographical references and index. ISBN 978-1-4511-1894-0 (alk. paper) I. Title. II. Series: 5-minute consult.

[DNLM: 1. Anesthesia-Handbooks. 2. Perioperative Period-Handbooks. 3. Surgical Procedures, Operative-Handbooks. WO 231]

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10 9 8 7 6 5 4 3 2 1

To my parents, Dilip and Madhulika Singh, for their unconditional love and support throughout my life and career and

teaching me by example about kindness, honesty, and dedication. Children cannot choose their parents, but if I had been

given the opportunity, I would choose them. I also need to give a special thanks to Carmen, my first child, who helped me edit the book while in utero. And finally to my husband, Dr. Kris Radcliff, who served as an Associate Editor to this book.

Words cannot convey my gratitude for his contribution to, and support, with this text. I have known Kris for almost one-third of my life and he remains the most intelligent, kind, patient, humble, and wonderful person I know. He still makes my heart flutter when I see him. He is the best thing that has ever happened to me and I am truly blessed to be able to call him my husband and share my life with him.

CONTRIBUTORS Ali R. Abdullah, MBChB

Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Erik E. Abel, PharmD, BCPS Clinical Assistant Professor Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Benjamin Abraham, MD Department of Anesthesiology The Cleveland Clinic Cleveland, Ohio Andaleeb Abrar Ahmed, MBBS, MD, MPH Resident Physician Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Moustafa Ahmed, MD Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Interim Chief, Philadelphia VA Medical Center Philadelphia, Pennsylvania Jane C. Ahn, MD Assistant Professor Department of Anesthesiology and Perioperative Care

University of California, Irvine School of Medicine University of California, Irvine Douglas Hospital Irvine, California Arun Alagappan, MD

Resident Physician Department of Anesthesiology Mount Sinai School of Medicine St. Joseph’s Hospital and Regional Medical Center Paterson, New Jersey Brooke Albright, MD, MAJ, MC

Assistant Professor of Anesthesiology Critical Care Air Transport Team Physician United States Air Force Landstuhl, Germany Tayab R. Andrabi Associate Professor Department of Anesthesiology & Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Jonathan Anson, MD Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania John L. Ard Jr., MD Assistant Professor Department of Anesthesiology New York University School of Medicine NYU Langone Medical Center New York, New York Radha Arunkumar, MD Associate Clinical Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Alan Ashworth, MBChB, FRCA, FFICM

Consultant in Cardiothoracic Anaesthesia and Intensive Care University Hospital of South Manchester Manchester, UK Kalliopi Athanassiadi, MD, PhD

Senior Thoracic Surgeon Department of Surgery University of Athens Medical School Athens, Greece Joshua A. Atkins, MD, PhD

Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Ahmed Fikry Attaallah, MD, PhD Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia John G. T. Augoustides, MD, FASE, FAHA Associate Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Naola Austin, MD Resident Physician Department of Anesthesiology and Pain Medicine University of Washington Medical School University of Washington Medical Center Seattle, Washington Stephen O. Bader, MD

Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia

Sean M. Bagshaw, MD, MSc, FRCPC Assistant Professor Division of Critical Care University of Alberta Edmonton, AB Canada Timothy R. Ball, MD

Assistant Clinical Professor Department of Anesthesiology Texas A&M College of Medicine Scott & White Memorial Hospital Temple, Texas Andrew L. Barker, MD Resident Physician Department of Anesthesiology Texas A&M College of Medicine Scott and White Hospital Temple, Texas Viachaslau Barodka, MD Assistant Professor Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Amy Barulic, BS, MHS Research Assistant Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Colin Bauer, MD Chief Resident Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Shawn T. Beaman, MD Assistant Professor Associate Residency Program Director

Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania John F. Bebawy, MD Assistant Professor of Anesthesiology and Neurological Surgery Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois A. Katharina Beckmann, MD

Fellow, Cardiac Anesthesia Department of Anesthesiology Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois Sascha Beutler, MD, PhD Assistant Professor Assistant Program Director Department of Anesthesiology, Perioperative and Pain Medicine Harvard Medical School Brigham and Women’s Hospital Boston, Massachusetts Dmitri Bezinover, MD, PhD Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Amar M. Bhatt, MD Resident Physician Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Shreyas Bhavsar, DO Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center

Houston, Texas Jeanna Blitz, MD

Assistant Professor Department of Anesthesiology New York University School of Medicine NYU Langone Medical Center New York, New York J. Scott Bluth, BS Medical Student University of Texas Medical School at Houston Houston, Texas Michael L. Boisen, MD Fellow, Cardiothoracic Anesthesiology Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Eric Bolin, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Mark R. Bombulie, BS

Medical Student University of Texas School of Medicine at Houston Houston, Texas James D. Boone, MD Instructor Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois Mary Brady, MD, FASE Assistant Professor Medical Director, Post-Anesthesia Care Unit Director, Intraoperative Transesophageal Echocardiography Program Department of Anesthesiology and Critical Care Medicine

The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Michelle Braunfeld, MD

Clinical Professor Department of Anesthesiology and Critical Care Medicine David Geffen School of Medicine at UCLA Chief, Department of Anesthesiology Greater Los Angeles Veterans Affairs Hospital Los Angeles, California Tod A. Brown, MD

Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Charles H. Brown IV, MD Assistant Professor Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Kelly Bruno, BS, MD Medical Student University of North Carolina School of Medicine Chapel Hill, North Carolina Ethan O. Bryson, MD Associate Professor Department of Anesthesiology and Psychiatry Mount Sinai School of Medicine The Mount Sinai Hospital New York, New York Arne O. Budde, MD, DEAA

Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania

James Cain, MD

Department of Anesthesiology and Pediatrics University of Pittsburgh School of Medicine Children’s Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania James M. Callas, MD

Chief, Department of Radiology King’s Daughters Clinic Temple, Texas Neal Campbell, MD

Assistant Professor Department of Anesthesiology & Pediatrics University of Pittsburgh School of Medicine Children’s Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania Elena C. Capello, MD Universita di Torino Dipartimento di Discipline Medico-Chirurgiche Sezione di Anestesiologia e Rianimazione Ospedale S. Giovanni Battista John B. Carter, MD Associate Professor Department of Anesthesiology Oklahoma University College of Medicine Oklahoma University Health Sciences Center Oklahoma City, Oklahoma Michael Carter, MD, PhD Resident Physician Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Daniel Castillo, MD

Assistant Professor Department of Anesthesiology University of Florida College of Medicine Shands Jacksonville Medical Center Jacksonville, Florida

Davide Cattano, MD, PhD

Associate Professor Department of Anesthesiology University of Texas Medical School at Houston Memorial Hermann Hospital Houston, Texas Laura F. Cavallone, MD

Assistant Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri John T. Chalabi, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Vinay Chandrasekhara, MD Instructor Division of Gastroenterology, Department of Medicine Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Jean Charchaflieh, MD, DrPH, FCCM, FCCP Associate Professor Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Verghese T. Cherian, MBBS, MD, FFARCSI Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Jason Choi, MD Resident Physician

Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Christopher G. Choukalas, MD, MS Assistant Professor Department of Anesthesia and Perioperative Care University of California, San Francisco San Francisco VA Medical Center San Francisco, California Jason Han Chua, MD

Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Theodore J. Cios, MD, MPH Resident Physician Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Carlee Clark, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Matthew D. Cohen, DO Assistant Professor Chief, Division of Acute Pain and Regional Anesthesia Department of Anesthesiology University of Oklahoma The University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma Seth R. Cohen, DO Resident Physician Department of Anesthesiology

University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania John F. Coleman, MD

Clinical Fellow Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Lydia A. Conlay, MD, PhD

Russell D and Mary B Sheldon Professor Vice Chairwoman for Academic Affairs Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Craig R. Cook, MD, PhD Resident Physician Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Daniel Cormican, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Charles E. Cowles Jr., MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Ryan Crowley, MD Staff Physician Department of Anesthesiology Legacy Good Samaritan Hospital Portland, Oregon

William C. Culp Jr., MD, FASE

Associate Professor Department of Anesthesiology Texas A&M University College of Medicine Scott and White Hospital Temple, Texas Cristina Cunanan, MD

Resident Physician Department of Anesthesiology and Critical Care Medicine David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Priti G. Dalal, MD, FRCA Associate Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Patricia Dalby, MD Associate Professor Department of Anesthesiology University of Pittsburgh School of Medicine Magee-Women’s Hospital of UPMC Pittsburgh, Pennsylvania Lori Dangler, MD, MBA Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Nisha Dave, DO, PharmD Resident Physician Mount Sinai School of Medicine St. Joseph’s Regional Medical Center Paterson, New Jersey Alberto J. de Armendi, MD, AM, MBA Professor Chief, Pediatric Anesthesia Department of Anesthesiology

Oklahoma University College of Medicine Children’s Hospital of Oklahoma Oklahoma City, Oklahoma Stephen Dechter, DO N. Matthew Decker, BS Medical Student Loyola University Chicago Stritch School of Medicine Maywood, Illinois Matthew Delph, MD

Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Jagan Devarajan, MD, FRCA Associate Staff Department of Anesthesiology The Cleveland Clinic Cleveland, Ohio Anahat Dhillon, MD Assistant Clinical Professor Department of Anesthesiology and Critical Care Medicine David Geffen School of Medicine at UCLA Ronald Reagan Medial Center Los Angeles, California Bradley T. Dollar, MD Assistant Professor Residency Program Director Department of Radiology Texas A&M College of Medicine Scott and White Hospital Temple, Texas Kathleen S. Donahue, DO, FAAP Associate Professor Associate Vice Chair, OR Management Department of Anesthesiology Penn State College of Medicine

Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Shawna Dorman, MD

Instructor Department of Anesthesiology New York University School of Medicine NYU Langone Medical Center New York, New York Corey C. Downs, MD

Staff Anesthesiologist Surgical and Perioperative Careline VA Greater Los Angeles Healthcare System Los Angeles, California Emily L. Drennan, MD Assistant Professor Department of Anesthesiology University of Texas Medical School at Houston Memorial Hermann Hospital Houston, Texas Rebecca A. Drinkaus, MD Assistant Professor Department of Anesthesiology Oklahoma University College of Medicine Oklahoma University Health Sciences Center Oklahoma City, Oklahoma Peter Drocton, MD Department of Anesthesiology Cedars-Sinai Medical Center Los Angeles, California Department of Anesthesiology Olive View - UCLA Medical Center Sylmar, California Mirsad Dupanovic, MD

Assistant Professor Department of Anesthesiology Kansas University School of Medicine Kansas University Medical Center Kansas City, Kansas

Victor Duval, MD

Assistant Clinical Professor Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Ramana V. Duvvuri, MD

Assistant Clinical Professor Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California J. Andrew Dziewit, MD Attending Physician Department of Anesthesia Crozer Chester Medical Center Upland, Pennsylvania Jill Eckert, DO Assistant Professor Residency Program Director Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Nabil Elkassabany, MD Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Matthew Ellison, MD Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia Trent Emerick, MD Resident Physician

Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Thomas I. Epperson III, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Zhuang-Ting Fang, MD, MSPH

Associate Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Jared Feinman, MD Fellow, Cardiothoracic Anesthesia Department of Anesthesia, Critical Care and Pain Medicine Harvard Medical School Massachusetts General Hospital Boston, Massachusetts Larry C. Field, MD Assistant Professor Medical Director, Medical/Surgical ICU Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Robert S. Fitzgerald, LittB, STB, MA, STM, PhD Professor Environmental Health Sciences, Physiology, Medicine The Johns Hopkins University Baltimore, Maryland Linzy Fitzsimons, MD Resident Physician Department of Anesthesiology David Geffen School of Medicine at UCLA

Ronald Reagan Medical Center Los Angeles, California Melissa Flanigan, DO

Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia Andrew Fond, MD

Assistant Clinical Professor Department of Anesthesiology and Pain Management University of Southern California Los Angeles, California Siyavash Fooladian, MD, MPH Fellow, Cardiothoracic Anesthesiology Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Caroline Fosnot, DO, MS Clinical Instructor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania John J. Freely Jr., MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Megan M. Freestone-Bernd, MD Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania

Katy E. French-Bloom, MD

Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas John C. Frenzel, MD

Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas David Frey, BA

Medical Student Ohio University College of Osteopathic Medicine Athens, Ohio David P. Frey, DO Resident Physician Department of Anesthesiology and Pain Medicine University of Washington Medical School University of Washington Medical Center Seattle, Washington Elizabeth A.M. Frost, MD Professor of Anesthesiology Mount Sinai School of Medicine The Mount Sinai Hospital New York, New York Kamilia S. Funder, MD Physician Department of Anesthesia Copenhagen University Hospital, Rigshospitalet Copenhagen, Denmark Jorge A. Galvez, MD Fellow, Pediatric Anesthesiology Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Wei Dong Gao, MD, PhD

Associate Professor Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Stephanie Gargani, MD

Resident Physician Department of Anesthesiology Mount Sinai School of Medicine St. Joseph’s Regional Medical Center Paterson, New Jersey Andrew Geller, MD Resident Physician Department of Anesthesiology Charles Drew University of Medicine and Science Cedars-Sinai Medical Center Los Angeles, California Matthew C. Gertsch, MD Resident Physician Department of Anesthesia, Critical Care and Pain Medicine Harvard Medical School Massachusetts General Hospital Boston, Massachusetts Ileana Gheorghiu, MD Assistant Professor Department of Anesthesiology University of Maryland School of Medicine University of Maryland Medical Center Baltimore, Maryland Brian Gierl, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Lori Gilbert, MD Assistant Clinical Professor Department of Anesthesiology and Critical Care

Perelman School of Medicine at the University of Pennsylvania Philadelphia VA Medical Center Philadelphia, Pennsylvania Ronnie J. Glavin, MB, ChB, MPhil, FRCA, FRCP (Glas) Consultant Anesthetist Victoria Infirmary Glasgow, United Kingdom

Christine E. Goepfert, MD, PhD, DESA Instructor and Visiting Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Emily Gordon, MD Instructor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Shannon M. Gossett-Popovich, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Amitabh Goswami, DO, MPH Fellow, Pain Management Department of Anesthesiology and Pain Medicine University of California, Davis School of Medicine UC Davis Medical Center Sacramento, California Ori Gottlieb, MD Assistant Professor Department of Anesthesia and Critical Care Pritzker School of Medicine, University of Chicago The University of Chicago Medicine Chicago, Illinois Vijaya Gottumukkala, MB, BS, MD, FRCA

Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Basavana G. Goudra, MD, FRCA, FCARCSI Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Andreas Grabinsky, MD

Assistant Professor Department of Anesthesiology University of Washington School of Medicine Harborview Medical Center Seattle, Washington Ashley Greene, DO Resident Physician Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Michael S. Green, DO Assistant Professor Interim Chair Department of Anesthesiology and Perioperative Medicine Drexel University College of Medicine Hahnemann University Hospital Philadelphia, Pennsylvania Alina M. Grigoire, MD, MHS, FASE Associate Professor Director, Division of Cardiothoracic Anesthesiology Department of Anesthesiology University of Maryland School of Medicine University of Maryland Medical Center Baltimore, Maryland Michael Grover, MD Resident Physician

Department of Anesthesiology University of Texas School of Medicine, San Antonio University of Texas Health Science Center at San Antonio San Antonio, Texas Anthony H. Guarino, MD Director, Pain Management Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Vadim Gudzenko, MD

Assistant Clinical Professor Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Maged N. Guirguis, MD Department of Anesthesiology and Pain Management The Cleveland Clinic Cleveland, Ohio Gregory MT Hare, MD, PhD Associate Professor Department of Anesthesia St. Michael’s Hospital Toronto, Canada Jagtar Singh Heir, DO Clinical Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Rachel Helle, DO Resident Physician Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Laura B. Hemmer, MD

Assistant Professor Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois John Henao, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Andrew Herlich, DMD, MD, FAAP

Professor Department of Anesthesiology University of Pittsburgh School of Medicine Chief, UPMC Mercy Pittsburgh, Pennsylvania Ibetsam Hilmi, MBChB, FRCA Associate Professor Department of Anesthesiology Institute of Clinical and Translational Sciences University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Jonathan K. Ho, MD Assistant Clinical Professor Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California John W. Hoffman, Jr., DO, MS Clinical Instructor Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Michael P. Hofkamp, MD Assistant Professor Department of Anesthesiology

Texas A&M, -College of Medicine Scott and White Hospital Temple, Texas Allen Alexander Holmes, MD, MS

Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Joe C. Hong, MD

Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Kimberly Howard-Quijano, MD Clinical Instructor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Tyken C. Hsieh, MD Staff Cardiac Anesthesiologist Department of Anesthesiology Mills-Peninsula Health Services Burlingame, California Angela T. Hsu, MD Attending Physician Department of Anesthesiology Kaiser Permanente Downey, California Eric S. Hsu, MD Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Allen Hu, MD

T. Kate Huncke, MD

Clinical Associate Professor Department of Anesthesiology New York University School of Medicine NYU Langone Medical Center New York, New York Catherine Ifune, MD, PhD

Associate Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Mohamad Iravani, MD Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Selma Ishag, MB, BS, MD Assistant Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri % Jonathan S. Jahr, MD Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Ranu Jain, MD Assistant Professor Assistant Director, Pediatric Anesthesia Department of Anesthesiology The University of Texas School of Medicine at Houston Children’s Memorial Hermann Hospital-Texas Medical Center Houston, Texas Piotr K. Janicki, MD, PhD

Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Richard C. Jensen, MD

Resident Physician Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Rongjie Jiang, MB, MS Resident Physician Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Quinn L. Johnson, MD Assistant Clinical Professor Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Praveen Kalra, MBBS, MD, FCCP Assistant Professor Department of Anesthesiology Oklahoma University College of Medicine Oklahoma University Health Sciences Center Oklahoma City, Oklahoma Mandip S. Kalsi, MD Fellow, Regional Anesthesia Hospital for Special Surgery New York, New York Valbona Kanarek, MD Chief Resident Department of Anesthesiology Mt. Sinai School of Medicine St. Joseph’s Hospital and Regional Medical Center

Paterson, New Jersey Revati Kanekar, MD

Resident Physician Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Ivan M. Kangrga, MD, PhD Associate Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Susan Kaplan, MD Clinical Associate Department of Anesthesiology and Critical Care University of Pennsylvania Philadelphia, Pennsylvania Menelaos Karanikolas, MD, MPH Assistant Professor Department of Anesthesiology Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Keyvan Karkouti, MD, FRCPC, MSc Associate Professor Department of Anesthesia University of Toronto Toronto, Ontario Jeffrey Katz, MD Chief Resident Department of Anesthesia and Critical Care Pritzker School of Medicine, University of Chicago The University of Chicago Medicine Chicago, Illinois Paul Kerby, MB, BS Chief Resident

Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Patrick Kim, MD Resident Physician Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Peter H. Kim, MD Andrew A. Klein, MD Consultant Anaesthesia and Intensive Care Papworth Hospital Cambridge, United Kingdom Antoun Koht, MD Professor of Anesthesiology, Neurological Surgery & Neurology Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois Iosifina Kolliantzaki, MD Department of Anesthesiology Aghia Sophia Children’s Hospital Athens, Greece James J. Konvicka, MD Assistant Professor Department of Anesthesiology Texas A&M College of Medicine Scott and White Healthcare Temple, Texas Edward Kosik, DO John D. Kot, MD

Resident Physician Department of Anesthesiology David Geffen School of Medicine at UCLA

Ronald Reagan Medical Center Los Angeles, California Joseph Koveleskie, MD

Assistant Professor Department of Anesthesiology Tulane University School of Medicine Tulane Medical Center New Orleans, Louisiana Alan J. Kover, MD, PharmD

Clinical Assistant Professor Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Kenneth F. Kuchta, MD Associate Clinical Professor Chief, Vascular Anesthesiology Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Anand Lakshminarasimhachar, MBBS, FRCA Assistant Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Daniel A. Lazar, MD Attending Anesthesiologist North Shore Manhasset Hospital Manhasset, New York Stephane Ledot, MD Hadassah Hebrew University School of Medicine Jerusalem, Israel Thomas Ledowski, MD, PD, DEAA, FANZCA Professor of Anesthesiology University of Western Australia

School of Medicine and Pharmacology Perth, Australia Annie D. Lee, MD

Resident Physician Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Jonathan D. Leff, MD

Assistant Professor Chief, Cardiothoracic Anesthesiology Department of Anesthesiology Albert Einstein College of Medicine Montefiore Medical Center Bronx, New York Philip Levin, MD Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Jinlei Li, MD, PhD Assistant Professor Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Yun Rose Li, BS Medical Student Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania Jeffrey W. Lim, MD, PhD Assistant Professor Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut

Sharon L. Lin, MD

Attending Physician Department of Anesthesiology Swedish Medical Center Seattle, Washington Keith E. Littlewood, MD

Associate Professor Vice Chair for Education Department of Anesthesiology Assistant Dean for Clinical Skills Education University of Virginia School of Medicine University of Virginia Health System Charlottesville, Virginia Marc A. Logarta, MD, DABA, FANZCA Consultant Anesthetist Campbelltown Hospital Canterbury Hospital Sydney, Australia David W. Lui, DMD, MD Assistant Professor Department of Oral and Maxillofacial Surgery Virginia Commonwealth University School of Dentistry and School of Medicine VCU Medical Center Richmond, Virginia Calvin Lyons, MD Resident Physician Department of Surgery The Methodist Hospital Houston, Texas Edna Ma, MD Attending Physician Department of Anesthesiology Olive View - UCLA Medical Center Sylmar, California Aman Mahajan, MD, PhD Professor Chief, Cardiothoracic Anesthesiology Vice Chair of Anesthesiology

David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Victor L. Mandoff, MD

Associate Professor Department of Anesthesiology and Critical Care Medicine The University of Arkansas College of Medicine The University of Arkansas for Medical Sciences Little Rock, Arkansas Gerard R. Manecke, Jr., MD

Professor and Chair Department of Anesthesiology University of California, San Diego School of Medicine University of California, San Diego Medical Center San Diego, California Federica Manfroi, MD Michael Mangione, MD

Associate Professor Department of Anesthesiology University of Pittsburgh School of Medicine Chief of Anesthesiology VA Pittsburgh Healthcare System Pittsburgh, Pennsylvania Natesan Manimekalai, MD Assistant Professor Department of Anesthesiology University of Florida College of Medicine Shands Jacksonville Medical Center Jacksonville, Florida Ana Maria Manrique-Espinel, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Brian L. Marasigan, MD Assistant Professor

Residency Program Director Department of Anesthesiology University of Texas Medical School at Houston Memorial Hermann Hospital Houston, Texas Julie Marshall, MD

Assistant Professor Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Jayson T. Maynes, MD, PhD Assistant Professor Hospital for Sick Children/SickKids Research Institute University of Toronto Toronto, Canada Richard McAffee, MD Assistant Professor Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Mary E. McAlevy, MD Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Russell K. McAllister, MD Associate Professor Residency Program Director Department of Anesthesiology Assistant Dean of Quality and Patient Safety Texas A&M College of Medicine Scott & White Memorial Hospital Temple, Texas Dwayne E. McClerkin, MD Assistant Professor

Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Stephen M. McHugh, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Julie McSwain, MD, MPH

Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Li Meng, MD, MPH Associate Professor Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Spyros D. Mentzelopoulos, MD, PhD Assistant Professor Department of Critical Care University of Athens Medical School Athens, Greece David G. Metro, MD Associate Professor Residency Program Director Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Berend Mets, MB, ChB, PhD, FRCA, FFASA Eric A. Walker Professor and Chair Department of Anesthesiology Penn State College of Medicine

Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Tricia A. Meyer, PharmD, MS, FASHP Associate Professor Department of Anesthesiology Director, Department of Pharmacy Texas A&M College of Medicine Scott and White Hospital Temple, Texas Agnes Miller, MD

Director, Resident Education Department of Anesthesiology Maimonides Medical Center New York, New York Sara Miller, MD Resident Physician Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Brian Milne, MD, MSc, FRCPC Professor Department of Anesthesiology and Perioperative Medicine Queen’s University Kingston General Hospital Kingston, Ontario Beth H. Minzter, MD, MS, FIPP Department of Pain Management Anesthesiology Institute The Cleveland Clinic Cleveland, Ohio Nanhi Mitter, MD Assistant Professor Director, Adult Cardiothoracic Anesthesiology Fellowship Department of Anesthesiology and Critical Care Medicine The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland

Kanishka Monis, MD

Fellow, Pain Management Department of Anesthesiology University of Texas School of Medicine, San Antonio University of Texas Health Science Center at San Antonio San Antonio, Texas Richard C. Month, MD

Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Teresa L. Moon, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Kenneth R. Moran, MD Assistant Clinical Professor Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Allyson J.A. Morman, MD Resident Physician Department of Anesthesiology University of Virginia School of Medicine University of Virginia Health System Charlottesville, Virginia Juan Moya-Amor’s, PhD Professor of Surgery Chief, Department of Thoracic Surgery Hospital Universitari de Bellvitge L’Hospitalet de Llobregat Barcelona, Spain Daniel Mulcrone, MD Resident Physician Department of Anesthesiology

University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Eman Nada, MD, PhD

Fellow, Neuroanesthesia The Cleveland Clinic Cleveland, Ohio Carsten Nadjat-Haiem, MD Associate Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Sharanya Nama, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Gundappa Neelakanta, MD Clinical Professor of Anesthesiology Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Jacques Prince Neelankavil, MD Assistant Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Eric W. Nelson, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina

Sara C. Nelson, MD

Attending Physician Department of Anesthesiology Naval Medical Center San Diego San Diego, California Edward C. Nemergut, MD

Associate Professor of Anesthesiology and Neurosurgery University of Virginia School of Medicine University of Virginia Health System Charlottesville, Virginia Anh-Thuy Nguyen, MD

Associate Clinical Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Linh Trang Nguyen, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Teodora Orhideea Nicolescu, MD Associate Professor Chief, Division of Cardiothoracic Anesthesiology Department of Anesthesiology Oklahoma University College of Medicine Oklahoma University Health Sciences Center Oklahoma City, Oklahoma Daniel R.C. Nieva, MD Assistant Professor Department of Anesthesiology Washington University School of Medicine St. Louis Children’s Hospital St. Louis, Missouri Dave Nisha Davendra, PharmD, DO Assistant Clinical Professor Department of Anesthesiology Mount Sinai School of Medicine St. Joseph’s Hospital and Regional Medical Center

Paterson, New Jersey Mark E. Nunnally, MD, FCCM

Associate Professor Department of Anesthesia and Critical Care Pritzker School of Medicine, University of Chicago The University of Chicago Medicine Chicago, Illinois Satoru Ogawa, MD Department of Anesthesiology Emory University School of Medicine Emory University Hospital Atlanta, Georgia Olutoyosi Ogunkua, MD Resident Physician Department of Anesthesiology and Pain Management University of Texas Southwestern School of Medicine University of Texas Southwestern Medical Center at Dallas Dallas, Texas Erik Olness, MD Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia Onyi Onuoha, MD, MPH Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Todd M. Oravitz, MD Associate Professor Chief, Liver Transplantation Anesthesiology Department of Anesthesiology The University o Pittsburgh School of Medicine VA Pittsburgh Healthcare System Pittsburgh, Pennsylvania

Pascal O. Owusu-Agyemang, MD

Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Nirvik Pal, MD

Clinical Instructor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Edward Park, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Dorothea Rosenberger Parravano, MD, PhD Associate Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Andrea Parsons, MD Assistant Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Parisa Partownavid, MD Associate Clinical Professor Associate Director, Ambulatory Surgery Center Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Mitesh Patel, MD Chief Resident

Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Neesa Patel, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Shetal H. Patel, MD

Fellow, Obstetric Anesthesiology Department of Anesthesiology Charles Drew University of Medicine and Science Cedars-Sinai Medical Center Los Angeles, California Swati Patel, MD Clinical Professor of Anesthesiology Chief, Division of Pediatric Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Tara L. Paulose, MD Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Katerina Pavenski, MD, FRCPC Department of Laboratory Medicine St. Michael’s Hospital, Toronto, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, Canada Alison R. Perate, MD Assistant Professor Department of Anesthesiology Perelman School of Medicine at the University of Pennsylvania Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Lauren Mai Pieczynski, MD

Resident Physician Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Raymond M. Planisic, MD

Professor of Anesthesiology Director, Transplantation Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Keyuri Popat, MD Associate Professor Department of Anesthesiology and Pain Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Wanda M. Popescu, MD Associate Professor of Anesthesiology Yale-New Haven Hospital New Haven, Connecticut Marek Postula, MD, PhD Assistant Professor at the Department of Experimental and Clinical Pharmacology Medical University of Warsaw Senior Assistant at the Department of Noninvasive Cardiology and Hypertension Central Clinical Hospital The Ministry of the Interior Warsaw, Poland Debra Domino Pulley, MD Associate Professor Department of Anesthesiology and Pain Medicine Washington University of School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Carlos A. Puyo, MD Assistant Clinical Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine

Barnes-Jewish Hospital St. Louis, Missouri Farooq A. Qureshi, MD

Fellow, Pain Management Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Henry Ra, MD

Resident Physician Department of Anesthesiology and Critical Care Medicine David Geffen School of Medicine at UCLA Ronald Reagan Hospital Center Los Angeles, CaliforniaFabrizio Racca, MD S.C. Anestesia e Rianimazione Pediatrica Azienda Ospedaliera SS Antonio Biagio e Cesare Arrigo Alessandria, Italy Siamak Rahman, MD Associate Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Niraja Rajan, MB, BS, FAAP Assistant Professor Medical Director, Hershey Outpatient Surgery Center Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Sivam Ramanathan, MD Associate Professor of Anesthesiology Charles Drew University of Medicine and Science Cedars-Sinai Medical Center Los Angeles, California Chitra Ramasubbu, MD

Fellow, Pain Management Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland George J. Ranier, MD

Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia V. Marco Ranieri, MD Universita di Torino Dipartimento di Discipline Medico-Chirurgiche Sezione di Anesthesiologia e Rianimazione Ospedale S. Giovanni Battista Torino, Italy Srikantha L. Rao, MBBS, MS Associate Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Rashmi R. Rathor, MD Fellow, Abdominal Organ Tranplant Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Elizabeth Rebello, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Venugopal S. Reddy, MD, EDIC, FFARCS Associate Professor Department of Anesthesiology Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania Rebecca L. Reeves, DO

Resident Physician Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Wendy HP Ren, MD, FAAP Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan UCLA Medical Center Los Angeles, California Joseph Resti, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Cameron J. Ricks, MD Assistant Professor Department of Anesthesiology and Perioperative Care University of California, Irvine School of Medicine University of California, Irvine Douglas Hospital Irvine, California Horst Rieke, MD, PhD Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Francisco Rivas-Doyague, MD Medical Doctor Department of Thoracic Surgery Hospital Universitari de Bellvitge L’Hospitalet de Llobregat Barcelona, Spain

Laura L. Roberts, MD

Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Adam Romanovsky, MD

Assistant Clinical Professor Divisions of Critical Care and Nephrology University of Alberta Edmonton, AB Canada Harvey K. Rosenbaum, MD Clinical Professor of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan UCLA Medical Center Los Angeles, California Jay A. Roskoph, MD, MBA Clinical Assistant Professor Department of Anesthesiology University of Pittsburgh School of Medicine Chief Department of Anesthesiology UPMC-St. Margaret Hospital Pittsburgh, Pennsylvania Marc A. Rozner, PhD, MD Professor of Anesthesiology and Perioperative Medicine Professor of Cardiology University of Texas MD Anderson Cancer Center Houston, Texas Daniel M. Rusu, MD Assistant Professor Department of Anesthesia and Critical Care University of Kentucky College of Medicine University of Kentucky Healthcare Lexington, Kentucky Ali Salehi, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA

Ronald Reagan Medical Center Los Angeles, California Alain A. Salvacion, MD

Fellow, Cardiothoracic Anesthesia Department of Anesthesiology Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois Samuel Samuel, MD

Associate Fellowship Director of Pain Management The Cleveland Clinic Cleveland, Ohio Mona G. Sarkiss, MD, PhD Associate Professor Department of Anesthesiology and Perioperative Medicine Department of Pulmonary Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Poovendran Saththasivam, MD Resident Physician Department of Anesthesiology Drexel University College of Medicine Hahnemann University Hospital Philadelphia, Pennsylvania Matthew V. Satterly, MD Fellow, Pain Management Department of Anesthesia and Critical Care Pritzker School of Medicine, University of Chicago The University of Chicago Medicine Chicago, Illinois Shashank Saxena, MD Clinical Assistant Professor Department of Anesthesiology University of Pittsburgh School of Medicine Staff Anesthesiologist VA Pittsburgh Health Care System Pittsburgh, Pennsylvania

R. Alexander Schlichter, MD

Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Peter M. Schulman, MD

Assistant Professor Department of Anesthesiology and Perioperative Medicine Oregon School of Medicine Oregon Health and Science University Portland, Oregon Jeffrey J. Schwartz, MD Associate Professor Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Johanna C. Schwarzenberger, MD Clinical Professor Director, Pediatric Cardiac Anesthesiology Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Korrin Scott, MD Resident Physician Department of Anesthesiology University of Virginia School of Medicine University of Virginia Health System Charlottesville, Virginia Jennifer Scovotti, MA Research Associate Department of Anesthesiology David Geffen School of Medicine at UCLA Los Angeles, California Khaled Sedeek, MD Associate Professor

Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania E. Gail Shaffer, MD, MPH Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Kirk H. Shelley, MD, PhD

Professor Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Justin C. Shields, MD Resident Physician Department of Anesthesiology Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Shawn T. Simmons, MD Associate Clinical Professor Medical Director, Hyperbaric Medicine Service Department of Anesthesia University of Iowa Carver College of Medicine University of Iowa Hospitals Iowa City, Iowa Amrik Singh, MD Associate Professor Residency Program Director Department of Anesthesiology and Pain Medicine University of California, Davis School of Medicine UC Davis Medical Center Sacramento, California Davinder Singh, MD Assistant Professor

Department of Anesthesiology and Perioperative Care University of California, Irvine School of Medicine University of California, Irvine Douglas Hospital Irvine, California Sukhdip Singh, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Sumit Singh, MD

Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Nina Singh-Radcliff, MD Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Christopher A. Skorke Assistant Professor Medical Director, Medical/Surgical ICU Department of Anesthesiology and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Jose M. Soliz, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Dmitri Souzdalnitski, MD, PhD Pain Management Department The Cleveland Clinic Cleveland, Ohio

Martin M. Stechert, MD

Associate Clinical Professor Department of Anesthesiology and Perioperative Care University of California, San Francisco School of Medicine UCSF Medical Center San Francisco, California Chris A. Steel, MD

Attending Physician Director of Anesthesia Services White River Health System Batesville, Arizona Jacob Steinmetz, MD, PhD Consultant Department of Anesthesia Copenhagen University Hospital Rigshospitalet, Copenhagen Jochen Steppan, MD Fellow, Cardiothoracic Anesthesia Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Joel Stockman, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California William David Stoll, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Bradley A. Stone, MD Attending Anesthesiologist Mission Hospital Asheville, North Carolina

Suzanne Strom, MD

Assistant Clinical Professor Residency Program Director Department of Anesthesiology and Perioperative Care University of California, Irvine School of Medicine University of California, Irvine Douglas Hospital Irvine, California Adam M. Stuart, MD

Medical Student Virginia Commonwealth University School of Medicine Richmond, Virginia Mariya Svilik, MD Staff Physician Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Rajeshwary Swamidurai, MD Attending Physician Department of Anesthesiology Lodi Memorial Hospital Lodi, California Kenichi A. Tanaka, MD, MSc Associate Professor Department of Anesthesiology Emory University School of Medicine Atlanta, Georgia Rob C. Tanzola, MD, FRCPC Assistant Professor Department of Anesthesiology and Perioperative Care Queen’s University Kingston General Hospital Kingston, Ontario Vijay Tarnal, MBBS, FRCA Clinical Assistant Professor Department of Anesthesiology The University of Texas Medical Branch School of Medicine at Galveston The University of Texas Medical Branch at Galveston

Galveston, Texas Adam Thaler, DO

Resident Physician Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Ilka Theruvath, MD, PhD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Svjetlana Tisma-Dupanovic, MD Assistant Professor Department of Cardiology Kansas University School of Medicine Kansas University Medical Center Kansas City, Kansas Catherine Dawson Tobin, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Lan Chi Tran, MD Resident Physician Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Timothy T. Tran, MD Resident Physician Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri

Ravi S. Tripathi, MD

Assistant Clinical Professor Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Angela Truong, MD

Associate Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Dam-Thuy Truong, MD Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas January Y. Tsai, MD Assistant Clinical Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Judith A. Turner, MD, PhD Assistant Clinical Professor Residency Program Director Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Kalpana Tyagaraj, MD Residency Program Director Director, Obstetric Anesthesiology Department of Anesthesiology Maimonides Medical Center New York, New York Shital Vachhani, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center

Houston, Texas Dierk A. Vagts, MSc, DEAA, EDIC

Professor Department of Anesthesiology and Intensive Care Medicine, Emergency Medicine, Pain Therapy and Palliative Care Academic Teaching Hospital of Johannes Gutenberg University Mainz, Neustadt Weinstrasse, Germay Sonia Vaida, MD Professor of Anesthesiology, Obstetrics and Gynecology Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Elizabeth Valentine, MD Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Andrea Vanucci, MD, DEAA Assistant Professor Department of Anesthesiology Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Swarup S. Varaday, MBBS, FRCA, FCARSI Assistant Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Malina M. Varner, MD Instructor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania

Aditya Venkataraman, MD

Chief Resident Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Thomas Verbeek, MBChB

Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Bruce Vrooman, MD Department of Pain Management Cleveland Clinic Cleveland, Ohio Samuel H. Wald, MD Clinical Professor Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Cynthia Wang, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Ellen Y. Wang, MD Clinical Assistant Professor Department of Anesthesiology Stanford University Lucile Packard Children’s Hospital Palo Alto, California Steve Wang, MD Assistant Professor Department of Anesthesiology and Pain Medicine University of Texas MD Anderson Cancer Center

Houston, Texas Izabela M. Wasiluk, MD

Assistant Professor Department of Anesthesiology University of Florida College of Medicine Shands Jacksonville Medical Center Jacksonville, Florida Huafeng Wei, MD, PhD Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Jiadong Wei, MD Yoram G. Weiss, MD, MBA, FCCM Associate Professor in Anesthesiology and Critical Care Medicine Hadassah Hebrew University School of Medicine Jerusalem, Israel Adjunct Associate Professor Department of Anesthesiology and Critical Care University of Pennsylvania Philadelphia, Pennsylvania Gregory E. R. Weller, MD, PhD Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Joseph R. Whiteley, DO Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina J. Aaron Williams, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine

University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Sylvia H. Wilson, MD

Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Stephen P. Winikoff, MD

Professor Department of Anesthesiology Mount Sinai School of Medicine St. Joseph’s Hospital and Regional Medical Center Paterson, New Jersey Jeremy Wong, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Christopher Wray, MD Assistant Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Jennifer Wu, MD, MBA Assistant Professor Department of Anesthesiology University of Texas Medical School at Houston Memorial Hermann Hospital Houston, Texas Sulin G. Yao, MD Attending Physician Department of Anesthesiology Atlanticare Regional Medical Center Pomona, New Jersey

Peter K. Yi, MD

Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Dirk Younker, MD

Russell D and Mary B Sheldon Professor of Anesthesiology Vice Chairman for Clinical Affairs Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Zdravka Zafirova, MD Assistant Professor Department of Anesthesia and Critical Care Pritzker School of Medicine, University of Chicago The University of Chicago Medicine Chicago, Illinois Alan P. Zaggy, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Mark Zakowski, MD Associate Professor of Anesthesiology, Adjunct Charles Drew University of Medicine and Science Chief, Obstetric Anesthesiology Cedars-Sinai Medical Center Los Angeles, California Sherif Zaky, MD, PhD Assistant Professor of Anesthesiology The Cleveland Clinic Cleveland, Ohio Sessunu M. Zemo, MD Resident Physician Department of Anesthesiology

Baylor College of Medicine Ben Taub Hospital Houston, Texas Fei Zheng, MD, MPH, MS

Resident Physician Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Dayna Zimmerman, BS

Research Assistant Department of Anesthesiology David Geffen School of Medicine at UCLA Los Angeles, California Keren Ziv, MD Associate Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Zachary M. Zumbar, MD, MPH Attending Physician Midwest Pain Physicians Uniontown, Ohio

FOREWORD

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t is a pleasure to introduce the 5 Minute Anesthesia Consult to readers around the globe. This concise compendium of topics pertinent to modern anesthesiology practice will be useful as a rapid reference for busy anesthesiology clinical practitioners, anesthesiology residents, medical students and others in training, nurse anesthetists, anesthesiology assistants, perioperative nurses, post-operative intensive care personnel, and other allied health professionals caring for patients before and after anesthetic administration. The contents are offered in both text format as well as applications for smart devices, to be readily at hand in any clinical situation in any clinical location.

The editor has drawn from a wide spectrum of expert authors from multiple institutions to compile approximately 480 two-page chapters, in template formats for easy-to-retrieve information. The content is organized into sections on important topics in physiology, pertinent issues for major co-existing diseases/co-existing conditions, key information for important surgical procedures, and guidance for managing a variety of complications encountered in anesthetic practice. In addition, the 5 Minute Anesthesia Consult contains a drug section in a condensed, easily accessible format with current information about anesthetic drugs and adjuvants, chronic medications that patients may be taking in the perioperative period, and medications used to treat complications encountered in the perianesthetic period. As anesthesiology care is extending to encompass the spectrum from early evaluation and optimization/management of pre-procedural risk factors, through post-procedural care to minimize subsequent complications and/or re-admission, every practitioner can benefit from timely access to a “one-stop” content source to support evidence-based anesthesiology care, a source that concisely presents the most important concepts on a topic in an accessible manner. I look forward with enthusiasm to the broad distribution and availability of the 5 Minute Anesthesia Consult to support high quality patient outcomes on an international basis. PATRICIA A. KAPUR, MD Professor and Chairwoman Department of Anesthesiology David Geffen School of Medicine at UCLA Los Angeles, California, USA April 2012

PREFACE

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he 5 Minute Medicine Consult was amongst the medical texts and references that lined my mother’s bookshelf when I was in high school. I was drawn to the unique style that made it “easy to read,” even at my level. The topic-specific and highly templated format was the first of its kind amongst medical references. Years later, I have been given the amazing opportunity to add to The 5 Minute Consult Series.

The goal of The 5 Minute Anesthesia Consult is to emulate that style by creating an evidence-based, focused, and practical textbook that will be relevant to students, trainees, nurse anesthetists, and physicians. The 480 topics are presented alphabetically, but are presented in a second table of contents organized in four sections: Physiology, Co-Existing Disease, Surgical Procedure, and Management. Each topic follows a two-page outline format that is consistent with the section and easy to read. Additionally, we have provided a focused Drug section. The chapters in the Physiology section were specifically written to simplify complex topics and then extrapolate them to pathophysiologic processes and apply them to relevant perioperative matter. The Surgical Procedures section describes key surgical steps, followed by anesthetic considerations for preoperative preparation, intraoperative care, and postoperative concerns. The goal of this section is to “involve” the anesthesia practitioner in the surgical procedure by providing an understanding of, and appreciation for, our surgical colleagues’ work. The chapters in the Co-Existing Disease Section describe basic pathophysiology concepts, followed by key considerations to optimizing and managing patients throughout the perioperative period.

The Management Section covers a comprehensive list of perioperative complications that can arise in anesthetic practice. For example, the author of the Anaphylaxis chapter had a patient who “crumped” after being exposed to medication. Despite appropriately treating the patient with epinephrine and following ACLS protocol, the patient remained unresponsive to therapy. The author saved her patient’s life by administering glucagon, which she describes in her chapter as the treatment for refractory anaphylaxis that may be seen in patients who are beta-blocked. Each chapter provides a list of additional complementary topics that are available within the book to allow readers the opportunity to supplement their knowledge of a given topic. I sincerely hope that the practical nature and quality of this text will contribute to your learning and benefit our patients in the ever-growing field of anesthesia. I welcome feedback and suggestions at [email protected].

ACKNOWLEDGEMENTS

T

he completion of this text would not have been possible without a number of special people. The authors have given their time and expertise to prepare, revise, and re-revise their chapters to attain the overarching vision for this textbook. I enjoyed the opportunity to meet (and learn from) so many talented and enthusiastic practitioners and teachers, as well as work with so many of my close friends, colleagues, former attendings, and mentors. I would like to express my utmost gratitude for their quality contributions; their work has resulted in what I believe is one of the best anesthesia texts out there. My Publisher, Brian Brown, Senior Product Manager, Nicole Dernoski, and Lippincott Williams & Wilkins/Wolters Kluwer Health provided me with mentorship, a team of highlevel professionals, and invaluable resources. I would like to thank them for providing me with this tremendous opportunity to expand the highly successful 5 Minute Consult Series. Thank you Drs. Patricia A. Kapur, Randy Steadman, Sam Wald, Rima Matevosian, Susan Chan, Jordan Miller, Aman Mahajan, Barbara Van de Wiele, Phil Levin, Victor Duval, Nir Hoffman, Carsten Nadjat-Haiem, Keren Ziv, Eric Hsu, Kenneth Kuchta, Michael Ferrante, Michelle Braunfeld, Zhuang Fang, Swati Patel, Mitchell Lin, Michael Sopher, Ali Salehi, Siamak Rahman, Parisa Partownavid and the UCLA Department of Anesthesiology for teaching me to think critically, being patient, and serving as role-models. Your efforts, dedication, and love for teaching and your patients have had far-reaching influences on me.

12 LEAD EKG

Elizabeth Valentine, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• The 12-lead EKG is a noninvasive test that provides information on the electrical function of the heart and aids in the diagnosis of pathophysiologic processes. • Serves as a baseline for perioperative changes and as a screening tool to identify cardiac abnormalities. • Continuous 3- or 5-lead EKG is an American Society of Anesthesiologists (ASA) standard monitor used for general anesthesia and monitored anesthesia care. PHYSIOLOGY PRINCIPLES

• P wave (80 ms): Denotes atrial depolarization. Myocardial depolarization is normally initiated by spontaneous sinoatrial (SA) node depolarization. The signal is quickly and efficiently conducted along a specialized conduction pathway. In the atria, this pathway is via interatrial tracts (anterior, middle, and posterior); they begin by depolarizing the right, followed by the left, atria. The conduction cells depolarize adjacent myocardial cells, which have a different histology. • QRS (80–120 ms): Denotes the varying stages of ventricular depolarization. The Q wave is the initial negative deflection and results from septal depolarization. The R wave follows and is the first positive deflection. It results from depolarization of the larger, more muscular left ventricle; right ventricular depolarization is normally obscured. The S wave is the final negative deflection caused by lateral wall depolarization. • T wave: Denotes ventricular repolarization. The beginning of the wave represents a period of absolute refractoriness, where a subsequent depolarization (no matter how strong) cannot initiate a aberrant rhythm. The latter portion of the wave is a time of relative refractoriness, where a strong enough depolarization can result in a runaway rhythm. • PR interval (120–200 ms): Time from the start of atrial depolarization to atrioventricular (AV) nodal conduction to conduction through the His-Purkinje system. • QRS width: Represents the time for ventricular depolarization • J point: Describes the intersection between the QRS complex and ST segment. When the heart rate is increased, atrial repolarization may be observed at the very end of the QRS complex as J point depression. • ST segment: Denotes the end of depolarization to the beginning of repolarization and is usually isoelectric • QT interval (QTc 0.2 s. Second-degree AV block may be Type 1 (Mobitz 1, Wenckebach), defined as progressive prolongation of the PR interval with eventual dropped QRS; or Type II (Mobitz 2), where the PR remains unchanged prior to the sudden failure of conduction of a P wave and a dropped ventricular beat. In third-degree AV block, there is no association between P waves and QRS complexes. While first-degree and Mobitz I AV block are generally benign conditions, Mobitz II (can progress to complete heart block) and third-degree AV blocks are indications for cardiac pacing. • P waves: Abnormal P wave morphology may indicate an ectopic atrial rhythm, whereas a changing P wave morphology may suggest either a wandering atrial pacemaker or multifocal atrial tachycardia. An irregular rhythm with no clear P waves suggests atrial fibrillation. A regular “saw tooth” pattern may suggest atrial flutter. • Arrhythmias: A narrow QRS suggests a supraventricular (above the ventricles) rhythm while a wide QRS suggests either a ventricular source or aberrant conduction of a supraventricular rhythm. • QT prolongation: Prolonged QTc is a risk factor for developing ventricular arrhythmias (Torsades de Pointes) and is an independent risk factor for sudden cardiac death. QTc may be prolonged due to genetic causes (long QT syndrome), drugs (haloperidol, methadone), or diseases (hypothyroidism). • Delta waves: Describes a slurred upstroke of the QRS complex and is found in patients with Wolff–Parkinson–White (WPW) syndrome. WPW is caused by the bypass of the AV node via an accessory pathway called the bundle of Kent. This accessory pathway does not have the rate-slowing property of the AV node, thus allowing for extremely fast heart rates and potential hemodynamic instability. The combination of cardiac arrhythmias and an accessory pathway may degenerate into ventricular fibrillation. • R on T phenomenon: The beginning of the T wave is a time of absolute refractoriness; the latter portion of the wave is a time of relative refractoriness. An abnormal depolarization signal (aberrant pacemaker, PAC, PVC, cardioversion) cannot depolarize the entire ventricle during the absolute refractory period; however, it may potentially do so during the relative refractory period. This can result in degeneration into ventricular tachycardia or fibrillation. • Artificial pacemaker: May be identified by tell-tale “pacer spikes” on EKG or telemetry. May be atrial, ventricular, or sequentially paced. QRS will appear widened if ventricularly paced. • Medication toxicities: – Digoxin: Characteristic downward sloping of the ST segment. May also see an increased PR and decreased QTc interval. – Tricyclic antidepressants (TCAs): Characteristic rightward change in the frontal plane QRS vector. A large R wave in aVR is quite sensitive for TCA toxicity; may also see an increased QRS and QTc interval. • Electrolyte abnormalities: – Hypokalemia: EKG changes result from delayed ventricular repolarization. May include T wave flattening and/or inversion, ST segment depression, prominent U wave, increased P wave amplitude, and prolonged PR interval. Increased myocardial cell automaticity may predispose to atrial or ventricular arrhythmias. – Hyperkalemia: EKG changes are due to delayed depolarization and hastened

repolarization. Changes commonly progress in order from symmetrically peaked T waves → widened QRS → prolonged PR interval → loss of P wave → loss of R wave → ST depression → EKG that resembles sine wave → ventricular fibrillation → asystole. – Hypocalcemia: QTc prolongation and cardiac irritability leading to arrhythmias – Hypercalcemia: Shortened ST segment and QTc interval – Hypomagnesemia: PR and QT interval prolongation, cardiac irritability – Hypermagnesemia: May see PR prolongation and QRS widening

PERIOPERATIVE RELEVANCE

• Intraoperative bovie, electrical interference, patient shivering, tremors, or movement may closely resemble an intraoperative arrhythmia. Close inspection may reveal the QRS “marching through” the interference; other times, it may be indistinguishable from a true arrhythmia. Close evaluation of other monitors (blood pressure, pulse oximetry or arterial plethysmograph, verification of palpable peripheral pulses) may provide clues in this circumstance. • Malpositioning of leads may result in the appearance of ST changes. Thus, it is good practice to place leads in proper position if it does not interfere with the surgical field and to note baseline abnormalities in the EKG tracing. • Body habitus: Large breasts or obesity may result in low-voltage EKG. • Pulmonary artery catheters and central lines: For patients with LBBB, there is a risk of complete heart block with insertion. In this circumstance, it is prudent to have pacing capabilities readily available. Similarly, in patients with WPW, the pulmonary artery catheter or a wire for central line placement can induce a hemodynamically intolerable tachyarrhythmia. • Extracorporeal shock wave lithotripsy: Older machines time shocks to be delivered during the R wave to prevent R on T phenomenon. • Cardioversion: Machines synchronize the delivery of electrical discharge to the R wave to prevent R on T phenomenon.

GRAPHS/FIGURES

FIGURE 1. EKG waves, segments, and intervals

FIGURE 2. The 12 leads allow for assessment of the electrical function of the three-dimensional heart.

REFERENCES

1. Correll DJ, Hepner DL, Chang C, et al. Preoperative electrocardiograms: Patient factors predictive of abnormalities. Anesthesiology. 2009;110(6):1217–1222. 2. Eagle KA, Berger PB, Calkins H, et al. Practice advisory for preanesthesia evaluation: An updated report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. Anesthesiology. 2012;116:522–538.

ADDITIONAL READING

• ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery. Circulation. 2002;105:1257–1267. • Guidelines for electrocardiography: A report of the American College of Cardiology/American Heart Association Task Force on assessment of diagnostic and therapeutic cardiovascular procedures. J Am Coll Cardiol. 1992;19:473–481.

See Also (Topic, Algorithm, Electronic Media Element) • Myocardial ischemia • QT prolongation • Wolff–Parkinson–White (WPW) syndrome • Cardiac action potentia • Coronary arteries

CLINICAL PEARLS

• The axis of lead II is parallel to that of atrial depolarization; thus, it has the largest P wave and helps to determine rhythm. Lead II also represents the inferior wall of the left ventricle, which is typically supplied by the right coronary artery. EKG abnormalities in this area may suggest ischemia or disease in this distribution. • Lead V5 is most sensitive for detecting ST segment changes when a single lead is monitored

(detects abnormalities in 75% of cases). The combination of monitoring leads V5 and II increases sensitivity to 80% and leads V4 and V5 increases sensitivity to 90% for detecting intraoperative ST changes (1). • Preoperative guidelines: The ASA Task Force on Preanesthesia Evaluation does not support the ordering of any routine preoperative testing; instead, preoperative tests should be ordered on a selective basis based on patient history, exam, and surgical risk factors (2). – Important clinical factors that may make preoperative EKG evaluation useful include cardiovascular diseases (CAD, CHF, significant valvular disease), respiratory diseases (COPD, OSA, lung cancer), or highly invasive procedures. – While age >65 years old is an independent predictor for significant preoperative EKG abnormalities, there was no consensus minimum age for asymptomatic patients undergoing low-risk procedures, or in low-risk patients. • Preoperative EKG may be useful in risk-stratification in intermediate-risk and high-risk surgical patients for predicting cardiovascular death. An abnormal EKG in patients with documented CAD or at high risk for CAD and undergoing major noncardiac surgery was shown to predict long-term outcome.

ABDOMINAL AORTIC ANEURYSM Adam M. Thaler, DO Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• The normal aortic diameter is approximately 20 mm (2 cm). The aorta is considered widened, dilated, or aneurismal when it increases to 1.5 times the normal diameter. • Patients may present perioperatively for aneurismal repair as well as for nonvascular surgeries with a known (or unknown) diagnosis of an abdominal aortic aneurysm. EPIDEMIOLOGY Incidence

• 12–19% of patients with an AAA have a first-degree relative with a history of AAA. • Total incidence in the adult population: 2–4%

Prevalence

• Approximately 90% of AAAs that are found incidentally on screening are 5.5 cm in diameter) as well as growth >1 cm/year should be considered for endovascular or surgical repair. • Acute coronary or cerebral event

CLASSIFICATIONS

• There are many classification systems in determining the risk of AAA rupture which take into account the rate of increase, size, comorbid factors, etc (2). • Biggest predictors of risk of rupture (annually) are diameter of the aneurysm and rate of expansion. – 65 years old (1)[C]. • Estimated to occur in 7.7 to 26.8 per 100,000 person-years in recent large European study (remarkable variation was noted across countries). Morbidity

• Respiratory insufficiency (5–10%) • Myocardial infarction (10–15%) • Renal insufficiency (2–5%) • GI complications (3–4%) • Lower extremity ischemia (2–5%)

Mortality

• rAAA is the 13th leading cause of death in the US, with up to 15,000 deaths annually. • 30–50% of patients with a rAAA do not survive transport to a hospital. • Operative mortality after rupture ∼ 50%

ETIOLOGY/RISK FACTORS

• Risk factors associated with AAA rupture (6)[C]: – Anteroposterior aneurysm diameter >5 cm – Elevated diastolic pressure – Obstructive pulmonary disease • Causes of AAA: – Atherosclerosis (most common) (2–5)[C] – Connective tissue diseases (e.g., Marfan syndrome, Ehlers–Danlos syndrome, and cystic medial necrosis) (2)[C] – Infectious etiologies are uncommon (e.g., syphilis, salmonellosis, brucellosis, tuberculosis) (2)[C].

• Risk factors associated with presence of AAA: – Smoking: Duration (years) of tobacco exposure is more important than absolute number of cigarettes (2)[C]. – Age >65 years old – Male gender: Incidence is 4 times higher in men; women have delayed development of AAA by ∼10 years compared with men. – Hypertension – Presence of peripheral arterial aneurysms (e.g., popliteal or femoral arterial aneurysm) – Family history of AAA (first-degree relative) – Decreased serum high-density lipoprotein – Caucasian ethnicity PATHOPHYSIOLOGY

• Collagen and elastin fibers provide most of the tensile strength of the aortic wall. An imbalance between aortic wall matrix metalloproteinases and their inhibitors, chronic inflammatory infiltrates, smooth muscle apoptosis, and increased production of proinflammatory cytokines contribute to aneurysm formation. • The average rate of growth of a AAA is 0.4 cm/year • Risk of rupture is proportional to wall stress/tension, which increases as the AAA expands (Laplace’s law).

ANESTHETIC GOALS/GUIDING PRINCIPLES • Intravascular volume replacement • Inotropic support of cardiac output • Maintenance of adequate tissue oxygenation • Immediate surgical control of rupture

PREOPERATIVE ASSESSMENT SYMPTOMS

Back, chest, or abdominal pain History

• Comorbidities are common. – Atherosclerosis associated with coronary artery disease, stroke, peripheral vascular disease, and renal insufficiency – Smoking associated with obstructive pulmonary disease • Presence of connective tissue disease • Medical optimization is not feasible due to the emergent nature of the surgery.

Signs/Physical Exam

• Pulsatile abdominal mass • Hypotension

TREATMENT HISTORY

Pre-existing vascular grafts or repairs MEDICATIONS

• Vasodilators (nitroglycerin and/or nitroprusside) • Short acting beta blockers (e.g. esmolol) are utilized to decrease the heart rate.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Baseline and serial cardiac biomarkers, BUN/Cr, CBC with platelets, coagulation profile, and TEG if available • ECG may be normal or show nonspecific ST segment or T wave changes, left ventricular hypertrophy, ischemia, or infarction. • Chest radiograph may suggest concomitant pulmonary disease. • CT angiography is quick, highly sensitive, and specific; 64-slice multidetector CT with cardiac gating may allow for simultaneous evaluation of pulmonary and coronary arteries. • TEE allows rapid evaluation of cardiac function, volume status, and valvular integrity. • MRI/MRA has high sensitivity and specificity, avoids radiation, and iodinated contrast; but is more time-consuming and contraindicated with metallic implants. CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular: Coronary artery disease (30–40%), hypertension, peripheral vascular disease • Neurologic: Cerebrovascular disease • Pulmonary: Chronic obstructive pulmonary disease (COPD), smoking history • Renal: Chronic renal insufficiency • Endocrine: Diabetes mellitus

CIRCUMSTANCES TO DELAY/ CONDITIONS

None; rAAA has a mortality that exceeds 80% if not repaired. CLASSIFICATIONS

• Anterior intraperitoneal rupture (20%): Rapid bleeding into the peritoneal cavity usually results in exsanguination and death before the patient arrives at the hospital (1)[C]. • Retroperitoneal rupture (80%): Tamponade effect limits internal hemorrhage. Associated with a lower mortality rate (1)[C].

TREATMENT PREOPERATIVE PREPARATION Premedications

• Analgesia: Small incremental doses of opioids • Sedation: Avoid in hemodynamically unstable patients • Bronchodilators: Symptomatic patients with COPD • Antihypertensive/anti-anginal: Continued until time of surgery if hemodynamically stable • Blood products: pRBCs, platelets, FFP, cryoprecipitate

Special Concerns for Informed Consent • May not be possible in emergency • Blood consent

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia • Continuous epidural anesthesia may be considered if rupture is contained and coagulation status is normal. However, placement should not occur in hemodynamically unstable patients or if it will delay surgery.

Monitors

• ECG with ST-segment analysis • Arterial line: Pre-induction placement in radial artery is commonly performed. Femoral artery insertion may permit monitoring of distal perfusion pressures. • Central venous access is appropriate for monitoring pressures and administration of vasoactive medications. • TEE facilitates continuous evaluation of intravascular volume, valvular integrity, and ventricular function. • Pulmonary artery catheterization provides SvO2, SVR, CO, PAP. • Temperature (central and peripheral sites if bypass is to be used) • Foley catheter • Cell salvage, rapid infuser

Induction/Airway Management

• Slow, controlled titration of induction medications: In patients at risk for pulmonary aspiration, the decision to proceed with an RSI should be balanced against the potential for hypertension. – Control of hypertensive response to laryngoscopy and intubation can be accomplished with moderate-dose narcotics. – Avoid hypotension which may contribute to cardiac ischemia and further deterioration of peripheral perfusion. • Single-lumen endotracheal tube is sufficient for surgery contained to the abdominal cavity. Lung isolation with a double-lumen tube or bronchial blocker is preferred for procedures extending into the thorax. • Positive pressure ventilation may decrease venous return and further decrease cardiac output and peripheral perfusion.

Maintenance

• Position: Supine with transperitoneal approach; the lateral decubitus position and retroperitoneal approach may be preferred in certain situations. • Thermoregulation: Forced air and fluid warming systems are necessary due to significant heat loss with open procedures. • Fluid management: Maintenance of intravascular volume may be challenging due to

significant hemorrhage and evaporative losses; no specific colloid or crystalloid strategy has emerged as superior. • Coagulation: Consumption and dilution of coagulation factors and platelets may be significant; replacement is guided by conventional coagulation studies as well as TEG, if available. • Renal protection: Maintenance of renal blood flow and urine output is essential. IV sodium bicarbonate, mannitol, and fenoldapam may decrease the risk of kidney injury (mannitol and fenoldapam should not be used in hemodynamically unstable patients). • Placement of aortic cross-clamp – Increase in left ventricle (LV) afterload and potential for cardiac collapse. Acute increases in systemic vascular resistance (SVR) can be mitigated with vasodilators (nitroprusside, nitroglycerin, calcium channel blockers, propofol). – Decrease in venous return: Gentle administration of IV fluids may augment preload. – Suprarenal clamping decreases renal perfusion. Consider administration of mannitol (0.25–0.5 g/kg) prior to clamping. • Removal of aortic cross-clamp – Release of vasoactive metabolites into the central circulation can lead to hypotension and cardiac arrhythmias. – Decreases in the SVR are mitigated with IV fluids and vasopressors (phenylephrine or epinephrine). Profound, unresponsive hypotension can be temporarily treated with reinstigation of the aortic clamp.

Extubation/Emergence

• Ongoing cardiac or pulmonary instability, bleeding, hypothermia, or neurologic injury may necessitate continued mechanical ventilation; otherwise patients may be extubated at the conclusion of the procedure. • Pain, hypertension, and tachycardia should be anticipated and addressed.

POSTOPERATIVE CARE BED ACUITY

• Intensive care unit • Monitoring of BP, HR, and LV function • Analgesia with intravascular or neuraxial opioids • Continued assessment of graft patency and peripheral perfusion

COMPLICATIONS

• Hemorrhage • Coagulopathy • Myocardial ischemia/infarction • Renal failure • Incision and/or graft infection • Spinal cord ischemia, paralysis • Impotence • Bowel ischemia

• Embolism • Lower extremity ischemia • Pneumonia, respiratory insufficiency • Hypothermia

REFERENCES

1. Assar A, Zairians C. Ruptured abdominal aortic aneurysm: A surgical emergency with many clinical presentations. Postgrad Med J. 2009;85:268–273.

2. rattheim BJ, Elkemo TA, Altreuther M, et al. Regional disparities in incidence, handling and outcome of patients with symptomatic ruptured abdominal aortic aneurysms in Norway. Eur J Endovasc Surg. 2012.

3. ozniak F, LaMuraglia GM, Musch G, et al. Anesthesia for open abdominal surgery. Int Anesth Clin. 2005;43(1):61–78. 4. Thompson R, Geaghty P, Lee J. Abdominal aortic aneurysms: Basic mechanisms and clinical implications. Curr Probl Surg. 2002;39:110–130. 5. Adam van der Vliet J, Boll A. Abdominal aortic aneurysms. Lancet. 1997;349:863–866. 6. Bernstein E, Chan E. Abdominal aortic aneurysm in high risk patients: Outcome of selective management based on size and expansion rate. Ann Surg. 1984;200(3):255–263. 7. Falk J, Rackow EC, Blumenberg R, et al. Hemodynamic and metabolic effects of abdominal aortic cross-clamping. Am J Surg. 1981;142:174–177. 8. Subramaniam B, Singh N, Roscher C, et al. Innovations in treating aortic diseases: The abdominal aorta. J Cardiothorac Vasc Anesth. 2011 (article in press). 9. Gelman S. The pathophysiology of aortic cross clamping and unclamping. Anesthesiology. 1995;82(4):1026–1060.

See Also (Topic, Algorithm, Electronic Media Element) • Abdominal aortic aneurysm • Abdominal aortic aneurysm dissection

CODES ICD9 441.3 Abdominal aneurysm, ruptured ICD10 I71.3 Abdominal aortic aneurysm, ruptured

CLINICAL PEARLS

• rAAA is a surgical emergency. Mortality exceeds 80% without intervention; with repair it can decrease to ~50%. • Patients often present with significant cardiac, cerebral, and/or renal vascular disease.

• Application of the aortic cross-clamp leads to an abrupt increase in afterload and may precipitate cardiac collapse. • Removal of the aortic cross-clamp causes a decrease in SVR and release of vasoactive metabolites into the central circulation.

ABDOMINOPERINEAL RESECTION (APR) Vijaya Gottumukkala, MB, BS, MD, FRCA

BASICS DESCRIPTION General

• Ernest Miles (1869–1947) devised the approach in the 1930s as a curative procedure for all rectal cancers. It involves resection of the anus, rectum, and a portion of the sigmoid colon, as well as a wide perineal and lymph node dissection. • Abdominoperineal resection (APR) is now reserved for conditions where the rectum needs to be removed and there is involvement of the primary sphincter complex or tumors in the lower third of the rectum that do not have adequate clearance for sphincter preservation. It requires a permanent colostomy. • Laparoscopy-assisted APR and low anterior resection (LAR) are more commonly performed today. LAR is a modified technique that allows for sphincter preservation. Position

• Modified lithotomy • Trendelenburg, as needed

Incision

Midline abdominal and perineal Approximate Time 5–10 hours

EBL Expected

500–1,500 mL Hospital Stay 7–10 days

Special Equipment for Surgery

• 2 table set-up (abdominal and pelvic sets) • Long pelvic instruments, stapling devices • Cystoscopy set with ureteric stents

EPIDEMIOLOGY Incidence

• Colorectal cancer is the 4th most common cancer and the second leading cause (10%) of all cancer-related deaths.

• From 2003 to 2007, the median age at diagnosis for colorectal cancer was 70 years of age. At diagnosis, about 20% had distant metastasis. • 5–10% of all colorectal cancers are associated with a familial colorectal cancer syndrome, and an additional 15–20% are associated with a familial disposition. • Risk for colorectal cancer increases with age (90% of cases occur in patients >50 years), and with a diet rich in red meat and animal fat. • Aspirin, NSAIDs, and COX-2 inhibitors have been reported to have protective effects against colorectal cancer.

Prevalence

• As of January 1, 2007, in the US there were approximately 1,112,493 men and women alive with a history of colon and/or rectal cancer. • Based on rates from 2005 to 2007, 5.12% of men and women born today will be diagnosed with cancer of the colon and/or rectum during their lifetime. • High incidence of local recurrence despite margin-free resection

Mortality

• The overall 5-year relative survival in the US for 1999–2006 was 65.0%; for high-risk patients it is 20%. • Hormone replacement therapy has been shown to significantly reduce mortality in women with colorectal cancer.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patient population with sequelae related to the primary pathology and significant medical comorbidities (age, smoking, diabetes, hypertension, atherosclerosis, coronary artery disease, malnutrition). Optimize preoperative comorbid burden for optimal postoperative recovery. • Maintenance of tissue oxygenation, perfusion, and euvolemia. Patients are often placed on a clear liquid diet 1–3 days prior to surgery, combined with bowel prep (laxative, enemas, whole gut irrigation with saline via a nasogastric tube, polyethylene glycol electrolyte lavage, or mannitol solution). • Effective analgesia (epidural preferred for open procedures) • Extubation at the end of surgery • Postoperative monitoring in a high-dependency unit for 48 hours

PREOPERATIVE ASSESSMENT SYMPTOMS

• Symptomatic, depending on the size and location of the tumor • Change in bowel habits and pencil stools • Rectal or lower abdominal pain, spotting of blood in stool, lower GI bleeding, hematochezia, and tenesmus • May be acutely or chronically ill depending on the primary pathology (Crohns disease, ulcerative colitis)

History

• Inflammatory bowel diseases (Crohns disease, ulcerative colitis), inherited colon cancers (familial adenomatous polyposis, Gardner syndrome, Peutz–Jeghers syndrome, juvenile polyposis, and hereditary non-polyposis colon cancer) • Careful assessment of the sequelae and complications of the primary colonic/rectal pathology, medical comorbidities, nutritional and functional status Signs/Physical Exam

• Systemic signs of inflammatory bowel disease (IBD) • Anemia, weight loss, fever of unknown origin • Abdominal wall and/or internal colonic fistulae • Palpable mass in the recto-sigmoid on examination

MEDICATIONS •

Therapy for IBD: Antidiarrheals, aminosalicylates (5-ASA), corticosteroids, immunomodulators (azathioprine and 6-mercaptopurine, cyclosporine), antibiotics, and pain medications • Patient may have recently completed adjuvant chemoradiation prior to surgery and/or planned for after surgery. • Chemotherapy for colorectal cancer is 5-FU and leucovorin based. Irinotecan or oxaliplatin is added in metastatic disease. • Medications for the comorbidities (antihyperglycemics, antihypertensives, anticholesterol medications, aspirin, etc.) DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC, PT/PTT, creatinine, prealbumin, and LFTs • Electrolytes if on diuretics, ACE I, renal insufficiency • Colonoscopic evaluation (location, size, and number of masses) • CT scan (tumor location, size, perirectal and vascular involvement, peritoneal and liver metastasis) • Other tests (TEG, ECG, CXR, cardiac echocardiogram, exercise stress test, PFTs) as indicated

CONCOMITANT ORGAN DYSFUNCTION

• Anemia from bleeding or occult blood loss • Metastasis: Abdominal pain (hepatomegaly) and liver dysfunction from hepatic metastasis; skeletal pain from bony metastasis; ascites from peritoneal dissemination; bladder dysfunction, sacral or sciatic neuropathy, and vaginal discharge and bleeding from pelvic metastasis • Obesity/malnutrition • Inflammatory bowel disease and its associated sequelae • Age-related morbidities: Diabetes, hypertension, coronary artery disease

TREATMENT

PREOPERATIVE PREPARATION Premedications

• Anxiolytic and analgesic medications, as needed • Gastric volume reducing and acid-neutralizing medications, if indicated • Continue appropriate medications (antibiotics, anti-inflammatory/immunomodulators, antihypertensives, antiarrhythmics, and others) as needed • There is an increasing trend to use alvimopan to hasten recovery of bowel function.

Special Concerns for Informed Consent

• Blood consent for possible transfusion • Consent for epidural catheter for postoperative analgesia • Potential for postoperative intubation and intensive care

Antibiotics/Common Organisms

• Prophylactic cefotetan or cefoxitin; metronidazole plus an aminoglycoside may be used for cephalosporin allergy. • Gram-negative aerobes and anaerobic bacteria • Mechanical bowel preparation decreases fecal bulk, but does not decrease the concentration of bacteria in the stool.

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with ETT • Epidural catheter for postoperative analgesia: Need to rule out contraindications, review medication list (herbals, clopidogrel, low-molecular-weight heparin, or other drugs that alter coagulation), consider preoperative PT/PTT/INR or other advanced coagulation tests as needed (TEG, PFA). Not contraindicated with usual thromboprophylaxis for postoperative DVT (heparin 5,000 U SQ BID).

Monitors

• ASA standard monitors • Arterial line (beat-to-beat blood pressure monitoring, systolic pressure variation [SPV] to evaluate intravascular volume status, blood draws for lab work); consider placing the arterial line pre-induction for high-risk patients. • 2 large-bore IVs for volume resuscitation if needed. Central line access is not usually necessary unless there is poor IV access or a need for postoperative TPN. • Foley catheter: Ureteric stents are placed preoperatively to identify ureters during the resection.

Induction/Airway Management

Standard induction technique and strategies to maintain hemodynamic stability and full stomach precautions if indicated Maintenance

• Avoid nitrous oxide. Air–oxygen mixture with an FiO2 of 0.5 will help identify oxygenation

issues early. • Continuous epidural infusion of local anesthetic/narcotic mixture may be used for analgesia throughout the procedure. • Nasogastric tube placement may be requested. • Volume: APR is a major procedure with complex bowel resection; bleeding may be encountered from the presacral venous plexus. Additionally, insensible fluid losses can result. Intravascular volume status and maintenance of organ perfusion should be closely monitored. • Surgeon may request intraoperative indigo carmine to rule out injury to the ureters; it may temporarily result in a decrease in the pulse oximeter reading. • Blood glucose, serum electrolytes, ABG, ACT and other coagulation parameters as may be checked needed. Extubation/Emergence

• Standard extubation criteria • Post-extubation sensory–motor exam and evaluation of epidural puncture site for effectiveness and complications

POSTOPERATIVE CARE BED ACUITY

• High-dependency unit or ICU for 48 hours • May need monitoring of invasive hemodynamic parameters to guide fluid volume/blood product transfusion ANALGESIA

• Epidural: Follow ASRA guidelines for maintenance and removal of epidural catheters • Multimodal approach involving IV PCA if epidural contraindicated or laparoscopic procedure COMPLICATIONS

• Intra-abdominal abscess, wound infections (10%), anastomotic leaks (15%) • Postoperative ileus • Injury to the ureters, hypogastric or parasacral nerve plexus • Postoperative fever and leukocytosis are not uncommon. • Adverse cardiac events (hypotension, hypertension, arrhythmias, ischemia, infarct, and CHF) • Postoperative delirium in elderly • Postoperative neuropathies from positioning • Epidural site infection or hematoma (very rare)

PROGNOSIS

• Overall local recurrence is 30% after a margin-free resection. • The best prognosis in patients with locally advanced rectal cancer appears to be after preoperative chemoradiation, maximal surgical resection (margin free), and localized

intraoperative radiation therapy (IORT) in selected cases.

REFERENCES

1. Ferg BW, Berger DH, Fuhrman GM. Cancer of the colon, rectum and anus. In: Chang G, Feig BW. The M.D. Anderson surgical oncology handbook, 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2006:261. 2. Lindholm ML, Träff S, Granath F, et al. Mortality within 2 years after surgery in relation to low intraoperative bispectral index values and preexisting malignant disease. Anesthes Analges. 2009;108(2):508–512.

3. Green D, Paklet L. Latest developments in the peri-operative monitoring of the high risk surgical patient. Int J Surg. 2010;8(2):90–99. 4. Kimberger O, Arnberger M, Brandt S, et al. Goal-directed colloid administration improves the microcirculation of healthy and perianastomotic colon. Anesthesiology. 2009;110(3):496–504.

ADDITIONAL READING

• Cancer Facts and Figures 2010. Atlanta, GA: American Cancer Society, 2010. • Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute

See Also (Topic, Algorithm, Electronic Media Element) • Insensible fluid losses • International normalized ratio • Partial thromboplastin time • Prothrombin time

CLINICAL PEARLS

• Major bowel resection surgery can require significant blood products and fluid resuscitation in the perioperative period. • There exists a risk for positioning and surgery-related neuropathies. • Patients are prone to the occurrence of late DVTs.

ACE INHIBITORS AND HYPOTENSION John B. Carter, MD

BASICS DESCRIPTION

• Significant hypotension has been reported after the induction of general anesthesia in patients on angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs). • At this time, guidelines have not been established regarding preoperative management (withdrawal or continuation) of ACEI or ARBs. Large randomized controlled studies are lacking and most information stems from retrospective studies: – Elective, noncardiac surgical patients who have taken ACEI or ARBs on the morning of surgery appear to have an increased risk of moderate hypotension (systolic blood pressure [SBP] 70 mm Hg (7), with higher MAPs often necessary in chronic HTN. MAPs 50 • Baseline MAP 100 mm Hg) (7).

• Patients surviving anaphylaxis or malignant hyperthermia, or those with a difficult airway, should be given documentation they can bring for future operative encounters (7).

CLOSED CLAIMS DATA

• Death or brain damage was associated with induction of anesthesia in 62% of cases during 1985–1992, versus 35% of cases from 1993 to 1999 (8). • Caplan et al. describe 14 cases of high spinal, suggesting that bradycardia is an important early warning sign and that epinephrine is associated with ROSC (3).

Pregnancy Considerations

• The gravid uterus can compress the aorta and IVC after the 20th week of gestation. • Resuscitation of the mother may not be possible until the fetus is delivered by emergency hysterotomy. • During arrest, hysterotomy should be performed at the bedside since there is insufficient time to transport the patient to the OR.

Pediatric Considerations

• CPR recommendations in pediatric patients vary by the patient’s age. • Resuscitation drugs should be dosed according to the patient’s weight. • Intravenous access can be uniquely difficult in pediatric patients. Intraosseous lines are a method to get quick reliable access to the circulation. • Cardiac output in children frequently depends on heart rate (rather than on contractility), making the treatment of bradycardia an important part of pediatric resuscitation.

REFERENCES

1. American Heart Association. ACLS Provider Manual, 2010. 2. Newland MC, Ellis SJ, Lydiatt CA, et al. Anesthetic-related cardiac arrest and its mortality: A report covering 72,959 anesthetics over 10 years from a US teaching hospital. Anesthesiology. 2002;97:108–115. 3. Zuercher M, Ummenhofer W. Cardiac arrest during anesthesia. Curr Opin Crit Care. 2008;14:269–274. 4. Peterson GN, Domino KB, Caplan RA, et al. Management of the difficult airway: A closed claims analysis. Anesthesiology. 2005;103:33–39. 5. Gabrielli A, O’Connor MF, Maccioli GA. Anesthesia-centric ACLS. Available at: http://www.asahq.org/For-Members/Publications-and-Research/ ∼/media/For%2520Members/Publications/Other/Anesthesiology-CentricACLS.ashx. 6. Nichol G, Thomas E, Callaway CW, et al. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA. 2008;300:1423–1431. 7. Sprung J, Warner ME, Contreras MG, et al. Predictors of survival following cardiac arrest in patients undergoing noncardiac surgery: A study of 518,294 patients at a tertiary referral center. Anesthesiology. 2003;99:259–269.

8. Caplan RA, Ward RJ, Posner K, et al. Unexpected cardiac arrest during spinal anesthesia: A closed claims analysis of predisposing factors. Anesthesiology. 1988;68:5–11.

ADDITIONAL READING

• Cheney FW. The American Society of Anesthesiologist closed claims project: What have we learned, how has it affected practice, and how will it affect practice in the future? Anesthesiology. 1999;91:552–556. • Cheney FW, Posner KL, Lee LA, et al. Trends in anesthesia-related death and brain damage: A closed claims analysis. Anesthesiology. 2006;105:1081–1086.

CODES ICD9 427.5 Cardiac arrest ICD10 I46.9 Cardiac arrest, cause unspecified

CLINICAL PEARLS

• Cardiac arrest associated with anesthesia is different; good recovery is frequent with timely intervention. • Hypovolemia is a common cause of arrest and vigilance is important. Pulse pressure variation >15% can be an important clue to volume responsiveness. • Take no more than 10 seconds to find a pulse before starting compressions. • Bradycardia and asystole are often related to reversible factors.

ACROMEGALY Adam Thaler, DO

BASICS DESCRIPTION

• The term acromegaly comes from the Greek words for “extremities” and “enlargement.” • Acromegaly is a condition caused by an abnormal overproduction of growth hormone (GH) from the anterior pituitary, usually by a pituitary tumor. The result is an overgrowth of skeletal, soft, and connective tissues. Enlargement is seen in: – Major organs including the heart, lungs, liver, and kidney – Hands, feet, jaw, and tongue – Airway anatomy including the tongue, epiglottis, mandible, and generalized soft tissue (making airway management potentially difficult) EPIDEMIOLOGY Incidence

• Annual new patient incidence: 3–4 per million per year • In the US: 1:20,000 persons

Prevalence

• Most common age at diagnosis is 40–45 years. • All ethnic groups and gender are affected equally.

Morbidity

• Increased prevalence of cardiovascular risk factors • Difficult airways are seen in 10–43% of patients (compared to 3.6% in the general population). Mallampati Class I and II may present with airway difficulty in up to 20% of patients. Mortality

• Premature death can occur twice as frequently when GH concentration is >10 ng/mL. • Cardiovascular causes are the most frequent cause of death in untreated acromegaly; the majority of patients die before the age of 50 years. • Survival in patients with uncontrolled disease is reduced by an average of 10 years compared with age-matched controls. ETIOLOGY/RISK FACTORS

• No major risk factors • Weak risk factors include: – MEN type I syndrome – McCune–Albright syndrome

– Isolated familial acromegaly – Carney complex – Family history of aryl hydrocarbon-receptor interacting protein (AIP) mutation

PATHOPHYSIOLOGY

• Hypothalamus: Growth hormone-releasing hormone (GHRH) is produced and secreted by the hypothalamus via the hypophyseal tract to the anterior pituitary gland (as is somatostatin). • Pituitary gland: GHRH stimulates the anterior pituitary gland to produce and secrete GH into the bloodstream, whereas somatostatin inhibits GH production and secretion. • Tissues: GH travels to and stimulates the liver to produce another hormone called insulinlike growth factor 1 (IGF-1). IGF-1, in turn, promotes growth of bone and other tissues. • “Feedback loop”: Normally, levels of GHRH, GH, somatostatin, and IGF-1 are tightly controlled by each other. Levels are affected by: Sleep, exercise, stress, food intake, and blood sugar levels. • Excessive GH results from pituitary adenomas in >95% of cases. Secretion of GH by a pituitary tumor is not controlled by the feedback loop resulting in excessive IGF-1 with subsequent abnormal tissue growth. – Carbohydrate and fat processing is affected causing diabetes and high levels of fats in the blood. This, in turn, can lead to atherosclerosis and heart disease. – Myocardial growth can result in conduction disturbances. – Hepatomegaly – Kidneys: Positive fluid balance may be due to chronic hypertension, causing vasoconstriction, preoperative hypovolemia, lower cardiac output, fluid volume dysautoregulation, and/or renal dysfunction. – Lungs: Lower arterial pH – Tumors can also grow to considerable size and cause problems by pressing on and invading surrounding tissues. • Gigantism is the term used when acromegaly occurs in children.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients with acromegaly may have glottic or subglottic stenosis, nasal turbinate enlargement, vocal cord thickening, or recurrent laryngeal nerve involvement. Be aware of the potential for a difficult airway, perform a careful exam, and consider having backup airway devices available. • Address comorbid conditions including diabetes, hypertension, and cardiac disease.

PREOPERATIVE ASSESSMENT SYMPTOMS

• May be divided into 2 groups: Tumor compression of surrounding tissues or those caused by excess GH and IGF-1 in the blood. Compression of surrounding tissues can present as headaches or partial loss of vision in one or both eyes. Bitemporal hemianopsia is due to pressure on the optic chiasm.

• Pituitary tumors also can damage the pituitary gland itself, disrupting hormone production. Hormone imbalances are responsible for symptoms such as impotence, low sex drive, and changes in the menstrual cycle. • Symptoms due to excess GH or IGF-1 include increase in ring size or tightness of rings (“sausage-like” fingers), shoe size, sweating, jaw prominence, as well as coarseness or thickening of facial features (especially the nose), macroglossia, or skin tags. History

• Onset: The average time from onset to symptoms to diagnosis is 12 years. • Snoring may suggest obstructive sleep apnea; present in 75% of patients. If on CPAP, establish settings. • If the patient has diabetes mellitus, assess blood sugar control; present in 25% of patients.

Signs/Physical Exam

• Musculoskeletal: – Prognathism – Osteoarthritis – Osteoporosis – Kyphosis – Skeletal muscle weakness • Airway: – Macroglossia – Vocal cord thickening with hoarseness – Thickening of the laryngeal and pharyngeal soft tissues: Leading to subglottic narrowing – Enlarged epiglottis – Hypertrophy of the periepiglottic folds – Calcinosis of the larynx – Recurrent laryngeal nerve injury • Endocrine: – Peripheral neuropathy – Thyroid nodule; goiter (25%): May compress trachea • Cardiovascular: – Increased prevalence of valvular heart disease Significant AI (30%) Significant MR (5%) – Hypertension (46%)—volume overload Cardiomegaly Dysrhythmias (40%) LV dysfunction: EF ∼ 42% CHF (3–10%)

MEDICATIONS

• Octreotide is a somatostatin analog that inhibits GH secretion. It is capable of causing GI side effects such as nausea, bloating, and gas in up to 30% of patients. • Dopamine agonists, bromocriptine and cabergoline, work at the level of the pituitary to

reduce GH and subsequent IGF-1 secretion. • Pegvisomant is a GH receptor blocker and a new category of drugs. Studies have shown that it normalized IGF-1 levels in >90% of people treated. Side effects include reaction at the injection site, sweating, headache, and fatigue.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• GH and IGF-1 levels • GH suppression test is a confirmatory test measured before and after drinking 75 g of glucose. The inability to sufficiently suppress serum GH confirms the diagnosis. • ECG changes, such as ST-segment depression, T-wave abnormalities, and conduction defects, are noted in >50% patients. • Chest radiography can show bone thickening. • CT or MRI of the head to confirm that an adenoma is in the pituitary gland. • CT scans of the abdomen/pelvis and chest look for tumors of the pancreas, adrenal glands, ovaries, or lung that might secrete GH or GHRH.

CONCOMITANT ORGAN DYSFUNCTION • Hypertension • Diabetes mellitus • Arthritis • Colonic polyps • Coronary artery disease • Conduction disturbances

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Severe symptoms such as CHF or critical aortic stenosis • Returning GH levels to normal can reduce the incidence of upper respiratory tract complications. Regression of the mucosal hyperplasia and thickening could be achieved preoperatively.

CLASSIFICATIONS

• Biochemical criteria: – Elevated age- and sex-matched plasma IGF-1, random plasma GH >0.4 mcg/L, and lack of GH suppression below 1 mcg/L following an oral glucose load – Severity is judged according to GH levels, which correlate with the tumor mass. • Imaging criteria: Severity of pituitary adenoma judged according to: – Pituitary tumor volume – Suprasellar extension and compression of neural structures – Invasion of sphenoid bone and cavernous sinuses • Pathology criteria: Positive GH immunostaining confirms the diagnosis of a pituitary GHsecreting adenoma. On the basis of the number of cytoplasmic granules, somatotroph adenomas are divided into 2 types: – Densely granulated – Sparsely granulated (more aggressive)

TREATMENT PREOPERATIVE PREPARATION Premedications

• Antihypertensive medications, as needed • Insulin, as needed

INTRAOPERATIVE CARE Choice of Anesthesia

Regional blocks may be considered to avoid airway instrumentation; however, in the event of a complication, or failed block, it would require airway instrumentation in less than ideal conditions or emergently. Monitors

• Standard ASA monitors • Arterial line may be considered in patients with poorly controlled hypertension or diabetes, or with coronary artery disease. • Foley catheters may be placed to carefully monitor fluid management; patients may be 1,200–1,500 mL overloaded.

Induction/Airway Management

• Preparations should be made for a potential difficult airway. – Larger face mask may be required because of prognathism. – Smaller ETT may be needed because of subglottic narrowing and distortion. – If direct laryngoscopy is difficult, fiberoptic intubation can also be challenging.

Maintenance

• Balanced anesthetics with volatiles and intravenous agents have been utilized. • Hypertension may be seen intraoperatively, especially after the nasal septum is prepped with cocaine, epinephrine, or phenylephrine. • In patients with aortic regurgitation, “fast and loose” describes providing afterload reduction and higher heart rates. Bradycardia and increases in SVR increase the regurgitant volume in patients with aortic regurgitation. • Glucose monitoring may be necessary in long cases or in poorly controlled diabetics. • Fluid regulation may be altered: Urine output is significantly lower in acromegalic patients resulting in greater positive fluid balance.

Extubation/Emergence

Patients are at increased risk for airway obstruction and may have difficult airways; ensure that the patient is fully awake and following commands before extubating.

POSTOPERATIVE CARE BED ACUITY

• Consider supplemental oxygen (nasal cannula, face mask) • Prepare for the potential backward displacement of the already large tongue post-extubation that may cause respiratory compromise.

COMPLICATIONS

• Airway difficulties • Mild perioperative metabolic problems occur with respect to blood glucose and fluid balance.

REFERENCES

1. Nemerget EC, Dumont AS, Barry UT, et al. Perioperative management of patients undergoing transsphenoidal pituitary surgery. Anesth Analg. 2005;101:1170–1181.

2. Seidman PA, Kofke WA, Policare R, et al. Anaesthetic complications of acromegaly. Br J Anaesth. 2000;84(2):179–182. 3. Hakala P, Randell T, Valli H. Laryngoscopy and fiberoptic intubation in acromegalic patients. Br J Anaesth. 1998;80(3):345–347. 4. Scacchi M, Cavagnini F. Acromegaly. Pituitary. 2006;9(4):297–303. 5. Nabarro JD. Acromegaly. Clin Endocrinol (Oxf). 1987;26(4):481–512.

ADDITIONAL READING

• Katznelson L, Atkinson JL, Cook DM, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly-2011 update: Executive summary. Endocr Pract. 2011;17(4):636–646.

See Also (Topic, Algorithm, Electronic Media Element) • Cushing syndrome • Diabetes mellitus • Difficult airway

CODES ICD9 253.0 Acromegaly and gigantism ICD10 E22.0 Acromegaly and pituitary gigantism

CLINICAL PEARLS

• Greater than 50% of patients develop cardiac complications: Cardiomyopathy with arrhythmias, left ventricular hypertrophy, decreased diastolic function, hypertension • Greater than 60% of patients develop respiratory complications: Upper-airway obstruction with sleep apnea, associated with soft-tissue laryngeal airway obstruction and central sleep

dysfunction

ACUTE ADRENAL INSUFFICIENCY Cristina Cunanan, MD Anahat Dhillon, MD

BASICS DESCRIPTION

• Also called adrenal crisis, acute adrenal insufficiency is a life-threatening condition secondary to inadequate adrenal steroid production not matching increased demands during stress (e.g., infection, surgery) (1). • Manifestations result from mineralocorticoid deficiency, in association with prostaglandin excess, and decreased responsiveness to norepinephrine and angiotensin II (2): – Severe hypotension – Circulatory collapse – Hypothermia – Altered mental status – Hypoglycemia • Primary adrenal insufficiency (PAI) (3): – All 3 layers of the adrenal cortex are affected. – Involves glucocorticoid, mineralocorticoid, and adrenal androgen deficiencies – Seen with autoimmune adrenalitis, adrenal hemorrhage, adrenalectomy, AIDS, and tuberculosis • Secondary adrenal insufficiency (SAI) (2): – Results from disorders of the hypothalamic–pituitary–adrenal (HPA) axis that may involve tumors, irradiation, trauma, surgery, exogenous glucocorticoid therapy (most common), enzyme inducers that enhance the clearance of synthetic glucocorticoids (rifampin and carbamazepine), or drugs that inhibit cortisol synthesis (ketoconazole, etomidate) (3) – These conditions can cause a deficiency in adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone (CRH), leading to atrophy of the adrenal zona fasciculata where glucocorticoids are synthesized. – Mineralocorticoid function is better maintained, and hence, less likely to cause an adrenal crisis. • Initiation of thyroxine replacement in patients with hypothyroidism may induce adrenal crisis due to increased cortisol metabolism (4).

EPIDEMIOLOGY Incidence

3.3–6.3 adrenal crisis per 100 patient years (4,5) Prevalence

• Of PAI, 93–140 per million; age of diagnosis peaks in the 4th decade of life; women more frequently than men (5).

• Of SAI, 150–280 per million; age of diagnosis peaks in the 6th decade of life; women more frequently than men (5).

Morbidity/Mortality

• Data regarding morbidity and mortality in patients with adrenal insufficiency are scarce (6). • The risk ratio for death is more than 2-fold higher in patients with PAI; it is attributed to malignancy and cardiovascular and infectious diseases (7). • In patients with PAI, mean age at death for females is 75.7 years, and for males mean age is 64.8 (this is 3.2 and 11.2 years less than the estimated life expectancy, respectively) (8). • In children with PAI, there is a 3- to 4-fold increase in mortality compared with the general population (8).

ETIOLOGY/RISK FACTORS

• Risk of adrenal crisis is higher in: – PAI compared to SAI (3.3–6.6 per 100 vs. 2.5–5.8 per 100) – Women compared to men (4.4 per 100 vs. 1.6 per 100 years) (4,5) • In SAI patients, there is a higher risk of adrenal crisis in female patients and with the presence of diabetes insipidus. • Precipitating factors for adrenal crisis include (5): – Infectious disease (particularly GI infections) – Surgery – Strenuous physical activity – Cessation of glucocorticoid replacement – Psychic distress – Heat – Pregnancy

PHYSIOLOGY/PATHOPHYSIOLOGY

• HPA axis is vital to the body’s ability to cope with severe stress, such as that induced by natural or iatrogenic trauma or infection. • Adrenal cortex produces glucocorticoids (mainly cortisol) and mineralocorticoids (mainly aldosterone); these hormones are required for the maintenance of metabolic control, blood volume, and normal cardiovascular function. • Surgery, anesthesia, trauma, and severe illness result in elevated ACTH and cortisol levels, from a normal cortisol secretion rate of 10 mg/d to 75–150 mg/d during stress; and this response is absent in patients with adrenal insufficiency. • Mineralocorticoids are produced by the zona glomerulosa under the control of the renin– angiotensin system: – Facilitates sodium and potassium homeostasis and the maintenance of intravascular volume – Primary target is the kidney, where it stimulates reabsorption of sodium and secretion of potassium and hydrogen ions. – Deficiency results in salt wasting and volume depletion. • Glucocorticoids have multiple effects on body tissues including: – Increased gluconeogenesis

– Increased angiotensin synthesis by the liver – Increased vascular reactivity to vasoconstrictors – Decreased capillary permeability – Decreased production and activity of nitric oxide – Alteration of kinin and prostaglandin systems – Facilitate conversion of norepinephrine to epinephrine in the adrenal medulla • Glucocorticoid deficiency, therefore, results in decreased vascular responsiveness to angiotensin II and norepinephrine, decreased synthesis of renin substrate, and increased prostacyclin production which can aggravate the circulatory collapse seen in mineralocorticoid deficiency. • Chronic use of exogenous corticosteroids given in supraphysiologic doses leads to the development of SAI, and the amount of adrenal suppression depends on the dose, duration, frequency, time and route of administration and can occur as early as 1 week after commencing therapy (3).

PREVENTATIVE MEASURES

• Anesthetic plan should avoid the use of drugs that inhibit cortisol synthesis (e.g., etomidate) in patients at risk. • Controversy remains over whether supplemental perioperative steroids are required for patients on maintenance doses of corticosteroids who undergo surgery (9). A 2009 Cochrane review of randomized controlled trials of supplemental perioperative steroids concluded that there is inadequate evidence to support or refute the use of supplemental perioperative steroids, but it is likely that the administration of daily maintenance steroid dose may be sufficient and supplemental doses are not required. • While this topic is controversial and the optimal dose and duration of perioperative glucocorticoid coverage have also not been established, the following recommendations are based on a review of expert opinion and clinical experience (3): – For minimal stress procedures (5 days is at risk for suppression of the HPA axis; if on therapy for 1 month, HPA axis suppression can last up to 6–12 months after cessation of therapy (10). – Other modes of steroid administration should be noted, such as topical, inhaled, and regional (10). • Maintain a high level of suspicion for adrenal crisis in cases of unexplained hypotension refractory to catecholamines, especially in patients with increased risk (e.g., prior glucocorticoid therapy, autoimmune disease, AIDS) (2). • ACTH stimulation test involves the administration of cosyntropin 250 mcg IV (synthetic ACTH hormone), followed by serum cortisol measurements at 30 minutes and 60 minutes. Plasma cortisol values: – 20 mg/d of prednisone equivalent for >5 days is at risk for SAI. • There is inadequate evidence to support empiric use of supplemental corticosteroids in patients with risk factors for SAI.

ACUTE NORMOVOLEMIC HEMODILUTION Teresa L. Moon, MD

BASICS DESCRIPTION

• Acute normovolemic hemodilution (ANH) is a strategy that may be implemented to decrease the need for blood transfusions and their associated risks; it is a form of autologous blood transfusion. Other commonly utilized techniques include preoperative autologous donation and cell salvage. • The process of ANH entails the controlled removal of whole blood from the patient prior to incision and blood loss and simultaneous replacement with an appropriate volume of crystalloid or colloid (non-red cell containing), in order to maintain normovolemia and avoid hypotension. • The goal is to decrease the loss of red cell mass (as well as other blood cells and proteins) during surgical bleeding. ANH has the following advantages: – No risk of transfusion error – No risk of disease transmission – Simple – Inexpensive – Minimal use of collective resources – Stored in the operating room – Whole blood with all components is returned to the patient; minimal loss of coagulation factors and platelets secondary to limited storage time. – Does not require significant coordination with the patient and blood bank (unlike autologous blood donation) PHYSIOLOGY PRINCIPLES

• Transient intraoperative anemia is achieved by removing whole blood to a target hematocrit while concurrently administering crystalloid or colloid to maintain normovolemia. By decreasing the hematocrit, there is a reduced loss of erythrocyte mass during surgical bloodshed. • Hemodynamics during dilutional anemia – Combination of decreased blood viscosity and local vasoregulatory factors. The endothelium senses changes in intraluminal blood flow, shear stress, and the chemical environment that result from hemodilution and changes in cardiac output; it appears to respond by releasing NO and causing vasodilation. Additionally, studies have suggested that hemodilution may decrease the blood’s ability to scavenge and inactivate NO (results in increased levels). Autonomic nervous system-mediated vasodilation does not appear to play a significant role. – Cardiac output is increased (stroke volume) secondary to decreased viscosity (decreased afterload/tension of the left ventricle); the myocardium is capable of ejecting more

volume. – Mean arterial pressure is usually maintained within the limits of normal, secondary to the compensatory increase in cardiac output. – Heart rate may increase with profound anemia. • Critical red cell mass: A concept that describes the lower limit of hemoglobin that is capable of maintaining effective oxygen delivery. Below this threshold, ischemia and anaerobic metabolism/lactate production can result. • Unlike techniques such as deliberate hypotension, ANH does not directly decrease surgical blood volume loss.

ANATOMY

• Phlebotomy may be performed via a: – Large vein in the periphery; newly placed or pre-existing large-bore IV catheter or onetime stick – Central line – Arterial line

DISEASE/PATHOPHYSIOLOGY

• Decreased blood oxygen carrying capacity occurs secondary to hemodilution. Studies have demonstrated that tissue oxygenation is usually not sacrificed if normovolemia is maintained. • Cardiac ischemia: Usually presents with tachycardia and ECG changes as a result of decreased oxygen delivery • Edema may be present postoperatively if large volumes of crystalloid and/or colloids are used to maintain normovolemia.

PERIOPERATIVE RELEVANCE

• Indications: – Spinal surgery – Prostatectomy – Hysterectomy – Hip arthroplasty – Major liver resections: The reported rate of blood transfusion is rarely and target Hct 28%: [(70 mL/kg × 70 kg) × (40 − 28)]/[(40 + 28)/2] = 1,729 mL • For a 70 kg man with starting Hct of 35%: [(70 mL/kg × 70 kg) × (35 − 28)]/[(35 + 28)/2] = 1,089 mL • Volume replacement with appropriate amounts of crystalloid (3 × volume withdrawn) or colloid (1 × volume withdrawn)

REFERENCES

1. Doss DN, Estafanous FG, Ferrario CM, et al. Mechanism of systemic vasodilation during normovolemic hemodilution. Anesth Analg. 1995;81:30–34. 2. Epstein NE. Bloodless spinal surgery: A review of the normovolemic hemodilution technique. Surg Neurol. 2008;70:614–618.

3. Matot I, Scheinin O, Jurim O, et al. Effectiveness of acute normovolemic hemodilution to minimize allogenic blood transfusion in major liver resections. Anesthesiology. 2002;97:794–800. 4. Monk TG. Acute normovolemic hemodilution. Surg Infect. 2005;6(Suppl 1):S9–S15. 5. Murray D. Acute normovolemic hemodilution. Eur Spine J. 2004;13(Suppl 1):S72–S75. 6. Pape A, Habler O. Alternatives to allogenic blood transfusions. Best Pract Res Clin Anesthesiol. 2007;21(2):221–239. See Also (Topic, Algorithm, Electronic Media Element) • Cell salvage • Autologous blood transfusion • Anemia • Myocardial oxygen supply • Blood oxygen carrying capacity

CLINICAL PEARLS

• Normovolemic hemodilution is a technique that can help prevent or decrease the need for allogenic blood transfusion in patients who can sustain moderate anemia intraoperatively. • In comparison to autologous or homologous blood transfusions, normovolemic hemodilution eliminates the need for blood bank storage or testing. Since the collected blood remains in the operating room with the patient, transfusion errors and disease transmission are eliminated. • The amount of whole blood collection is directly related to the preoperative hematocrit. Safe post-hemodilution hematocrits depend upon surgical blood loss and comorbidities. • The efficacy of ANH has produced conflicting results, which have been attributed to the heterogeneity of the surgeries it is used for, differences in study protocol, as well as the definition of outcome variables. • During cardiopulmonary bypass grafting, when ANH was implemented in lieu of homologous blood transfusion, significantly lower bilirubin levels were observed. However, it may be associated with increased postoperative bleeding.

ACUTE RESPIRATORY DISTRESS SYNDROME Carlos A. Puyo, MD

BASICS DESCRIPTION

• Acute respiratory distress syndrome (ARDS) is a form of noncardiogenic pulmonary edema. It results from lung inflammation and presents as acute hypoxemia and bilateral pulmonary infiltrates. – Acute lung injury (ALI) is a milder form of ARDS. – Hyaline membrane disease is a pediatric form of ARDS (caused by a decrease in surfactant). • Causes stem from either pulmonary or extrapulmonary sources. • Histologically, affected alveolar units are filled with protein-rich edematous fluid and cellular debris; this occurs in a heterogenous manner. • Diagnosis is based on the history, ABG, and chest radiography. • Treatment consists of supportive measures (supplemental oxygen, mechanical ventilation) while the lungs heal. EPIDEMIOLOGY Incidence

In the US, approximately 200,000 cases per year Morbidity

• Can lead to multiorgan failure syndrome, GI ulcers, cardiac dysfunction, acute renal failure, malnutrition, and chronic issues such as myopathy and psychiatric problems • Lung function recovers significantly 6–12 months after initial injury.

Mortality

Estimated 25–40%, but is influenced by a variety of coexisting conditions such multisystem organ failure ETIOLOGY/RISK FACTORS

• Lung dysfunction due to direct lung injury: – Pneumonia (frequent cause, high mortality) – Aspiration – Mechanical ventilation – Lung contusion – Inhalational injury – Near drowning • Extrapulmonary sources: – Sepsis (frequent cause, high mortality; elderly patients are more susceptible)

– Trauma – Pancreatitis – Polysubstance abuse: Cocaine, opioid – Massive blood transfusions – Ischemia-reperfusion injury – CNS injury – Air/fat embolism – Cardiopulmonary bypass

PHYSIOLOGY/PATHOPHYSIOLOGY

• Early: “Exudative phase” translates into ventilation/perfusion mismatch (shunting) and hypoxia, decreased lung compliance, and increased work of breathing. It is associated with the following: – Diffuse alveolar and capillary endothelial injury – Influx of protein-rich fluid into alveoli – Release of tumor necrosis factor, interleukin-1, and interleukin-8 – Procoagulant activity as protein C and S levels fall and levels of tissue factor and plasminogen activator inhibitor-1 increase – Pneumocyte type 1 apoptosis with resultant accumulation of necrotic cellular debris in the alveolar lumen. Pneumocyte type 2 dysfunction reduces surfactant production. • Late: Fibroproliferative changes occur later and are characterized by: – Chronic inflammation resulting from the proliferation of pneumocyte type 2 and macrophages, and neutrophils filling the alveolar space. – Fibrosis (associated with increase mortality). – Neovascularization

PREVENTATIVE MEASURES

• Pneumonia should be diagnosed and treated aggressively. • Identify patients at risk for pulmonary aspiration (e.g., full stomach, reflux disease, active vomiting, recent oral contrast for radiological study, altered mental status) and implement appropriate maneuvers to reduce risk (gastric tube suctioning, prokinetic agents, reverse Trendelenburg, rapid sequence induction). • Mechanical ventilation should be weaned as tolerated. • Prevention of multiorgan dysfunction: – Diagnose and treat sources of infection aggressively (e.g., urinary tract infection in the elderly) to avoid sepsis. – Limit blood transfusions, as appropriate. Consider blood salvaging techniques, blood filters, and collection from donors without multiple HLA exposures.

DIAGNOSIS • The diagnosis of ARDS can coexist with other (extrapulmonary) diagnoses. – History: Acute dyspnea or hypoxemia related to trauma, sepsis, drug overdose, massive transfusion, aspiration, or acute pancreatitis – Physical examination: Tachypnea and tachycardia are nonspecific. Auscultation may

reveal bilateral rales. Cyanosis, fever, hypothermia. – ABG: PaO2/FiO2 ratio 30% oxygen when an ignition source is used.

ALCOHOL ABUSE

Zhuang-Ting Fang, MD, MSPH

BASICS DESCRIPTION

• Alcohol abuse is a chronic disease with profound societal implications. More than 19% of cases resulting in deaths of young automobile drivers were related to alcohol. Additionally, the annual total cost of alcohol-related problems reaches a staggering $180 billion. • Both acute alcohol intoxication and chronic alcohol abuse can increase anesthetic complications. EPIDEMIOLOGY Prevalence

In the US, the rate of alcohol use disorders, including abuse and dependence, is ~8.26%; this correlates to ~15 million people. Morbidity

• In the perioperative period, patients with alcohol abuse have been shown to have an increased risk of infections, bleeding disorders, need for ventilator support, and cognitive dysfunction. • Maternal alcohol consumption during pregnancy can lead to fetal alcohol disorders; 1% incidence. Mortality

• Alcohol withdrawal during surgery may be associated with a mortality rate as high as 50%. • Alcohol use is the third leading cause of preventable death in the US, and accounts for ∼85,000 deaths annually. ETIOLOGY/RISK FACTORS

• Gender: Men are 5 times more likely than women to develop alcohol abuse. • Family history: The rate of alcohol abuse is about 30% in men with one alcoholic parent. • Genetic factors: May affect the process and response to alcohol in the human body • Cultural factors: The high rate of alcohol abuse in the US and Europe may relate to the common use and social acceptance of alcohol use. • Psychiatric disorders: Higher in persons with depression, anxiety, antisocial behaviors, posttraumatic stress disorder, high self-expectations, or low frustration tolerance PATHOPHYSIOLOGY

• Alcohol has been shown to affect the following receptors in the human brain: – GABA: Alcohol binds to the GABA receptor and increases chloride ion movement into the cell with resultant hyperpolarization (decreases neural activity, by making the cell

membrane potential more negative). Responsible for the sedative and anxiolytic effects (similar to hypnotic drugs and benzodiazepines). – Glycine: Alcohol binds to the glycine receptor and potentiates its role as the major inhibitory neurotransmitter in the spinal cord and brain stem. – Serotonin: Alcohol increases levels either via increased release and/or decreased breakdown, as well as potentiates its effects on receptor function. Serotonin may enhance the release of other neurotransmitters that play a key role in tolerance and contribute to alcohol withdrawal syndrome (AWS). – Glutamate: Alcohol decreases glutamate’s excitatory effect on NMDA receptors. Chronic consumption, however, makes NMDA receptors hypersensitive to glutamate while desensitizing the GABAergic receptors; believed to play a role in AWS. – Opiates: Alcohol induces the release of endogenous opioid peptides (can cause euphoria and blunt the sensation of pain). The body’s endogenous opioid system (enkephalins, endorphins) is linked with the brain’s reward pathway; may play a role in addiction. – Dopamine: The increased levels/effects that are seen with alcohol abuse is a poorly understood mechanism. It has been postulated to result from disinhibition of dopaminergic neurons, decreased breakdown, and increased release. Dopamine pathways play a role in reward and reinforcement and may play a role in addiction. • Alcohol is absorbed directly through the stomach wall (∼20%) and small intestines (∼80%). The liver functions to break down alcohol. • Effects on other organs may result from direct inflammation or possibly from “blood sludging.” Blood sludging describes the clumping of red blood cells with resultant plugging of small vessels, ischemia, and cell/tissue death distally. The increased pressure can result in capillaries breaking (red eyes, blotchy skin, “drinker’s nose”).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperative evaluation should determine concomitant organ dysfunction. A high index of suspicion for alcohol cardiomyopathy should be present, as this is often underdiagnosed. • Prevent aspiration in patients with cirrhosis and ascites • Anticipate prophylaxis and treatment of alcohol withdrawal and delirium tremens

PREOPERATIVE ASSESSMENT SYMPTOMS

• A high index of suspicion is required to diagnose alcohol abuse. • Nonspecific, but suggestive, symptoms include gastritis, tremor, and history of falling.

History

• Despite the brief preoperative encounter, a social history including alcohol use should be elicited. If suspected, consider further focused questioning. • Alcohol Use Disorders Identification Test (AUDIT) is 92% effective in detecting hazardous or harmful drinking. A total score of ≥8 indicates harmful drinking behavior. It is also helpful in identifying those at greatest risk for postoperative complications. • Inquire about other substances of abuse

Signs/Physical Exam

• Usually nonspecific; abnormalities are usually related to the systemic diseases associated with chronic use. • “Drinker’s nose”: A purple nose that results from tiny broken capillaries

MEDICATIONS

No specific medications, unless being treated for abuse. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Glucose: May be low, particularly in diabetics • CBC with platelets: Anemia • Liver function tests, PT and aPTT: May be abnormal due to alcoholic hepatitis or cirrhosis. • EKG: May show left ventricular hypertrophy and arrhythmias. • CXR: May show aspiration, pleural effusions and cardiomegaly.

CONCOMITANT ORGAN DYSFUNCTION

• Nervous system: Cerebellar degeneration, tremors, delirium tremens, dementia, depression, memory loss, Wernicke–Korsakoff syndrome, peripheral neuropathy (burning, numbness, weakness) • Cardiovascular: Alcoholic cardiomyopathy, hypertension • Pulmonary: Aspiration, pleural effusion, and pulmonary hypertension (may occur in end stage liver disease). • Hepatic: Alcoholic hepatitis, cirrhosis • Gastrointestinal: Absorption of B vitamins and other nutrients may be impaired. Gastritis, ulcers, and increased risk of stomach cancer. Acute and chronic pancreatitis; may eventually result in diabetes. • Metabolic: Impairs fat and glucose metabolism in the liver and pancreas. Acute alcohol ingestion can result in a steep rise in blood sugar that is met by an increased release of insulin, with resultant hypoglycemia. • Hematologic: Anemia can result from malnutrition or direct suppression of bone marrow. • Malnutrition is very common and can lead to anemia (folic acid, vitamin B12 deficiency), or hypoalbuminemia (low protein intake) and Wernicke–Korsakoff syndrome (vitamin B1 deficiency). • Other: Sexual dysfunction (decreased testosterone), birth defects, osteoporosis

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Elective surgery should be postponed in patients with acute alcohol toxicity, alcoholic hepatitis, or decompensated systemic diseases. • Treatment of alcohol abuse or dependence should be considered before elective surgery in order to decrease perioperative morbidity and mortality. • Severe dehydration or electrolyte imbalance should be corrected prior to surgery.

CLASSIFICATIONS

• Alcohol abuse is defined by the following characteristics: Drinking even when it is dangerous; excessive drinking; legal problems related to drinking; and interpersonal problems with family, coworkers, and friends because of alcohol use. • Alcohol dependence (alcoholism) is characterized by: Drinking excessive amount frequently; the inability to stop drinking despite social, psychiatric, or medical complications; increased tolerance of alcohol; and the occurrence of alcohol withdrawal symptoms when drinking is discontinued.

TREATMENT PREOPERATIVE PREPARATION Premedications

Benzodiazepines are helpful in reducing anxiety and preventing withdrawal. INTRAOPERATIVE CARE Choice of Anesthesia

Regional anesthesia (spinal, epidural, or peripheral nerve blocks) may decrease systemic effects and CNS disturbance with general anesthesia. It is also easier to monitor mental status changes in awake patients, especially in those at risk of alcohol withdrawal. In patients with liver disease, however, coagulopathy may preclude neuraxial techniques. Monitors

• Standard ASA monitors • Invasive monitoring may be considered when alcoholic cardiomyopathy is suspected or present, and depending upon the surgical procedure. Induction/Airway Management

• Acute alcohol intoxication may reduce anesthetic dose requirement. • Chronic alcohol abuse may require higher anesthetic doses due to cross-tolerance (e.g., increased propofol induction doses). Cirrhotics have an increased volume of distribution which may necessitate increased doses (but may have increased sensitivity to drugs and decreased clearance). In alcoholic cardiomyopathy, intravenous induction should be accomplished by careful titration to avoid hypotension. • Rapid-sequence induction with cricoid pressure should be considered in patients with delayed gastric emptying due to ascites. Intoxicated trauma patients are at an increased risk for aspiration. Maintenance

• In cirrhotic patients, maintenance doses may need to be decreased due to impaired liver metabolic function. • Non-depolarizing muscle relaxants should be cautiously titrated due to impaired hepatic function. • “Banana bag” infusion may be considered.

Extubation/Emergence

Normal extubation criteria apply; however, alcoholics may have impaired clearance of muscle relaxants and gastric motility. Ensure full recovery from NMBDs and a protective gag reflex.

FOLLOW-UP BED ACUITY

• ICU admission may be required if alcohol withdrawal or delirium tremens is suspected. • Supplemental oxygen should be provided, especially when the patient is receiving narcotics.

COMPLICATIONS

• AWS may be seen in patients who abuse or are dependent on alcohol when they stop drinking abruptly because of injury, surgery, or acute illness. Typically develops 6–24 hours after their last drink. Symptoms are related to autonomic hyperactivity and include sweating, nausea, vomiting, anxiety, agitation, tachycardia, and hand tremor. Neuronal excitation, including grand mal seizures, usually occurs within 24–48 hours of abstinence. Delirium tremens is the most intense and serious form of AWS. It is characterized by visual or auditory hallucinations, confusion, clouding of consciousness, impaired attention, and pronounced autonomic hyperactivity. It usually appears 2–4 days after the patient’s last use of alcohol. Death from cardiovascular and respiratory collapse may occur, if untreated. Prophylaxis is with benzodiazepines. Treatment of AWS involves establishing the diagnosis and severity with the CIWA-Ar Score and transferring to the ICU. Medical treatment involves a combination of benzodiazepines, haloperidol, clonidine, and beta-blockers; in some instances, a drink with meals may be ordered. Supportive care includes the treatment of nutritional deficiency, hypoglycemia, arrhythmias, congestive heart failure, alcoholic hepatitis, alcoholic pancreatitis, GI bleeding, and nervous system impairment. • Postoperative cognitive dysfunction is increased in patients aged 55 years and older after noncardiac surgery with general anesthesia. • Increased risk of infections may be due to alteration of T-cell mediated immunity as well as altered immune response to surgical stress.

REFERENCES

1. Lian J, Cagetti E, Richard W, et al. Altered pharmacology of synaptic and extrasynaptic GABAA receptors on CA1 hippocampal neurons is consistent with subunit changes in a model of alcohol withdrawal and dependence. J Pham and Exp Therap. 2004;310(3):1234– 1245. 2. Lovinger DM. Serotonin’s role in alcohol’s effects on the brain. Alcohol Health Res World. 1997;21(2):114–120. 3. Publications from the Institute on Alcohol Abuse and Alcoholism, NIH. www.niaaa.nih.gov.

4. Spies CD, Rommelspacher H. Anesthestic alcohol withdraw in the surgical patients: Prevention and treatment. Anesth Analg. 1999;88:946–954. See Also (Topic, Algorithm, Electronic Media Element)

• Alcohol cardiomyopathy • Pregnancy substance abuse • Cirrhosis • Alcohol withdrawal syndrome

CODES ICD9

• 303.90 Other and unspecified alcohol dependence, unspecified • 305.00 Alcohol abuse, unspecified • 305.01 Alcohol abuse, continuous ICD10 • F10.10 Alcohol abuse, uncomplicated • F10.129 Alcohol abuse with intoxication, unspecified • F10.20 Alcohol dependence, uncomplicated

CLINICAL PEARLS

AUDIT (Alcohol Use Disorders Identification Test) utilizes 10 questions; scoring is on a scale of 0–4 per question. A total score of ≥8 indicates alcohol abuse or dependence. (Note: A unit is equal to one small glass of wine, a single purchased measure of spirits or half a pint of beer.) The questions include: • How often do you have a drink containing alcohol? • How many units of alcohol do you drink on a typical day when you are drinking? • How often do you have 6 or more units of alcohol on one occasion? • How often during the last year have you found that you were not able to stop drinking once you had started? • How often during the last year have you failed to do what was normally expected from you because of drinking? • How often during the last year have you needed a first drink in the morning to get yourself going after a heavy drinking session? • How often during the last year have you had a feeling of guilt or remorse after drinking? • How often during the last year have you been unable to remember what happened the night before because you had been drinking? • Have you or someone else been injured as a result of your drinking? • Has a relative or friend or doctor or another health worker been concerned about your drinking or suggested you should cut down?

ALCOHOL WITHDRAWAL SYNDROME Martin M. Stechert, MD Christopher G. Choukalas, MD, MS

BASICS DESCRIPTION

• Alcohol withdrawal syndrome (AWS) develops after the cessation of chronic alcohol use/abuse, generally within 6–48 hours. Alcohol abuse is characterized by impaired control over drinking, preoccupation with alcohol, use of alcohol despite adverse consequences, and denial. • AWS exists as a spectrum of presentations: – Mild: Cravings and psychomotor agitation – Severe: Hallucinations, autonomic instability (sweating, tachycardia, hypertension), fever, and disorientation. This constellation of symptoms is known as delirium tremens (DT). • If withdrawal symptoms are not present within a week after the last alcohol consumption, future development is unlikely. EPIDEMIOLOGY Prevalence

In general, outpatient estimates are between 4% and 15%, whereas 15–40% of all inpatients are thought to have abuse or withdrawal. Of those who experience withdrawal symptoms, 5% have severe symptoms characterized as DT. Morbidity

• AWS: Dysrhythmias, myocardial ischemia, delirium, and seizures • Chronic alcohol abuse: Immunosuppression, wound infections, malnutrition, and the complications of cirrhosis and liver failure Mortality

• Has decreased over time; historical estimates from severe AWS or DT reached levels as high as 40%, but the current rate is probably under 5%. • Results from dysrhythmia, aspiration pneumonia, or underlying illness that may have been the cause of alcohol cessation in the first place (e.g., infection, pancreatitis, etc.). ETIOLOGY/RISK FACTORS

• Alcohol use and abuse are obvious risk factors for developing AWS. Use and abuse are associated with a number of demographic characteristics, including: – Male sex – Lower socioeconomic status – White or Native American ethnicity – Certain psychiatric conditions (e.g., depression, anxiety disorders)

• Risk factors for the development of DT include: – Previous history of DT – Presence of AWS despite elevated level of blood alcohol – History of sustained drinking

PHYSIOLOGY/PATHOPHYSIOLOGY

• The pathophysiology of AWS is probably related to the neurophysiologic changes thought to be caused by chronic alcohol use. Although the functional consequence of receptormediated effects of alcohol remain to be elucidated, ingested ethanol has a number of receptor targets: – NMDA-related transmission is reduced. – GABA function is enhanced. – Glycine transmission (complex and location specific) are enhanced – Cholinergic and serotonergic activities are enhanced. • In order to maintain a normal arousal state, an adaptive response to chronic alcohol exposure yields decreased GABAA sensitivity and increased NMDA sensitivity. When ethanol is acutely withdrawn, reduced central inhibition (via GABAA) and aberrant activation of

excitatory NMDA receptors appear to be responsible for the acute withdrawal symptoms, including altered mental state and noradrenergic overdrive during AWS.

PREVENTATIVE MEASURES

• Prevention of AWS is a crucial aspect of treatment in the clinical arena, whereas public health efforts to curb alcohol abuse are necessary to prevent AWS on a societal level. • Perioperatively, prevention of AWS starts with an early identification of patients at risk for this condition. – The duration of potential abstinence from alcohol should be discussed with the primary care physician and the patient, and possible management solutions must be negotiated with the patient. – Nutrition including multivitamin administration should be optimized preoperatively. – Optimal medical management can be organized according to the degree of risk going into withdrawal, including additional invasive monitoring intraoperatively and appropriate designation (ICU, TCU) postoperatively. – Long-acting benzodiazepines (e.g., chlordiazepoxide) administered preoperatively may reduce the severity of AWS.

PREOPERATIVE ASSESSMENT • AWS is a clinical diagnosis and requires a detailed history and physical examination. – Key elements of the history include chronic alcohol use, recent cessation, and determining whether cessation was caused by some other illness. – Screening tools like the PAT (Paddington Alcohol Test) and AUDIT (Alcohol Use Disorders Identification Test) questionnaires can identify patients at risk for AWS. • Clinical manifestations of alcohol withdrawal often follow a timely schedule after the last consumption of alcohol:

– Early symptoms, including anxiety, tremulousness, palpitations, nausea, anorexia, typically begin after 6–8 hours. – Generalized seizures typically occur after 6–48 hours. – Alcoholic hallucinations after 12–48 hours – Delirium tremens after 48–96 hours • The latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) provides more precise diagnostic criteria that can be summarized as 2 or more of the following signs and symptoms occurring (1) in the context of cessation or reduction of previously heavy alcohol use and (2) not due to some other medical or mental disorder: – Sweating or tachycardia – Hand tremor – Insomnia – Nausea or vomiting – Hallucinations – Agitation – Anxiety – Generalized tonic–clonic seizure • It is important to note that in an anesthetized patient, symptoms may be obscured and limited to sympathetic surge (i.e., tachycardia, hypertension).

DIFFERENTIAL DIAGNOSIS

• Other causes of agitation and tremor, including caffeine overdose, cocaine and other stimulant use, as well as withdrawal from nicotine, illicit drugs, and medications (e.g., clonidine) • Other causes of hallucinations such as psychotic disorders, acute intoxication, sleep withdrawal, and drug side effects • Other causes of seizures such as metabolic or electrolyte derangements, intracranial pathology, meningitis, or underlying seizure disorder • Other hyper-metabolic syndromes that can mimic DT, such as malignant hyperthermia, thyroid storm, neuroleptic malignant syndrome, and serotonin syndrome

TREATMENT • Essential elements of therapy include: – Excluding alternate diagnoses (see above) – Seizure prophylaxis – Correcting metabolic and hemodynamic derangements – Treating symptoms such as anxiety and hallucinations – Managing complications (e.g., aspiration pneumonia and malnutrition) – Appropriate monitoring • Benzodiazepines bind to GABA receptors and are cross-tolerant with alcohol; they remain the cornerstone of treatment for AWS. They are effective at reducing anxiety, agitation, and the incidence of seizures; and they often reduce tachycardia and hypertension. They can also be dosed prophylactically, in a scheduled fashion, or in response to symptom severity.

The latter has been associated with decreased complications and lower doses of administered drug. • Propofol in intubated, mechanically ventilated patients produces results similar to those of benzodiazepines (e.g., anxiolysis, seizure prophylaxis, etc.). Patients receiving propofol rarely need additional benzodiazepines to treat agitation or seizures associated with AWS. • Other agents have been used, but none have completely replaced benzodiazepines: – Antipsychotics, such as haloperidol or quetiapine, may reduce agitation and hallucinations but may also reduce the seizure threshold. – Antiepileptics, such as carbamazepine, may decrease the development of seizures but have little effect on the other manifestations of AWS. – Intravenous infusion of ethanol can precipitate a metabolic acidosis. – Alternative sedatives, such as clonidine and dexmedetomidine, almost certainly reduce benzodiazepine requirements but provide no seizure prophylaxis. Dexmedetomidine reduces ICU delirium and may reduce delirium associated with AWS. • The Clinical Institute for Withdrawal Assessment (CIWA) provides a symptom-driven dosing scheme that calculates a score based upon signs and symptoms of withdrawal (e.g., tremor, sweats, delirium). Higher scores signify more severe withdrawal and would trigger administration of benzodiazepine. • Bed acuity: The appropriate level of monitoring for patients with AWS has never been defined. The frequent assessments required suggest that general ward care may be inadequate. Additionally, managing hemodynamic abnormalities requires active monitoring of hemodynamics, such as in a telemetry, step-down, or ICU unit. The presence of the following may necessitate ICU care: – Coexisting cardiac, pulmonary, or renal disease – Having a history of or being at high risk for DTs – Requiring propofol or a continuous infusion of sedatives to control symptoms during past admissions • Thiamine deficiency: Common in patients who abuse alcohol. Thiamine is critical in order to avoid Wernicke’s encephalopathy, and must be administered prior to initiating glucose or nutritional therapy. Further treatment should target specific nutritional deficiencies identified by serology.

REFERENCES

1. Tetrault JM, O’Connor PG. Substance abuse and withdrawal in the critical care setting. Crit Care Clin. 2008;24:767–788. 2. De Wit M, Jones DG, Sessler CN, et al. Alcohol-use disorders in the critically ill patient. Chest. 2010;138(4):994–1003. 3. Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348:1786–1795.

ADDITIONAL READING

• Spanagel R. Alcoholism: A systems approach from molecular physiology to addictive behavior. Physiol Rev. 2009;89:649–705.

• Sullivan JT, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: The revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Brit J Addict. 1989;84:1353–1357.

See Also (Topic, Algorithm, Electronic Media Element) • Alcohol abuse

CODES ICD9

291.81 Alcohol withdrawal ICD10 F10.239 Alcohol dependence with withdrawal, unspecified

CLINICAL PEARLS

• Cessation of receptor-mediated activity during alcohol abstinence is likely at the root of AWS. It may be that chronic exposure to ethanol decreases sensitivity of GABA receptors, and that cessation reduces GABA output, leading to a state of generalized CNS arousal. • Seizure may be an early symptom of AWS (“rum-fit”) which can occur as early as 2 hours after the last consumption of ethanol. • Alcohol-dependent, ambulatory patients may never exhibit AWS syndromes during the hospital stay. • Whenever AWS is suspected, thiamine should be given intravenously. The administration of glucose in thiamine deficiency can precipitate Wernicke’s encephalopathy.

ALCOHOLIC CARDIOMYOPATHY Christopher Wray, MD

BASICS DESCRIPTION

• Alcoholic cardiomyopathy (ACM) is classified as a non-ischemic, dilated cardiomyopathy (CM) that results from exposure to a myocardial toxin. • ACM shares common characteristics with all dilated CMs (depending on the clinical stage of the disease progression): – Dilated chambers – Diastolic dysfunction (asymptomatic stage) – Left ventricular dysfunction (symptomatic stage) – Left ventricular hypertrophy (asymptomatic stage; followed by wall thinning in symptomatic stage) • Diagnosis is clinically based upon a history of significant chronic alcohol exposure in conjunction with the exclusion of other causes of dilated CM. PHYSIOLOGY PRINCIPLES

• Epidemiology of ACM: – Second most common cause of dilated CM (4% of all CMs) – Prevalence in Western countries is variable, but ranges from 20% to 40% of all nonischemic dilated CMs. – Significantly more prevalent in men (approximately 15% prevalence in women) – The incidence of dilated CM is much higher in chronic alcoholics than in the total population. – The 5-year incidence ranges from 20% to 26% in chronic alcoholics. • Amount and duration of alcohol exposure: – Studies have demonstrated variability and a lack of a specific linear relationship between the amount and duration of alcohol exposure and the development of asymptomatic and symptomatic ACM (1,2,3). – Studies have shown changes in cardiac structure and function consistent with ACM in patients with a history of consuming >90 g/day of alcohol for >5 years (one drink contains approximately 12 g of alcohol). Studies in patients with symptomatic ACM have shown a history of longer durations of drinking (>10 years) (4,5). – Despite the correlation between chronic heavy drinking and the development of ACM, not all heavy drinkers will progress to ACM. – Although there may be other variables responsible for the occurrence of heart failure in alcoholics, the duration of heavy daily alcohol use is the most reliable predictor for the development of ACM. PHYSIOLOGY

• Myocardial wall tension is closely related to myocardial oxygen consumption. – Left ventricle wall tension (T) is a function of the change in pressure (ΔP), left ventricle radius (R), and left ventricle wall thickness (h). It can be described by the law of Laplace: T = (ΔP × R)/2h. – ΔP reflects the afterload that the left ventricle must pump against (directly related) – Radius is a function of preload (left ventricular end-diastolic volume) (directly related). – Wall thickness is a function of the number of myoctes (inversely related) – Although not intrinsically contained within the equation, heart rate also is a determinant of myocardial oxygen; it determines the number of times that tension needs to be generated. • The left ventricle is ellipsoid and facilitates low wall tension

DISEASE/PATHOPHYSIOLOGY

• The pathophysiology is not completely understood, despite a large number of studies. Animal studies have demonstrated characteristic histologic and cellular changes associated with chronic alcohol exposure, including (1): – Myocyte death – Intracellular organelle dysfunction – Interference of contractile protein function – Abnormalities of calcium homeostasis – Generation of reactive oxygen species (ROS) – Changes in neurohormonal systems (sympathetic, renin-angiotensin, natriuretic peptide) – Individual variations in the development of myocardial toxicity from alcohol suggest that other variables including genetic or environmental factors may play a role. • Clinical presentation: ACM presents in stages and can progress from asymptomatic to symptomatic. – Asymptomatic stage: Studies have demonstrated that in the early preclinical stage of ACM, LV remodeling occurs in the form of LV dilation (increased end-diastolic and systolic dimensions), increased LV mass, and LV hypertrophy (increased septal thickening). Echocardiographic studies have demonstrated that diastolic dysfunction (impaired early diastolic filling of the LV) appears to be an early feature of asymptomatic ACM, regardless of LV mass and the presence of hypertension. Early ACM is often associated with a normal LV ejection fraction (EF) (3,4,5,6). – Symptomatic stage: Characterized by progressive increases in LV dilation and LV mass, as well as the occurrence of systolic dysfunction with a decreased EF. Studies have demonstrated significantly greater LV end-diastolic and systolic dimensions in symptomatic ACM patients when compared to asymptomatic ACM patients (2,7). • Tension: Dilated cardiomyopathy results in a more spherical left ventricle with subsequent increases in wall stress (radius is increased). In the asymptomatic stage, the myocardial wall hypertrophies and can decrease wall tension. However, in symptomatic stages, wall thickness decreases with resultant increases in wall tension (and myocardial oxygen demand). • Diagnosis is clinically based upon having a history of significant alcohol consumption after ruling out other causes of dilated CM. – History: After excluding other causes of dilated CM, the most important factor for

diagnosis is a chronic history of heavy alcohol use. – Symptoms/physical exam: Signs and symptoms of heart failure may be noted in patients with symptomatic disease. – EKG abnormalities are common and include nonspecific ST and T wave changes, QT prolongation, and atrial arrhythmias including atrial fibrillation. – Echocardiography allows for a noninvasive delineation of the LV chamber size, diastolic function, and systolic function. – There are no specific pathologic or immunologic tests for the diagnosis of ACM. • Natural history and treatment – Although the amount of alcohol required to cause progression of asymptomatic ACM to overt heart failure appears variable, studies clearly show that decreases in systolic function are significantly related to the amount and duration of alcohol consumption (1). – Partial to complete regression of the pathologic cardiac changes associated with ACM may occur in some patients with abstinence alone. – LV function in ACM patients may improve with standard medical therapy for dilated CM (diuretics, cardiac glycosides, ACE inhibitors, and beta blockade), although no therapies specific for ACM have been studied or described. Despite improvements in the LV function, survival is not improved in patients who continue to drink. The most important factor impacting survival in symptomatic patients receiving medical therapy is abstinence from further drinking.

PERIOPERATIVE RELEVANCE

• Chronic alcoholism results in a significantly higher incidence of postoperative cardiac complications, hypoxemia, and infections. • The anesthesia provider should maintain an appropriate index of suspicion for the presence of ACM in patients with a history of chronic alcohol use. The presence of ACM can have worsened and even deleterious effects during the perioperative period. Even asymptomatic patients can have a limited cardiac reserve when exposed to severe perioperative stress that occurs with major surgery, trauma, or shock. Preoperative cardiac evaluation, including echocardiography, should be considered for risk-stratification and determination of the need for medical therapy for prospective surgical patients with a history of chronic alcohol use. • Alcoholics presenting for emergency surgery may be acutely intoxicated or at risk for alcohol withdrawal syndrome, both of which can adversely affect a patient with ACM (8).

REFERENCES

1. Piano MR. Alcoholic cardiomyopathy: Incidence, clinical characteristics, and pathophysiology. Chest. 2002;121:1638–1650. 2. Fernandez-Sola J. Diastolic function impairment in alcoholics. Alcohol Clin Exp Med. 2000;24:1830–1835. 3. Fauchier L. Comparison of long-term outcome of alcoholic and idiopathic dilated cardiomyopathy. Eur Heart J. 2000;21:306–314. 4. Kupari M. Left ventricular filling impairment in asymptomatic chronic alcoholics. Am J Cardiol. 1990;66:1473–1477.

5. Lazarevic AM. Early changes in left ventricular function in chronic asymptomatic alcoholics: Relation to the duration of heavy drinking. J Am Coll Cardiol. 2000;35:1599– 1606. 6. McKenna CJ. Alcohol consumption idiopathic dilated cardiomyopathy: A case control study. Am Heart J. 1998;135:833–837.

7. Mathews EC. Echocardiogrphic abnormalities in chronic alcoholics with and without overt congestive heart failure. Am J Cardio. 1981;47:570–578. 8. Spies C. Perioperative morbidity and mortality in chronic alcoholic patients. Alcohol Clin Exp Res. 2001;25:164S–170S.

ADDITIONAL READING

• Laonigro I. Alcohol abuse and heart failure. Eur J Heart Failure. 2009;11:453–462. • Spies CD. Effects of alcohol on the heart. Curr Opin Crit Care. 2001;7:337–343.

See Also (Topic, Algorithm, Electronic Media Element) • Congestive heart failure • Alcohol abuse

CODES ICD9 425.5 Alcoholic cardiomyopathy ICD10 I42.6 Alcoholic cardiomyopathy

CLINICAL PEARLS

• ACM is a type of dilated CM that is diagnosed clinically, based on a history of significant chronic alcohol exposure in conjunction with the exclusion of other causes of dilated CM. • The duration of heavy daily alcohol use is the most reliable predictor for the development of ACM. • The most important factor impacting survival in ACM patients is abstinence from further drinking; medical therapy does not improve survival in patients who continue to drink alcohol. • The presence of ACM in the surgical patient can have deleterious effects; the anesthesia provider should maintain an appropriate index of suspicion for the presence of ACM in patients with a history of chronic alcohol use.

ALDOSTERONE Joe C. Hong, MD

BASICS DESCRIPTION

• Aldosterone is a steroid hormone in the mineralocorticoid family that plays a vital role in the maintenance of intravascular volume status and sodium balance. • Aldosterone is synthesized and secreted by the zona glomerulosa of the adrenal cortex in response to low intravascular volume, decreased renal perfusion, hyperkalemia, and acidosis. • Disease states include Addison disease (hypoaldosteronism) and Conn syndrome (hyperaldosteronism). PHYSIOLOGY PRINCIPLES

• Aldosterone is synthesized from cholesterol within the adrenal cortex by a series of steroidogenic reactions catalyzed by enzymes of the cytochrome p450 family. It is a steroid hormone that exerts its action by binding to an intracellular cytoplasmic receptor. This bound complex enters the cell nucleus and stimulates DNA transcription, resulting in protein production that mediates the ultimate effects of aldosterone. • Renin–angiotensin system (RAS) regulation: Aldosterone secretion is regulated primarily by RAS via the following mechanism: – Intravascular volume depletion triggers a decrease in renal perfusion pressure. – Renin is secreted by the juxtaglomerular cells of the afferent arteriole in response to this decrease in renal perfusion pressure. – Renin catalyzes the conversion of angiotensinogen to angiotensin I in plasma. – Angiotensin-converting enzyme (ACE) catalyzes the conversion of angiotensin I to angiotensin II, primarily in the lungs. – Angiotensin II stimulates the synthesis and secretion of aldosterone. • Adrenocorticotropic hormone (ACTH): Aldosterone is also under tonic control by ACTH (secreted by the anterior pituitary gland). • Aldosterone hormone regulates volume and blood pressure via: – Binding to mineralocorticoid receptors located in the principal cells of nephrons. This upregulates sodium/potassium pumps with resultant sodium and water reabsorption and potassium sercetion by the distal tubules and collecting ducts. The net effect is the restoration of intravascular volume and blood pressure. – Acting on alpha-intercalated cells of the late distal tubule and collecting duct, resulting in increased renal hydrogen ion secretion. ANATOMY

• Aldosterone is produced by cells within the zona glomerulosa of the adrenal cortex. • The adrenal gland is composed of the inner medulla which produces catecholamines and the

outer cortex which is divided into 3 histologic zones. Going from outside and moving inwards: – The outermost zona glomerulosa is the source of aldosterone production. – Just beneath is the zona fasciculata, the source of glucocorticoid production. – The inner-most layer of the cortex is the zona reticularis, responsible for the production of androgens.

DISEASE/PATHOPHYSIOLOGY

• Primary adrenocortical insufficiency (Addison disease)—a hypoaldosterone state: – Most common cause is autoimmune destruction of the adrenal cortex, resulting in acute adrenal crisis (1). Other causes of adrenocortical insufficiency include metastatic disease to the adrenal cortex, adrenal hemorrhage, infection of the adrenal gland (tuberculosis, opportunistic infections with HIV, fungemia), and amyloid infiltration. – Characterized by elevated ACTH levels but decreased levels of glucocorticoids and mineralocorticoids – Clinical features are related to the adrenocortical hormone deficiency. Hypoglycemia is caused by cortisol deficiency. Hypotension, hyperkalemia, metabolic acidosis, and volume contraction are caused by aldosterone deficiency. Hyperpigmentation is caused by elevated ACTH secretion. Other signs and symptoms include weakness, fatigue, lethargy, anorexia, nausea, abdominal pain, prerenal azotemia, hypercalcemia, convulsions, fever, and syncope. – Treatment: Replacement of glucocorticoids (hydrocortisone, prednisone, methylprednisolone) and mineralocorticoids (fludrocortisone) • Secondary adrenocortical insufficiency is caused by decreased ACTH secretion, resulting primarily in a glucocorticoid deficiency. Mineralocorticoid deficiency is also seen but to a lesser degree. – Most common cause of secondary adrenocortical insufficiency is sudden withdrawal of long-term corticosteroid therapy (2). Other causes include pituitary tumor, pituitary surgery or radiation, postpartum hypopituitarism (Sheehan syndrome), and sarcoid infiltration of the pituitary gland. – Chronic corticosteroid therapy suppresses the hypothalamus and anterior pituitary, resulting in decreased production of corticotropin-releasing hormone (CRH) and ACTH, respectively. Decreased levels of CRH and ACTH cause atrophy of the zona fasciculata, resulting in glucocorticoid deficiency. During times of physiologic stress, the patient is unable to acutely increase cortisol production, resulting in acute secondary adrenocortical deficiency. • Primary hyperaldosteronism is caused by aldosterone-secreting tumors. – Conn syndrome (aldosterone-secreting adrenocortical adenoma) is the most common cause. Bilateral adrenal hyperplasia occurs less commonly. – Characterized by hypertension, hypokalemia, metabolic alkalosis, and a low renin state. Other signs and symptoms include tetany, polyuria, and an inability to concentrate urine. – Primary hyperaldosteronism may be present in 0.5–1% of patients with hypertension (3). – Treatment: Medically by spironolactone (aldosterone receptor antagonist), surgically with adrenalectomy

PERIOPERATIVE RELEVANCE

• Hypoaldosterone states: – Patients with adrenocortical insufficiency should continue their mineralocorticoid and glucocorticoid replacement therapy up until their time of surgery. Clinical features of overt hypoaldosteronism include hyperkalemia, hyponatremia, acidosis, and myocardial conduction defects. Administration of mineralocorticoids (fludrocortisone 0.05–0.1 mg/d) should occur preoperatively (1). Doses must be carefully titrated to avoid hypertension. – Additional perioperative stress dose of glucocorticoids may be necessary since these patients may not be able to mount an adequate stress response. The traditional recommendation is 200 mg hydrocortisone per 70 kg body weight per day. However, smaller doses of 100 mg per 70 kg body weight per day have been used with success (2). – The amount of perioperative hydrocortisone is based on the anticipated stress of the procedure. The relative degree of trauma and depth of anesthesia should be considered. • Hyperaldosterone states: – Patients presenting for elective surgery should be medically optimized in terms of their adrenocortical disorder. Preoperative EKG, glucose, and serum electrolytes (particularly sodium and potassium) should be checked. Volume status and blood pressure should be optimized. – Primary aldosteronism (Conn syndrome) should be suspected in patients who present with concurrent hypertension and hypokalemia, severe refractory hypertension, adrenal incidentaloma and hypertension, or onset of hypertension at a young age. – Antihypertensive medications (e.g., spironolactone) should be maintained up to the time of surgery. Careful cardiac assessment is necessary because these patients have increased cardiac comorbidity. Serum sodium and especially serum potassium should be checked prior to surgery. Hypokalemia is common. Severely hypokalemic patients should have their potassium replaced preoperatively.

REFERENCES

1. Dorin RI, Qualis CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med. 2003;139:194–204. 2. Symreng T, Karlberg BE, Kagedal B, et al. Physiological cortisol substitution of long-term steroid-treated patients undergoing major surgery. Br J Anaesth. 1981;53:949–954. 3. Young WF Jr. Adrenal causes of hypertension: Pheochromocytoma and primary aldosteronism. Rev Endocr Metab Disord. 2007;8:309–320.

ADDITIONAL READING

• Graham GW, Unger BP, Coursin DB. Perioperative management of selected endocrine disorders. Int Anesthesiol Clin. 2000;38:31–67. • Lampe GH, Roizen MF. Anesthesia for patients with abnormal function of the adrenal cortex. Anesthesiol Clin North Am. 1987;5:245–268. • Udelsman R, Ramp J, Gallucci WT, et al. Adaptation during surgical stress: A reevaluation of the role of glucocorticoids. J Clin Invest. 1986;77:1377–1381.

See Also (Topic, Algorithm, Electronic Media Element) • Cortisol • Acute adrenal insufficiency

CLINICAL PEARLS

• Patients with adrenocortical insufficiency have deficiencies in both mineralocorticoids and glucocorticoids. Hydrocortisone has both glucocorticoid and mineralocorticoid activity. Therefore, it is an ideal agent to use for the management of adrenocortical insufficiency. • Patients with aldosterone deficiency should continue their fludrocortisone up until the time of surgery. Hypokalemic acidosis or hypovolemia must be treated preoperatively. Supplementation of mineralocorticoids (fludrocortisone 0.05–0.1 mg/d) should occur preoperatively. Doses must be carefully titrated to avoid hypertension. • Primary hyperaldosteronism (Conn syndrome) should be suspected in patients who present with concurrent hypertension and hypokalemia, severe refractory hypertension, adrenal incidentaloma and hypertension, or onset of hypertension at a young age.

ALVEOLAR ARTERIAL GRADIENT AND RATIO Sharanya Nama, MD Michael Mangione, MD

BASICS DESCRIPTION

• The alveolar–arterial gradient and ratio provide a useful, objective means to determine how effectively oxygen from the alveolus moves into the pulmonary circulation. It aids with: – Identifying increases in venous admixtures, even in the presence of increased inspired oxygen concentrations – Monitoring improvement or worsening of the venous admixture – Assessing effectiveness of treatment and interventions – Differentiating between causes of hypoxia (impaired uptake vs. decreased alveolar oxygen availability) PHYSIOLOGY PRINCIPLES

• Definitions: – PAO2 = alveolar PO2. It is determined by the alveolar gas equation and is calculated as follows: PAO2 = [FiO2 × (Patm – PH2O) – (PaCO2/0.8)]; measured in units of mm Hg.

– PaO2 = arterial PO2. It is determined by direct arterial blood gas values and is measured

in units of mm Hg. Small amounts of oxygen are dissolved in the plasma, which are in equilibrium with the oxygen bound to hemoglobin. Thus, a decrease in arterial oxygen content would reflect a decrease in hemoglobin binding and decreased oxygen saturation. • A-a gradient: The difference between the alveolar and arterial partial pressure of oxygen – Normal adult values in nonsmokers are Ppa > Ppv). Zone 1 therefore has ventilation without perfusion and is essentially dead space. – Zone 2: The middle zone where the perfusion pressure is greater than the alveolar pressure so blood flows easily (Ppa > PA > Ppv). Zone 2 is the area of “best matched” ventilation and perfusion; it also contains the most number of alveoli. – Zone 3: Located at the lung base, where the perfusion pressure is much greater than the alveolar pressure so blood flow is high (Ppa > Ppv > PA). Zone 3 has very good perfusion, but less ventilation which results in shunting.

DISEASE/PATHOPHYSIOLOGY

• Atelectasis is the term used to describe “collapsed” alveoli; the term can be applied to a single unit, lobe, or the entire right or left lung. Blood that perfuses the collapsed cannot pick up oxygen or offload carbon dioxide, resulting in pulmonary shunting. As the number of atelectatic units increases, it is less likely that the blood will be oxygenated by a proximal or distal unit before returning to the left atrium. • Neonatal respiratory distress syndrome (RDS) can be present in premature infants due to a lack of surfactant. The increase in surface tension results in alveolar collapse (atelectasis), with resultant hypoxemia, decreased compliance, and problems re-inflating the lungs.

Surfactant may be present by week 24 and is almost always present by gestational week 35. If there are mature levels of surfactant, the amniotic fluid will have a lecithin:sphingomyelin ratio >2:1. Corticosteroids may be given to encourage formation of surfactant in cases of pre-term labor. • Emphysema is a disease where alveoli undergo destruction and elastic recoil is decreased; this results in increased alveolar size. It is most commonly caused by smoking, but can also result from alpha-1 antitrypsin deficiency. Bronchoalveolar lavage will demonstrate the presence of neutrophils; these cells cause damage to the lung parenchyma by secretion of proteolytic enzymes. Alveolar damage decreases gas exchange area, leading to hypoxemia, hypercarbia, and chronic dyspnea. • Pulmonary fibrosis describes thickening of the alveolar wall; this impairs the diffusing capacity of gas through the alveoli. • Cystic fibrosis is a genetic disease of the epithelial chloride channel to open normally in response to cyclic AMP. This defect decreases water passage across the epithelial membrane, leading to abnormally thick mucous in the airways. Mucus can obstruct small airways (plugs) and result in frequent pulmonary infections. • Aspiration pneumonitis of acidic solutions may lead to destruction of surfactant-producing type II pneumocytes and the capillary endothelium. Damage to these cells may lead to atelectasis and leakage of fluid into the lungs. Arterial hypoxia may ensue, which leads to pulmonary vasoconstriction with associated pulmonary hypertension, as well as tachypnea and bronchospasm. • Congestive heart failure describes cardiac dysfunction with “back-up” into the pulmonary vasculature (increased capillary pressure). This initially causes dilation and recruitment of pulmonary capillaries making it more difficult for alveoli to expand (results in decreased lung compliance, and increased work of breathing). As capillary pressures increase, fluid will eventually extravasate into the interstitial space around the alveoli. With further increases in pressure, fluid will eventually enter into the alveoli. • Acute respiratory distress syndrome (ARDS) is defined as severe hypoxemia, diffuse shadows on CXR, low pulmonary compliance, and pulmonary edema not from left-sided heart failure. The lung parenchyma is severely damaged due to chemical mediators and fibroblasts. There is an inflow of protein-rich fluid into the alveoli due to increased permeability of the alveolar capillary membranes. Diseases that may precipitate ARDS include: septic shock, aspiration of gastric contents, pneumonia, pulmonary contusions, near drowning, severe trauma with associated shock, and inhalation of toxic gases or smoke.

PERIOPERATIVE RELEVANCE

Positive end-expiratory pressure (PEEP) is effective in improving arterial oxygenation and should be used when indicated. PEEP helps prevent alveolar collapse at the end of expiration and in doing so may decrease the shear stress associated with the opening and closing of alveoli with mechanical ventilation. PEEP also helps ventilation-to-perfusion matching as well as decreasing right-to-left intrapulmonary shunt. Because PEEP recruits alveoli that were previously collapsed, it helps to increase lung volumes and functional residual capacity (FRC). However, by increasing the intrathoracic pressure, it can decrease preload to the right atrium and decrease cardiac output.

EQUATIONS

Law of Laplace: P = 2T/r, where P = pressure, T = surface tension, and r = radius

REFERENCES

1. Daniels CB, Orgeig S. Pulmonary surfactant: The key to the evolution of air breathing. News Physiol Sci. 2003;18:151–157. 2. Smetana GW. Preoperative pulmonary evaluation. N Engl J Med. 1999;340:937–944. 3. Staton GW, Ingram RH. Pulmonary edema. Sci Am Med. 1997:1–10.

4. Tobin MJ. Culmination of an era in research on the acute respiratory distress syndrome. N Engl J Med. 2000;342:1360–1361. See Also (Topic, Algorithm, Electronic Media Element) • Atelectasis • Surfactant • Pulmonary ventilation and perfusion matching • Acute respiratory distress syndrome • Cardiogenic pulmonary edema • Noncardiogenic pulmonary edema

CLINICAL PEARLS

• During normal spontaneous ventilation, the alveolar-to-dead space ventilation ratio is 1:1. During mechanical ventilation under anesthesia, dependent lung regions will have alveolar collapse, and ventilation is preferably distributed to the nondependent areas (ratio changes to 1:2). These alveoli may become over-aerated if high levels of PEEP are used.

AMNIOTIC FLUID EMBOLISM Kanishka Monis, MD Poovendran Saththasivam, MD

BASICS DESCRIPTION

• Amniotic fluid embolism (AFE) is a rare, but often fatal, obstetric emergency. It was first described by Dr. Meyer in 1926. • Entry of amniotic fluid into the maternal circulation via the placenta can occur during pregnancy or in the immediate postpartum period. • Amniotic fluid contains: – Epithelial squamous cells from the fetal skin – Mucin which originates from meconium – Lanugo – Fat from vernix caseosa EPIDEMIOLOGY Prevalence

Hard to assess due to a lack of sensitive and specific diagnostic studies; however, estimated to be 7.7 in 100,000 births in the US. Morbidity

Neurologic impairment is seen in 61% of women and 50% of infants who survive AFE Mortality

• AFE is the fifth most common cause of maternal mortality in the world. • Maternal mortality approaches 60%. • Fetal mortality rate is around 21%.

ETIOLOGY/RISK FACTORS

• Advanced maternal age • Tumultuous labor • Placental abnormalities (placenta previa, abruptio placentae) • Operative deliveries (Cesarean section, assisted vacuum deliveries, forceps-assisted deliveries) • Eclampsia • Polyhydramnios • Cervical lacerations • Uterine rupture • Medical induction of labor

PHYSIOLOGY/PATHOPHYSIOLOGY

• 4 main physiologic alterations in AFE: – Maternal cardiovascular collapse – Coagulopathy – Respiratory distress – Altered mental status • Amniotic fluid entry. It is hypothesized that the combination of breaches to the maternal circulation along with increased intrauterine pressures can facilitate entry of amniotic fluid into the circulation. – Breaches in the physical barrier can occur at the level of endocervical veins, the placental attachement site, or at uterine trauma sites. – Increased intrauterine pressure (and incidence of AFE) is seen in conditions such as polyhydramnios, placenta previa, placenta abruption, operative deliveries, uterine rupture, and cervical lacerations. • Maternal cardio-respiratory collapse may result from the following mechanisms – Mechanical obstruction of the pulmonary arteries (dead space; ventilation, but no perfusion) Amniotic debris obstructs the pulmonary artery leading to pulmonary hypertension and acute right ventricular failure. The increased right ventricular afterload results in a dilated right ventricle and deviation of the inter-ventricular septum. This can impair left ventricular filling with resultant left ventricular failure. Transesophageal echocardiography supports these findings. – Immunologic responses. Generalized constriction of the pulmonary vasculature results in relative shifting of blood flow to areas of lower ventilation from higher ventilation (shunt; perfusion, but inadequate ventilation). The complement cascade is activated and the subsequent immunologic reactions can result in pulmonary vasoconstriction. Of note, low levels of complement (C3 and C4) have been observed in some parturients with AFE Endothelin has also been found in amniotic fluid and can lead to pulmonary vasoconstriction Other humoral mediators, such as histamine, serotonin, prostaglandins, and leukotrienes have been linked to the onset of shock, myocardial depression, and disseminated intravascular coagulopathy • Coagulopathy associated with AFE is mainly related to consumption. – Amniotic fluid contains tissue factors that activate the extrinsic pathway by binding to factor VII. – Amniotic fluid is also found to have a thromboplastin-like effect and factor X activating property.

PREVENTATIVE MEASURES

• Avoid trauma to the uterus during insertion of a pressure catheter or during artificial rupture of the membrane. • During a Cesarean section, incision on the placenta should be avoided. • Excessively strong and frequent uterine contractions, as may be seen with oxytocin administration, should be minimized.

PREOPERATIVE ASSESSMENT • A diagnosis of exclusion, based on clinical presentation, or postmortem findings • AFE usually occurs during the intrapartum period or immediately postpartum. • Symptoms: – Sudden breathlessness – Nausea/vomiting – Dizziness – Chest pain – Panic attack – Pin and needle sensation in fingers – Bleeding • Signs: – Hypotension – Respiratory distress – Cyanosis – Fetal distress • Diagnostic tests and imaging: – Nonspecific tests include CBC, coagulation profile, ABG, BUN, and cardiac enzymes. – EKG may shown an acute right ventricular strain pattern. – Chest radiograph may indicate a dilated right heart, prominent pulmonary arteries, and pulmonary edema. – Transesophageal echocardiography may reveal pulmonary hypertension, acute right ventricular failure with leftward deviation of the inter-ventricular and inter-atrial septum and severe tricuspid regurgitation. – Serum markers for AFE: Specific markers include zinc coproporphyrin (a component of meconium) and sialyl Tn antigen (a component of meconium and amniotic fluid). Nonspecific serum markers include serum tryptase (marker of mast cell degranulation) and complement factors. The presence of fetal squamous cells in the maternal circulation is suggestive but not diagnostic of AFE.

DIFFERENTIAL DIAGNOSIS

• Pulmonary thromboembolism • Air embolism • Myocardial infarction/cardiac arrhythmia • Aortic dissection • Anesthetic-related complication (total or high spinal block) • Allergic anaphylaxis • Abruptio placentae • Uterine rupture • Sepsis

TREATMENT • Treatment is mainly supportive care aimed at the: – Correction of hypoxia and maintenance of oxygenation: Administer oxygen immediately with a goal of SpO2 >90%

Ventilate by face mask, Ambu bag, or endotracheal intubation – Correction of hypotension and maintenance of cardiac output: Initiate cardiopulmonary resuscitation (CPR) immediately Rapid restoration of preload using crystalloid solution Inotropic support in cases where hypotension is refractory to fluid therapy Maintain a systolic blood pressure >90 mm Hg – Correction of coagulopathy: Transfuse packed red blood cells to maintain adequate blood oxygen-carrying capacity and oxygen delivery to tissues. Fresh frozen plasma, platelet, and cryoprecipitate can be transfused to correct specific laboratory coagulation derangements. Recombinant activated factor VIIa has been used to manage severe DIC not responding to blood products transfusion • Pulmonary hypertension may be treated with inhaled nitric oxide, prostacyclin, and sildenafil.

FOLLOW-UP • Risk of recurrence in the subsequent pregnancy is unknown. • Neurologic disability in the mother and infant remains a common complication following AFE.

REFERENCES

1. Abenhaim HA, Azoulay L, Kramer MS, et al. Incidence and risk factors of amniotic fluid embolisms: A population-based study on 3 million births in the United States. Am J Obstet Gynecol. 2008;199(1):49.e1–49.e8. Conde-Agudelo A, Romero R. Amniotic fluid embolism: An evidence-based review. Am J Obstet Gynecol. 2009;201(5):445.e1–445.e13. Erratum in: Am J Obstet Gynecol. 2010;202(1):92. 2. Harboe T, Benson MD, Oi H, et al. Cardiopulmonary distress during obstetrical anaesthesia: Attempts to diagnose amniotic fluid embolism in a case series of suspected allergic anaphylaxis. Acta Anaesthesiol Scand. 2006;50(3):324–330. 3. Kane SK. Historical perspective of amniotic fluid embolism. Int Anesthesiol Clin. 2005;43(4):99–108. 4. Moore J, Baldisseri MR. Amniotic fluid embolism. Crit Care Med. 2005;33(Suppl 10):S279– S285. See Also (Topic, Algorithm, Electronic Media Element) • Venous air embolism

• Dead space

CODES ICD9

• 673.10 Amniotic fluid embolism, unspecified as to episode of care or not applicable • 673.11 Amniotic fluid embolism, delivered, with or without mention of antepartum condition • 673.12 Amniotic fluid embolism, delivered, with mention of postpartum complication ICD10

• O88.111 Amniotic fluid embolism in pregnancy, first trimester • O88.112 Amniotic fluid embolism in pregnancy, second trimester • O88.119 Amniotic fluid embolism in pregnancy, unspecified trimester

CLINICAL PEARLS

• Due to significant morbidity and mortality, a high index of suspicion is warranted. • Suspect AFE when the laboring patient complains of sudden breathlessness, or incurs hypotension or cardiac arrest. • Rule out pulmonary thromboembolism and anesthetic complications (e.g., high spinal) in the parturient suspected of AFE. • The mainstay of therapy is to support oxygenation and circulation to prevent end-organ damage with severe debilitating neurologic sequelae. • Parturients have improved prognosis when AFE is diagnosed early and aggressive treatment is administered.

AMYLOIDOSIS

Ahmed Fikry Attaallah, MD, PhD

BASICS DESCRIPTION

• Amyloidosis is a progressive connective tissue disease caused by the deposition of amyloid proteins. • It can involve various body systems but sometimes only one organ may be affected. Factors leading to the specific pattern of organ involvement are not understood. EPIDEMIOLOGY Incidence

New cases: 8 persons per million annually Prevalence

• 95% of cases are seen in people >40 years of age. • 66% of cases are men. • 15–20% of primary amyloidosis patients have associated multiple myeloma.

Morbidity

Varies between patients reflecting the extent of spread and the degree of organ dysfunction Mortality

• The average survival with primary amyloidosis is 12 months. • Amyloidosis associated with multiple myeloma is rapidly progressive and the life expectancy is usually women 1.5:1 in sporadic ALS • Men = women in familial ALS • Rapid decrease after 80 years of age

Prevalence

• In the US: 2–5.2 per 100,000 • Peak age at onset: Overall 60 years. This value is usually lower in familial disease.

Morbidity

High risk of postoperative pulmonary complications (PPCs) secondary to the inability to clear secretions and carbon dioxide retention. The risk increases even further with a vital capacity that is 50% of predicted levels. Mortality

• Respiratory failure is the most common cause of death in over 84% of patients. • Average lifespan after diagnosis: 3–5 years. However, multidisciplinary care can increase survival. • Poorer prognosis is associated with bulbar palsy, advanced age.

ETIOLOGY/RISK FACTORS

Multifactorial with complex interaction between genetic and molecular pathways

• Genetic susceptibility: To date, 13 genes and loci have been identified (SOD1, TARDBP, FUS, ANG, OPTN). Familial ALS has a Mendelian pattern (5–10%). • Sporadic (SALS): Overlap with neurodegenerative disorders • Environmental factors: Extensive physical exertion (footballer), active service in US armed forces, cigarette smoking, neurotoxins (beta-methyl-amino-L-alanine), statins (under

discussion)

PATHOPHYSIOLOGY

The disease process involves glutamate-induced excitotoxicity, oxidative stress, mitochondrial dysfunction, impaired axonal transport, neurofilament aggregation, intra-cytoplasmic protein aggregates, inflammatory dysfunction, deficits in neurotrophic factors, and dysfunction of signaling pathways. ANESTHETIC GOALS/GUIDING PRINCIPLES

• There is an increased risk of PPCs, and perioperative efforts should aim at maintaining respiratory muscle strength and avoiding pulmonary aspiration. • Succinylcholine is absolutely contraindicated; the proliferation of extrajunctional receptors can result in life-threatening hyperkalemia.

PREOPERATIVE ASSESSMENT SYMPTOMS

Clinical hallmark is the presence of UMN and LMN features, involving brainstem and spinal cord regions: • Spinal onset in 75% (limbs, most common) • Bulbar onset in 25% • Initial trunk or respiratory involvement in 5% • Atypical onset: Weight loss, cramps without muscle weakness, cognitive dysfunction

History

Duration and progression: The median time to diagnosis is ∼14 months due to the insidious onset. Signs/Physical Exam

• Pulmonary: Observation of breathing, respiratory rate; auscultation; swallowing; coughing; salivation • Neurologic exam

TREATMENT HISTORY

• Supportive, palliative, and multidisciplinary management has been demonstrated to decrease the risk of death by 45% at 5 years. Symptomatic treatment is the cornerstone and involves: – Noninvasive ventilation: Prolongs survival and improves quality of life – Diaphragmatic pacing (DPS) – Invasive ventilation via tracheostomy (avoided in most patients) – Gastrostomy tube – Nutrition (50–60% of patients are hypermetabolic)

MEDICATIONS

• Riluzole (glutamate antagonist): Only drug shown to extend survival by ~2–3 months

– Most common side effects: Fatigue, nausea – ALT/SGPT levels rise in about 50% of patients. – Decreased lung function – Less common: Neutropenia, pain, dizziness, anorexia – Overdose: Encephalopathy with stupor/coma, methemoglobinemia • Common medications for symptomatic care: – Glycopyrronium, atropine, hyoscyamine – N-acetylcysteine – Benzodiazepines such as lorazepam – Dextromethorphan and quinidine – Baclofen and tizanidine – Anticonvulsants, e.g., carbamazepine – Opioids, e.g., morphine, in late state – Antidepressants, e.g., amitriptyline or SSRI – Modafinil

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC to assess for neutropenia from riluzole • Liver enzymes, especially ALT (affected by riluzole) • ABG to assess for hypercarbia • Pulmonary function tests – Spirometry: FVC – Maximum inspiratory pressure, sniff nasal inspiratory pressure of 25:1 supports the underlying mechanism of tissue hypoxia or Type A lactic acidosis. A normal lactate-to-pyruvate ratio (10:1) supports Type B lactic acidosis. • Anaerobic metabolism is not an uncommon physiologic derangement seen in the perioperative arena; it can result when there is a mismatch of oxygen delivery and demand: – Hypoxia/hypoxemia: Esophageal or mainstem intubation, hypoxic mixture, hypoventilation, V/Q mismatch, shunt – Hypoperfusion: Hypotension, hypovolemia, hemorrhage, myocardial impairment, shock – Vasodilation: Anesthetic medications, neuraxial blocks; anaphylactic or septic shock • Cardiopulmonary bypass: Lactate is associated with malperfusion (2). It not only allows for prognostication, but also serves as an indicator of the efficacy of therapies used to restore tissue perfusion. – Hyperlactatemia is associated with longer intensive care stays and increased postoperative ventilatory support, renal dysfunction, infectious complications, and circulatory disorders. – Titrating therapies to traditional endpoints may not ensure that the microvascular bed is perfused. For example, a normal or high blood pressure may be a vasoconstrictive response to a low cardiac output state. • Septic shock: Hyperlactatemia is typically present in patients with sepsis or septic shock and the etiology is multifactorial (3). – Hypovolemia: Septic shock is associated with fluid-responsive physiology. Thus, an elevated lactate level could indicate a “dry” patient. – Hypoperfusion: Sepsis is also accompanied by a hypermetabolic state with enhanced glycolysis. Patients with “normal” filling pressures (e.g., central venous pressure) and cardiac indices (e.g., cardiac index) may not have adequate oxygen delivery. – Cytopathic hypoxia: Despite adequate volume status and perfusion, tissue dysfunction at

the cellular level may persist in sepsis and represents impaired cellular function. – Lactate is a well-established prognostic indicator in sepsis and septic shock. Obtaining serial serum lactate levels aids in identifying tissue hypoperfusion in patients who are not hypotensive but are at risk for septic shock; an elevated lactate (>4 mmol/L or 36 mg/dL) likely indicates inadequate oxygen delivery. Early goal-directed therapy should be considered in patients with sepsis and/or an elevated lactate level. – As part of the Surviving Sepsis Guidelines, a resuscitation bundle for patients with sepsis includes, but it is not limited to: A minimal initial crystalloid bolus of 20 mL/kg or equivalent Vasopressor therapy to maintain a mean arterial pressure >65 mm Hg Obtaining blood cultures and administering appropriate antibiotic therapy Maintaining adequate central venous pressure and central venous oxygen saturation

EQUATIONS

• Glucose + 2 ADP + 2 Pi → 2 Lactate + 2 ATP + 2 H2O • Pyruvate + NADH + H+ ←→Lactate + NAD+

REFERENCES

1. Cassavaugh J, Lounsbury KM. Hypoxia mediated biological control. J Cellular Biochem. 2010;112(3):735–744. 2. Javidi L. Pathophysiology of lactic acidosis and its clinical importance after cardiac surgery. Iran J Cardiac Surg. 2008;2:18–24. 3. Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock. Crit Care Med. 2008;36:1394–1396.

ADDITIONAL READING

• Chaitman BR. Exercise stress testing. In: Bonow RO, Mann DL, Zipes DP, et al, eds. Braunwald’s heart disease—a textbook of cardiovascular medicine, 9th ed. Philadelphia, PA: Saunders/Elsevier, 2011, chap. 14. • Levy B. Lactate and shock state: The metabolic view. Curr Opin Crit Care. 2006;12(4):315– 321. • Surviving Sepsis Campaign. www.survivingsepsis.org See Also (Topic, Algorithm, Electronic Media Element) • Base excess • Metabolic acidosis • Septic shock • Cardiopulmonary bypass (CPB)

CLINICAL PEARLS

• Lactate production can serve as a marker of anaerobic metabolism and tissue hypoxia. • When there is concern for adequate oxygen delivery, lactate and base deficit measurements can serve as markers of adequate tissue perfusion.

ANAPHYLAXIS Lori Gilbert, MD

BASICS DESCRIPTION

• An acute, life-threatening reaction with an onset of minutes to hours. It is usually, but not always, the result of an immunologic mechanism that involves IgE-mast cell or basophil mediator release; such mediators can include histamine, leukotrienes, and prostaglandins. • The newest definition of anaphylaxis encompasses 1 of 3 scenarios: – Acute onset (minutes to hours) of skin and mucosal manifestations, as well as respiratory compromise, hypotension, or shock – Signs as above, after exposure to a likely antigen, in addition to GI symptoms – Hypotension after exposure to a known antigen EPIDEMIOLOGY Prevalence

• During anesthesia: Ranges from 1:4,000 to 1:25,000 anesthetics • Hospital inpatients in the US: 1:3,000; in Europe, the incidence is reported to be much lower. • In the US, it is estimated that between 1.25% and 16% of the general population is at risk for possibly experiencing an episode of anaphylaxis. Prevalence

• Lifetime prevalence from all triggers: 0.05–2% • Food triggers: 90% of anaphylaxis cases are caused by milk, soy, eggs, wheat, peanuts, tree nuts, fish, and shellfish. Morbidity

• Food allergies account for 30,000 ER visits a year; it is more common among children than adults. • Latex anaphylaxis is responsible for >200 cases/year.

Mortality

• In the US: ∼2 in 100,000 anaphylaxis cases • In the UK: 0.65–2% of anaphylaxis cases • Risk factors age 10–35 years old: Active asthma, peanut allergy, and delayed administration of epinephrine • Risk factors age 55–85 years old: Cardiovascular or respiratory illness, use of antibiotics or anesthetic agents. ETIOLOGY/RISK FACTORS

• History of a prior anaphylactic episode remains the most important factor in establishing cause and risk factors. • Outpatient setting: – Drug-induced: Penicillin and other antibiotics, aspirin, and NSAIDs – IV contrast dye – Food: Peanuts, tree nuts, fish, shellfish, soy, egg, cow’s milk – Other: Exercise-induced, idiopathic, insect stings, seminal fluid • Perioperative setting: – Neuromuscular blockers (most common) – Natural rubber latex – Antibiotics – Hypnotics (propofol, thiopental) – Aprotinin – Bupivacaine – Radiographic contrast material – Opioids – Protamine – Blood transfusions – Methylmethacrylate (bone cement; associated with hypotension but no IgE mechanism has been found) – Rare causes include etomidate, ketamine, midazolam, and amide local anesthetics.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Anaphylactic and anaphylactoid reactions stem from the systemic release of mediators from mast cells and basophils. The pathogenesis of anaphylactic reactions involves an immunologic mechanism in which IgE is created in response to allergen exposure. Receptors on the surface of mast cells and basophils bind with IgE. • Re-exposure of the allergen results in activation of IgE-bound mast cells and basophils with the resultant release of pre-formed mediators that are stored in cellular granules (histamine, tryptase, heparin, chymase, cytokines). In addition, arachidonic acid is metabolized to prostaglandins and leukotrienes and also released. • Anaphylaxis often produces signs and symptoms within minutes of exposure but there are also biphasic reactions that can occur 1–72 hours after the initial attack. • Increased vascular permeability is a hallmark of anaphylaxis that allows the transfer of large amounts of intravascular fluid into the extravascular space within 10 minutes. As a result, cardiovascular collapse may be the first sign of anaphylaxis with little or no cutaneous or respiratory signs.

PREVENTATIVE MEASURES

• Primary prevention is based on allergen desensitization through immunotherapy. • Venom immunotherapy is highly successful in preventing anaphylaxis. • Pharmacologic prophylaxis (steroids, antihistamines) can be used to help prevent occurrences to radiographic contrast material, fluorescein, and other dyes. • For idiopathic anaphylaxis, prophylaxis with daily oral prednisone, combined with H1 antagonists, has resulted in decreased incidence.

• Most importantly, patient education and avoidance of known triggering substances is key in prevention. • A “TIME OUT" should be performed prior to any procedure and identify the presence of any known drug allergies.

PREOPERATIVE ASSESSMENT • Acute onset of reaction (minutes to hours) • Cutaneous: Skin, mucosa, or both can present with hives, urticaria, angioedema, pruritus, flushing, swollen lips and tongue. • Respiratory: Bronchospasm, wheezing, dyspnea, stridor, reduced peak expiratory flow, hypoxemia, respiratory arrest • Cardiovascular: Hypotension or symptoms of end-organ dysfunction (cardiovascular collapse), tachycardia • Gastrointestinal: Persistent vomiting, diarrhea • RAST testing (radioallergosorbent test) detects specific IgE antibodies to suspected or known allergens. The suspected antigen is bound to an insoluble material and the patient’s serum is added. If the serum contains antibodies to the allergen, those antibodies bind to the allergen. Radiolabeled anti-human IgE antibody is added where it binds to those IgE antibodies already bound to the insoluble material. • Skin manifestations may be masked by surgical drapes and are not as common in the setting of general anesthesia as in other settings. • Bradycardia is, surprisingly, more common with anaphylaxis in the setting of general anesthesia (not tachycardia). • Cardiovascular collapse may be the only sign of anaphylaxis.

DIFFERENTIAL DIAGNOSIS

• Acute asthma exacerbation • Syncope • Panic attack/anxiety disorders • Acute generalized hives • Vocal cord/paradoxical vocal cord dysfunction • Vasovagal reactions • Nonimmunologic reactions that involve mechanisms outside of IgE mediation (transfusion reactions, IgG or IgM antibody-mediated, antigen–antibody complexes and complement) • Anaphylactoid reactions: The World Allergy Organization has suggested that the term be eliminated in favor of calling all similar reactions “anaphylaxis.” Generally, the term is used to describe non-IgE-mediated reactions; the initial treatment is the same, regardless of the mechanism. • Cardiovascular disorders: Pulmonary embolism, cardiogenic shock, etc. • Flushing disorders: Carcinoid, “red-man” syndrome from vancomycin, medullary carcinoma of the thyroid • Other: Mastocytosis (systemic mast cell disease [SCMD]) is a clonal disorder characterized by overproduction of mast cells in different tissues. • Postprandial syndromes

• Diagnostic tests and interpretation: – Serum tryptase peaks 60–90 minutes after the onset of anaphylaxis and persists for 6 hours; obtain between 1 and 2 hours after the first symptoms appear. – Plasma histamine levels begin to rise within 5–10 minutes and remain elevated for 30–60 minutes. – 24-hour urinary histamine metabolite – Urinary vanillylmandelic acid to rule out pheochromocytoma and carcinoid syndrome – Skin tests (or in vitro tests) determine the presence of specific IgE antibodies to foods, medications (e.g., penicillin).

TREATMENT • Discontinuation of the inciting factor (e.g., anesthetic agent or drug) • Place the patient in the recumbent position (pertinent if antibiotics or medication is being given on the floor or preoperative holding area) • ABC’s: Manage airway, delivery 100% oxygen, and intubate (if appropriate) • Rapid IV fluid replacement • Epinephrine is the most important aspect of treatment for anaphylaxis and should be administered immediately: – IV: 5–10 mcg boluses – IV drip: 1 mcg/min – SQ: 200–500 mcg q5 minutes (aqueous 1:1,000 dilution which is equivalent to 1 mg/mL or 0.2–0.5 mL) – IM: 200–500 mcg into the vastus lateralis, or lateral aspect of the thigh (aqueous 1:1,000 dilution which is equivalent to 1 mg/mL or 0.2–0.5 mL) – Cardiopulmonary arrest during anaphylaxis: 1–3 mg IV over 3 minutes, followed by 4–10 mcg/min infusion – Severe or refractory anaphylaxis that is unresponsive to epinephrine has been reported with patients on beta-blockers; it has been characterized by bradycardia, profound hypotension, and severe bronchospasm; consider treating with glucagon 1–5 mg IV over 4 minutes, followed by an infusion of 5–15 mcg/min. • Histamine 1 blocker. Diphenhydramine 1–2 mg/kg or 25–50 mg IV dose. • Histamine 2 blockers. Ranitidine 50 mg IV diluted in 5% dextrose (total volume of 20 mL) can be administered over 5 minutes. Alternatively, cimetidine 4 mg/kg IV may be given. • Inhaled beta-2 agonists if bronchospasm is present • Glucocorticoids are not helpful acutely but potentially can help prevent recurrences and shorten the duration of attack. • Monitors: Large-bore IV access, if not already in place, should be placed. Arterial line placement can aid with monitoring blood pressure (particularly if chest compressions); however, it should not interfere with immediate resuscitation with IV fluids and epinephrine.

FOLLOW-UP

• Biphasic anaphylaxis can occur in up to one-fourth of episodes, and symptoms may recur within hours after apparent resolution of initial presentation. • Following resolution of the initial episode, patients should be provided with an epinephrine pen and instructions for administration as well as instructions to go to the nearest emergency room at the first hint of recurrence of symptoms. • Patients should also be referred to an allergist/immunologist for further workup, possibly including skin testing and desensitization, if appropriate.

REFERENCES

1. ieberman P, Nicklas R, Oppenheimer J, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010;126:477–480.

2. Hepner D, Castells M. Anaphylaxis during the perioperative period. Anesth Analg. 2003;97:1381–1395. 3. Estelle F, Simons R. Anaphylaxis. J Clin Immunol. 2010;S161–S180. 4. Kemp S, Lockey R. Anaphylaxis: A review of causes and mechanisms. J Allergy Clin Immunol. 2002;110(3):341–348. 5. Leiberman P. Anaphylactic reactions during surgical and medical procedures. J Allergy Clin Immunol. 2002;110(2):s64–s69. 6. Matasar M, Neugut A. Epidemiology of anaphylaxis in the United States. Curr Allergy Asthma Rep. 2003;3:30–35.

ADDITIONAL READING • www.aaaai.org • www.acaai.org • www.aafa.org

See Also (Topic, Algorithm, Electronic Media Element) • Latex allergy

CODES ICD9 • 995.0 Other anaphylactic reaction • 995.60 Anaphylactic reaction due to unspecified food ICD10 • T78.00XA Anaphylactic reaction due to unspecified food, init encntr • T78.2XXA Anaphylactic shock, unspecified, initial encounter • T78.2XXD Anaphylactic shock, unspecified, subsequent encounter

CLINICAL PEARLS

• Epinephrine, patient position, and oxygen are the most important therapeutic modalities in treating anaphylaxis. Treatment (in order of importance) includes: – Epinephrine – Patient position (recumbent) – Oxygen – IV fluids – Nebulized beta-2 agonists – Vasopressors – Antihistamines – Corticosteroids • Propofol and egg allergy: This topic has been a source of some controversy among anesthesia providers. Propofol is formulated in a lipid emulsion containing soybean oil, glycerol, egg lecithin, and disodium edetate with sodium hydroxide to adjust for pH. – The egg lecithin component is a highly purified egg yolk component. The principal protein of eggs is ovalbumin which is present in the egg white. Most egg allergies are related to the egg white (albumin) and not the egg yolk (lecithin). – Most allergic-type reactions to propofol are nonimmunologic because propofol can cause direct stimulation of histamine release. – Skin testing of egg-allergic patients is not consistent with allergies to propofol. – However, there are case reports in the literature of anaphylaxis associated with propofol in egg-allergic individuals. – Furthermore, the propofol package insert monograph clearly states under contraindications: “Propofol Injectable Emulsion is contraindicated in patients with allergies to eggs, egg products, soybeans or soy products.” • It is the author’s opinion that if propofol can be avoided in egg-allergic individuals, then an appropriate substitute should be used. If propofol cannot be avoided, epinephrine, largebore IV access, and resuscitation equipment should be readily available.

ANEMIA

Gregory M. T. Hare, MD, PhD Katerina Pavenski, MD, FRCPC

BASICS DESCRIPTION

• Anemia is defined as a hemoglobin concentration 20 seconds, or – >10 seconds if associated with bradycardia (340 bpm may be seen with atypical AFL. • Echocardiogram: Evaluate atrial size and ventricular function – TEE is used to evaluate for the presence of atrial thrombus prior to synchronized cardioversion in patients with AFL lasting longer than 48 hours.

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Uncontrolled ventricular rate, myocardial ischemia, or cardiac decompensation. • Synchronized cardioversion in hemodynamically unstable patients.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics can decrease sympathetic output. • Rate control: Calcium channel blockers or beta-adrenergic blockers can be titrated to effect.

Special Concerns for Informed Consent

• Increased risk of intraoperative rapid ventricular rate, myocardial ischemia, cardiac decompensation, and thromboembolic events. • Risks and benefits of delaying the surgery to evaluate and treat paroxysmal AFL must be

explained. Non-urgent surgery should be postponed until adequate control of the ventricular rate has been achieved.

INTRAOPERATIVE CARE Choice of Anesthesia

Insufficient evidence to suggest that either general or regional anesthesia is preferred for patients with AFL. Monitors

• Standard ASA monitors including ECG with ST segment analysis. • Arterial catheter for close monitoring of blood pressure or frequent blood gas evaluation. • Central venous catheter for infusion of vasopressors or transvenous pacing. • Pulmonary artery catheter for evaluation of cardiac output or mixed venous oxygenation, if indicated. • Transesophageal echocardiography, if indicated.

Induction/Airway Management

• Risk of hemodynamic instability – Vasodilation and myocardial depression from induction agents (propofol and thiopental). – Sympathetic stimulation from laryngoscopy. – Dexmedetomidine is associated with prolonged hypotension and increased AV nodal blockade. • Avoid pharmacologic agents associated with sympathetic activation (ketamine) or vagolytic effects (pancuronium).

Maintenance

• Use of either volatile anesthetic or total intravenous anesthetic is acceptable. • Conservative fluid management in the setting of reduced myocardial function. • Intraoperative occurrence may be treated with rate control medications, vagal maneuvers, or cardioversion if the patient is hemodynamically unstable.

Extubation/Emergence

• Avoid sympathetic stimulation. • Ensure adequate analgesia. • Balance reversal of neuromuscular block (excessive anticholinergics can provoke AFL); consider slow titration to reduce incidence.

POSTOPERATIVE CARE BED ACUITY

ICU with hemodynamically unstable or poorly controlled AFL MEDICATIONS/LAB STUDIES/ CONSULTS

• Medications: Rate control agents and anticoagulation as indicated. • Labs: Electrolytes, digoxin level, cardiac enzymes, and thyroid function tests.

COMPLICATIONS

• Systemic thromboembolism • Coronary and/or cerebral ischemia secondary to hemodynamic insufficiency • Tachycardia-induced cardiomyopathy • Sinus bradycardia following administration of AV nodal blocking agents

REFERENCES

1. Lee KW, Yang Y, Scheinman MM. Atrial flutter: A review of its history, mechanism, clinical features, and current therapy. Curr Probl Cardiol. 2005;30:121–168.

2. Nattel S, Singh BN. Evolution, mechanisms, and classification of antiarrhythmic drugs: Focus on class III actions. Am J Cardiol. 1999;84:11R–19R.

3. Van Gelder IC, Hagens VE, Bosker HA, et al. Pharmacologic versus direct-current electrical cardioversion of atrial flutter and fibrillation. Am J Cardiol. 1999;84:147R–151R. See Also (Topic, Algorithm, Electronic Media Element) • Atrial fibrillation • Electrical cardioversion • Wolff–Parkinson–White

CODES ICD9 427.32 Atrial flutter ICD10 • I48.3 Typical atrial flutter • I48.4 Atypical atrial flutter • I48.92 Unspecified atrial flutter

CLINICAL PEARLS

• Atrial flutter (AFL) commonly occurs in patients after open heart surgery and those with underlying cardiac disease. • ECG manifestations include flutter waves with variable AV conduction. • Ventricular rate control is achieved with beta-blockers or calcium channel blockers. • Hemodynamically unstable patients require immediate synchronized cardioversion.

ATRIAL SEPTAL DEFECT (ASD) Jason Choi, MD John G. T. Augoustides, MD, FASE, FAHA

BASICS DESCRIPTION

• A defect of the interatrial septum that allows communication between the right and left atria. It is the most common congenital heart defect in adults. • 3 types: – Ostium secundum (75% of all ASDs): Patent foramen ovale (PFO) is a subtype of ostium secundum and is the most common ASD. – Ostium primum (15%): Associated with mitral regurgitation from the cleft mitral valve – Sinus venosus (10%): Associated with anomalous partial drainage of the pulmonary veins into the right atrium or superior vena cava • ASD is often benign and asymptomatic until the 4th or 5th decade of life. Virtually all adults with an ASD become symptomatic by the 6th decade. – Moderate or severe defects present in a child with congestive heart failure (CHF). – First presentation of ASD in adults may be a stroke or transient ischemic attack (TIA). – Diagnosis is common during pregnancy due to increased blood volume. • Clinical sequelae of ASD correspond to the degree and direction of shunting. – Most common is left-to-right cardiac shunt. – Right-to-left shunt indicates a more severe disease. – PFO is the main cause of transient right-to-left shunt and paradoxical emboli. EPIDEMIOLOGY Incidence

ASD is diagnosed in 1 out of 1,500 live births. Prevalence

• ASDs account for 10% of all congenital heart diseases and 30% of adult congenital heart diseases (1)[A]. • ASDs are 2–3 times more common in women. • PFOs present in about 25% of adults (2)[A]. A majority of PFOs are undiagnosed.

Morbidity

• ASDs have low morbidity. • Pulmonary hypertension is rarely seen before the 3rd decade of life (3)[B].

Mortality

• ASDs are associated with low mortality. • Decreased life expectancy is seen with ASD, but patients can reach advanced age without

intervention. Mortality rate from ASD repair is close to zero if performed before the 4th decade in patients without significant pulmonary hypertension (2)[B].

ETIOLOGY/RISK FACTORS

• Spontaneous genetic mutations lead to aberrant embryologic septal development (4)[B]. • Inheritance of ASD is not fully understood. • Ostium primum is associated with Down syndrome. • CHF symptoms in an infant with ASD indicate additional congenital heart defects (3)[C].

PATHOPHYSIOLOGY

• Size of defect, ventricular compliance, and direction of venous inflow determine the degree and direction of interatrial shunting. – Defects 20 mm cause clinically significant shunting (1)[A]. • Left-to-right shunt is a result of greater right ventricle compliance and lower pulmonary vascular resistance (PVR). – Chronic left-to-right shunt increases pulmonary blood flow and can lead to pulmonary vascular congestion and right ventricular strain. – Severe pulmonary hypertension and right heart failure may develop. Pulmonary flow can reach 4 times that of systemic flow in severe disease. Right-to-left shunt (Eisenmenger syndrome) can develop over time secondary to increased pulmonary pressures. This “shunt reversal” results in cyanosis as a significant fraction of blood bypasses the pulmonary circulation and gets ejected into the systemic circulation, unoxygenated. • Patients most commonly present with dyspnea, palpitations, and decreased exercise tolerance. Atrial arrhythmias, especially atrial fibrillation, are commonly seen in the 4th decade. • PFO is unique as a dynamic shunt occurring under certain physiologic situations that transiently elevate right atrial pressures (e.g., coughing, Valsalva maneuver, and increased PVR). – All other ASDs can have transient right-to-left shunting, but usually shunt left-to-right continuously.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Decrease the risk of paradoxical emboli (e.g., avoid air entry in IV lines). • To prevent worsening of left-to-right shunt, avoid increases in systemic vascular resistance (SVR), fluid overload, steep Trendelenburg positioning, and over-transfusion. • Be aware of scenarios that cause transient right-to-left shunting: Pulmonary embolism, high positive end-expiratory pressure (PEEP), venous air embolism, pneumoperitoneum with laparoscopy, and cardiac tamponade. • Be prepared to treat pulmonary hypertension with direct pulmonary vasodilators.

PREOPERATIVE ASSESSMENT SYMPTOMS

• ASD is an acyanotic defect (left-to-right shunt).

• Cyanosis and clubbing with only an ASD reflect right-to-left shunt and severe disease. • Atrial fibrillation • CHF symptoms: Orthopnea

History

• Clinical presentations of ASD vary. • ASD is often undiagnosed until adulthood due to a lack of symptoms and physical findings. • Rule out a history of stroke, TIA, new onset dyspnea on exertion, and palpitations from atrial arrhythmias. • Assess progression/worsening of symptoms. • Ask about a history of murmur or previous assessment by a cardiologist.

Signs/Physical Exam

• Fixed-split S2 heart sound on auscultation is pathognomonic for ASD. • Systolic ejection murmur is heard from increased output through the pulmonic valve. • Ostium primum is associated with significant mitral regurgitation. • S4 heart sound reflects right ventricular hypertrophy and pulmonary hypertension.

TREATMENT HISTORY

Closure of the defect with open heart surgery or cardiac catheterization. If the patient has not had an ASD closure, they are most often asymptomatic. MEDICATIONS

There is no specific medical therapy.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• ECG: Incomplete right bundle branch block (invariably present), atrial arrhythmia (e.g., atrial fibrillation), prolonged PR interval, right ventricular hypertrophy, or right axis deviation • CXR: Prominent pulmonary vasculature often noted from vascular congestion • Echocardiography: Important to note the degree of shunting, size and strain of right ventricle, and pulmonary artery pressures – TEE with bubble study is the gold standard diagnostic study (4)[A]. • Cardiac catheterization: Pulmonary artery pressures should be recorded.

CONCOMITANT ORGAN DYSFUNCTION

Other organ dysfunction, such as pulmonary edema, pulmonary hypertension, or complications of right heart failure, is only seen with moderate/severe disease from ASD. CIRCUMSTANCES TO DELAY/ CONDITIONS

• Presence of right-to-left shunt requires correction or medical optimization prior to elective surgery (4)[B]. • Pulmonary blood flow >1.5 times the systemic flow warrants closure of the ASD (1)[A].

CLASSIFICATIONS

• Asymptomatic • Symptomatic left-to-right shunt • Right-to-left shunt with pulmonary hypertension

TREATMENT PREOPERATIVE PREPARATION Premedications

• For most patients with ASD, there is no restriction on premedication. • Premedication with midazolam can help with facilitating parental separation in the pediatric population. Special Concerns for Informed Consent

Risk of paradoxical emboli leading to stroke is minimal but present. INTRAOPERATIVE CARE Choice of Anesthesia

For the typical asymptomatic ASD patient, choice of anesthesia and technique can be tailored to provider and/or patient preference. Monitors

• Standard ASA monitoring • Monitors should be tailored to extent of surgery and its risks. • For open ASD repair on bypass, TEE, arterial line, and central line +/– pulmonary artery catheter are recommended for intra-operative management. Induction/Airway Management

• No special airway considerations • Drug dilution occurs from increased pulmonary blood flow, but is unlikely to have clinical relevance or to affect induction time. • There is no indication for endocarditis prophylaxis (4)[B], unless concomitant valvular disorder warrants it. Maintenance

• Imperative to prevent air emboli • Prevent increases to the left-to-right shunt – Use techniques that decrease the SVR (promotes forward flow into the aorta) or increase the PVR – Avoid a high FiO2 and hyperventilation; they can cause pulmonary vasodilatation. – Maintain higher mean airway pressures – Avoid fluid overload and over-transfusion

Extubation/Emergence

Bucking and coughing upon emergence increases the risk of paradoxical emboli by causing

transient right-to-left shunting.

POSTOPERATIVE CARE BED ACUITY

ICU postoperative care is not warranted unless the patient has significant pulmonary hypertension or has had closure of the ASD. MEDICATIONS/LAB STUDIES/ CONSULTS

If symptoms or complications of ASD manifest during the perioperative period, cardiology should be consulted. COMPLICATIONS

• Paradoxical embolism: Stroke, TIA, fat embolism • Transient supraventricular dysrhythmias and atrioventricular conduction defects are common post-closure of ASD. • Post-ASD closure, interpretation of central venous pressure (CVP) must account for a previously dilated right atrium. Maintaining normal CVP values may cause volume overload.

REFERENCES

1. Rigatelli G, Ronco F. Patent foramen ovale: A comprehensive review for pulmonologist. Curr Opin Pulm Med. 2010;16:442–447. 2. ensley FA, Martin DE, Gravlee GP. A practical approach to cardiac anesthesia, 3rd ed. Philadelphia: Lippincott Williams and Wilkins, 2003. 3. Augoustides JG, Ochroch EA. Assessment of intracardiac shunts: Perioperative echocardiography. Int Anesthesiol Clin. 2008;46:83–95.

ADDITIONAL READING

• Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: Executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2008;118(23):2395–2451.

See Also (Topic, Algorithm, Electronic Media Element) • Ventricular septal defect • Cardiopulmonary bypass • Patent foramen ovale • Venous air embolism • Chest x-ray

CODES

ICD9

• 745.5 Ostium secundum type atrial septal defect • 745.8 Other bulbus cordis anomalies and anomalies of cardiac septal closure ICD10

• Q21.1 Atrial septal defect • Q21.2 Atrioventricular septal defect

CLINICAL PEARLS

• 25% of adults have patent foramen ovale (PFO) and most are undiagnosed. • Avoid air entry in IV lines in ASD patients. • A fixed-split S2 heart sound is pathognomonic for ASD. • PFOs can transiently shunt right-to-left during the anesthetic course (high peak inspiratory pressure [PIP], coughing, abdominal insufflation, Trendelenburg positioning, etc).

ATRIAL TACHYCARDIAS Svjetlana Tisma-Dupanovic, MD Mirsad Dupanovic, MD

BASICS DESCRIPTION

• Atrial tachycardias (ATs) encompass several types of arrhythmias driven by one or more ectopic sources outside the sinus node and do not require the participation of the AV node for maintenance of tachycardia. ATs may be based on micro-reentrant, triggered, or automatic mechanisms causing focal atrial tachycardia (FAT) or multifocal atrial tachycardia (MAT) (1)[A]. • FAT may present as transient, recurrent, sustained, and incessant with usual rates of 130– 250 bpm. MAT may be persistent and easily misinterpreted as atrial fibrillation (2)[A]. EPIDEMIOLOGY Prevalence

FAT accounts for 5–15% of patients undergoing electrophysiologic studies. The rates are higher in children (1)[A].

Prevalence

• FAT: 0.34% in asymptomatic individuals and 0.46% in symptomatic patients (1)[A] • MAT in the hospitalized population has been estimated to be 0.05–0.32% (2)[A].

Morbidity/Mortality

• Incessant AT may result in dilated cardiomyopathy, which may be reversible after the tachycardia has been terminated. • Patients being hospitalized with MAT are usually elderly and may have high mortality as a consequence of underlying chronic obstructive pulmonary disease (COPD) (2)[A].

ETIOLOGY/RISK FACTORS

• FAT: Open heart surgery (especially for correction of CHD), younger age, and disturbances of the autonomic nervous system • MAT: COPD, congestive heart failure (CHF), hypoxemia, use of theophylline, electrolyte abnormalities (hypomagnesemia, hypokalemia), and increased age (2)[A].

PHYSIOLOGY/PATHOPHYSIOLOGY

• FAT is characterized by atrial activation starting rhythmically at a small area (focus) from which it spreads out centrifugally. Usual locations of such foci are the area along the crista terminalis and near the right and left pulmonary veins. It may be caused by micro-reentrant, triggered, or automatic mechanisms (3)[A]. – Micro-reentry may be initiated and terminated with programmed electrical stimulation.

Verapamil, adenosine, and dipyridamole can terminate this arrhythmia. – Triggered activity may also be initiated and terminated with electrical stimulation (atrial extrastimuli or rapid atrial pacing). Verapamil, propranolol, adenosine, carotid sinus massage, and dipyridamole can terminate triggered FAT. – Automatic FAT cannot be initiated or terminated with programmed electrical stimulation, but it can be initiated by isoproterenol infusion and terminated with propranolol. The rhythm is insensitive to adenosine, verapamil, and carotid sinus massage. Episodes of automatic FAT commonly show a “warm-up” phenomenon at the beginning (the rate gradually increases) and a “cool-down” phenomenon at termination (the rate gradually slows down with transition to normal sinus rhythm). Since automaticity decreases with aging, automatic FAT is less common in geriatric patients (1)[A]. • MAT (chaotic AT) may be initiated by delayed after-depolarizations arising from multiple atrial foci. The definition of MAT requires at least 3 distinct P’ wave morphologies (2)[A].

Pediatric Considerations

FAT during infancy is typically incessant. Patients often present with tachycardia-induced cardiomyopathy. MAT is an uncommon, well-tolerated, and self-limiting rhythm in most pediatric patients. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Drugs that modulate the autonomic nervous system may be useful in the anesthetic regimen of patients presenting with FAT. • Treatment of the underlying medical diseases is the primary and the most successful therapy for MAT. It is also important to avoid hypoxemia as well as medications or procedures that could worsen the pulmonary status. • Cardioversion has no effect on the sites of ectopy that produce automatic FAT and is not effective in converting MAT to sinus rhythm (1)[A], (2)[A].

PREOPERATIVE ASSESSMENT SYMPTOMS

• Symptoms of ATs may range from none to syncope to symptoms of heart failure. • The severity of FAT presentation depends on the ventricular rate and presence of ventricular dysfunction. • The gradual increase in heart rate at the beginning and slowing at termination may make it difficult for a patient to recognize the tachycardia. • Some patients may perceive fast ventricular rates as palpitations, chest discomfort, or dizziness. Exercise intolerance results from the inappropriately high ventricular rate that does not change with increasing workload. • Symptoms or signs of CHF are due to decreased left ventricular contractility, AV valve regurgitation, and atrial dilatation.

History

• Review for presence of a cardiac or pulmonary disease, recent heart surgery, and the arrhythmogenic effects of current medications.

• Review for previous episodes, management, and current duration of AT. • FAT may resolve spontaneously. However, failure to perceive the FAT of incessant nature can lead to depression of myocardial function and tachycardia-induced cardiomyopathy. If the tachycardia is not treated aggressively, the myocardial function can continue to decline, resulting in an irreversible cardiomyopathy. This occurs in 80% of cases due to FAT of abnormal automaticity. Patients with faster rates may be at higher risk (1)[A]. • The MAT usually occurs in elderly and seriously ill patients. It may resolve within days following successful management of the underlying disease. If management of the underlying disease is not successful, onset of MAT implies a poor prognosis. MAT may be preceded by or progress to atrial fibrillation or atrial flutter in 50% of cases. The choice of pharmacologic agents may depend on the presence of coexisting medical diseases. Signs/Physical Exam

• The pulse rate may not be reflective of the atrial rate because of variable AV node conduction. • The heart rates seen in FAT vary based on the patient’s age and catecholamine state. In case of chronic FAT the rate tends to vary from hour to hour influenced by a variety of physiologic factors modifying autonomic tone. Ventricular rate is usually regular. • In MAT, the rhythm is irregular and the physical examination findings clinically resemble atrial fibrillation. • Dyspnea, hypoxemia, rales, and crackles are signs of cardiac decompensation.

TREATMENT HISTORY

• Review type, length, success of treatment, and recurrence of symptoms • History of interventional management: Overdrive pacing and cardioversions are usually not successful in automatic FAT and MAT. • History of arrhythmia ablation: The treatment of choice for poorly controlled FAT and MAT has become radiofrequency catheter ablation. MEDICATIONS

• Termination of AT using adenosine makes it highly unlikely that automatic FAT is present. • Primary acute treatment strategy of FAT is slowing or terminating the tachycardia. AV nodal blocking is the secondary strategy. IV beta-adrenergic blockers may terminate automatic FAT while nonautomatic FATs are frequently terminated by verapamil (1)[A]. • Class I antiarrhythmic medications may decrease automaticity, prolong refractory period, and can terminate FAT. • Class III drugs that slow myocardial conduction and AV conduction have had modest success in treatment of ATs. These medications, except amiodarone, have the potential to decrease myocardial performance and must be used with caution in patients with decreased LV function. • Digoxin slows AV conduction by enhancement of vagal activity and is a positive inotropic agent. • Calcium channel blockers (Class IV drugs) slow the AV conduction, but are negative inotropes and should be used selectively and cautiously. • The management strategies of MAT also rely on suppression of the tachycardia focus and/or

slowing of AV conduction. It may take a combination of drugs to control the rate. • Metoprolol and high doses of IV magnesium can be useful in treating MAT.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, digoxin level • The majority of FATs can be diagnosed from the ECG; however, differentiation from other forms of supraventricular tachycardia (SVT) may be difficult. – FAT presents on the ECG with P’ waves that generally show an abnormal axis and configuration, but remain similar in shape. When the focus arises from the left atrium, the P’ wave is negative in lead I; those with focus in the low right atrium show a negative P’ wave axis in the lead aVF with a positive wave in lead I. Occasionally, the focus is in an area close to the sinus node or in the high right atrium and the P’ wave axis is similar to sinus tachycardia. When the rhythm resembles sinus tachycardia, it can lead to a delay in diagnosis and institution of therapy. – The atrial rate during FAT is generally between 100 and 180 bpm. Each P’ wave is usually followed by a QRS complex, and the PR interval is typically not prolonged. Thus the P’P’ intervals do not vary by more than 50 ms unless an exit block from the focus of FAT is present. – AV block may be present during FAT and is due to decreased sympathetic tone or digitalis toxicity. – Tachycardia-induced ST segment depression and T wave inversion may occur and may persist for some time after the cessation of long-lasting FAT. – During MAT there are ≥3 distinct P’ waves of varying morphology in the same ECG lead; there is no dominant atrial pacemaker (difference from sinus rhythm with frequent premature atrial complexes and focal AT); AV conduction may be variable; and there is an isoelectric baseline with varying PP, PR, and RR intervals. Multiple P’ wave morphologies and variable P-R and R-R intervals may contribute to confusion of MAT and atrial fibrillation. The ventricular rate is usually 100–150 bpm but may be as high as 250 bpm. • Ambulatory (Holter) monitoring is very helpful in establishing the FAT diagnosis. • Exercise testing is frequently not useful because the sinus heart rate increases and the automatic focus is suppressed.

CONCOMITANT ORGAN DYSFUNCTION • COPD, pulmonary infection • Congestive heart failure

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Uncontrolled ventricular rate, hemodynamic instability, signs of myocardial ischemia, or cardiac decompensation • Cardiac consultation may be necessary.

CLASSIFICATIONS

Varies; depends on pathophysiologic characteristics or clinical presentation

TREATMENT PREOPERATIVE PREPARATION Premedications

• A combination of benzodiazepines and opioids will decrease anxiety and modulate sympathetic tone. • Anticholinergic agents may worsen AT. • Consider medications that decrease automaticity and AV conduction without decreasing cardiac output.

Special Concerns for Informed Consent Increased risk of cardiac complications INTRAOPERATIVE CARE Choice of Anesthesia

Depends on the surgical procedure. There is insufficient evidence to suggest that either general or regional anesthesia is more beneficial for patients with ATs. Monitors

• Standard ASA monitors including ECG with ST segment and T wave trends • Arterial catheter for cases of expected blood pressure instability or need for frequent blood gas evaluation (COPD) • Central venous catheter is optional, but if utilized, intracardiac stimulation should be minimized during catheter placement. • Pulmonary artery catheter may be used in cases of cardiomyopathy.

Induction/Airway Management

• Increased risk of hemodynamic instability due to cardiac depression caused by intravenous or inhalational anesthetics • Consider administration of higher doses of benzodiazepines and opioids to decrease sympathetic tone • Dexmedetomidine, an alpha-2 agonist, may be useful in decreasing the sympathetic tone and the heart rate, but the loading dose may cause significant hypotension. • Ketamine and pancuronium are relatively contraindicated. • Minimize the length of laryngoscopy or avoid laryngoscopy with the use of a laryngeal mask airway or intravenous sedation.

Maintenance

• Neither propofol nor volatile agents have significant electrophysiologic effects and are adequate maintenance agents. • Conservative fluid management in case of cardiomyopathy

Extubation/Emergence

• Balanced reversal of neuromuscular block, with slow administration

• Avoid sympathetic stimulation • Complications: – Hemodynamic instability, coronary ischemia – Tachycardia-induced cardiomyopathy

FOLLOW-UP BED ACUITY

Poorly controlled AT will dictate ICU care.

MEDICATIONS/LAB STUDIES/CONSULTS

• Rate control as indicated • Electrolytes, digoxin level, cardiac enzymes

COMPLICATIONS

• Hemodynamic instability, coronary ischemia • Tachycardia-induced cardiomyopathy

REFERENCES

1. Roberts-Thomson KC, Kistler PM, Kalman JM. Atrial tachycardia: Mechanisms, diagnosis and management. Curr Probl Cardiol. 2005;30:529–573. 2. McCord J, Borzak S. Multifocal atrial tachycardia. Chest. 1998;113:203–209. 3. Saoudi N, Cosio F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomic bases. Eur Heart J. 2001;22:1162–1182.

CODES ICD9 427.89 Other specified cardiac dysrhythmias ICD10 I47.1 Supraventricular tachycardia

CLINICAL PEARLS

• FAT usually occurs in young patients and may resolve spontaneously; however, failure to perceive an incessant FAT (e.g., in small children) can lead to a cardiomyopathy that may become irreversible if the tachycardia is not aggressively pharmacologically treated. • MAT usually occurs in elderly and seriously ill patients. It may resolve within days following successful management of the underlying disease. If management of the underlying disease is not successful, onset of MAT implies a poor prognosis. • Cardioversion has no effect on the sites of ectopy that produce automatic FAT and is not

effective in converting MAT to sinus rhythm. Radiofrequency catheter ablation may be curative.

AUTOLOGOUS BLOOD TRANSFUSION Andrew A. Klein, MD

BASICS DESCRIPTION

• Transfusion of the patient’s own blood or blood components back to them has the theoretical advantages of: – No risk of transmission of infection – No blood transfusion reaction – No graft versus host disease – No storage of blood required (except with preoperative autologous blood donation [PABD]) • There are 4 types of autologous blood transfusion: – Preoperative autologous blood donation – Intraoperative hemodilution – Cell salvage or saver – Postoperative blood collection and re-transfusion • Allogeneic transfusions are the “opposite” of autologous transfusions and involve giving a patient blood collected from another person and has been stored in the blood bank. • “You know what you’ve got inside you and therefore what you’re getting.”

PHYSIOLOGY PRINCIPLES

• Oxygen-carrying capacity: In a normal person breathing room air, arterial blood carries approximately 20 mL O2/100 mL; 19.7 mL combined with hemoglobin (Hb) and only 0.3

mL dissolved in plasma. Hemoglobin molecules within red blood cells contain iron that can bind reversibly to oxygen molecules to form oxyhemoglobin. Normal Hb is 13–16 g/dL in men and 12–16 g/dL in women. • Viscosity is the tendency of fluids to resist flow. Blood viscosity depends largely on hematocrit (increasing exponentially as hematocrit increases), red cell characteristics, and blood protein concentration. Increasing viscosity (from blood transfusion) leads to reduced flow, especially in vessels 160 mm Hg or diastolic pressure >90 mm Hg. – Definitive treatment is delivery of the fetus and placenta. • Thrombotic thrombocytopenia purpura (TTP) – Thrombocytopenia is a result of platelet aggregation due to impaired vWF protease. – Occurs anytime during pregnancy (first trimester through postpartum period). – Severe cases can be treated with plasmapheresis. • Hemolytic uremic syndrome (HUS) – Microangiopathic hemolytic anemia from microvascular injury (6). – 90% of cases occur postpartum with a mean onset of 26 days postdelivery (7). – May require plasmapheresis

PERIOPERATIVE RELEVANCE

• Hypercoagulable states increase the risk of thromboembolism. – Complications include uteroplacental thrombosis, fetal loss, DVT, PE, CVA, and cortical venous thrombosis. – Prophylaxis against thromboembolism (following surgical procedures and Cesarean section) include: Graduated compression stockings, sequential leg compression devices, early ambulation, and thromboprophylaxis. • Some inherited congenital coagulopathies may improve or worsen depending on whether the given factor increases or decreases with pregnancy. – Hypofibrinogenemia and von Willebrand disease may improve. – Factor XI deficiency may worsen. • Hypocoagulable states may cause: – Increased risk of postpartum hemorrhage – Increased risk of placental abruption – Increased risk of non-reassuring fetal status during labor – A contraindication to neuraxial anesthesia due to increased risk of bleeding and epidural hematoma formation. Generally a stable platelet count >80,000/mL is sufficient for neuraxial anesthesia.

ALERT • Management of anticoagulation pre-delivery

– Low molecular weight heparin (LMWH) should be switched to SQ or IV unfractionated heparin 36 hours before elective induction or C-section. – Many prefer to switch to unfractionated heparin at 36 weeks, to avoid going into labor on LMWH, which might delay or preclude epidural placement. – IV heparin should be turned off 4–6 hours before anticipated delivery. • Management of anticoagulation prior to neuraxial block – SQ heparin is not a contraindication for neuroaxial anesthesia if the total daily dose is 10 mcg/kg/min). Initially, the vasoconstricting effects predominate in the skeletal muscle vascular beds; with increasing doses, circulation in the limbs may become compromised. – Epinephrine: When exogenously administered, it causes alpha-1 agonism at higher dosages. – Vasopressin: V1 receptor agonism functions to increase sarcoplasmic release of calcium

and vascular smooth muscle constriction, primarily in capillaries and small arterioles. This functions to shift blood flow away from splanchnic, muscle, fat and skin tissues to vital organs. – Phosphodiesterase inhibitors block enzymatic breakdown of cAMP to cGMP. In the myocardium, this results in increased intracellular calcium with resultant enhanced inotropy. However, in vascular smooth muscle, increased cAMP results in vasodilation. • Vasodilators – Nitrovasodilators: Nitroglycerin breaks down into NO, which consequently causes calcium sequestration within vascular smooth muscle. At lower doses, venous and coronary arteries are primarily affected; at higher doses, arterial dilation occurs. Nitroprusside similarly breaks down into NO, but has a greater effect on arterial smooth muscle. – Angiotensin-converting enzyme inhibitors (ACE I) block the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent endogenous vasoconstrictor. – Angiotensin II receptor blockers (ARBs) competitively antagonize angiotensin II binding to receptors on blood vessels. – Calcium channel blockers (CCB) block voltage-gated calcium channels in the sarcoplasmic reticulum, resulting in decreased intracellular calcium and decreased vasomotor tone. – Hydralazine is a direct vasodilator. It increases cGMP levels with resultant decreases in

calcium release from the endoplasmic reticulum causing arterial vessel dilation (diastolic pressure is decreased to a greater extent than systolic blood pressure) and venodilation. • Anesthetic medications with vasodilatory properties: – Propofol – Volatile agents – Lidocaine • Resistance to blood flow also provides the basis for calculations obtained from pulmonary artery catheter data.

EQUATIONS

• Ohm’s law: R = V/I, where R is resistance, V is voltage, and I is current • Fluid dynamics extrapolation: R = ΔP/CO, where R is resistance, ΔP is change in pressure, and CO is cardiac output • Poiseuille’s law: R = (8 × L × n)/r4, where R is resistance, L is length, n is viscosity, and r is radius

REFERENCES

1. Khalafbeigui F, Suga H, Sagawa K. Left ventricular systolic pressure-volume area correlates with oxygen consumption. Am J Physiol. 1979;237:H566–H569. 2. Maughan WL, Sunagawa K, Burkhoff D, et al. Effect of arterial impedance changes on the end-systolic pressure-volume relation. Circ Res. 1984;54:595–602. [A] 3. Rose WC, Shoukas AA. Two-port analysis of systematic of systemic venous and arterial impedances. Am J Physiol. 1993;265:H1577–H1587. [C] 4. Sasse SA, Chen PA, Mahutte CK. Relationship of changes in cardiac output to changes in heart rate in medical ICU patients. Intens Care Med. 1996;22:409–414. 5. Suga H. Total mechanical energy of a ventricle model and cardiac oxygen consumption. Am J Physiol. 1979;236:H498–H505. 6. Sunagawa K, Sagawa K. Models of ventricular contraction based on time-varying elastance. Crit Rev Biomed Eng. 1982;6:193–228. 7. Wallace A, Lam HW, Mangano DT. Linearity, load dependence, hysteresis, and clinical association of systolic and diastolic indices of left ventricular function in man. Multicenter Study of Perioperative Ischemia (McSPI) Research Group. J Card Surg. 1995;10:460–467. [B] See Also (Topic, Algorithm, Electronic Media Element) • Laminar flow • Cardiac output • Cerebral blood flow • Septic shock • Anaphylactic shock

CLINICAL PEARLS

• Circulation is influenced by the resistance of the vascular bed against which the heart is pumping. Cardiac output is directly influenced by BFR. • The most important determinant of BFR is vessel radius, which is regulated by the sympathetic nervous system (SNS), hormones, metabolites, and autoregulation. The SNS can increase the blood pressure 3-fold via increasing the heart rate, inotropy, and both arterial and venous resistances. • Therapy for arterial blood pressure management is aimed at changing the BFR (changing the vessel radius or blood flow viscosity). • Pulmonary artery catheter data and its calculations, as well as echocardiography imaging, aid with clinical decision-making and guidance of therapy. • Several anesthetic medications cause vasodilation, with resultant decreases in BFR.

BLOOD OXYGEN CARRYING CAPACITY Onyi Onuoha, MD, MPH Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• The blood oxygen-carrying capacity is the milliliters of oxygen present in 1 deciliter of blood. • In blood, oxygen can exist in 2 forms: Dissolved and attached to hemoglobin. Hemoglobin is the primary transporter of oxygen in mammals. • In the event of decreased oxygen delivery, the blood provides a limited cushion against hypoxia. PHYSIOLOGY PRINCIPLES

• Oxygen is necessary for aerobic metabolism and cell integrity. However, despite its absolute necessity, the body only has minimal storage capacity (unlike glucose). When apneic, oxygen stores are limited to the oxygen in the lungs (FRC) and the blood; both of which are unable to sustain life beyond a few minutes. • In a healthy adult at rest, oxygen consumption is ∼200–250 mL O2/min and oxygen delivery is ∼950–1,150 mL O2/min. Thus, ∼25% of the arterial oxygen is used every

minute, and the deoxygenated blood returning to the lungs has ∼75% saturation (mixed venous oxygen saturation) (1). • Hemoglobin provides the most efficient means of carrying and transporting blood. At full oxygen saturation, 1 g of hemoglobin in 1 dL of blood is capable of carrying 1.34 mL of O2. Thus, Hgb × 1.34 × SaO2 determines the milliliters of oxygen bound to hemoglobin in 1

dL of blood. Oxygen bound to hemoglobin does not exert partial pressure. • Oxygen is poorly soluble in blood with a coefficient of 0.003 milliliters of oxygen per deciliter of plasma per millimeter of mercury oxygen. Hence, a patient breathing room air with an approximate PaO2 of 100 mm Hg has 0.3 mL of oxygen dissolved in 1 dL of blood. • Oxygen–hemoglobin (O2–Hgb) dissociation curve: PaO2 on the x-axis, and SaO2 on the y-

axis. As PaO2 increases, SaO2 increases. The curve is not linear, but sigmoid in shape. This

represents hemoglobin’s desire to be fully bound or fully dissociated from oxygen; it is unstable in intermediate states. This characteristic facilitates its physiologic function; at the lungs, hemoglobin will fully saturate and at the tissue level, it will easily dissociate and unload to oxygenate the tissues. • Assuming normal hemoglobin moieties and conditions, the PaO2 is in equilibrium with oxyhemoglobin and dissolved oxygen. For example, a PaO2 of 100 mm Hg has an SpO2 of

98% and 0.3 mL O2/dL of blood. A PaO2 of 500 mm Hg has an SpO2 of 100% and 1.5 mL

O2/dL of blood. ANATOMY

• Hemoglobin is an iron-containing protein that is composed of 4 polypeptide chains or subunits. The iron-containing heme group of each polypeptide reversibly binds up to 4 molecules of oxygen (2). • The adult hemoglobin (HbA) molecule is made of 2α globin and 2β globin subunits. • The binding of the first oxygen molecule to hemoglobin induces conformational changes in the structure of the hemoglobin that allows the binding of other molecules of oxygen more readily. At normal resting conditions, 25% of the oxygen bound to hemoglobin is extracted by the tissues (equivalent to a partial pressure of 40 mm Hg). • Fetal hemoglobin (HbF), on the other hand, has 2α and 2γ subunits that possess a strong affinity for oxygen. The fetus is exposed to much lower oxygen pressures from the placenta; ∼21% of the level found in the adult lung (1). DISEASE/PATHOPHYSIOLOGY

• Low oxygen-carrying capacity is the result of a low PaO2, low hemoglobin, impaired

oxygen-to-hemoglobin binding, or an increased oxygen demand/consumption. – Low PaO2: Hypoxic mixture (low inspired oxygen), hypoventilation, V/Q mismatching,

shunting, impaired diffusion – Low hemoglobin: Chronic or acute anemia – Impaired oxygen-to-hemoglobin binding: Abnormal hemoglobins (fetal, thalassemia, sickle cell disease), carboxyhemoglobin, cyanhemoglobin, methemoglobin, sulfhemoglobin – Increased oxygen demand/consumption: Hyperthermia, hyperthyroidism, sepsis, pregnancy, vigorous exercise • Acute anemia: The initial hemodynamic response is a fall in systemic vascular resistance (SVR) that is partly due to the decrease in blood viscosity and in part, the result of nitric oxide-mediated vasodilation. The decrease in SVR reduces blood pressure and causes a baroreceptor-mediated neurohormonal activation, identical to that seen in patients with severe low-output heart failure. Eventually, sympathetic and renin–angiotensin–aldosterone activity cause peripheral vasoconstriction and decrease in renal blood flow and glomerular filtration rate. Kidneys retain salt and water (3). • Chronic anemia results in hemodynamic and non-hemodynamic (erythropoiesis) compensatory responses to enhance oxygen-carrying capacity (2,4). – Hemodynamic responses are complex and involve a vasodilation-mediated high-output state with neurohormonal activation (as described above in acute anemia). The highoutput state initially helps to increase oxygen transport. However, compensatory mechanisms have deleterious long-term consequences and could contribute to anemia’s role as an independent risk factor for adverse outcomes. – Non hemodynamic responses: Increased levels of 2,3-diphosphoglycerate (2,3-DPG) shift the O2–Hgb dissociation curve to the right. This is the least energy-consuming mechanism to support increased oxygen delivery to the tissues (lacks significant increase in cardiac output). Erythropoiesis also serves to increase red blood cell production. • In elevated altitudes, ventilation and heart rate are elevated with a minimum reduction in

stroke volume. In addition, plasma volume is reduced over 24–48 hours to improve the oxygen-carrying capacity of the blood. Prolonged sojourn at altitudes is compensated for with enhanced erythropoiesis and a larger hemoglobin mass, allowing for a partial or full restoration of the blood volume and arterial oxygen content.

PERIOPERATIVE RELEVANCE

• General anesthesia causes a 15% reduction in metabolic rate and a subsequent decrease in oxygen requirement. Artificial ventilation further decreases the oxygen requirement by 6% with the removal of the work of breathing. Anesthetic agents, however, do not affect the transport of oxygen by hemoglobin or its solubility in blood. • The increased utilization of oxygen when metabolic rate is increased (postoperative shivering, malignant hyperthermia, etc.) leads to a decrease in PaO2 which activates normal

protective responses to hypoxia (aortic and carotid chemoreceptors, sympathetic nervous system) to increase cardiac output. However, these protective responses are usually reduced by anesthetic drugs intraoperatively, and can extend into the postoperative period. • Blood transfusion: It remains the clinician’s responsibility to determine the transfusion “trigger” for an individual patient based on multiple elements that determine the demand for the delivery of oxygen and the physiological reserve. The decision should be based on the premise that the oxygen-carrying capacity is increased to prevent oxygen consumption from exceeding oxygen delivery. Additionally, the following should be considered: – Theoretically, the oxygen-carrying benefit of red blood cells should hasten recovery from respiratory failure, and transfusion would therefore be expected to shorten the duration of mechanical ventilation. However, evidence to the contrary has been reported. – Storage of packed red blood cells (pRBCs) is associated with a decline in 2,3-DPG that leads to a subsequent left shift of the O2–Hgb dissociation curve. Therefore, while

transfusion increases the patient’s hemoglobin, it results in a less efficient oxygen delivery when compared to the native hemoglobin at that same hematocrit. 2,3-DPG levels return to normal over 12–24 hours. – The need to restore blood viscosity may precede the need to restore oxygen-carrying capacity during hemodilution or anemic conditions. A minimum level of blood viscosity appears to be necessary for generating shear stress and stimulating the release of vasoregulatory factors such as nitric oxide and prostacyclin (3). – Studies in subpopulations (renal failure, Jehovah’s Witnesses, military casualties) have shown that considerably greater amounts of anemia than was previously believed can be well tolerated. – Patients that are unable to increase their cardiac output (coronary artery disease, prior/acute myocardial infarction, beta-adrenergic blockade, decreased SVR such as sepsis or post-cardiopulmonary bypass) or have impaired oxygenation (pulmonary disease, high altitude) have limited compensatory responses to hypoxia. • Isovolemic hemodilution to hemoglobin levels of 5 g/dL in normal volunteers is well tolerated. A robust cardiovascular response manifested by increases in heart rate and stroke volume leads to compensation. • Blood substitutes are being investigated to increase oxygen-carrying capacity. At this time, there are no available products for clinical use.

EQUATIONS

• Oxygen content = [(Hgb × 1.39 × SaO2) + (PaO2 × 0.003)]. Units are as follows: Hgb is in g/dL; 1.39 is mLO2/dL; SaO2 is % (0.01) but no units (5).

• Oxygen arterial content (CaO2) = [(Hgb × 1.39 × SaO2) + (PaO2 × 0.003)] (5).

• Oxygen venous content (CvO2) = [(Hgb × 1.39 × SvO2) + (PvO2 × 0.003)]. If obtained at the pulmonary artery (PAC), it is a representation of the true mixed venous oxygen (5). • Oxygen delivery (DO2) (mL/min) = cardiac output (CO) × blood oxygen content GRAPHS/ FIGURES

Oxygen–hemoglobin dissociation curve

REFERENCES

1. aw R, Biukwirwa H. The physiology of oxygen delivery. Update Anaesth. 1999;10(3):1–2. 2. reacher DF, Leach RM. Oxygen transport. BMJ. 1998;317(7168):1302–1306.

3. abrales P, Martini J, Intaglietta M, et al. Blood viscosity maintains microvascular conditions during normovolemic anemia independent of blood oxygen-carrying capacity. Am J Physiol Heart Circ Physiol. 2006;291(2):H581–H590. Anand IS. Heart failure and anemia: Mechanisms and pathophysiology. Heart Fail Rev. 2008;13:379–386. 4. Martin L. The four most important equations in clinical practice. Available at: http://www.globalrph.com/martin_4_most2.html

ADDITIONAL READING

• Bartsch P, Saltin B. General introduction to altitude adaptation and motion sickness. Scand J Med Sci Sports. 2008;18(Suppl 1):1–10. • Henig NR, Pierson DJ. Mechanism of hypoxemia. Respir Care Clin N Am. 2000;6(4):501– 521. • Ouellette DR. The impact of anemia in patients with respiratory failure. Chest. 2005;128(5 Suppl 2):576S–582S.

See Also (Topic, Algorithm, Electronic Media Element) • Blood substitutes • Isovolemic hemodilution • Mixed venous oxygen saturation

CLINICAL PEARLS

• Pulse oximetry is not a reliable monitoring modality in the presence of dyshemoglobins (hemoglobin that is unable to bind to oxygen). The 2 major dyshemoglobins seen in clinical practice are carboxyhemoglobin (COHb) and methemoglobin (MetHb). Co-oximeters are able to separate out oxyhemoglobin from MetHb and COHb and are therefore more accurate for quantifying oxygen-carrying capacity/content. • Blood substitutes: Include hemoglobin-based oxygen carriers (HBOCs) which transport oxygen when introduced intravenously. Synthetic analogs, such as perfluorocarbon emulsions (PFCs), have also been used as substitutes. These chemicals are able to dissolve large amount of gases such as oxygen. Unlike blood, PFCs exhibit a linear oxygen dissociation curve with an increase in PaO2 enhancing oxygen transport by these molecules and increasing the driving pressure of diffusion of oxygen into tissues. With a linear relationship however, the need for oxygen remains greater since most of the oxygen is released prior to the arrival of the oxygen-laden molecule to the capillary network where the partial pressure of oxygen is low. These also require high FiO2 to dissolve adequate

amounts of oxygen. However, optimal oxygen transport still remains difficult to reproduce and continues to differentiate real blood from blood substitutes and volume expanders.

BLOOD PRESSURE Mitesh Patel, MD Lydia A. Conlay, MD, PhD

BASICS DESCRIPTION

• Blood pressure (BP) is the pressure exerted by circulating blood upon the walls of blood vessels and is one of the principal vital signs. • During each heartbeat, BP varies between a maximum (systolic) and a minimum (diastolic) pressure. • The mean BP is a function of pumping by the heart and resistance to flow in blood vessels; it decreases as the circulating blood moves away from the heart through arteries (1,2).

PHYSIOLOGY PRINCIPLES

• Mean arterial pressure (MAP) is the average pressure over a cardiac cycle and is determined by the cardiac output (CO), systemic vascular resistance (SVR), and central venous pressure (CVP); it can be calculated by the equation MAP = (CO × SVR) + CVP. • Pulse pressure (PP) is the difference between systolic and diastolic BP which results from the pulsatile nature of cardiac output. PP = SBP − DBP. • BP regulation is modulated by several reflexes on a minute-to-minute basis. – Arterial baroreflex is mediated by stretch-sensitive sensory nerve endings located in the carotid sinuses and the aortic arch. The rate of firing of these baroreceptors increases with arterial pressure, and the net effect is a decreased sympathetic outflow, resulting in decreased arterial pressure and heart rate. – The renin–angiotensin–aldosterone system contributes to the regulation of arterial pressure primarily via the vasoconstrictor properties of angiotensin II and the sodiumretaining properties of aldosterone (3). – Chemoreceptors located in the carotid and aortic bodies regulate BP by monitoring blood pO2, pCO2, and pH. • Diastolic BP plays an important role in coronary perfusion pressure. Coronary perfusion pressure (CPP) is the difference between the aortic diastolic pressure and left ventricular end-diastolic pressure (LVEDP). CPP = DBP − LVEDP. • Manual intermittent measurement techniques: Auscultation remains the most widely used and was originally described by Nikolai Korotkoff in 1905. A sphygmomanometer, cuff, and stethoscope measure BP by auscultating sounds generated by turbulent arterial flow beyond the partially occluding cuff. The first sound is heard at the systolic pressure (phase I). Its character progressively changes (phases II and III), becomes muffled (phase IV), and is finally absent (phase V). Diastolic pressure is recorded at phase IV or V. • Automated intermittent measurement techniques: Most automated noninvasive BP devices are based on oscillometry, where variations in cuff pressure resulting from arterial pulsations during cuff deflation are sensed. The pressure at which the peak amplitude of

arterial pulsations occurs corresponds closely to MAP; systolic and diastolic pressures are derived from proprietary formulas that examine the rate of change of the pressure pulsations. • Direct measurement techniques of arterial BP: Arterial cannulation with continuous pressure transduction and waveform display remains the accepted reference standard for BP monitoring. It is invasive, more costly, and requires technical expertise to perform (4).

DISEASE/PATHOPHYSIOLOGY

• Acute hypertension is a risk factor for myocardial ischemia, stroke, and bleeding from the surgical sites. • Chronic hypertension doubles the risk of cardiovascular disease including coronary heart disease (CHD), congestive heart failure (CHF), ischemic and hemorrhagic stroke, renal failure, and peripheral arterial disease. Because most patients with long-standing hypertension are assumed to have some element of coronary disease and cardiac hypertrophy, excessive BP elevations are undesirable. • Uncontrolled hypertension (>180/120 mm Hg) and/or clinical signs and symptoms of hypertensive emergency warrant cancellation of elective surgery until the BP is optimized. Patients should receive emergency medical care and not simply be sent home. Warning signs and symptoms of hypertensive emergency include: – Headache – Confusion – Visual changes – Seizures – Focal neurologic changes – Nausea and vomiting – Papilledema – Exudative hemorrhages – Shortness of breath – Chest pain – Azotemia, oliguria, and proteinuria

PERIOPERATIVE RELEVANCE

• In the operative setting, systolic and diastolic pressures should generally be kept within 10– 30% of preoperative levels (5). • The systolic BP (generated from myocardial ventricular contraction) helps estimate the risk for a heart attack or stroke according to the Framingham study. Intraoperatively, systolic BP correlates with the amount of surgical bleeding. • MAP is commonly referred to during cardiac surgery (particularly during bypass) and is a determinant of cerebral perfusion pressure (CPP = MAP – ICP). Cerebral blood flow is autoregulated between MAPs of 60 and 180 mm Hg; should the MAP fall below 60 mm Hg, the cerebral blood flow becomes severely decreased. In hypertensive patients, the autoregulation curve is shifted to the right (6). • Severe intraoperative hypotension is an anesthetic emergency, and treatment is vital to ensure adequate organ blood flow, particularly to the brain, heart, kidneys, and the placenta in pregnancy. Consequences of hypotension can include stroke, myocardial infarction, acute

tubular necrosis, fetal compromise, acidosis, and death. Because hypotension can be harmful, this symptom is often treated before the cause has been ascertained. Hypotension can result from abnormalities in preload, contractility, afterload, heart rate, cardiac rhythm, intravascular volume, or SVR. Common causes of hypotension include: – Hypovolemia can reduce preload and may be due to hemorrhage, vomiting, diarrhea, burns, or sepsis. – Increased intrathoracic pressure, as seen with positive pressure ventilation and tension pneumothorax, can reduce preload. – Spinal and epidural anesthesia cause vasodilatation and decreased preload due to sympathetic block; if the block is above T4, it may also result in decreased myocardial contractility and bradycardia. – Excessive anesthesia: General anesthetics (both inhalation and intravenous) may cause hypotension by reducing CO and SVR. – Obstruction of major vessels can increase afterload and cause pump failure. Causes include pulmonary embolism or aortocaval compression by tumor or pregnancy. – Decreased myocardial contractility, as from beta-blockers, cardiac arrhythmias, cardiac tamponade, and myocardial infarction – Bradycardia, as from heart block or vagal overtone – Shock, as from spinal, cardiogenic, or anaphylaxis shock or sepsis • Treatment of intraoperative hypotension often precedes treating the cause: – Optimize preload: Administer an intravenous fluid bolus. – Elevate legs or head down tilt to improve venous return. – Reduce anesthetic agent if appropriate. – Use sympathomimetic drugs. • Causes of intraoperative hypertension include: – “Light” anesthesia or pain – Hypercarbia – Medication error (inadvertent administration of pressors) – Preeclampsia/eclampsia – Acute increase in intracranial pressure – Volume overload – Full bladder – Pheochromocytoma – Autonomic hyperreflexia – Decreased vascular compliance (arteriosclerosis) – Disorders with increased cardiac output (aortic regurgitation, thyrotoxicosis) – Renal parenchymal diseases – Aortic coarctation – Medications (such as monamine oxidase inhibitors, cocaine, or methamphetamine) • Autonomic hyperreflexia or dysreflexia (AD) is a life-threatening condition which occurs most often in individuals with spinal lesions above the T6 spinal cord level. At this level, the lesion is cephalad to the sympathetic cell bodies in the spinal cord and is believed to disrupt descending CNS impulses that normally regulate sympathetic outflow. AD is a reaction of the autonomic (involuntary) nervous system to overstimulation which is characterized by

severe hypertension, (reflex) bradycardia, profuse sweating, vasodilation above the level of the lesion (including flushing of the skin, nasal stuffiness, severe headaches), apprehension, anxiety, and occasionally cognitive impairment. AD is believed to be triggered by afferent stimuli originating below the level of the lesion, which increase BP via sympathetically mediated vasoconstriction in muscle, skin, and splanchnic vascular beds (7). The stimuli that trigger AD often result from the distension of a viscous such as the bladder or intestine.

GRAPHS/FIGURES See Table See Table

REFERENCES 1.

Health and Life. Normal blood pressure range adults. Available http://healthlifeandstuff.com/2010/06/normal-blood-pressure-range-adults/ 2. labunde R. Cardiovascular physiology concepts. Lippincott Williams & Wilkins, 2005.

at:

3. Klabunde RE. Cardiovascular physiology concepts: Mean arterial pressure. Available at: http://www.cvphysiology.com/Blood%20Pressure/BP006.htm [Accessed September 29, 2008; Archived version October 3, 2009. 4. Karlsson AK. Autonomic dysreflexia. Spinal Cord. 1999;37:383–391. 5. Rohrig R, Junger A, Hartmann B, et al. The incidence and prediction of automatically detected intraoperative cardiovascular events in noncardiac surgery. Anesth Analg. 2004;98(3):569–577.

ADDITIONAL READING

• Morgan GE, Mikhail MS, Murray MJ. Anesthesia for patients with cardiovascular diseases. In: Clinical Anesthesiology, 4th ed., McGraw Hill, 2005, chapter 20.

See Also (Topic, Algorithm, Electronic Media Element) • Autonomic hyperreflexia • Controlled hypotension • Arterial waveform • Perioperative hypertension • Mean arterial pressure

CLINICAL PEARLS

• Maintaining an adequate BP is essential to maintain perfusion to vital organs. BP should be maintained within 10–30% of the patient’s baseline. • The consequences of hypotension are sufficiently serious to potentially warrant treatment even before the cause of the hypotension is ascertained. Intraoperative hypotension most commonly reflects “deep” anesthesia, hypovolemia, or the use of specific drugs or anesthetic techniques. • Uncontrolled hypertension is associated with an increase in perioperative morbidity and

mortality. Elective cases should be cancelled when a patient demonstrates signs of a hypertensive emergency. Anesthesiologists are often faced with the decision to cancel or proceed with uncontrolled BPs exceeding 180/110 mm Hg. • Titrating therapies to traditional endpoints such as blood pressure does not ensure that the microvascular bed is being adequately perfused. For example, a normal or high blood pressure may be a vasoconstrictive response to a low cardiac output state.

BLOOD SUBSTITUTES Jonathan S. Jahr, MD Dayna Zimmerman, BS

BASICS DESCRIPTION

• “Blood substitutes” have been studied for >50 years and are either derivatives of hemoglobin or perfluorocarbons; they are designed to carry and offload oxygen to tissues. – Hemoglobin-based oxygen carriers are termed (HBOCs); attained from human or bovine sources. – Perfluorocarbon-based oxygen carriers are termed (PFBOCs). • No products discussed are FDA approved for human use. One product (Hemopure®, OPK Biotech, Cambridge, MA) has been approved in South Africa and Russia. Another product (Oxyglobin®, OPK Biotech) is FDA and European Union approved for canine anemia. PHYSIOLOGY PRINCIPLES

• Blood substitutes have been designed to carry oxygen to ischemic tissue as well as tested as a resuscitation fluid. • HBOCs are: – Synthesized from human or bovine blood cells in a process that removes the red cell membrane, purifies and deactivates pathogens (prions), and re-polymerizes the purified hemoglobin (via glutaraldehyde pegylation, encapsulation, or zero-link polymerization). – Prepared as a bag of solution around 250–500 mL, or the equivalent amount of hemoglobin as a unit of packed red blood cells. Some of the HBOCs offload oxygen more easily and may be more efficient than banked blood. – Newer generations have attempted to link oxygen carrying with diminished extravasation from the vascular compartment, block nitric oxide scavenging, and serve as antiinflammatory agents to diminish the deleterious effects of ischemia. • “First-generation” HBOCs are designed to have a normal hemoglobin (10–13 g/dL), normal viscosity, elevated colloid oncotic pressure, shift the oxyhemoglobin dissociation curve to the right, and a normal Hill coefficient. – They include α-α cross-linked hemoglobin, 2,3 diaspirin cross-linked hemoglobin (HemAssist®, Baxter, Deerfield, IL), and hemoglobin raffimer (Hemolink™, Hemosol, Toronto, ON). • “Second-generation” HBOCs are designed with the same goals as first-generation HBOCs but with fewer side effects. They too have a normal hemoglobin (10–13 g/dL), normal viscosity, elevated colloid oncotic pressure, shift the oxyhemoglobin dissociation curve to the right, and a normal Hill coefficient. To date, they remain the most successful HBOCs. – Human polyhemoglobin (PolyHeme®, Northfield, Evanston, IL) and hemoglobin glutamer (bovine) 200 and 250 (Hemopure® and Oxyglobin®, OPK Biotech) have completed FDA Phase III testing but were not approved in the US.

• “Third-generation” HBOCs have a low hemoglobin (5–6 g/dL), normal to high viscosity, lower colloid oncotic pressure, shift the oxyhemoglobin dissociation curve to the left, and a normal Hill coefficient. – There are a number of “third-generation” HBOCs currently undergoing preclinical and clinical testing (Maleimide-Polyethylene Glyco-modified Hemoglobin [MP4], Hemospan®, Sangart, San Diego, CA; Zero-linked Hemoglobin Polymer Oxyvita®, OXYVITA, New Windsor, NY).

DISEASE/PATHOPHYSIOLOGY

• “First-generation” HBOCs had serious complications including renal failure and increased mortality in trauma trials (HemAssist®). • “Second-generation” HBOCs cause increased systemic and pulmonary blood pressure, increased lipase without clinical signs or symptoms of pancreatitis, and transient jaundice, secondary to breakdown of the hemoglobin by the reticuloendothelial system. • “Third-generation” HBOCs may avoid the hypertension, but may still have other complications. • In one study, elderly patients tended to have worse outcomes with the particular blood substitute, suggesting that patients with pre-existing hypertension, cardiac, renal, and cerebrovascular disease may be susceptible to the hypertensive effects.

PERIOPERATIVE RELEVANCE

• The concept of blood substitutes is attractive in that they are: – Stable at room temperature – Do not require cross-matching and are immediately available – Do not carry infectious disease risk – Not dependent on a limited donor supply • Possible indications for blood substitutes include: – Shock – Organ ischemia – Red blood cell incompatibility – Acute lung injury – Transplant organ preservation – Cardioplegia – Sickle cell anemia – Tumor therapy – Air embolism – Anemia refractory to allogenic blood transfusion – Emergency civilian or military setting of severe trauma or perioperative bleeding • Allogenic blood transfusions have multiple risks, including infectious, immunologic, metabolic, and critical illnesses. – Screening of blood has reduced the incidence of HIV and Hepatitis C; however, new infections take time to be detected and removed from the donor supply. – Immunomodulation can result in increased surgical wound infection and recurrence of cancer (especially colon cancer) as well as decreased graft survival of transplanted organs.

– Transfusion-related acute lung injury (TRALI) can occur in 1:5,000 transfusions and carries a high mortality ranging from 6% to 9%. – Transfusion reactions from laboratory or transfusion error can result in serious morbidity and mortality. – Metabolic derangements include hypothermia, hyperkalemia, and decreased 2,3-DPG. – Transfusion-associated circulatory overload (TACO) is due to rapid transfusion of a large volume of blood and can cause dyspnea, orthopnea, peripheral edema, and rapid increases in blood pressure. It carries an incidence of 1:100–10,000. – However, even if a blood substitute is developed and has minimal complications, blood donation cannot be replaced; donor blood is fractionated to multiple products including platelets, fresh frozen plasma, and cryoprecipitate.

GRAPHS/FIGURES

Hypothesized Mechanism of Action

Nitric Oxide (NO) Scavenging of Hemoglobin

REFERENCES

1. Jahr JS, Walker V, Manoochehri K. Blood substitutes as pharmacotherapies in clinical practice. Curr Opin Anaesthesiol. 2007;20:325–330. 2. ahr JS, Moallempour M, Ellis JE. Transfusion update—triggers, targets, and will we ever have a blood substitute? Curr Rev Clin Anesth. 2008;28(21):249–260. 3. Jahr JS, Moallempour M, Lim JC. HBOC-201, Hemoglobin glutamer 250 (bovine), Hemopure® (Biopure Corporation, Cambridge, MA). Expert Opin Biol Ther. 2008;8(9):1425–1433. 4. Jahr JS, Mackenzie C, Pearce B, et al. HBOC-201 as an alternative to blood transfusion: Efficacy and safety evaluation in a multicenter phase III trial in elective orthopedic surgery. J Trauma Injury Infect Crit Care. 2008;64(6):1484–1497. http://www.nhlbi.nih.gov/health/dci/Diseases/bt/btrisk.html • Jahr JS, Sadighi Akha A, Doherty L, et al. Hemoglobin-based oxygen carriers: History, limits, brief summary of the state of the art, including clinical trials. In: Mozzarelli A, Bettati S. Chemistry and biochemistry of oxygen therapeutics: From transfusion to artificial blood.

London: John Wiley and Sons Ltd, 2011, chap. 22.

See Also (Topic, Algorithm, Electronic Media Element) • Blood transfusion • Blood transfusion infectious risks

CLINICAL PEARLS

• Ideally, blood substitutes could benefit patients who refuse allogenic blood transfusions, trauma patients (military or civilian) for whom blood is not easily available, patients who are unable to receive allogenic blood for immunologic reasons (hemolytic anemia), and to augment acute normovolemic hemodilution. • Side effects of blood substitutes that limit their use include: • Vasoactivity • Nephrotoxicity • Interference with complement • Mononuclear phagocytic system activation • Histamine release • Antigenicity • Oxidation in storage • Activation of kinin and coagulation • Iron deposition • Lack hemoglobin’s ability to scavenge nitric oxide • At this time, there are no FDA-approved products available for human use.

BONE MARROW TRANSPLANT (HARVEST PROCEDURE) Lori Dangler, MD, MBA

BASICS DESCRIPTION General

• Bone marrow transplants (BMT) are used to help patients with various kinds of serious illnesses: – Marrow failure (aplastic anemia) – Hematologic malignancy (AML, ALL, CML, CLL, myeloma) – Selected chemotherapy-responsive solid tumors (lymphoma, Hodgkin’s, non-Hodgkin’s) – Immunodeficiency syndromes – Other genetic disorders • Bone marrow harvesting and transplantation procedures were first developed in the 1950s and the first successful bone marrow transplantation occurred in 1968. • Spaces in the bone marrow hold both blood and stem cells. Stem cells are multipotent hematopoietic cells that have the ability to grow into various types of future blood cells. • During a harvest, a small portion of marrow is collected to be used for transplantation. Multiple large-bore needle aspirations of marrow are taken from the posterior iliac crests. At the end of the procedure, aspiration sites are cleaned and covered with pressure dressings. • Transplantation terms: – Autologous BMT is when one has marrow harvested and frozen for future use. – Allogenic BMT is when marrow is harvested for a relative. – Syngeneic BMT is harvested for an identical twin. – Unrelated BMT is when there is a donation through the registry. • Marrow donor patient types: – Autologous: Patients with malignancies who respond to chemotherapy (should be free of active disease and have functioning bone marrow) – Allogenic: HLA-matched healthy donors (often related) for recipient with malignancy or marrow failure Position

• Supine for intubation, then prone • Prep around iliac crests

Incision

• Operating physician is often a hematologist. • Large-bore needle insertion into the posterior iliac crests (other sites less common)

Approximate Time 1–2 hours

EBL Expected

• 1–2 quarts of bone marrow are commonly collected from adults. • Cell count of marrow determines volume needed (1–4 × 108 cells/kg recipient body weight).

Hospital Stay

• Outpatient to overnight maximum (healthy donors) • Prolonged hospitalization for autologous donors/future recipients with anticipated support for anemia, thrombocytopenia, neutropenia, and graft versus host issues

Special Equipment for Surgery

• Bone marrow aspiration needles • Collection bags • Padding/chest rolls/head support for prone positioning • Pathologist on standby to determine the cell count

EPIDEMIOLOGY Incidence

• 950 transplants were performed using bone marrow during 2010. – Children (0–17 years) received 21% of transplants. – Adults 18–50 years received 38% of transplants. – Adults >50 years received 41% of transplants.

Prevalence

15,000 people in the US are diagnosed with life-threatening illnesses yearly where a BMT or cord blood transplant from a matched donor is their best treatment option. Morbidity

• Autologous donor: Postoperative morbidity ranges from moderate to high secondary to underlying malignancy. • Allogenic: Life-threatening complications are extremely rare (0.27%) for healthy donors.

Mortality

• Rare • Between 1993 and 2005, there were 27,770 first BMTs, with only 1 fatal event (pulmonary embolism) reported and 12 serious adverse events were observed. The most frequent adverse events were cardiac (European Group for Blood and Marrow Transplantation analysis).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Familiarity with the patient’s specific chemotherapy. Avoid unnecessary oxygen enrichment if the patient had Bleomycin. • Avoid nitrous oxide since it inhibits methionine synthetase. • Volume status and blood loss assessment; replacement with crystalloids, albumin, and irradiated products

• Prior steroid therapy usage can lower adrenal reserves. • Careful positioning to avoid prone position-related injuries

PREOPERATIVE ASSESSMENT SYMPTOMS

• Healthy donor may be asymptomatic. • Assessment points apply primarily to autologous donors. – GI: Vomiting, diarrhea, melena

History

When autologous harvesting, attain a thorough history of underlying disease, complications of chemotherapy (e.g., pericardial effusion, impaired cardiac function), and presence of infection. Signs/Physical Exam

• CV: Focused exam to assess for congestive heart failure (jugular venous distention, pitting edema, murmurs, rales or crackles) • Peripheral: Edema, orthostasis • Heme: Ecchymosis, petechiae

MEDICATIONS

• Iron supplementation • Erythropoietin • Granulocyte colony stimulating factor (Filgrastim, Pegfilgrastim) • Chemotherapy; last dosage

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Urinalysis to rule out urinary tract infections • Electrolytes if recent chemotherapy • CBC for platelets, hemoglobin (baseline) • Coagulation profile if bleeding history • ECG, echocardiogram, and/or stress testing if there is a concern for cardiac dysfunction • Type and cross for 2 units irradiated blood if autologous donation was not performed

CONCOMITANT ORGAN DYSFUNCTION

Autologous donors: Prior chemoradiation treatments resulting in temporary/permanent organ dysfunction

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines • Opioids • Steroid coverage

Special Concerns for Informed Consent Blood transfusion highly probable INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal most common used for prone positioning • Neuraxial block with a spinal or epidural may be appropriate if the patient is hydrated and without coagulopathies

Monitors

• Minimum of 2 large-bore IVs; central line access may be considered if venous access is difficult. • Foley catheter if large fluid shifts and replacement are anticipated • Arterial access may be useful if the BP is labile. • Monitor ETCO2 closely; an acute drop may indicate marrow embolism (dead space pathophysiology).

Induction/Airway Management

• Consider lower doses of induction agent when there is a history of orthostasis and cardiotoxic chemotherapy use. • Endotracheal tube provides a secure airway.

Maintenance

• After induction of anesthesia, establish prone positioning and careful padding of pressure points. • Heparin is administered pre-harvest. • The total volume of marrow harvested is dependent on the body mass of the recipient as well as the cellularity of the donor marrow. The target number of donor stem cells for allogenic engraftment of unmanipulated marrow is 2–3 × 108 nucleated marrow cells/kg. • If the patient requires a pRBC transfusion, irradiated units should be administered to avoid potential engraftment of random donor nucleated cells.

Extubation/Emergence

Return to supine position for extubation

POSTOPERATIVE CARE BED ACUITY

• Often performed on an outpatient basis • Most donors are admitted to a same-day surgical unit on the morning of donation (volume status changes).

• PACU monitoring is typically for 1–2 hours. • Check pressure dressing on back • May need transfusion; most donors will store 1–2 units of autologous blood.

ANALGESIA

• Local anesthetic at harvest puncture sites • Tylenol with codeine • Consider NSAIDs such as ketorolac if the patient is not coagulopathic.

COMPLICATIONS

• Pain is the most common complication of bone marrow harvesting and results from trauma of the iliac bones and overlying soft tissue. • Anemia • Transfusion-related complications • Fever • Orthostasis • Vomiting • Bleeding/hematoma • Infection • Compressive neuropathies (should resolve with reabsorption of the hematoma) • Anesthesia-related complications

REFERENCES

1. Bolwell BJ, Maurer W, Anderson J, et al. Outpatient bone marrow harvest: The Cleveland Clinic experience. Bone Marrow Transplant. 1995;16(5):703–705. 2. Borton MM, Buckner CD. Major complications of marrow harvesting for transplantation. Exp Hematol. 1983;11:916–921. 3. Bosi A, Bartolozzi B. Safety of bone marrow stem cell donation: A review. Transplant Proc. 2010;42(6):2192–2194. 4. Buckner CD, Clift RA, Sanders JE, et al. Marrow harvesting from normal donors. Blood. 1984;64:630–634. 5. Burmeister MA, Standl T, Brauer P, et al. Safety and efficacy of spinal vs. general anaesthesia in bone marrow harvesting. Bone Marrow Transplant. 1998;21(11):1145– 1148. 6. Chern B, McCarthy N, Hutchins C, et al. Analgesic infiltration at the site of bone marrow harvest significantly reduces donor morbidity. Bone Marrow Transplant. 1999;23:947–949. 7. Filshie J, Pollock AN, Hughes RG, et al. The anaesthetic management of bone marrow harvest for transplantation. Anaesthesia. 1984;39(5):480–484. 8. Jin NR, Hill RS, Petersen FB, et al. Marrow harvesting for autologous marrow transplantation. Exp Hematol. 1985;13(9):879–884. 9. Knudsen LM, Johnsen HE, Gaarsdal E, et al. Spinal versus general anaesthesia for bone marrow harvesting. Bone Marrow Transplant. 1995;15(3):486–487.

10. Lederhaas G, Brock-Utne JG, Negrin RS, et al. Is nitrous oxide safe for bone marrow harvest? Anesth Analg. 1995;80(4):770–772.

11. Machaczka M, Kalaitzakis E, Eleborg L, et al. Comparison of general vs. regional anaesthesia for BM harvesting: A retrospective study of anaesthesia-related complications. Bone Marrow Transplant. 2010;45(1):53–61. 12. Miller JP, Perry EH, Price TH, et al. Recovery and safety profiles of marrow and PBSC donors: Experience of the National Marrow Donor Program. Biol Blood Marrow Transplant. 2008;14(9 Suppl):29–36.

13. Stein RA Jr, Messino MJ, Hessel EA 2nd. Anaesthetic implications for bone marrow transplant recipients. Can J Anaesth. 1990;37(5):571–578. 14. Stroncek DF, Holland PV, Bartch G, et al. Experiences of the first 493 unrelated marrow donors in the National Marrow Donor Program. Blood. 1993;81:1940–1946.

15. Thorne AC, Malbin KF, Jain M, et al. Autologous bone marrow harvesting in outpatients. J Clin Anesth. 1996;8(7):551–556. 16. Thorne AC, Stewart M, Gulati SC. Harvesting bone marrow in an outpatient setting using newer anesthetic agents. J Clin Oncol. 1993;11(2):320–323. 17. Vanhelleputte P, Nijs K, Delforge M, et al. Pain during bone marrow aspiration: Prevalence and prevention. J Pain Symptom Manage. 2003;26(3):860–866. See Also (Topic, Algorithm, Electronic Media Element) • Blood transfusion

CODES ICD9 • V42.81 Bone marrow replaced by transplant • V59.3 Bone marrow donors ICD10 • Z52.3 Bone marrow donor • Z94.81 Bone marrow transplant status

CLINICAL PEARLS

• Patients should hold aspirin or aspirin-containing compounds for 10 days prior to the procedure; ibuprofen and ibuprofen-containing compounds should be held for 3 days prior. • The procedure is performed under sterile conditions to avoid infection; autologous harvests may involve immunocompromised patients.

BOWEL RESECTION/COLECTOMY Dmitri Bezinover, MD, PhD Priti G. Dalal, MD, FRCA

BASICS DESCRIPTION General

• Small bowel and colon resections are performed for elective and acute abdominal conditions and may be performed either open or laparoscopically. – Elective indications include tumors, diverticulitis or diverticulosis, Crohn’s disease, ulcerative colitis, angiodysplasia, familial adenomatous polyposis, radiation enteritis, and intestinal fistula. – Acute conditions include bowel or colon obstruction or perforation, mesenteric infarction, bleeding, volvulus, intussusception, and trauma. – Laparoscopy has the advantage of decreased pain, earlier return of GI functions, and quicker discharge from the hospital. However, it can be technically challenging, or may not be appropriate in coagulopathic or acute abdomens. • Bowel resections involve identifying, mobilizing, and confining the affected bowel. Bowel clamps are applied proximally and distally to the site and then resected. – Re-anastomosis is performed by one of the following techniques: Open end-to-end, closedend-to-end, stapled, or functional end-to-end. – Stomas are created when inflammation is present to allow time to heal. – Colon resection procedures include right or left hemicolectomies, sigmoid colectomies, and total colectomies. – Malignant disease processes can involve the removal of lymph nodes or mesentery. Incision

Vertical or transverse depending on the procedure Approximate Time

Variable—may increase with adhesions, obesity, or “re-do” abdomen EBL Expected

Variable—may increase with proximity to vascular structure, vascularity of malignancy, or inadvertent vessel penetration Hospital Stay

2–5 days; based upon return of bowel function, perioperative complications, and comorbidities Special Equipment for Surgery

Laparoscopic equipment as appropriate EPIDEMIOLOGY Prevalence

Acute abdomen: Bowel obstruction 0.13%; mesenteric infarction 0.3–8.5%; bowel/colon perforation 1.8–4.1% Prevalence

Increases with age and a family history Morbidity

Complications associated with resection: Ileus 210 ms at slow heart rates). – Second-degree AV block is divided into 2 types: Mobitz type I: The block is within the AV node and there is progressive PR interval prolongation, preceded by a nonconducted P wave. It is often transient and asymptomatic. Mobitz type II: The block is usually below the AV node, within the His-Purkinje system. During normal conduction, the PR interval remains unchanged prior to the P wave. However, there is paroxysmal failed conduction to the ventricles. This block is often symptomatic, with the potential to progress to complete (third-degree) AV block. – Third-degree or complete AV block may occur at the AV node, bundle of His, or bundle branches. When third-degree AV block is present, no impulses pass between the atria and ventricles. – Idiopathic progressive cardiac conduction disease (i.e., fibrosis and sclerosis of the conduction system) accounts for approximately 50% of AV blocks. – Ischemic heart disease accounts for about 40% of cases of AV block. – Cardiomyopathy and myocarditis can result from hypertrophic obstructive cardiomyopathy and infiltrative processes such as amyloidosis and sarcoidosis. Causes of myopathy include: rheumatic fever, Lyme disease, diphtheria, viruses, systemic lupus erythematosus, toxoplasmosis, bacterial endocarditis, and syphilis. – Congenital heart disease – Iatrogenic AV block Drugs: Digitalis, calcium channel blockers (especially verapamil and to a lesser extent diltiazem), amiodarone, adenosine, and beta-blockers Cardiac surgery Transcatheter closure of VSD Alcohol (ethanol) septal ablation

PREOPERATIVE ASSESSMENT • Palpate the patient’s pulse, assess EKG and pulse oximetry (strength of pulse) • Assess EKG to determine if sinus bradycardia (P wave preceded QRS complex) is present.

• Review recent events: Vagal stimulation, medications, ischemic insult, hypoxemia, hypothermia • Consider checking labs: – Electrolyte levels, magnesium, calcium – Glucose level

DIFFERENTIAL DIAGNOSIS EKG interference

TREATMENT • Bradycardia may be well tolerated if it develops slowly or is >50 bpm. Acute onset of bradycardia is more likely to be symptomatic. • Treatment should be instituted independently of the heart rate when bradycardia becomes symptomatic. In most cases the treatment threshold lies between 30 and 40 bpm. • Cease vagal stimulation – Oculocardiac reflex – Carotid sinus stimulation – Laparoscopic insufflation of the abdomen – Bladder catheterization – Electroconvulsive therapy (ECT) • Medications should be implemented when bradycardia is persistent and affecting the cardiac output. – Atropine is the drug of choice irrespective of the etiology Recommended dosing: 0.5 mg IV q 3–5 minutes to a maximum of 3 mg. Paradoxical slowing of the heart rate may be seen with doses 18 mm Hg, pulmonary edema from other causes typically has a PCWP 90%

FOLLOW-UP • Treatment of the underlying cause should be the initial step in managing these patients once they are stabilized. • Any arrhythmias must be corrected. • If CPE is caused by an acute valvular dysfunction, emergent valve surgery is required. • CPE from an acute MI typically requires either aggressive medical management, percutaneous intervention, or bypass surgery • Left ventricular assist device (LVAD) or heart transplants may be warranted.

REFERENCES

1. eConte P, Coutant V, Nguyen JM, et al. Prognostic factors in acute cardiogenic pulmonary edema. Am J Emerg Med. 1999;17(4):329–332. 2. Mattu A, Martinez JP, Kelly BS. Modern management of cardiogenic pulmonary edema. Emerg Med Clin North Am. 2005;23(4):1105–1025. 3. Annane D, Bellissant E, Pussard E. Placebo-controlled, randomized, double-blind study of intravenous enalaprilat efficacy and safety in acute cardiogenic pulmonary edema. Circulation. 1996;94(6):1316–1324. 4. Dupuis J. Nitrates in congestive heart failure. Cardiovasc Drugs Ther. 1994;8(3):501–507. 5. Karlsberg RP, DeWood MA, DeMaria AN. Comparative efficacy of short-term intravenous infusions of milrinone and dobutamine in acute congestive heart failure following acute myocardial infarction. Milrinone-Dobutamine Study Group. Clin Cardiol. 1996;19(1):21–

30. 6. Gropper MA, Wiener-Kronish JP, Hashimoto S. Acute cardiogenic pulmonary edema. Clin Chest Med. 1994;15(3):501–515. 7. Teerlink JR. Overview of randomized clinical trials in acute heart failure syndromes. Am J Cardiol. 2005;96(6A):59G–67G.

ADDITIONAL READING • www.uptodate.com

See Also (Topic, Algorithm, Electronic Media Element) • Myocardial oxygen demand • Myocardial oxygen supply • Atrial fibrillation • Coronary artery disease

CODES ICD9 428.1 Left heart failure ICD10 I50.1 Left ventricular failure

CLINICAL PEARLS

• CPE carries a high mortality. Treatment should focus on the underlying cause, while supporting pump function, and providing supportive measures as appropriate. – Oxygenation should be optimized by titrating the FiO2 and PEEP to keep the SpO2 >90% – Rate control, maintenance of sinus rhythm, preload reduction, and inotropic support

CARDIOPLEGIA Ali Salehi, MD

BASICS DESCRIPTION

• Cardioplegia is a specialized solution that is delivered to the myocardium during cardiopulmonary bypass (CPB) to cease electrical activity and hence mechanical function. It – Brings the heart to a standstill and provides a quiet operating environment for the surgeon – Decreases oxygen (O2) demand by decreasing electrical activity and mechanical contraction – Supplies the myocardium with O2 and nutrients in order to protect it from ischemic injury

PHYSIOLOGY PRINCIPLES

• Cardiac myocardium has a high O2 demand and requires a high, sustained supply of O2 and nutrients. – Normal myocardium: 8 mLO2/100 g/min

– Empty beating heart: 5.6 mLO2/100 g/min – K+ arrested heart: 1.1 mLO2/100 g/min

– Myocardial arrest and cooling decreases consumption to 0.3 mLO2/100 g/min (1,2).

• Ischemia results when there is an imbalance in O2 supply and demand. O2 delivery depends on the following: – Hemoglobin concentration – Arterial O2 saturation

– Blood flow to the heart. This is dependent on the coronary perfusion pressure and is equal to diastolic blood pressure minus the left ventricular end diastolic pressure. • Cardiac contractility is dependent on adenosine triphosphate (ATP). Aerobic metabolism produces 36 ATP for each glucose molecule; anaerobic metabolism produces only 2 ATP and also results in lactic acid and H+ accumulating in the myocardium (suppresses glycolysis). • Cardioplegia during CPB functions to: – Provide a quiet surgical field to facilitate the surgical procedure (arrest electrical activity and hence myocardial contractility). – Decrease myocardial energy requirements and O2 demand in order to protect and preserve myocardial function during the period in which aortic cross-clamp is placed and myocardial perfusion is disrupted. – Provide O2 and nutrients to the myocardium while it is ischemic (no coronary artery perfusion). – Of note: Myocardial arrest time can be prolonged or shortened by the administration of additional cardioplegia or washing out of cardioplegia.

• Composition of cardioplegia: Crystalloid or crystalloid and blood: – Crystalloid cardioplegia only contains dissolved O2 due to the lack of hemoglobin. Its O2 carrying capacity is sufficient to provide enough O2 to cold myocardium, hence, it

requires a hypothermic strategy for myocardial protection. Its composition can be altered by the addition of additives that replace substances present in blood cardioplegia. Intracellular solutions have a [Na+] similar to the intracellular [Na+]; this abolishes the Na+ gradient and thereby prevents action potentials and myocardial contraction. The lack of Ca++ further hinders myocardial contractility. Procaine chloride and magnesium chloride are added to provide membrane stability, and mannitol maintains the osmolarity of the solution. Today, it is mostly used for organ preservation in cardiac transplantation. Extracellular solutions have a [Na+] similar to the extracellular [Na+] but with a high [K+], 8–30 mmol/L, that is responsible for causing diastolic arrest of cardiac action potentials. Today, it is more commonly used during CPB. – Blood cardioplegia is made by mixing blood and crystalloid cardioplegia. The ratio of blood:crystalloid is typically 4:1, but may vary based on the practitioner or institution. It has a higher O2 carrying capacity because it contains hemoglobin and can be used for

both cold and warm cardioplegia. Cold cardioplegia, however, causes a left-shift on the oxyhemoglobin saturation curve; thus, hemoglobin has an increased affinity and will not offload O2 to tissues as readily. Benefits of blood cardioplegia include having natural

buffers, free radical scavengers, and colloids, thus decreasing the need for additives. Blood cardioplegia solution is used more commonly than crystalloid cardioplegia. The most recent meta-analysis of the current literature indicates that blood cardioplegia is associated with a decreased incidence of low cardiac output state and creatine phosphokinase isoenzyme MB (CK-MB) release, but there is no difference in the incidence of myocardial infarction or mortality (3). • Cardioplegia temperature, desired myocardial temperature, and protective strategies: The optimal myocardial temperature is dependent on the particular patient and surgery; it affects the choice between cold and warm cardioplegia as well as other protective strategies. – Cold (hypothermic) cardioplegia at a temperature of 4–10°C is typically administered to produce myocardial cooling. Myocardial metabolic rate and O2 consumption decrease by 50% for every 10°C drop in temperature; the greatest benefit is achieved at a myocardial temperature of 25°C. Further cooling of the heart will result in smaller reductions in O2

demand. Drawbacks of hypothermia include myocardial edema and injury that can result in post-CPB myocardial dysfunction (4). – Warm cardioplegia is used to achieve a “warm induction,” or arrest prior to the initiation of ischemia. Electrical and mechanical arrest results from a high [K+] of 20–25 mEq/L (decreases O2 consumption to ∼1.1 mLO2/100 g/min), while providing O2 and nutrients to the myocardium (maintains O2 supply). It can be used throughout the entire procedure

if prolonged ischemia is not anticipated. However, because it is not hypothermic, it does not aid with decreasing cellular metabolism. It also requires blood cardioplegia (contains

hemoglobin and hence a higher O2 carrying capacity) and continuous administration.

Studies have shown that warm cardioplegia results in a decreased incidence of myocardial dysfunction and impaired cardiac output in the post-bypass period, particularly in the setting of significant prebypass myocardial dysfunction and low ejection fraction (i.e., cardiogenic shock, progressing myocardial infarction, and advanced valvular disease) (4,5,6). • Route of delivery: – Anterograde delivery is through a cannula placed in the ascending aorta proximal to the aortic cross-clamp. Flow is usually adjusted to achieve and maintain a pressure of 70–100 mm Hg in the aortic root. A rapid rate or low perfusion pressure will result in uneven distribution of cardioplegia. – Retrograde delivery is through a cannula placed in the coronary sinus (CS). Right ventricular (RV) venous return enters the CS near the CS ostium or directly into the right atrium (RA) which may result in inadequate RV myocardial protection through retrograde cardiolegia. – Additionally, cardioplegia can be delivered directly in the coronary ostia (Ostial), or through the bypass grafts to the distal coronary arteries (7). • Frequency of delivery. Single dosing is appropriate when bypass time is short and there is no coronary disease. Multiple dose delivery is used in most cases, however, and is given to replace the solution washed away through noncoronary collateral flow. It is given for 1–2 minutes every 10–20 minutes. Advantages of multiple dose delivery include the following: – Maintain myocardial arrest – Maintain myocardial hypothermia (cold cardioplegia) – Supply substrates – Clear metabolites – Counteract myocardial edema • Additives. Counteract the potential myocardial injury and dysfunction during myocardial arrest and reperfusion. Blood cardioplegia needs fewer additives in comparison to crystalloid cardioplegia, as previously discussed. – Calcium reduces the risk of reperfusion injury. – Magnesium not only stabilizes the myocardial cell membrane but also antagonizes the effect of calcium (preventing the need to eliminate Ca++ from the solution). It has been shown that there is no benefit to adding magnesium to calcium-free cardioplegia. – Buffers. Natural (histidine, imidazole groups on proteins, bicarbonate) and synthetic buffers (THAM) are added to offset the accumulation of lactic acid in the myocardium during CPB. Blood cardioplegia contains only natural buffers. – Increasing osmolality to that of extracellular fluid helps prevent myocardial edema and preserve ventricular function. Mannitol, albumin, and glucose are used to increase the osmolarity of solutions. – Energy substrates. Addition of glutamate and aspartate can help replete the high-energy phosphates in the myocardium and preserve myocardial function.

ANATOMY

• Anterograde cannula is placed just proximal to the site selected for aortic cross-clamp in the

ascending aorta. The cannula has 3 ports, one for delivering cardioplegia, one for pressure monitoring, and one for venting. If the patient is undergoing aortic aneurysm repair or aortic valve surgery, anterograde cardioplegia can be delivered directly into the relative coronary ostia. • Retrograde cannula is placed through a small incision through the RA after the placement of the venous cannula. The surgeon feels the inferior vena cava–right atrial junction and guides the tip of the cannula into the CS ostium. This can also be guided by transesophageal echocardiography. Presence of a large Thebesian valve in the entrance of the CS can prevent the placement of the cannula. The cannula is advanced until resistance is felt or a pressure of >20 mm Hg is measured. This means that the cannula is wedged and is at the junction of the CS and great coronary vein; it should be pulled back 1 cm and secured. • The left ventricular free wall is perfused and cooled equally well by anterograde and retrograde techniques in the presence of a patent coronary vasculature. Subendocardial muscle is perfused as well as the epicardial muscle or even hyperperfused (Endo:Epi 1.4:1). If the left anterior descending artery is obstructed and anterograde cardioplegia is used, subendocardial muscle will be underperfused (Endo:Epi 20 mm Hg after insertion, or >50 mm Hg while on pump, means that the cannula is too far or wedged and needs to be pulled back and resecured. The cannula has a self-inflating balloon 1.8 cm in length with low intramural pressure and flows of 200–250 cc/hr to prevent barotrauma during infusions. • Return of electromechanical activity after 2–5 minutes of administration of cardioplegia indicates that the cardioplegia solution was washed away by noncardioplegic blood. This could be due to inadequate venous drainage, low perfusate potassium concentration, or incomplete aortic clamping. • Preparation for separation from CPB. The temperature is raised to 37°C and reperfusion is done with substrate enriched blood cardioplegia to buffer acidosis and limit the calcium load. Rewarming is started about 5 minutes before warm reperfusion. Warm reperfusate has a low potassium concentration (8–10 mmol/L) and is rich in substrates (aspartate, glutamate), CPD (to reduce calcium), and buffers (THAM). The first dose is given via anterograde cardioplegia and then alternated between anterograde and retrograde cardioplegia; the flow rate is 150 cc/hr for 3–5 minutes. The aortic cross-clamp is then removed and electromechanical activity usually resumes within 1–2 minutes. If this does not occur, it is indicative of a high serum and myocardial K+. Usually furosemide (0.5 mg/kg) and 1 g CaCl2 are given to ease the return of rhythm and contractility.

REFERENCES

1. uckberg GD, Braizer JR, Nelson RI, et al. Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. I. The adequately perfused beating, fibrillating, and arrested heart. J Thorac Cardiovasc Surg. 1977;73:87– 94. 2. Sink JD, Hill RC, Attarian DE, et al. Myocardial blood flow and oxygen consumption in the empty-beating, fibrillating, and potassium arrested hypertrophied canine heart. Ann Thorac Surg. 1983;35:372–379. 3. Hayashida N, Economides JS, Weasel RD, et al. The optimal cardioplegic temperature. Ann Thoracic Surg. 1994;58:961–971. 4. Rosenkranz ER, Buckberg GD, Mulder DG, et al. Warm induction of cardioplegia with glutamate enriched blood in coronary patients with cardiogenic shock who are dependent on inotropic drugs and intra-aortic balloon pump support: Initial experience and operative strategy. J Thorac Cardiovasc Surg. 1983;86:507. 5. aylaor CD, Lichtenstein SV, Fremes SE, et al. Randomised trial of Normothermic vs Hypothermic coronary bypass surgery. Lancet. 1994;343:559–563.

6. Buckberg GD. Antegrade/retrograde blood cardioplegia to ensure cardioplegic distribution: Operative techniques and objectives. J Card Surg. 1989;4(3):216–238. 7. Jacob S, Kallikourdis A, Sellke F, et al. Is blood cardioplegia superior to crystalloid cardioplegia? Interact Cardiovasc Thorac Surg. 2008;7:491–498.

ADDITIONAL READING

• Hensley FA, Martin DE, Gravlee GP, ed. A Practical Approach to Cardiac Anesthesia, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2008:604–624. • Shiroishi MS. Myocardial perfusion: The rebirth of potassium based cardioplegia. Tex Heart Inst J. 1999;26(1):71–86.

See Also (Topic, Algorithm, Electronic Media Element) Cardiopulmonary bypass

CLINICAL PEARLS

Blood cardioplegia is most commonly used for CPB procedures; the choice between warm and cold solution depends on the procedure and patient factors; additives are surgeon and center dependent.

CARDIOPULMONARY BYPASS Sascha Beutler, MD, PhD Daniel Castillo, MD

BASICS DESCRIPTION

• Cardiopulmonary bypass (CPB) machines temporarily take over the function of the heart and lungs. It is often referred to as a “heart-lung-machine.” – It redirects venous blood return away from the heart to the bypass machine where it adds oxygen and removes carbon dioxide. It returns the blood to the systemic circulation via a large artery. – Nearly all blood flow through the heart and the lungs stops. – Machines are operated by allied health professionals known as perfusionists. • Surgical procedures in which CPB are used: – Coronary artery bypass surgery – Cardiac valve repair and/or replacement – Repair of large septal defects – Repair and/or palliation of congenital heart defects – Repair of some large aneurysm (cerebral aneurysm, aortic aneurysm) – Pulmonary thrombectomy – Heroic measures when oxygenation or perfusion of organs cannot be maintained by other means (e.g., local anesthetic systemic toxicity, anterior mediastinal mass). PHYSIOLOGY PRINCIPLES

• Basic circuit of the CPB machine: – Venous cannulae are placed in the right atrium and/or in the inferior or superior vena cava to receive and redirect the patient’s blood away from the heart and lungs into a venous reservoir. – Oxygenator: From the venous reservoir, the blood passes through an oxygenator where oxygen is added (membrane oxygenators are less traumatic than bubble oxygenators). – Heat exchanger: The blood then passes through a heat exchanger that functions to cool or warm the patient to the desired temperature. – Main pump: either a roller head pump or a centrifugal pump. Roller pump: The pump console is made of several rotating motor-driven pumps that peristaltically “massage” the tubing. This action gently propels the blood through the tubing. Centrifugal pump: By altering the speed of revolution of the pump head, blood flow is produced by centrifugal force. This type of pumping action is considered by many to be superior to the action of the roller pump because it is thought to produce less blood damage. – Arterial cannula: Placed in the ascending aorta; the main pump returns the blood through

an arterial cannula to the patient’s systemic circulation. – Arterial line filter: Is incorporated in the CPB circuit to minimize the embolic load delivered to the patient. • Other components of CPB Machine: – “LV vent” is a cannula that suctions blood out of the left ventricle to prevent its dilatation (per LaPlace’s law, Tension = {Pressure * Radius}/Wall thickness; increases in radius increase tension and myocardial oxygen consumption). The blood originates from Thebesian and bronchial veins that empty directly into the left ventricle. – “Cardiotomy suction” is a suction cannula that removes and salvages undiluted or “clean” blood from the open cardiac chambers or the surgical field. – “Cellsaver” system collects and washes red blood cells from diluted field blood and blood that has been exposed to potentially harmful elements (e.g., inflammatory cytokines). – “Cardioplegia pump” administers a cardioplegic solution. • Monitoring and access: – Arterial line is placed prior to initiation of CPB: The flow on bypass is usually nonpulsatile and thus a noninvasive BP cuff will not work. – Large-bore intravenous access is also established in case of significant fluid shifts and/or blood loss prior to or after CPB. – Central venous access is routinely placed after induction; a pulmonary artery catheter (PAC) may be considered. – Transesophageal echocardiography probe is placed as indicated by the procedure in the absence of contraindications. • Anesthetic management: – Balanced anesthesia with shorter-acting narcotics (fentanyl), short-acting intravenous agents, such as propofol, and modern volatile agents are utilized. Volatile agents appear to improve cardiac cell conditioning when administered prior to the onset of ischemia. – High-dose narcotic techniques are not commonly used today. – Supplemental techniques have increased in popularity (e.g., paraspinal blocks) to reduce the use of systemic agents, improve analgesic control, and improve postoperative pulmonary function.

DISEASE/PATHOPHYSIOLOGY

• Systemic inflammatory response syndrome (SIRS): can result from cardiac surgery with CPB. – Possible causes include contact of the blood components with the artificial surface of the bypass circuit, ischemia-reperfusion injury, endotoxemia, and operative trauma. – Data indicate that a complex sequence of events leads to the activation of leukocytes and endothelial cells, which is responsible for cell dysfunction in different organs. – There may be some benefit of steroid use in patients undergoing CPB (see additional reading). • Complications of CPB (3)[B]: – Capillary leak syndrome secondary to inflammatory response (see above) – Hemolysis – Clotting of blood can block the circuit (particularly the oxygenator) or send a clot into the patient. – Air embolism

– Exsanguination (loss of blood perfusion of tissues) if a line becomes disconnected. – Type I CNS events in 3–6% of patients. – Long-term cognitive dysfunction in up to 15% of patients. – Acute respiratory distress syndrome in up to 1.5% of patients. – Renal dysfunction, with 1–2% of patients requiring hemodialysis. • As a consequence, CPB is only used during the several hours a cardiac surgery may take. Most oxygenators come with a manufacturer’s recommendation that they are only used for a maximum of 6 hours, although they are sometimes used for up to 10 hours. When longer periods of cardiopulmonary support are required, extra- corporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD) should be utilized.

PERIOPERATIVE RELEVANCE

• Initiation of bypass is defined as the moment that the patient’s venous blood is allowed to flow through the venous cannula, away from the heart into the bypass machine. A clamp is typically placed on the venous cannula while preparing for CPB; thus removal of the clamp usually marks initiation. – Use of CPB requires suppression of the clotting cascade with heparin because the components of the bypass pump and the surgical wound are powerful stimuli for thrombus formation. – Heparin is given intravenously before placement of the aortic cannula and the activated clotting time (ACT) is checked; the targeted ACT varies with the type of CPB used (heparin-coated versus nonheparin coated) and the type of surgical procedure. – After acceptable pump flows have been achieved and the mean BP is stabilized, the aorta is cross-clamped, cold cardioplegia (see below) is infused, and the heart is also topically cooled with a saline slush solution to stop it from beating. • Cardioplegia is a solution that contains a high concentration of potassium and other electrolytes. It is designed to arrest and protect the heart muscle. The solution is typically administered every 20–30 minutes throughout the on-bypass time when there is no blood flow through the heart. – Anterograde cardioplegia is administered through the coronary artery os and the flow is anterograde. – Retrograde cardioplegia is administered through a catheter in the right atrium directly into the coronary sinus. The flow is retrograde through the coronary veins. • Optimal conduct of CPB: – Currently, the management of patients during CPB varies substantially by institution and practitioner (surgeon, anesthesiologist, perfusionist involved). – Evidence-based guidelines for best perfusion practices have been developed (1)[A,B], (2) [A]. The guidelines describe physiologic parameters (mean arterial BP, pump flow rate, hematocrit, temperature) and technologies (heparinized versus nonheparinized circuits, arterial line filters, pulsatile versus nonpulsatlie pumps, centrifuge versus roller pumps) that may optimize perfusion. • Alpha stat versus pH stat: – Alpha stat arterial blood gases are not temperature corrected. During hypothermia on bypass, an alkaline shift occurs as carbon dioxide leaves the gas form and dissolves in the blood (less kinetic energy to keep in gas form; resulting in decreased PaCO2). This leads to

a leftward shift of the oxyhemoglobin dissociation curve that remains uncorrected; carbon dioxide is not added to the system and total body carbon dioxide remains the same. Alpha stat is most commonly used in adults. – pH stat arterial blood gases are temperature corrected. Carbon dioxide is added to the oxygenator to correct for the alkaline drift at lower temperatures and increases the PaCO2

to normal levels. This counteracts the leftward shift of the oxyhemoglobin dissociation curve. It is most commonly used in neonatal and infant cardiac surgery as it may offer neurologic protection for this patient population. • Comparison of adult and pediatric CPB: There are significant differences in the conduct of CPB between adult and pediatric patients (see Table 1). Table 1. Comparison of adult versus pediatric cardiopulmonary bypass

• Deep hypothermic circulatory arrest (DHCA) describes maintaining the body without any perfusion (blood flow). – It is most frequently used in pediatric cardiac surgery and aortic arch aneurysm repairs in adults. – The patient is put on the CPB and cooled to induce total body hypothermia, which is the prerequisite for initiation of DHCA. – Additional measures are instituted in an attempt to further reduce the metabolic requirement of the brain and provide brain protection during DHCA: Ice packing of the head, administration of barbiturates and mannitol. – Finally, blood flow to all organs, including the brain, is stopped. – In adults, DHCA may offer brain protection for up to 30–45 minutes. • Termination of CPB: – Weaning from CPB is only begun once the patient’s core temperature is adequate (about 36.5°C) and ventilation is re-established. – The aortic cross-clamp is removed and the heart beat most often resumes spontaneously; temporary pacing wires can be used if heart rate is inadequate. – Weaning from CPB is usually done gradually: The pump flow rates are slowly reduced, while the amount of blood flow back into the heart is slowly increased at the same time (“partial bypass”). – Once the patient is completely off CPB and vital signs are stable, venous and arterial cannulae are removed. – Protamine is then administered to reverse the heparin-induced anticoagulation. Always start with a test dose of protamine (typically 10 mg IV) before giving the full dose in case of an allergic reaction (severe pulmonary hypertension requiring reinstitution of the CPB).

REFERENCES

1. Murphy GS, Hessel EA II, Groom RC. Optiomal perfusion during cardiopulmonary bypass: An evidence-based approach. Anesth Analg. 2009;108(5):1394–1417. 2. Oakes DA, Managno CTM. Cardiopulmonary bypass in 2009: Achieving and circulating best practices. Anesth Analg. 2009;108(5):1368–1370. 3. Shann KG, Likosky DS, Murkin JM, et al. An evidence-based review of the practice of cardiopulmonary bypass in adults: A focus on neurologic injury, glycemic control,

hemodilution, and the inflammatory response. J Thorac Cardiovasc Surg. 2006;132:283– 290.

ADDITIONAL READING

• Conolly S, Arrowsmith JE, Klein AA. Deep hypothermic circulatory arrest. Contin Edu Anaesth Crit Care Pain. 2010;10:138–142. • Whitlock RP, Chan S, Devereaux PJ, et al. Clinical benefit of steroid use in patients undergoing cardiopulmonary bypass: A meta-analysis of randomized trials. Eur Heart J. 2008;29:2592–2600.

See Also (Topic, Algorithm, Electronic Media Element) • Coronary artery disease • Coronary artery bypass grafting • Circulatory arrest • Cardioplegia • Left ventricular assist device • Postoperative cognitive dysfunction • pH measurements

CLINICAL PEARLS

• CPB is a technique that temporarily takes over the function of the heart and lungs. • Certain surgical procedures are only possible to perform with the help of CPB. • CPB carries its own pathophysiology and complications. • There are significant differences in the indications and the conduct of CPB in adult and pediatric patients. • Evidence-based practice guidelines have been developed to optimize perfusion and outcome.

CAROTID BODY

Robert S. Fitzgerald, LittB, STB, MA, STM, PhD

BASICS DESCRIPTION

• The carotid body (CB) comprises chemoreceptors and their supporting cells at the bifurcation of the carotid artery. It functions to detect oxygen and carbon dioxide partial pressures as well as changes in pH, glucose, and temperature. • From the available literature, the CB was first reported in 1743 in a dissertation from the lab of the famous German physiologist, Albrecht von Haller. In 1938, Corneille Heymans received the Nobel Prize in Physiology or Medicine for his discovery of the role carotid and aortic mechanisms played in cardiopulmonary control. Heymans’ work owed a great debt to the pioneering histological work of Fernando De Castro who knew the difference between the CB and carotid sinus before the Heymans’ group (1). • The CB is sometimes confused with the carotid sinus, located at the base of the internal carotid artery; this latter structure is the principal detector and regulator of BP in mammals. • The CB, however, is arguably the most important interoreceptor in humans.

PHYSIOLOGY PRINCIPLES

• In human subjects, the CB is football-shaped with a volume of ∼12 mm3. The human CB weighs ∼14 mg but has an enormous blood flow, the highest of any organ measured. • The CB “tastes” the blood; that is, it is sensitive to qualitative changes in arterial blood composition. – When PaO2 or glucose drops, carbon dioxide tension (PaCO2) or hydrogen ion rises. The

neurotransmitter-containing chemosensitive glomus cells in the CB become depolarized and extracellular calcium rises in these cells. This provokes the release of excitatory (acetylcholine, adenosine triphosphate [ATP]) and inhibitory (dopamine) transmitters. – Serotonin and GABA, slower acting agents, are subsequently released (2). These neurotransmitters cross a synaptic-like cleft between the glomus cell and the abutting sensory afferent neuron, a branch of the glossopharyngeal nerve to bind to appropriate receptors. – The afferent neurons have their cell bodies in the petrosal ganglion and insert into nucleus tractus solitarii in the medulla. – The neurotransmitters also bind to autoreceptors on the glomus cells to promote or attenuate further release of the agents. • Stimulation of the CB initiates an impressive array of systemic reflex responses. – Pulmonary Increase in tidal volume Increase in respiratory frequency Increase in FRC (a static lung volume) Increase in airway resistance

Increase in secretions Decrease in pulmonary vascular resistance. – Cardiovascular Increase in sympathetic nerve output leading to tachycardia after an initial brief bradycardia Peripheral vasoconstriction Some of the cardiovascular responses are modified by the stimulated lung receptors due to the hyperpnea (increase in depth and rate of respiration). – Endocrine Release of some adrenal medullary contents as well as 17-OH corticosteroids Increase in plasma renin – Renal. CB stimulation increases renal sodium and water excretion in normoxic mammals. Bilateral CB denervation abolishes the natriuresis (3).

ANATOMY

Located bilaterally at the bifurcations of the common carotid arteries into their external and internal branches. DISEASE/PATHOPHYSIOLOGY

• Respiratory concerns – Obstructive sleep apnea (OSA). This condition, which affects over 11 million Americans including children, results from the relaxing and collapse of the upper airway muscles during sleep. Since metabolism continues, oxygen is consumed and PaO2 falls. Likewise CO2 is produced and PaCO2 rises.

This modest form of asphyxia strongly stimulates the CBs first; this provokes a minimal arousal and taking in of a breath. The stimulus to the CB also provokes a significant increase in sympathetic nervous system (SNS) output. This is not attenuated by input from the stretch receptors in the lung since the subject is apneic. As a consequence of the increased SNS output, heart rate and contractility increase as well as vascular resistance in some beds. This results in an increase in BP, a very undesirable consequence for subjects who have suffered a previous stroke. BP never returns to normal. The nocturnal hypertension frequently carries over into the daylight hours. Episodes of OSA can occur as frequently as 30–40 times per hour. Hypoxia also increases pulmonary arterial pressure by local mechanisms; this is somewhat attenuated by CB stimulation. – Sudden infant death syndrome. Though this condition has been greatly reduced by proper positioning of the infant during sleep, the CBs are still thought to function as above in the periodic apneas observed in children throughout their first year of postnatal life as their respiratory control system undergoes development. • Cardiovascular concerns – Chronic heart failure. As the population ages, the occurrence of heart failure (HF) is on the rise. In the US, almost 5 million people experience this condition with about 20%

mortality within 1 year and about 50% mortality within 5 years (4,5). Recent research using the rabbit as an animal model has illustrated that the CB plays a key role in CHF (6). Heart failure results in decreased blood flow in the common carotid artery with a resultant decrease in blood flow to the CB. The rabbits demonstrated an increase in CB neural output and renal sympathetic nerve activity. Decreased blood flow reduces sheer stress on the endothelial cells in the CB vasculature. This factor initiates a cascade of events that reduces nitric oxide synthase (nNOS) activity and NO in the CB. NO is a well-known attenuator of CB neural output (7,8). When an adenovirus was loaded with the gene for nNOS and injected into the CBs of the HF rabbits, CB neural output as well as SNS output were reduced (9). Modest exercise, which increases blood flow, also reduced CB neural output.

PERIOPERATIVE RELEVANCE

• Effect of sedation on the CB – Many drugs used in anesthesia depress regulation of breathing during acute hypoxia, among which are propofol, halogenated inhaled general anesthetics, and neuromuscular blocking agents. – In a recent study of human CBs, mechanisms behind this action were studied (5). And though many of the elements operating to depress ventilation and hypoxia-induced increases in CB neural output in animal models were the same in humans, not all of the implicated nonhuman elements could be found in human CBs. The authors speculate that in humans, propofol acts on the GABAA receptor in the CB, while inhaled halogenated anesthetics were found to target both K+ channels and neuronal acetylcholine receptors (nAChRs). Human CB nAChRs having the α3, α7, and β2 subunits would also be blocked by atracurium and vecuronium.

REFERENCES

1. DeCastro F. The discovery of sensory nature of the carotid bodies – Invited article. Adv Exptl Med Biol. 2009;648:1–18. 2. Nurse C. Neurotransmission and neuromodulation in the chemosensory carotid body. Auton Neurosc Bas Clin. 2005;120:1–9. 3. itzgerald RS, Shirahata M. Systemic responses elicited by stimulating the carotid body: Primary and secondary mechanisms. In: The Carotid Body Chemoreceptors, Ed. Gonzalez C. Heidelberg, Germany, Springer, 1997, pp. 171–191. 4. Paterson DJ. Targeting arterial chemoreceptor over-activity in heart failure with a gas. Circ Res. 2005;97:1–6. 5. Fagerlund M, Kahlin J, Ebberyd A, et al. The human carotid body – Expression of oxygen sensing and signaling genes of relevance for anesthesia. Anesthesiol. 2010;113:1270–1279. 6. Ding Y, Li YL, Schultz H. Role of blood flow in carotid body chemoreflex function in heart failure. J Physiol. 2011;589:245–257. 7. Wang ZZ, Stensaas L, Bredt D, et al. Mechanisms of carotid body inhibition. Adv Exptl Med Biol. 1994;360:229–235.

8. Fitzgerald RS, Shirahata M, Chang I, et al. L-arginine’s effect on the hypoxia-induced release of acetylcholine from the in vitro cat carotid body. Respir Physiol Neurobiol. 2005;147:11–17. 9. Schultz H, Li YL. Carotid body function in heart failure. Respir Physiol Neurobiol. 2007;157:171–185. 10. eath D, Smith P. Diseases of the human carotid body. London, Springer-Verlag, 1992, pp. 88–89. See Also (Topic, Algorithm, Electronic Media Element) • Congestive heart failure • Carotid endarterectomy • Carotid sinus

CLINICAL PEARLS

• Aging has an effect on the human CB: In three groups of adults with mean ages of 26, 52, and 79, the mean cross-sectional area of the CB (mm2) was 2.71, 3.12, and 4.42 respectively. But the mean percent of type I cell tissue was 45, 39, and 29. This suggests that the reflex responses to CB stimulation by hypoxia, hypercapnia, and hypoglycemia would become less as one ages. • A further consequence of aging is the diffuse infiltration of lymphocytes. In a group of 38 male and 37 female subjects, only 2 of 18 subjects under 50 years of age exhibited this phenomenon, while 32 of the 57 subjects greater than 50 years showed it. • The CB is affected by COPD. There is usually an accompanying right ventricular hypertrophy that is associated with alveolar hypoxia, hypercarbia, and muscularization of pulmonary arterioles. In emphysematous patients presenting without right ventricular hypertrophy, the mean weight of the combined CBs was 32.4 mg. In the presence of hypertrophy, the mean weight of the combined CBs was 56.2 mg. • In asthma, one might expect enlarged CBs due to the mild hypoxemia resulting from bronchospasm and mucus secretion. Stimulated CBs normally provoke contraction of airways smooth muscle. However, in asthmatic subjects who had undergone CB removal, the structures were not enlarged. But the proportion of sustentacular cells had doubled in the asthmatics compared to controls. And of the two types of type I (chief) cells, the dark type had increased from ∼28% of all type I cells in the normal CBs to 43% in the asthmatics. This suggests the possibility of an abnormal CB sensitivity (10). • A commonly used neuromuscular blocker during anesthesia, vecuronium has been shown in rats to decrease the neural output from the CB. It is believed that halothane, enflurane, and isoflurane prolong the effects of vecuronium, and this would suggest that the CB would remain hyporesponsive.

CAROTID ENDARTERECTOMY Jared Feinman, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION General

• Carotid endarterectomy (CEA) is an open surgical procedure to remove stenotic material from inside the carotid artery and improve perfusion to the brain. • An oblique incision is made along the anterior border of the sternocleidomastoid muscle and the platysma is divided on top of the carotid bifurcation; the omohyoid muscle will often also be divided. The carotid fascia is then incised and the common carotid artery (CCA) is exposed. • A soft, noncrushing clamp is applied to the internal carotid artery (ICA), and the external and CCA are subsequently clamped to provide a “bloodless" operating field. A shunt may be inserted above and below the clamps to maintain perfusion to the brain. • An arteriotomy is made in the CCA, extended past the occlusion in the ICA, and the plaque is removed. • Arterial closure is via a primary closure or patch, and the patient’s neurological status should be assessed before leaving the OR. • Embolic phenomena from the atheroma can be dislodged during clamping or plaque removal and travel up to the brain, causing infarction or TIAs. • The decision to proceed with a CEA versus medical management is based on the degree of stenosis, presence or absence of symptoms, and concomitant risk factors (1). – 70–99% stenosis/symptomatic: Proceed with CEA, shown to reduce 2-year stroke risk from 26% to 9% – 50–69% stenosis/symptomatic: Consider CEA, especially if male, >5-year life expectancy and surgical risk of stroke/death is halothane.

– Order of vasodilating potency: Halothane>>enflurane>isoflurane = sevoflurane = desflurane. After initially increasing the CBF, there is a substantial fall in CBF until a steady state is reached (usually after 2.5–5 hours after exposure). – Therapeutic use: Decreases in CMRO2 can develop quickly.

– Carbon dioxide responsiveness remains well maintained. • Nitrous oxide (N2O). Results have been mixed; however, it is generally accepted that the CMRO2, CBF, and ICP increase, likely from sympatho-adrenal-stimulating effects.

GRAPHS/FIGURES See Table See Table

REFERENCES

1. Uludag K, Dubowitz DJ, Yoder EJ, et al. Coupling of cerebral blood flow and oxygen consumption during physiological activation and deactivation measured with fMRI. Neuroimag. 2004;23:148–155. 2. Jain V, Langham MC, Floyd TF, et al. Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapnia. J Cereb Blood Flow Metab. 2011;31(7):1504–1512. 3. Nofzinger EA, Buysse DJ, Miewald JM, et al. Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking. Brain. 2002;125(Pt 5):1105– 1115. 4. Ingvar M. Cerebral blood flow and metabolic rate during seizures. Relationship to epileptic brain damage. Ann N Y Acad Sci. 1986;462:194–206. 5. An H, Liu Q, Chen Y, Lin W, et al. Evaluation of MR-derived cerebral oxygen metabolic index in experimental hyperoxic hypercapnia, hypoxia, and ischemia. Stroke. 2009;40:2165–2172. 6. Nemoto EM, Klementavicius R, Melick JA, et al. Suppression of cerebral metabolic rate for oxygen (CMRO2) by mild hypothermia compared with thiopental. J Neurosurg Anesthesiol. 1996;8(1):52–59.

• Intracranial hypertension • Cerebral blood flow • Burst suppression

CLINICAL PEARLS

• Increases in CMRO2 can have detrimental effects, possibly resulting in intracranial

hypertension from increased CBF as well as ischemia from an imbalance in oxygen supply and demand. • Most IV anesthetics cause a decrease in both CBF and CMRO2, except ketamine that can cause an increase in both.

• Volatile agents “uncouple” CBF and CMRO2. In other words, while CMR decreases, CBF does not (can increase or remain the same). • For every degree (celsius) decrease, the CMRO2 falls ∼6–7%.

CEREBRAL PALSY

Marc A. Logarta, MD, DABA, FANZCA

BASICS DESCRIPTION

• Cerebral palsy (CP) is a term used to describe a large and diverse group of neurological disorders that result from injury to the developing fetal or infant nervous system. • It is associated with varying degrees of motor, sensory, and intellectual impairment. In mild cases, the patient can be almost completely functional and in severe cases patients can have profound morbidity and mortality even in childhood. • Nonprogressive condition; does not have an evolving neurologic clinical deterioration.

EPIDEMIOLOGY Prevalence

1:450 live births in developed countries Prevalence

1:350 children and adults in the US Morbidity

Although CP is often manifested as problems with posture and movement, the more severe forms affect neurologic, respiratory, GI, musculoskeletal, and genitourinary systems. ETIOLOGY/RISK FACTORS

• Congenital CP (80% of cases) – Prematurity (10 to 50-fold increase) – Neonatal asphyxia – Male gender – Chorioamnionitis – Preeclampsia – Peripartum hemorrhage – Advanced maternal age – Multiparous birth – Initial low Apgar score – Prenatal infection (toxoplasmosis, rubella, cytomegalovirus, herpes) – Vascular maldevelopments – Metabolic disorders – Intrauterine growth retardation – Trauma to fetus – Breech birth – Maternal hypothyroidism

– Fetal alcohol syndrome • Acquired CP (20%) within first 2 years of life – Intracerebral hemorrhage – Bacterial meningitis – Hyperbilirubinemia – Viral encephalitis – Brain injury – Neonatal seizures

PHYSIOLOGY/PATHOPHYSIOLOGY

• Clinical presentation may result from neurologic injury that occurs in the prenatal, perinatal, or postnatal periods. The injury may be due to toxins, infections, hypoxia, vascular insufficiency, trauma, or complications associated with prematurity. • Injury may occur at different points in brain development, therefore resulting in a wide spectrum of clinical presentations. • CP due to prematurity is most likely associated with the physical stress that the premature neonate brain is unable to compensate for. This results in cerebral white matter hypoperfusion, which can lead to varying degrees in subependymal and germinal matrix hemorrhage and/or leukomalacia. Because these areas carry fibers responsible for motor control to the lower extremities, the patient suffers from lower extremity weakness and spasticity. • If hemorrhagic lesions extend outward from the lateral ventricles toward the descending fibers of the motor cortex (centrum semiovale and corona radiata), then the upper extremities will be affected along with the lower extremities. • CP due to hyperbilirubinemia or hypoxic ischemic injury perinatally result in extrapyramidal signs often associated with hypertonicity. • In summary there is no one cause of CP as is outlined in the risk factors above, and most cases are likely to have multifactorial causes. By definition, CP is a nonprogressive disorder in which the injury has occurred and does not have an evolving neurologic clinical deterioration.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess severity of multiorgan disease • Assess the patient’s level of cooperation and cognition. • Optimize pulmonary function, minimize chance of aspiration • Return to normal regimen of anticonvulsant and antispasmodic medications as soon as possible so as to avoid adverse events such as withdrawal symptoms and seizures.

PREOPERATIVE ASSESSMENT SYMPTOMS

Cardiopulmonary symptomatology is difficult to evaluate because these patients will frequently be immobile, but may have ischemic heart disease, pulmonary hypertension, and cor pulmonale.

History

• Up to 70% may have intellectual impairment. • Enlist the help of the parent/guardian to take a thorough history including an evaluation of previous anesthetics – many of these patients will have had frequent surgical procedures. • Many patients will have an ASA classification of III or more due to other comorbid conditions. Assess the multiple organ systems involved. • Assess fluid status and hydration • Assess drug regimen and efficacy • Inquire about intrathecal baclofen pump • Assess level of cooperation • Inquire about chronic pain conditions

Signs/Physical Exam

• Muscle contractures, spasticity, and sometimes hypotonia • Abnormal neck or truncal tone • Asymmetric posture, strength, or gait • Temporomandibular joint (TMJ) dislocation • Scoliosis

MEDICATIONS

• Baclofen (oral or via intrathecal pump): Used to decrease spasticity, especially in lower extremities. Withdrawal symptoms can include confusion, painful muscle spasms, seizures, and hemodynamic instability. • Anticonvulsants: May be on multiple medications for chronic seizure disorder (can increase metabolism of anesthetic drugs). • Botulinum: Injections are often used to decrease muscle spasticity and progression to contractures. Botulinum can also be used to reduce drooling associated with CP. • Patients may also be on chronic regimens of antidepressants, antibiotics (for recurrent infections), and analgesics. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Chest Radiograph (CXR) (pneumonia, cardiomegaly, and congestive heart failure) • Electrocardiogram (right heart failure, ischemic heart disease) • Complete blood count, electrolytes, urea, and creatinine

CONCOMITANT ORGAN DYSFUNCTION

• Cardiac: Patients have been reported to have a higher incidence of ischemic heart disease. • Neurologic: CP often manifests as a motor disorder involving spasticity and contractures. Most will have cognitive dysfunction and seizure disorders. Also seen are visual, auditory, and sensory impairments. Neurosis and psychosis can occur. • Pulmonary: Chronic lung disease is a frequent manifestation due to either chronic aspiration pneumonia, neonatal respiratory distress syndrome, bronchopulmonary dysplasia, asthma/reactive airway disease, or scoliosis causing restrictive lung disease.

• Musculoskeletal: Because of chronic immobility, patients can have marked osteopenia and may be more prone to fracture. Contractures may also make vascular access and positioning difficult under anesthesia. Patients may have TMJ disorder with poor mouth opening. • GI: May have poor nutritional status, gastroesophageal reflux disorder (GERD), drooling, and constipation. Dental caries and poor dentition are also common. • Immunologic: May be immunosuppressed due to malnutrition. • Genitourinary: Chronic urinary tract infections due to neuropathic bladder. These patients are at increased risk of latex allergy due to repeated urinary catheterizations.

CIRCUMSTANCES TO DELAY/ CONDITIONS • Acute respiratory infection/pneumonia • Acute baclofen withdrawal • Acute heart failure

CLASSIFICATIONS

Classified according to resting tone and limb involvement: • Spastic hemiplegia: Predominantly on one side of the body, with the upper extremity more involved than the leg. • Spastic diplegia: Affecting bilateral lower extremities more than upper extremities. • Spastic quadriplegia: All extremities. • Athetoid/dyskinetic CP: Associated with mixed muscle tone and extrapyramidal signs. • Ataxic CP: Caused by damage to cerebellum. Balance while walking is affected. • Hypotonic CP: Limp musculature.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Consider anxiolytic medication if appropriate • In hypotonic patients, sedative premedication is best avoided because it can decrease airway reflexes. INTRAOPERATIVE CARE Choice of Anesthesia

As the CP patient population can have significant cognitive dysfunction as well as cardiopulmonary comorbidities, general anesthesia should be considered carefully. Monitors

• Standard ASA monitors • Consider measurement of urine output

Induction/Airway Management

• Airway management can be difficult because of TMJ disorder/dislocation and poor

dentition. • Patients can have reactive airway disease. • Because of the upregulation of acetylcholine receptors in the neuromuscular junction, the patient can have decreased sensitivity to nondepolarizing neuromuscular blockers. However, due to changes in volume of distribution, there may be an increased amount of medication available at the neuromuscular junction. These changes most likely counteract each other. • Succinylcholine is considered safe to use. • In patients where GERD is a concern, consideration of a rapid sequence induction is appropriate in patients with intravenous access. However, there is no strong evidence that this is safer than a well-positioned inhalational induction, so as to minimize passive regurgitation.

Maintenance

• Keep patients warm as CP patients are prone to hypothermia due to muscle atrophy. • Minimum alveolar concentration (MAC) and drug clearance may be affected by the use of anticonvulsants.

Extubation/Emergence

• Ensure full reversal if muscle relaxation was used. • CP patients often have increased secretions so an intact cough reflex is crucial to prevent postoperative pulmonary complications. • Consider prophylaxis for postoperative nausea and vomiting.

FOLLOW-UP BED ACUITY

• Consider monitoring in a high-dependency environment for those with significant comorbidities, seizure disorder, or the potential for baclofen withdrawal if unable to take usual therapy. • Vigilance for respiratory dysfunction, hypothermia, and hypoxia • Respiratory therapy and incentive spirometry • Consider supplemental oxygen (nasal cannula, face mask) • Ensure appropriate analgesia as patients will often have difficulty in communicating.

COMPLICATIONS

• Perioperative aspiration: Treat with supportive measures including supplemental oxygen, chest physiotherapy, and ventilatory support in severe cases. • Baclofen withdrawal: Can manifest as anxiety, confusion, pain, muscle spasm, seizures, and autonomic instability. Resume baclofen regimen as soon as appropriate. • Seizure: May be precipitated by inadequate blood levels of anticonvulsant medication or electrolyte abnormality. Look for other causes of perioperative lowering of seizure threshold. Treat with benzodiazepines, supportive care, and resume previous anticonvulsant regimen as soon as appropriate.

REFERENCES

1. Krigger KW. Cerebral palsy: An overview. Am Fam Physician. 2006;73:91–102.

2. Cans C, De-la-Cruz J, Mermet M-A. Epidemiology of cerebral palsy. Paediatr Child Health. 2008;18:393–398.

3. Prosser D, Sharma N. Cerebral palsy and anaesthesia. Contin Educ Anaesth Crit Care Pain. 2010;10(3):72–76. 4. Jacobsson B, Hagberg G. Antenatal risk factors for cerebral palsy. Best Pract Res Clin Obstet Gynaecol. 2004;18(3):425–436.

ADDITIONAL READING

• www.aacpdm.org • American Academy for Cerebral Palsy and Developmental Medicine

See Also (Topic, Algorithm, Electronic Media Element) • Gastroesophageal reflux disease • Aspiration • Asthma

CODES ICD9 • 343.0 Congenital diplegia • 343.1 Congenital hemiplegia • 343.9 Infantile cerebral palsy, unspecified ICD10 • G80.0 Spastic quadriplegic cerebral palsy • G80.1 Spastic diplegic cerebral palsy • G80.9 Cerebral palsy, unspecified

CLINICAL PEARLS

• Assess the severity of disease in order to plan an appropriate anesthetic technique. • Enlist the help of the parent/guardian as they sometimes have extensive knowledge about previous surgeries and anesthetics. • Evaluate cardiopulmonary status as these patients may have extensive comorbidities including pulmonary hypertension, chronic aspiration, scoliosis, and ischemic heart disease. • Resume normal anticonvulsants and antispasmodics as soon as possible to prevent seizures and withdrawal symptoms. • Ensure patients have adequate pain control postoperatively, as they will often have difficulty communicating.

CEREBRAL VASOSPASM Victor Duval, MD

BASICS • Cerebral vasospasm is defined as the constriction of one or more major cerebral arteries, usually secondary to subarachnoid hemorrhage (SAH) or craniocerebral trauma. • The amount of blood in the basal cistern and the presence of intraventricular blood correlate with the risk of developing clinically significant cerebral vasospasm. • The diagnosis can be made clinically, angiographically, or by transcranial Doppler (TCD). • The resulting decrease in cerebral blood flow (CBF) can lead to ischemia and infarction, and is a main cause of permanent neurologic injury and death after SAH. • Up to 70% of patients with SAH demonstrate angiographic evidence of vasospasm. • Clinical symptoms of cerebral ischemia and infarction develop in 30–40% of patients.

Up to 1.2 million patients per year are estimated to have permanent or fatal neurologic injury as a result of vasospasm following an intracranial bleed. Morbidity

Vasospasm may be detectable for up to 14 days after SAH. Symptoms can range from subtle focal deficits to debilitating neurologic injury, and typically peak between 3 and 12 days. Mortality

The risk of death in patients who develop vasospasm following SAH can reach 3 times that of patients who do not. • The cause of vasospasm following SAH is still unknown. It is thought that the presence of blood in the subarachnoid space can lead to cerebral vasoconstriction. Various components and breakdown products have been proposed as mediators. Oxyhemoglobin has several properties that make it one of the most likely candidates. • The Fisher grade on initial presentation is highly predictive of the development of clinically significant cerebral vasospasm. The presence of thick blood in the basal cistern and intraventricular or intraparenchymal hemorrhage is associated with the highest risk of poor neurologic outcome. • Although patients > 68 years of age are more likely to develop symptomatic vasospasm, younger patients are more likely to show angiographic evidence of vasospasm. • Female gender, hypertension, elevated intracranial pressure (ICP), smoking, and cocaine use also increase the risk of developing vasospasm. • Contraction of smooth muscle in the vessel wall leads to lumen narrowing and restricted blood flow. Cerebrovascular resistance shifts from the penetrating arterioles to the major branches of the Circle of Willis, which undermines the brain’s ability to autoregulate. BP then becomes the main determinant of CBF beyond the affected vessels. • There is also evidence that histological changes occur. These include thickening of all three

vascular layers, periadvential inflammation, and myointimal hyperplasia. However, the extent of the clinical significance of these findings is unclear.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Since autoregulation in the brain is impaired, hypotension should be avoided throughout the perioperative period; flow is pressure dependent. • Hypertension, hypervolemia, and hemodilution (triple-H therapy) can potentially minimize the risk of ischemia; however, it is associated with a significant risk of morbidity that must be carefully weighed against this unproven benefit. Invasive monitoring is recommended. • Consider avoiding volatile agents. Uncoupling of CBF and cerebral metabolic rate of oxygen consumption (CMRO2) may lead to lower cerebral vascular resistance in unaffected areas of the brain. This can decrease perfusion distal to spastic vessels. Intravenous agents such as propofol have a more favorable profile in the setting of vasospasm.

PREOPERATIVE ASSESSMENT • Decreased level of consciousness is the most common finding indicative of cerebral vasospasm. • Rarely, patients can present with focal neurologic findings without a global decrease in level of consciousness.

Cerebral vasospasm usually occurs within 2 weeks of SAH. Patients often have comorbid conditions associated with cerebrovascular disease, such as hypertension and smoking.

Focal neurologic deficits depend on the affected vessels. Associated findings are contralateral and can involve cranial nerves, motor function, and sensory function. Brainstem function and coordination are usually intact. TREATMENT HISTORY

• Patients with cerebral vasospasm may have had an aneurysm surgically clipped or endovascularly embolized. • Triple-H therapy is widely used.

MEDICATIONS

• Most patients with symptomatic vasospasm are treated with calcium channel blockers. Nimodipine has been shown to provide some benefit. Its intravenous equivalent nicardipine, on the other hand, has demonstrated inconclusive results. • Other medications that have been experimented with include fibrinolytic therapy, sodium nitroprusside, magnesium, cyclosporine, erythropoietin, and clazosentan. • Electrolytes should be checked, especially if the patient is suspect to have developed cerebral salt wasting syndrome or SIADH. • CBC • EKG: “Canyon T-waves" are common. Nonspecific T-wave changes, QT prolongation, STsegment depression, and U waves can also occur. The EKG changes usually do not reflect the degree of myocardial dysfunction, nor do they predict the development of cardiac

failure. The EKG should be monitored for potential lethal dysrhythmias, including Torsades de Pointes, in the setting of QT prolongation, which can frequently occur in patients with severe SAH. • Elevated troponin levels are common but are usually lower than those associated with cardiac ischemia.

CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular – Cerebral vasospasm may, in and of itself, lead to hypovolemia for unknown reasons. – Reversible myocardial stunning can occur in the setting of SAH. Its severity is associated with the degree of neurologic injury. – Aneurysms occur more frequently in certain genetic conditions such as polycystic kidney disease, coarctation of the aorta, fibromuscular hyperplasia, and connective tissue disorders. • Pulmonary function should be assessed in patients who are smokers. Also, patients with compromised neurologic status are at an increased risk of aspiration. • Patients on triple-H therapy are at risk of developing cardiac, pulmonary, and renal complications.

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Delay in surgical clipping after SAH or interventional radiologic procedures to treat vasospasm can have severe consequences, including rebleeding and devastating neurologic injury. • If ischemic heart disease is suspected, an echocardiogram may be helpful in guiding intraoperative management.

CLASSIFICATIONS

• The Fisher grade classifies the appearance of SAH on CT scan and correlates it to the risk of clinically significant vasospasm: – Grade 1: No hemorrhage evident – Grade 2: SAH < 1 mm thick – Grade 3: SAH > 1 mm thick – Grade 4: SAH of any thickness with intraventricular hemorrhage or parenchymal extension.

TREATMENT Premedications

Anxiolytics are seldom necessary and can interfere with neurological exam. Special Concerns for Informed Consent

Since vasospasm can affect sensorium, informed consent may not be obtainable from the patient. It is wise to identify a surrogate decision maker in light of the significant risk of neurologic complications.

Choice of Anesthesia

General endotracheal Monitors

• Standard ASA monitors • An arterial line should always be used, and can be most helpful if placed before induction. • Central line monitoring may be useful to help guide fluid management (especially in elderly patients) or pressor support, as well as in the setting of myocardial dysfunction.

Induction/Airway Management

• Specific anesthetic agents should be selected on a case-by-case basis to fulfill the anesthetic goals described above. • Poorly organized clot in the early stages after SAH is particularly prone to rebleeding secondary to systolic hypertension and tachycardia. A rebleed during induction is often lethal. It is therefore extremely important to avoid excessive, sustained systolic hypertension and secure the airway quickly in these patients. On the other hand, prolonged hypotension should also be avoided to minimize the risk of ischemia.

Maintenance

• Inhaled agents can increase the CBF. This undermines brain relaxation and the ability to maintain a high cerebral perfusion pressure (CPP); alternatively, propofol has a more favorable profile. • Elevation of the mean arterial pressure (MAP) may be achieved with phenylephrine or dopamine. • Recent evidence suggests that hyperventilation should be avoided unless absolutely necessary to temporarily decrease ICP; vasoconstriction can further worsen ischemia. • The dose and timing of mannitol administration varies per surgeon preference. Usual doses range between 1 and 2 g/kg, and may be given immediately following induction or on initial skin incision. Surgeons may also request an additional dose at the time of dural opening.

Extubation/ Emergence

• The objective is for the patient to be able to participate in a neurological exam yet comfortable enough to minimize reaction to extubation. Using a relatively low dose of fentanyl 15–20 minutes before extubation can be highly effective; alternatively a remifentanil infusion may be considered. Intravenous lidocaine can also be used to suppress the coughing reflex. • Hypertension and tachycardia on emergence is common and is usually not related to painful stimuli. This is usually best treated with beta-blockers. • Prophylaxis against postoperative nausea and vomitting should be given to decrease the risk of postoperative bleeding secondary to the sudden and severe rise in ICP associated with vomiting.

FOLLOW-UP

BED ACUITY

Patients at high risk for vasospasm, based on clinical and radiologic findings post-SAH, should be monitored at least every 2 hours for neurologic changes. This is usually done in an intensive care unit (ICU) setting. Lower risk patients can be monitored every 4 hours. MEDICATIONS/LAB STUDIES/ CONSULTS

• Patients at risk for cerebral vasospasm are almost always placed on a nicardipine drip. They may further be placed on a pressor such as norepinephrine to maintain MAPs that are 10– 20% above baseline. • Daily labs should include CBC, chemistry panel, and measures of urine function. • TCD can be a useful screening tool but is fraught with technical limitations. Magnetic resonance angiography (MRA) is more reliable. Cerebral angiography is the gold standard for diagnosis. • Consults should be obtained as clinically indicated if cardiac, pulmonary, or renal complications are detected. • One should be prepared for the risk of significant bleeding intraoperatively. This can lead to malignant brain swelling with devastating consequences. Brain protection and brain relaxation techniques should be immediately instituted in such an event. • As with any neurosurgical procedure, there is risk of intracranial hemorrhage. Patients should be monitored closely for changes in neurological function for at least 24 hours postoperatively. • There is also the potential for developing an intraoperative infarct, especially if hypotension is maintained. This may present in the postoperative period as delayed emergence, altered mental status, or focal neurologic deficits. • Any of the above complications resulting in neurologic injury can lead to compromised airway reflexes, which puts the patient at risk for aspiration. • Triple-H therapy can lead to additional complications, such as cerebral edema, cardiac ischemia, pulmonary edema, and hyponatremia. Patients should be closely monitored in an ICU. Central venous pressure monitoring is recommended.

REFERENCES

1. Alaraj A, Charbel FT, Amin-Hanjani S. Peri-operative measures for treatment and prevention of cerebral vasospasm following subarachnoid hemorrhage. Neurol Res. 2009;31(6):651–659. 2. Lee KH, Lukovits T, Friedman JA. “Triple-H” therapy for cerebral vasospasm following subarachnoid hemorrhage. Neurocrit Care. 2006;4:68–76. • Craniotomy, cerebral aneurysm clipping • Cerebral embolization • Cerebral blood flow

CODES

ICD9

435.9 Unspecified transient cerebral ischemia ICD10

G45.9 Transient cerebral ischemic attack, unspecified

CLINICAL PEARLS

• The extent of SAH and the patient’s subsequent neurologic status can predict the likelihood of developing cerebral vasospasm. • A change in the level of consciousness after SAH or postaneurysm clipping should always be investigated for the possibility of vasospasm in the first 2 weeks. • It is important to avoid prolonged periods of hypotension in order to minimize the risk of ischemia. • The benefit of triple-H therapy has yet to be proven; additionally, it can lead to significant complications, especially if the patient is not monitored closely.

CEREBROSPINAL FLUID Brooke Albright, MD, MAJ, MC

BASICS DESCRIPTION

Cerebrospinal fluid (CSF) is a clear, colorless fluid surrounding the central nervous system (CNS) that provides physical protection and a chemically stable environment. PHYSIOLOGY PRINCIPLES

• CSF is a direct extension of the extracellular fluid compartment of the CNS. – The volume of CSF in an adult is ∼150 mL and in infants 50 mL. – It is secreted and absorbed continuously throughout the day, with daily production in adults ∼500–600 mL. – Absorption is pressure dependent and linear over a wide range. • CSF provides nourishment to the brain as well as assists in removing by-products of neuronal metabolism. • Electrolyte composition – Differs from that of plasma due to the blood–CSF barrier, which allows free diffusion of water, gases, and lipid-soluble compounds but requires active or passive transport of glucose, amino acids, and ions. – CSF is composed primarily of sodium, chloride, and bicarbonate. – Proteins are largely excluded from CSF. See Table 1 for comparison of CSF to plasma (1). Table 1 Composition of CSF: Plasma

• A decrease in plasma pH results in a similar decrease in CSF pH due to the ability of carbon dioxide to easily cross the blood–brain barrier.

ANATOMY

• Site of production. Ninety percent of CSF is formed from blood in the choroid plexus of the lateral, 3rd, and 4th ventricles. The remaining 10% is formed from brain substance. • Nutrients reach neurons and glial cells either by – Crossing the blood–CSF barrier that is regulated by the choroid plexus or, – Crossing the blood–brain barrier of cerebral capillaries. • The blood–CSF barrier is formed by impermeable “tight junctions” between epithelial cells that regulate the diffusion of certain molecules. • Once molecules enter the CSF, they travel to the interstitial fluid surrounding neurons and glial cells by diffusing through a “leaky” ependymal layer. • Arachnoid villi (granulations) in the superior sagittal, transverse, and other venous sinuses absorb the majority of CSF. The rest is absorbed by veins in the cranial and spinal subarachnoid spaces and lymphatic vessels of the cranial and spinal nerves.

DISEASE/PATHOPHYSIOLOGY

• Normal intracranial pressure (ICP) is usually 5–15 mm Hg and is comprised of – Intracranial CSF – Brain tissue – Intracranial blood (arterial and venous) • Compensation. An increase in any one component of intracranial volume must be offset by a decrease in another component to prevent an increase in ICP. Initially, as the intracranial volume increases, CSF is shifted from the cranium to the spinal subarachnoid space, in order to prevent an increase in ICP. • Increased ICP. If the intracranial volume continues to increase beyond the ability of the CSF to translocate, then an exponential rise in ICP is likely with associated clinical symptoms. • Nonobstructive hydrocephalus is a condition of increased production or decreased absorption of CSF. Obstructive or noncommunicating hydrocephalus occurs when there is a blockage anywhere along the path of CSF flow (e.g., tumor, congenital structural abnormalities, infection, and trauma). Treatment depends on the etiology of the hydrocephalus. In certain situations, the placement of a CSF shunt is indicated in order to translocate CSF and lower the ICP, thereby maintaining cerebral perfusion (CPP = MAP − ICP, where CPP is cerebral perfusion pressure, MAP is mean arterial pressure). • CSF leak. Leakage of CSF into the nasal, oral, ear, or dermal sinus cavities can result from trauma, intracranial surgical procedures, infection, hydrocephalus, congenital malformations, or neoplasms. Interruption of the anterior cranial fossa floor allows leaks of CSF through the cribriform plate. It most commonly presents as otorrhea or rhinorrhea and is exacerbated by a Valsalva-type maneuver (coughing, sneezing, bending, heavy lifting, and straining). • Postdural puncture headache (PDPH) occurs most frequently after a “wet tap” and is a phenomenon related to the spontaneous loss of CSF from the subarachnoid to the epidural space. – Most common complication of neuraxial anesthesia due to a knick in the dura from a relatively large sized needle. – Manifests as pain or stiffness in the neck, nausea or emesis, diplopia due to unilateral or bilateral sixth nerve palsy, dizziness, changes in hearing, visual blurring, photophobia, intrascapular pain, facial numbness or weakness, galactorrhea, and/or radicular upper limb symptoms. – Debate exists over the timing and use of epidural blood patches in the treatment of PDPHs. Current literature does not support prophylactic epidural blood patches over other treatments because there are too few trial participants to allow reliable conclusions to be drawn. However, therapeutic epidural blood patch showed a benefit over conservative treatment based on available evidence (2)[A].

PERIOPERATIVE RELEVANCE

• Neuraxial anesthesia involves the injection of local anesthetics and/or narcotics either into the intrathecal space where CSF bathes the spinal cord (spinal anesthesia) or into the epidural space where the nerves exit the spinal cord through the dura. Neuraxial anesthesia is used primarily in surgeries involving the lower extremities, abdomen, and/or pelvis. Potential benefits of neuraxial techniques include reduced blood loss, blood clots, incisional pain with respiration, atelectasis, pneumonia, and need for narcotics; as well as a quicker

return of bowel function, ambulation, and patient satisfaction (3)[A]. For Cesarean section, it is considered advantageous over a general anesthetic in regard to the simplicity of the technique, reduced risk of systemic toxicity to mother and fetus, and maternal satisfaction. There is no difference between epidural and spinal anesthesia shown with respect to failure rate, need for additional intraoperative analgesia, conversion to general anesthesia intraoperatively, maternal satisfaction, and neonatal intervention (4)[A]. • Neuraxial local anesthetics used for spinal anesthesia are characterized according to their baricity (e.g., hypobaric, isobaric, or hyperbaric), which is the ratio of the density of the solution at a specified temperature compared to the density of CSF (1.0001–1.0005 at 37°C) (5). – Hypobaric solutions (density FRC). • General anesthesia reduces FRC by 0.4–0.5 L (5)[A]; this is presumed to occur from a loss of respiratory muscle tone and decreased chest wall compliance. Additionally, laying supine can reduce FRC by up to 1 L. When the FRC is reduced in this manner below CC, air trapping and shunting occurs. This has been hypothesized to be the cause of increased A-a gradient [P(A-a)O2] during surgery (6). This effect is further enhanced in patients with a baseline diminished FRC or elevated CC. Position and anesthesia do not affect the CC; however, they reduce the FRC, bringing it closer to the CC. • PEEP is often implemented to increase the FRC and improve the A-a gradient [P(A-a)O2] (5)

[A]. However, its use is limited since PEEP affects upper lung zones greater than lower zones. Conversely, airway closure occurs to a greater degree in the lower lung zones. In addition, an increase in intrathoracic pressure from PEEP may impede venous return and result in deterioration of cardiac output. • “Alveolar recruitment” may be achieved by applying a limited number of double TV breaths in an attempt to reopen closed airways and alveoli. An inflation pressure up to 30–40 cm H2O may be required (7)[A]. This must be done with caution as hemodynamic instability can result from an increase in intrathoracic pressure and decreased venous return. • Sitting a patient upright, or reverse Trendelenburg, >30° may increase FRC. This is useful

when trying to maximize respiratory function in the immediate postoperative period including extubation. • FRC remains decreased into the postoperative period. With reduced FRC, lung volumes are more likely to fall below CC during resting TVs, contributing to post-operative hypoxemia.

EQUATIONS

• CC = CV + RV • FRC = ERV + RV

REFERENCES

1. Wahba WM. Influence of aging on lung function—Clinical significance of changes from age twenty. Anesth Analg. 1983;62:764.

2. ilic-Emili J, Torchio R, D’Angelo E. Closing volume: A reappraisal (1967–2007). Eur J Appl Physiol. 2007;99:567–583. 3. Jubber AS. Respiratory complications of obesity. Int J Clin Pract. 2004;58:573. 4. Leblanc P, Ruff F, Milic-Emili J. Effects of age and body position on “airway closure” in man. J Appl Physiol. 1970;28:448–451. 5. Hedenstierna G, Edmark L. The effects of anesthesia and muscle paralysis on the respiratory system. Intensive Care Med. 2005;31:1327–1335. 6. Wahba RWM. Perioperative functional residual capacity. Can J Anaesth. 1991;38:384–400.

7. Rothen HU, Sporre B, Engberg G, et al. Re-expansion of atelectasis during general anesthesia: a computed tomography study. Br J Anaesth. 1993;71:788–795. 8. Nield MA, Hoo GWS, Roper JM, et al. Efficacy of pursed-lips breathing—A breathing pattern retraining strategy for dyspnea reduction. J Cardiopulm Rehabil Prev. 2007;27:237–244.

ADDITIONAL READING

• Alveolar-arterial gradient • Functional residual capacity • Spirometry • V/Q matching

CLINICAL PEARLS

• An increase in CC signifies that airway closure occurs at higher lung volumes. In other words, while exhaling, closure occurs earlier. • Premature small airway closure occurs as a result of decreased FRC and/or increased CC. It results in unventilated distal segments of lung that contribute to shunt and hypoxemia. • It is important to recognize patients at risk for early distal airway closure, such as those with advanced age, obesity, lung disease, or smoking history. • Patients with advanced COPD use pursed lip breathing to stabilize small airways and maintain their patency (8)[A]. Recognizing this breathing pattern can help identify patients

with advanced lung disease.

COCAINE ABUSE Nabil Elkassabany, MD

BASICS DESCRIPTION

• Cocaine is one of the oldest known psychoactive substances. Coca leaves have been chewed and ingested for thousands of years and the purified chemical, cocaine hydrochloride, has been a substance of abuse for more than 100 years (1). • Cocaine is available as a street drug in the form of a fine, white, crystalline powder. It is known as “coke,” “C,” “snow,” “flake,” or “blow.” It is frequently mixed with amphetamine or heroin; the latter combination is known as a “speedball.” • Today, it is used, legitimately, for its combined local anesthetic and vasoconstrictive effects (e.g., eye and ENT procedures and laceration repair in the emergency department); and is a Schedule II drug. It has been largely replaced by other local anesthetics that provide the same effects without the addictive potential. PHYSIOLOGY PRINCIPLES

• Mechanism of action. Blocks the reuptake of norepinephrine into the sympathetic nerve terminals; thus creates a sympathomimetic state (2). • Classification. Local anesthetic; ester • Pharmacokinetics – Peak plasma levels are attained within 1–3 minutes when inhaled or administered intravenously. – Plasma half-life ranges from 60 to 90 minutes – Metabolism is via plasma esterases. By-products include benzoylecgonine, ecgonine methyl ester (EME), and norcocaine. Some metabolites can be detected in the urine 3–5 days after ingestion. • Routes of administration include oral, intravenous, and transmucosal.

PHYSIOLOGY/PATHOPHYSIOLOGY

• CNS – Acute effects: Euphoria and heightened perception of space or time, irritability, restlessness, hyperthermia, and seizures (2). – Chronic effects: Physical dependence and addiction develop rapidly. Focal neurological deficits and coma have been reported; potential causes include vasoconstriction (transient ischemic attacks) and cerebral hemorrhage. – Withdrawal symptoms include fatigue, mental depression, and drug cravings. • Cardiac system – Acute effects: Tachycardia, hypertension, and coronary artery spasm can result in myocardial ischemia and/or myocardial infarction. Prolonged QT interval and ventricular arrhythmias can also result (3).

– Chronic effects: Left ventricular hypertrophy, systolic dysfunction, and dilated cardiomyopathy. • Respiratory system – Acute effects: Nonspecific respiratory complaints may be reported. Nasal bleeding and perforation of the nasal septum can result from snorting cocaine. “Crack lung” is a form of acute lung injury that has been reported after cocaine abuse (4). – Chronic effects: Diffuse alveolar infiltrates, alveolar damage, pulmonary infarction, and noncardiogenic pulmonary edema have been reported.

Pregnancy Considerations

• Low birth weight and premature delivery • Fetal intrauterine growth retardation (IUGR) has been attributed to decreased uteroplacental perfusion.

Pediatric Considerations

• Cognitive impairment and attention deficits are frequently encountered in children born to cocaine-abusing mothers. • Cocaine abuse among school children should not be overlooked. Recent data suggest declining numbers of 30-day prevalence of cocaine abuse among 8th, 10th, and 12th graders from its peak use in the late 1990s, as well as significant declines in past-month use among 10th and 12th graders from 2008 to 2009 (1). PERIOPERATIVE RELEVANCE

• Anesthetic implications of acute cocaine toxicity include the following: – Cardiac. An increased risk of perioperative myocardial ischemia, congestive heart failure (CHF), and ventricular arrhythmias. – CNS. An increased minimum alveolar concentration (MAC) requirement of inhaled anesthetic. • Preoperative evaluation – Obtain a detailed and complete history of substance abuse in every patient. – In patients with a positive history of abuse, associated comorbidities such as hypertension, coronary artery disease (CAD), arrhythmias, and CHF should be assessed. – Examine the nares – Labs. Urine drug screening can detect metabolites for up to 72–96 hours based on the halflife of the metabolite being tested. • Previously, cancellation was recommended for elective surgery in the event of a positive drug screening due to the potentially increased risk of perioperative myocardial ischemia. Recent evidence suggests that general anesthesia for elective procedures is possibly safe if the patient lacks symptoms and signs of acute cocaine toxicity on physical examination and has a QT interval 2 μg/kg/min (cyanide is produced faster than endogenous mechanisms can handle). • Cyanide toxicity may be more likely if a patient has hepatic dysfunction; thus consider reducing above-mentioned dosages. Thiocyanate toxicity may be more likely if there is renal dysfunction.

DIAGNOSIS • Patients can present with nonspecific signs and symptoms; furthermore there is no quick blood cyanide test to confirm toxicity. • Hypoxia, elevated lactic acid levels, and metabolic acidosis are considered to be the hallmarks of cyanide poisoning. • Perioperatively, anesthesia providers should maintain a high index of suspicion, presumptive diagnosis, and rule out cyanide toxicity in patients exposed to fire smoke, especially when the mouth and nares are tinged with soot (in addition to carbon monoxide poisoning). Additionally, patients on nitrovasodilators may also present with clinical symptoms and should be ruled out if appropriate • Central nervous system: Headache, confusion, dizziness, flushing, vertigo, seizures, and coma. At non-fatal levels, patients report the smell of almonds and feeling apprehensive. Survivors of cyanide toxicity may develop Parkinsonism due to damage to the basal ganglia. • Cardiac: Initial tachycardia and hypertension (sympathetic response to metabolic acidosis), followed by bradycardia and hypotension, AV block, and cardiovascular collapse. • Respiratory: An early sign is hyperventilation, which can increase the absorbed dose. This is followed by bradypnea, pulmonary edema, absence of cyanosis (due to increased mixed venous oxygen saturation), apnea, and respiratory arrest • GI: Vomiting, abdominal pain • Renal and hepatic failure • Dermatologic: Flushing and cherry red color of skin are late findings. • Chronic cyanide exposure can result in headache, Leber’s neuropathy, and tobacco amblyopia. Bright red retinal veins may be noticed due to elevated venous oxygen concentration

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Blood cyanide concentration. Laboratory measurement provides definitive diagnosis. Because results are not immediate or “on-the-spot,” they cannot aid in initial management. However, samples should be sent as soon as possible due to cyanide’s rapid metabolism and instability in blood samples. Toxicity threshold ranges from 0.5 to 1 mg/L, and the lethal threshold ranges from 2.5 to 3 mg/L • Arterial blood gas reveals a severe metabolic acidosis (low pH and low sodium bicarbonate) due to anaerobic metabolism with lactic acid production – PaO2 is high (represents cell’s inability to extract and utilize arterial oxygen, despite cell hypoxia). – Alveolar–arterial (A–a) gradient 15; gap is affected by changes in unmeasured ions, in this case lactic acid. Bicarbonate buffers and binds to lactic acid, thus decreasing its

concentration. • Mixed venous oxygen saturation. Venous blood has an abnormally high oxygen saturation that reflects tissue and cell inability to utilize oxygen (despite hypoxia).

Monitors

• Pulse oximetry: Normal, despite cellular hypoxia • EKG: Tachycardia followed by bradycardia, AV block • Noninvasive BP: Hypertension followed by hypotension. • Arterial line: Placement allows for frequent arterial blood gas measurements to follow therapy.

DIFFERENTIAL DIAGNOSIS

• Carbon monoxide poisoning • Tricyclic antidepressant poisoning • Isoniazid overdose • Organophosphate poisoning • Salicylate poisoning

TREATMENT • Cyanide poisoning is rapidly lethal; therefore, prompt recognition and early initiation of treatment are necessary to save live. • Decontamination. Prehospital care involves removing the victim from the source of cyanide to an area of fresh air and decontaminating the victim (removal of contaminated clothing, rinsing of skin if dermal exposure, gastric lavage and activated charcoal if ingested). If administering a nitrovasodilator (SNP), infusion should be immediately discontinued. • Supportive care. Administration of 100% oxygen can hasten respiratory excretion of cyanide and reactivate mitochondrial enzymes. Furthermore, carbon monoxide poisoning also requires high inspired oxygen and intubation (particularly with smoke inhalation injury due to the potential for airway swelling). • Benzodiazepines for seizure control and sodium bicarbonate can be administered to treat metabolic acidosis (pH 60 mEq/L are considered positive. • Preoperative studies – CBC/chemistry panel – Coagulation studies: PT, PTT, INR – LFTs may reveal posthepatic obstruction due to increased bile viscosity. – Baseline ABG – Chest x-ray (CXR): Hyperinflation, pneumothorax, peribronchial thickening – CT chest: Bronchiectasis, apical blebs – Pulmonary function tests (PFTs): Obstructive pattern with a decrease in FEV1 and peak expiratory flow, and increase in residual volume (RV).

CONCOMITANT ORGAN DYSFUNCTION

• Airway manifestations include an increased incidence of nasal polyps and chronic sinusitis. Nasal mucosa hypertrophy and hyperplasia may also be present. • Pulmonary disease manifests as airway obstruction, bacterial colonization, atelectasis, and hypoxia. It results from an increase in goblet cells and mucus production. PFTs demonstrate an obstructive pattern with decreased FEV1, vital capacity, and peak flows as well as

increased RV. – Although there are multiple hypotheses, there is no consensus on why bacterial colonization occurs, most commonly with organisms Pseudomonas aeruginosa, Haemophilus influenza, and Staphylococcus aureus. – Chronic disease leads to pulmonary hypertension and cor pulmonale; patients often require lung transplantation. • Pancreatic disease manifests as exocrine and endocrine dysfunction secondary to impaired bicarbonate secretion. The retention of digestive enzymes can cause autodigestion with an

increased risk for pancreatitis. – Pancreatic exocrine dysfunction describes protein and fat malabsorption, failure to thrive, deficiency of fat soluble vitamins (A, D, E, K) – Pancreatic endocrine dysfunction describes pancreatic beta-cell destruction and can often lead to diabetes mellitus (DM). Approximately 30% of patients develop DM by age 30 (2). • Hepatobiliary disease manifests as cholelithiasis and cholecystitis from pancreatic duct stenosis as well as cirrhosis, and hepatocellular carcinoma. Cirrhosis is the second most common cause of death and is present in 10% of patients; abnormal LFTs are seen in 33% of patients; fatty infiltration is present in 70% of patients. • GI tract disease presents as meconium ileus; thickened feces can result in distal intestinal obstruction syndrome. There is a high incidence of GERD. • Musculoskeletal abnormalities present as low bone mineral density, kyphosis, scoliosis, and rib fractures. This results from a combination of decreased vitamin D absorption, lack of exercise, chronic steroid therapy, and low androgen levels. • Coagulation abnormalities can manifest from pancreatic dysfunction (impaired absorption of vitamin K) and hepatic disease. • (In)Fertility. The majority of males are infertile due to the absence of a vas deferens. Females have thick cervical mucus that often prevents pregnancy.

Pregnancy Considerations

• Increased incidence of preterm labor. • Gravid patients are more susceptible to right heart failure.

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Acute pulmonary exacerbation • LFTs greater than 1.5 times normal should be investigated (2)[C]. • Coagulopathies should be corrected

CLASSIFICATIONS See ICD9 section

TREATMENT PRE-HOSPITAL Premedications

• Bronchodilators should be considered preoperatively when signs of bronchoconstriction or wheezing are present (2)[C]. • Mucolytics (DNAses) can be used to improve airway clearance. • Anticholinergics may further dry mucous and secretions; consider avoiding. • Acid reducers (H2 blockers) should be considered in patients with poorly controlled GERD (4)[C].

Special Concerns for Informed Consent

The potential for postoperative respiratory failure and the need for ventilator support

INTRAOPERATIVE CARE Choice of Anesthesia

Consider regional or neuraxial anesthesia to limit airway manipulation or as an adjunct for postoperative pain control (4)[C].

Monitors

• Consider arterial line for frequent ABGs or blood glucose levels in diabetics • TEE in patients with right heart failure

Induction/Airway Management

• Sedation should be considered whenever possible to avoid airway manipulation and mechanical ventilation. • For general anesthesia, IV or inhalational induction may be used. Patients may exhibit a prolonged inhalation induction secondary to increases in RV. If an inhalation induction is chosen, consider sevoflurane (favorable blood:gas solubility compared to isoflurane and less irritating to the airways than desflurane). Ketamine can increase secretions and should be avoided (4). • Laryngeal mask airways have the potential benefit of reduced airway reactivity; drawbacks include the inability to protect against GERD or airway secretions, provide significant positive pressure ventilation, or ventilate and oxygenate in the event of laryngospasm. • Avoid nasotracheal intubation (and nasal airways) due to nasal mucosa hyperplasia. • Large single lumen tubes are preferred to allow for lavage or bronchoscopy. • Neuromuscular blockade may lead to airway obstruction. • A RSI may be considered in patients with uncontrolled GERD.

Maintenance

• A balanced technique with volatile or total IV anesthesia. Volatile agents have the potential benefit of providing bronchodilation. • Humidifying inhaled gases can reduce thickening of secretions. • Frequent intraoperative suctioning should be considered. • Treat bronchospasm with bronchodilators, deepening of the anesthetic (volatile agent), epinephrine subcutaneous or IV, terbutaline, or theophylline as appropriate. • Avoid nitrous oxide due to an increased risk of pneumothorax (4)[C] • Opioids should be limited due to respiratory depression. Attempt to treat postoperative pain with NSAIDS and/or regional/neuraxial blocks (2)[C].

Extubation/Emergence

• Ensure adequate reversal of NMBDs • Endotracheal suctioning, alveolar recruitment measures should be performed; consider chest physiotherapy (2)[C]. • Position the patient with the head of the bed elevated 30–40° for extubation (4)[C]. • Early extubation improves morbidity and mortality (2)[C].

POSTOPERATIVE CARE

BED ACUITY

• Patients with mild disease and less complex procedures may be discharged home after being monitored in the PACU (2)[C]. • Patients with more severe pulmonary disease or those undergoing more invasive procedures should be monitored either in an intensive care unit (ICU) or monitored bed (4)[C].

MEDICATIONS/LAB STUDIES/CONSULTS

• Chest physiotherapy, CXR • Consider pulmonary consultation if postoperative mechanical ventilation is required.

COMPLICATIONS

• Respiratory depression, airway obstruction, atelectasis, pneumonia, pneumothorax • Postoperative jaundice

REFERENCES 1.

Cystic Fibrosis Clinical Validity. Sept 10 2007. http://www.lungusa.org/assets/documents/ALA_LDD08_CF_FINAL.PDF. Accessed on Jan 26, 2011. 2. Huffmyer JL. Perioperative management of the adult with cystic fibrosis. Anesth Analg. 2009;109(6):1949–1961. 3. Farrell PM. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic fibrosis foundation consensus report. J Pediatr. 2009;153(2):S4–S14. 4. Della Rocca G. Anaesthesia in patients with cystic fibrosis. Curr Opin Anaesthesiol. 2002;15(1):95–101.

ADDITIONAL READING

• Davis PB. Cystic fibrosis since 1938. Am J Respir Crit Care Med. 2005;173:475–482.

See Also (Topic, Algorithm, Electronic Media Element) • Ciliary function • Chloride • Cor pulmonale

CODES ICD9 • 277.00 Cystic fibrosis without mention of meconium ileus • 277.01 Cystic fibrosis with meconium ileus • 277.02 Cystic fibrosis with pulmonary manifestations ICD10 • E84.0 Cystic fibrosis with pulmonary manifestations

• E84.9 Cystic fibrosis, unspecified • E84.11 Meconium ileus in cystic fibrosis

CLINICAL PEARLS

• Optimize preoperative pulmonary function; intraoperative and postoperative management should aim at clearing secretions and managing as an “obstructive pulmonary disease” patient. Extubation is desired but must be balanced against risks. • Assess and treat CF-associated comorbidities.

CYSTOSCOPY Jonathan Anson, MD

BASICS DESCRIPTION General

• A cystoscopy is performed to visualize and examine the inner surface of the urethra and bladder; it is an endoscopic procedure. • The cystoscope is either flexible or rigid and is inserted into the urethra. The distal end has either a lens or fiberoptic apparatus to allow visualization via a proximal eyepiece or monitor, respectively. – To enhance visualization, sterile fluid is used to distend and stretch the bladder. – The cystoscope has extra channels that allow for instruments to be inserted in order to perform biopsies, stent placement, dilation, laser procedures, stone removal, or intravesical administration of medications (e.g., Bacillus-Calmette-Guérin (BCG): A live, attenuated strain of Mycobacterium bovis as adjuvant treatment for nonmuscle invasive bladder cancer). • Modifications/enhancements of this endoscopic procedure include transurethral resection of bladder tumor (TURBT) and transurethral resection of the prostate (TURP). A resectoscope is utilized to remove the tissue. • Indications include frequent urinary tract infections (UTIs), hematuria, unusual cells seen in urine samples, chronic pelvic pain, cystitis, dysuria, blockage from the prostate, stones, or abnormal growth/tumor/polyps. • A ureteroscope is a longer, thinner instrument that can be used to visualize and examine the ureters and upper urinary tract structures. Position

• Lithotomy • Often requires the Trendelenburg position

Incision

Natural orifice procedure via the urethra Approximate Time

5 minutes to 1 hour EBL Expected Minimal

Hospital Stay

Pathology dependent. Many procedures are performed on an outpatient basis.

Special Equipment for Surgery • Cystoscope • Ureteroscope • Resectoscope

EPIDEMIOLOGY Incidence

Approximately 67,000 new cases of bladder cancer per year. Prevalence

Bladder cancer is three times more common in males than females; more common in patients >55 years old; and twice as common in Caucasians as African Americans. Morbidity

• Pain • Urinary tract infection • Urinary tract obstruction • Bladder, urethral, or urethra perforation or injury

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The lithotomy and Trendelenburg positioning can result in decreased functional residual capacity (FRC) and decreased pulmonary compliance. • Akinesis should be maintained during the procedure to reduce the risk of bladder or ureteral perforation. Leg movement should be prevented at the end of the procedure and until the patient is out of the lithotomy position to avoid hip injury. • Patients are often elderly and with multiple comorbidities. Geriatric considerations and adjustment of drug dosages are often necessary. • Autonomic hyperreflexia can occur in patients with spinal cord injury; thus, neuraxial or general anesthesia is needed to prevent this occurrence with bladder distension. • If laser therapy is used, protective goggles for the patient and operating room personnel should be utilized.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Often asymptomatic • May present with hematuria • Abdominal pain, flank pain • Urinary frequency, urgency, or dysuria • Anuria if there is urinary tract obstruction

History

• Hematuria • Calculi

• Bladder tumor/cancer • UTI • Urinary tract obstruction • Hydronephrosis

Signs/Physical Exam

• Tachycardia or fever may suggest an infectious process • Cardiopulmonary exam

MEDICATIONS

• Alpha blockers for benign prostatic hypertrophy (BPH) can compound hypotensive effects of anesthetics • 5-alpha-reductase inhibitors for BPH • Antimuscarinics for overactive bladder • Drugs for erectile dysfunction are nitric oxide derivatives and can compound hypotensive effects of anesthetics • Anticoagulants and blood thinner for coexisting conditions may contraindicate neuraxial techniques. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Metabolic panel if acute kidney injury is suspected • CBC and coagulation factors if hematuria • Urinalysis and urine culture, if UTI • EKG and chest x-ray as per standard criteria • Renal ultrasound for urinary tract obstruction and hydronephrosis • Abdominal plain film or CT scan may show calculi

CONCOMITANT ORGAN DYSFUNCTION

• Acute kidney injury, especially in the face of urinary tract obstruction (postrenal failure) • Chronic kidney disease • Patients with prosthetic heart valves or atrial fibrillation may develop hematuria from heparin or warfarin. • Urosepsis in patients with UTI or pyelonephritis.

Pregnancy Considerations

• The incidence of calculi is the same in pregnancy as the general population. When it does occur, it is seen more commonly in the 2nd and 3rd trimester. Stones typically pass spontaneously but cystoscopy with stent placement may be necessary if the patient is septic or has a urinary tract obstruction. The complication rate of ureteroscopic stone removal is no different in pregnant patients than in nonpregnant patients (1)[A]. • A neuraxial or general technique can be utilized. Spinal and epidural blocks can decrease the amount of medication administered and should be considered in patients who are early in pregnancy or have a potentially difficult airway. • Goals should be to avoid teratogenic drugs, maintain oxygenation and baseline

hemodynamics, and provide left uterine displacement if possible. • Consult an obstetrician for guidance on preoperative, intraoperative, and postoperative fetal monitoring.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis as appropriate; use cautiously in elderly patients. • Opioids as appropriate

Special Concerns for Informed Consent

Patients undergoing monitored anesthesia care or a regional technique plus MAC should still be consented for general anesthesia as a backup. Antibiotics/Common Organisms

• First line: Fluoroquinolone within 1 hour of the procedure • Second line: Trimethoprim–sulfamethoxazole, or gentamicin with ampicillin • Escherichia coli is most common organism

INTRAOPERATIVE CARE Choice of Anesthesia

• Local anesthesia is often used for flexible diagnostic cystoscopy. • Monitored anesthesia care should be considered for diagnostic flexible cystoscopy in patients unable to tolerate local anesthesia. • Neuraxial anesthesia with a T10 level is adequate for most urologic procedures. However, it does not reliably block the obturator nerve. An awake patient is the best monitor for mental status changes in TURP syndrome. • Regional anesthesia. An obturator nerve block may be considered in conjunction with neuraxial techniques if inferolateral bladder wall resection is anticipated. It prevents patient movement if the nerve is stimulated and decreases the risk of bladder perforation (2)[A]. • General anesthesia is commonly used.

Monitors

• Standard ASA monitors • Invasive monitoring is dictated by the patient’s comorbidities

Induction/Airway Management

• General anesthesia with a laryngeal mask airway (LMA) or endotracheal tube (ETT). • LMA can be used if the patient is NPO, not at risk for aspiration, and has an “adequate" FRC. Supraglottic devices may decrease the incidence of airway reactivity in patients with asthma or chronic obstructive pulmonary disease (COPD). Muscle relaxation for the procedure may still be utilized. • ETT should be used if the patient is not NPO, possesses risk factors for aspiration, or if the

lithotomy and Trendelenburg positions may hinder spontaneous ventilation (e.g., truncal obesity, decreased pulmonary compliance). • In patients with renal failure or hyperkalemia, succinylcholine may be contraindicated. If a rapid sequence induction is indicated, consider rocuronium (drawback = duration may be prolonged) or cisatracurium (drawback = longer time to onset).

Maintenance

• Balanced anesthetic with volatile or IV medications. • Surgical irrigating fluids may be absorbed in some cases. TURP procedures pose the highest risk due to open prostatic venous sinuses; thus irrigating time should be kept as short as possible. • Hemodynamics should be maintained close to baseline values, particularly in patients with end-organ damage. • Hypothermia may occur due to cold irrigating fluids. Normothermia can be maintained with increased ambient room temperature, upper body forced air warming blanket, or warm IV fluids. • Narcotics. In patients who are spontaneously breathing with an LMA, titrate to respiratory rate. • Duration of action of nondepolarizing muscle relaxants may be prolonged if gentamicin is given or the patient is hypothermic. • Radiation safety precautions should be implemented if fluoroscopy is used. • Laser protective goggles should be implemented for the patient and OR staff if laser therapy is utilized.

Extubation/Emergence

• Antiemetic prior to emergence • Ensure complete akinesis until legs are out of lithotomy. • Awake extubation after reversal of muscle relaxation and when routine respiratory parameters are met.

POSTOPERATIVE CARE BED ACUITY

• PACU for immediate postoperative care • Nontelemetry floor bed is appropriate for most inpatients. • Telemetry unit if the patient has a history of arrhythmia or severe cardiovascular disease. • Intensive care unit (ICU) admission for TURP syndrome.

ANALGESIA

• Some patients feel more comfortable postoperatively (e.g., after stone removal) • IV opioids with transition to PO opioids

COMPLICATIONS

• Monitor urine output as clots may form in the urinary catheter. • Abdominal pain with referred shoulder pain warrants workup for bladder perforation.

• UTI • Stent migration • TURP syndrome • Ureteral perforation • Autonomic hyperreflexia • Hematuria/clots in Foley catheter • Acute kidney injury • Sepsis and cystitis from BCG; considerably higher incidence in patients >70 years old, especially with repeated doses (3)[B].

PROGNOSIS

Urinary obstruction may lead to irreversible kidney injury. Reversibility is dependent on duration and severity of obstruction.

REFERENCES

1. Khorrami MH, Javid A, Saryazdi H, et al. Transvesical blockade of the obturator nerve to prevent adductor contraction in transurethral bladder surgery. J Endourol. 2010;24(10):1651–1654. 2. Semins MJ, Trock BJ, Matlaga BR. The safety or ureteroscopy during pregnancy: A systematic review and meta-analysis. J Urol. 2009;181:139–143. 3. Heiner JG, Terris MK. Effect of advanced age on the development of complications from intravesical bacillus Calmette-Guérin therapy. Urol Oncol. 2008;(26)2:137–140.

ADDITIONAL READING

• http://www.auanet.org (American Urological Association). See clinical guidelines tab.

See Also (Topic, Algorithm, Electronic Media Element) • Acute renal failure • Postrenal failure • TURP syndrome • Radiation safety

CLINICAL PEARLS

• Patients are often elderly and have numerous comorbidities, requiring careful preoperative evaluation. • Obturator nerve block is an easy, effective means to avoid obturator stimulation during a TURBT. • Duration of action of nondepolarizing muscle relaxants may be extended with administration of gentamicin. • There are no studies showing improved renal outcome with general versus neuraxial anesthesia. • Neuraxial anesthesia allows early recognition of mental status change in TURP syndrome.

D-DIMER

Mark R. Bombulie, BS

BASICS DESCRIPTION

• D-dimer is an antigen that is produced from plasmin-mediated degradation of fibrin-rich thrombi. • D-dimer assays are a useful tool for the: – Exclusion of deep venous thrombosis (DVT) and pulmonary embolism (PE) – Diagnosis of disseminated intravascular coagulation (DIC) (1) • The D-dimer measurement is an adjunct test and should never be used in isolation for diagnosis or exclusion (2). PHYSIOLOGY PRINCIPLES

• In the final steps of the coagulation pathway, thrombin cleaves fibrinogen to produce fibrin monomers. These fibrin monomers polymerize with one another forming protofibrils, thus allowing factor XIII to bind. • Thrombin also serves to activate factor XIII bound to fibrin polymers (forming factor XIIIa). • Factor XIIIa catalyzes the formation of covalent bonds between the D-domains (the segment of the fibrin protein containing the D-dimer antigen sequence) in adjacent protofibrils of polymerized fibrin. • During fibrinolysis, activated plasmin degrades the cross-linked fibrin, which releases fibrin degradation products and exposes the D-dimer antigen, which is typically not present in the body except when the coagulation system has been activated. • The D-dimer assay – The required sample is venous blood in a light blue tube (the same tube used for PT/PTT). The tube must be completely filled. – Quantitative values are performed in the laboratory with plasma and have a sensitivity of 95% and specificity of 50%. Quantitative tests rely on either enzyme-linked immunosorbent assays (ELISA) or enzyme-linked fluorescent assays (ELFA) to detect the amount of D-dimer present. – Qualitative values can be obtained at the bedside with whole blood and have lower sensitivities (85%) but slightly higher specificities (70%) than quantitative values. Whole blood is mixed with a reagent (a D-dimer monoclonal antibody that is joined to a monoclonal antibody capable of binding to the surface of a red blood cell). When D-dimer is present above a threshold value, agglutination occurs (the conjoined antibodies cause D-dimer and RBCs to clump together). This technique has the advantage of yielding results quickly without advanced laboratory equipment, but it is unable to detect low levels of D-dimer (3). – Increased values suggest increased thrombus formation or breakdown in the body. DISEASE/PATHOPHYSIOLOGY

• DVTs can embolize and travel through the right heart and into the pulmonary vasculature, causing a mechanical obstruction to blood flow (pulmonary embolism) and a secondary immune-inflammatory response. Risk factors include: – Previous history – Hereditary causes: Antithrombin III deficiency Protein C and S deficiencies Factor V Leiden Prothrombin gene mutations – Acquired causes: Reduced mobility Cancer Pregnancy/postpartum Nephrotic syndrome Trauma Spinal cord injury – Medications: Hormone replacement therapy Oral contraceptives Chemotherapy Antipsychotics – Surgical factors: Major surgery Hip or leg fracture Hip or knee replacement General anesthesia compared to epidural/spinal anesthesia (4) • Dead space: Pulmonary emboli result in an increase in alveolar dead space with an associated right-to-left shunt and V/Q mismatch. Blood shunted away from the blocked pulmonary arteries can cause edema, loss of surfactant, and alveolar hemorrhage in the overly perfused lung segments (5). Acute blockage can cause right heart strain or acute cor pulmonale. • DIC causes include infection, malignancy, obstetric disorders, shock, liver disease, extracorporeal circulation, intravascular hemolysis; it is the end result of several disease processes and has a high mortality rate. DIC is characterized by continuous thrombin generation and fibrin formation in the microvasculature which ultimately deplete coagulation factors and their inhibitors, leading to bleeding and/or thrombotic state. The subsequent breakdown of formed fibrin leads to the elevated D-dimer seen in this condition.

PERIOPERATIVE RELEVANCE

• Pulmonary embolism – Perioperative PE has an incidence of 1.6% in patients undergoing general surgery. The incidence in patients undergoing orthopedic procedures, especially hip procedures, has been reported as high as 30%. – ELISA D-dimer assays have a sensitivity of 95% and specificity of 50% and are therefore helpful in ruling out perioperative PE in patients with low clinical suspicion. In patients

with high clinical suspicion, ordering a D-dimer does not change management and should not delay treatment. – Values >500 ng/mL are considered positive. – False positives may be seen in other conditions unrelated to PE, including infection, cancer, trauma, cardiac disease, rheumatoid arthritis, hyperbilirubinemia, hepatic disease, in the elderly, the surgical procedure itself, hemolysis, or other inflammatory states. • Disseminated intravascular coagulation – In pregnant women with microangiopathic hemolytic anemia, elevated liver enzymes, and low platelets (HELLP) syndrome, 15–38% can progress to DIC. – DIC can be diagnosed intraoperatively with thrombocytopenia, elevated PT, aPTT, and Ddimer (6). – D-dimer levels >200 ng/mL are considered elevated. Levels correlate with the severity of the disease and can be monitored to assess the effectiveness of therapy.

REFERENCES

1. Thachil A, Fitzmaurice DA, Toh CH. Appropriate use of d-dimer in hospital patients. Am J Med. 2010;123:17–19. 2. Frost SD, Brotman DJ, Michota FA. Rational use of D-dimer measurement to exclude acute venous thromboembolic disease. Mayo Clin Proc. 2003;78:1385–1391. 3. Adam SS, Key NS, Greenburg CS. D-dimer antigen: Current concepts and future prospects. Blood. 2008;113:2878–2887. 4. Martlew VJ. Peri-operative management of patients with coagulation disorders. Br J Anaesth. 2000;85(3):446–455. 5. Desciak MC, Martin DE. Perioperative pulmonary embolism: Diagnosis and anesthetic management. J Clin Anesth. 2011;23:153–165. 6. Garg R, Nath MP, Bhalla AP, et al. Disseminated intravascular coagulation complicating HELLP syndrome: Perioperative management. BMJ Case Rep. 2009. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary embolism

CLINICAL PEARLS

• A positive D-dimer may indicate an increased level of fibrin degradation products that can result from increased thrombus formation or breakdown in the body. It cannot identify the location or the cause. • D-dimer assay can be used to rule out PE in patients with low clinical suspicion. • D-dimer levels can be followed to monitor the effectiveness of treatment in patients with DIC. • D-dimer assay should never be used in isolation.

DEAD SPACE

Siamak Rahman, MD

BASICS DESCRIPTION

• Dead space (VD) describes the lung areas that are ventilated but not perfused. Perioperatively it includes: – Physiologic dead space: Anatomic and alveolar – Apparatus dead space: Most concerning for neonates • Increases in the dead space to alveolar ventilation (VD:VA) ratio result in the retention of carbon dioxide. Thus, any cause of increased VD would require increases in ventilatory support/parameters in order to maintain normocarbia. PHYSIOLOGY PRINCIPLES

• Physiologic dead space (VDtotal) does not participate in carbon dioxide or oxygen exchange.

It is composed of 2 different components of lung volume: – Anatomic (VDanatomic): Upper airway structures that do not contribute to gas exchange;

includes air in the nose, pharynx, larynx, trachea, and larger airways. This volume does not reach the alveolar level, will not participate in gas exchange, and is thus “wasted.” It is ∼1/3rd of the tidal volume, or 2 mL/kg. – Alveolar (VDalveolar): Ventilated alveoli receiving minimal blood flow; includes zone 1 and nondependent lung areas. – VDtotal = VDanatomic + VDalveolar

• Apparatus, mechanical, or equipment dead space: Perioperatively, the anesthetic delivery system and monitors can add dead space; it can become significant with pediatric patients. As the volume increases, less fresh gas moves into the patient’s alveoli to participate in gas exchange. This also applies to intubated and ventilated patients in the ICU. – Endotracheal tube or laryngeal mask airway; dead space volume exists in the portion that extends beyond the patient’s incisors (can be decreased by cutting the ETT). Of note, however, intubation results in ∼1/2 of the anatomical dead space being bypassed (volume of dead space in nasopharynx and mouth). – Airway adaptors: Straight and elbow can add ∼2 mL of dead space – End-tidal CO2 monitors can add ∼8 mL of dead space. The closer the ETCO2 monitor is positioned to the ETT, the less is the amount of dead space. – Extenders such as corrugated devices – Face masks – Humidification management exchangers (HME) – Y piece: Adults ∼8 mL; pediatric ∼4 mL – Malfunctioning one-way valves – Bain circuit with a cracked or broken center portion

– Exhausted soda lime: Unique in that it normally clears CO2 within the circuit; thus, when

it is exhausted, it no longer participates in “ventilation.” • Bohr equation was presented in the beginning of the 20th century. The dead space fraction could be determined by measuring the arterial CO2 (PaCO2) via blood gas measurements and the mean expired CO2 (PeCO2). The end-tidal CO2 (ETCO2) is often substituted for the

mean expired CO2 (1).

• Fowler’s method—a test for measuring the dead space via nitrogen washout during one or multiple breaths. The patient takes a breath of 100% oxygen and exhales through a one-way valve measuring nitrogen content and volume. It is not commonly used or available perioperatively. • Breathing efficiency—defined as the volume of fresh gas reaching the alveoli (alveolar tidal volume) divided by the total volume of the gas inhaled per breath (total tidal volume). In normal healthy adults who are breathing spontaneously at rest, it is normally between 60% and 70% (this means that ∼30–40% of inhaled fresh gas does not reach the alveoli).

DISEASE/PATHOPHYSIOLOGY

• Alveolar dead space can be increased in pathological states. Non-perfused, but ventilated, alveoli are defined as lung units with a V/Q ratio of infinity. They include: – Pulmonary embolus – Low cardiac output – Increased alveolar pressure from mechanical ventilation or positive end expiratory pressure (PEEP) – Chronic obstructive pulmonary disease • “Shunt dead space” is an erroneous description of right-to-left lung shunt that brings the higher CO2 concentration in venous blood to the arterial side, thereby producing an arterialto-end-tidal CO2 difference. However, the influence of shunt on dead space is fairly small

when shunt values are low; they become significant when the shunt has reached 50%. • Hypercarbia can potentially have profound effects: – Directly increases cerebral blood flow and intracranial pressure – Increases pulmonary arterial pressure • Sympathetic activation can result in tachycardia, hypertension, or arrhythmias.

PERIOPERATIVE RELEVANCE

• Assessing and measuring VD/VA or dead space will give insight into the matching of ventilation and perfusion and is useful in: – Evaluating mortality risk in acute respiratory distress syndrome; increases in VD/VA correlate with the severity of lung injury. – Indicating lung recruitment versus overdistention when PEEP is added or increased to

improve oxygenation – Predicting successful extubation in pediatric and adult patients – Diagnosing and assessing the severity of pulmonary embolism. The alveolar dead space can increase to excessive amounts (80–90% of the tidal volume in recurrent pulmonary embolism). – Providing valuable information on the ventilatory support of the critically ill by providing information regarding changes in volume of alveolar dead space (2) • Breathing pattern: Rapid, shallow breathing, as may be seen from abdominal or thoracic incisional pain, can result in small tidal volumes, and an increased fraction of dead space ventilation (may reach >50%). Continuous epidural anesthesia in the postoperative period may decrease this (as well as atelectasis); the benefits may be pronounced in pulmonary cripples with low reserves. • Pulmonary embolism: Fat, venous, air, or clot embolic phenomenon may result intraoperatively with sudden pulmonary vascular occlusion. The resultant V/Q mismatch can produce a sudden increase in alveolar dead space and decreased ETCO2 readings (PaCO2 will increase).

• Neonates and infants: Apparatus dead space is more concerning in this patient population. A 5 kg neonate has a dead space of ∼10 mL. The addition of apparatus can add several milliliters causing the VD/VA ratio to increase significantly. • Tracheostomy: Reduces dead space ventilation and improves the efficiency of ventilation. Studies have shown that tracheostomy can reduce VD by 70 mL and reduce the work of breathing by over 30% (3)[C]. • Compensatory breathing techniques: During respiratory distress in the spontaneously ventilating, non-intubated patient, an instinctive unidirectional breathing pattern may develop to avoid rebreathing air in the nose with a high CO2. This consists of inhaling via the nose, and exhaling through the mouth.

EQUATIONS

• VDtotal = VDanatomic + VDalveolar

• Bohr equation was presented in the beginning of the 20th century:

– Where PeCO2 is the partial pressure of CO2 in mixed expired gas and is equal to the mean expired CO2 or end-tidal CO2

– PaCO2 is equal to arterial CO2. GRAPHS/FIGURES

FIGURE 1. Total dead space is equal to the anatomic dead space plus the alveolar dead space.

REFERENCES

1. Blanch L, Romero PV, Lucangelo U. Volumetric capnography in the mechanically ventilated patient. Minerva Anestesiol. 2006;72(6):577–585. 2. Hedenstierna G, Sandhagen B. Assessing dead space: A meaningful variable? Minerva Anestesiol. 2006;72(6):521–528. 3. Chadda K, Louis B, Benaissa L, et al. Physiological effects of decannulation in tracheostomized patients. Intens Care Med. 2002;28:1761–1767. See Also (Topic, Algorithm, Electronic Media Element) • ETCO2

• Respiratory acidosis • Venous air embolism • Fat embolism • Tracheostomy

CLINICAL PEARLS

• Patients with normal lung function have narrow gradients between their ETCO2 and arterial CO2 concentration (PaCO2) of 0–5 mm Hg. Air in the physiologic dead space accounts for

this normal gradient. In diseased lungs, the gradient will increase due to ventilation– perfusion mismatch. • The increase in physiologic dead space and worsening of ventilation–perfusion matching that occurs with venous air embolism produce a sudden fall in ETCO2, which, although sensitive, is a nonspecific sign of venous air emboli and also occurs with other type of emboli, massive blood loss, circulatory arrest, or disconnection from the anesthesia circuit.

DEEP EXTUBATION (ANESTHETIZED EXTUBATION) Katy E. French-Bloom, MD

BASICS DESCRIPTION

Deep extubation describes removal of the endotracheal tube (ETT) from the trachea while the patient is still anesthetized, or deeply anesthetized (1). It requires that the: • Muscle relaxation is fully reversed. • Patient is maintaining an acceptable respiratory rate and tidal volume for their size. • Patient does not respond to pharyngeal suctioning. • Provider must remain vigilant in their attention to airway maintenance until the patient is fully awake. • Removal of the ETT occurs during a positive pressure breath. ALERT This is a controversial technique. It is not considered mandatory in most postoperative settings. When conducting a deep extubation, be aware you are giving up a secure airway (1).

Geriatric Considerations

Can be advantageous in patients with certain comorbidities, including hypertension and chronic obstructive pulmonary disease (2) Pediatric Considerations

Can be advantageous for certain pediatric procedures. Remember that the cricoid cartilage is the narrowest part of the pediatric airway. Use cautiously in cases where laryngeal edema is common. Children can be symptomatic as their small airway size is more severely compromised by edema (3). pregnancy considerations

Contraindicated in this patient population as they are always considered full stomach and at a high risk for pulmonary aspiration (4) PHYSIOLOGY PRINCIPLES

• There are 4 stages of anesthetic depth: – Stage 1 (Analgesia): Characterized by slow, regular breathing with diaphragm and intercostal muscles, and the presence of lid reflex – Stage 2 (Delirium): Characterized by irregular and unpredictable ventilation, reflex dilation of the pupils, and intact lid reflex. The risk of clinically important reflex activity such as vomiting, laryngospasm, or arrhythmias increases – Stage 3 (Surgical anesthesia): This stage has 4 planes: Plane 1: Slight somatic relaxation, regular periodic breathing, active ocular muscles

Plane 2: Breathing changes, inhalation becomes briefer than exhalation, eyes become immobile Plane 3: Abdominal muscles relax, diaphragmatic breathing becomes very prominent, eyelid reflex is absent Plane 4: Intercostal muscles become completely pararlyzed, rib cage movement paradoxical, breathing irregular, pupils dilate. – Stage 4 (Respiratory paralysis): Muscles are flaccid, eyes wide and dilated

ANATOMY

• Pharynx: The pharyngeal airway extends from the posterior aspect of the nose down to the cricoid cartilage. • Larynx: Lies at the level of the cervical vertebrae 3–6; it is an organ of phonation and acts as a valve to protect the lower airways from contents of alimentary tract. • Epiglottis: A fibrous cartilage that is a part of the larynx. It has a mucous membrane covering that reflects as the glossoepiglottic fold onto the pharyngeal surface of the tongue. The epiglottis projects into the pharynx and overhangs the laryngeal inlet. It is not absolutely necessary for sealing off the airway during swallowing.

PERIOPERATIVE RELEVANCE

• Advantages of deep extubation (1,2,5,6): – Decreases stress response to extubation; less fluctuation in blood pressure/hypertension and heart rate/tachycardia – Decreases coughing and bucking on the ETT – Less incidence of desaturation – Less laryngotracheal trauma – Less breath-holding, bronchospasm • Disadvantages/complications of deep extubation (4): – Laryngospasm and/or bronchospasm can occur if the patient is extubated in between the awake and anesthetized states (Stage 2). – Loss of a secure airway – Aspiration – Negative pressure pulmonary edema – May require nasal/oral airway or laryngeal mask airway (LMA) after removal of ETT • Indications for deep extubation: – Specific surgeries including (6): Unclipped intracranial aneurysms Open globe eye surgery Intracranial aneurysm clipping (5) Tympanoplasty surgery Thyroid/parathyroid surgery Tonsillectomy/adenoidectomy (7,8) Removal of laryngeal papillomatosis (9) – Patients with specific comorbidities: Hypertension (2) Tachydysrhythmias

Reactive airway disease (4) • Contraindications to deep extubation (1): – Difficult mask ventilation – Difficult intubation – Increased risk of aspiration/full stomach – Surgery that may cause airway edema – Obesity – Diagnosis of obstructive sleep apnea (relative) – Neuromuscular disorders such as primary muscle diseases, demyelinating diseases, myasthenic syndromes, ion channel myotonias • Prior to a deep extubation (same for adult and pediatric patients) – Muscle relaxants must be fully reversed. – An adequate anesthetic depth must be maintained; eyes in midline, indicating at least a Stage 3 depth of anesthesia. – Patient should be breathing 100% oxygen. – Patient must be maintaining an acceptable respiratory rate and depth. – The posterior pharynx of the patient must be thoroughly suctioned; there should be no reaction by the patient to this. – Placement of a well-lubricated nasal trumpet may be considered in patients at risk for obstruction (e.g., large tongue). – The ETT is removed after a positive pressure breath has been given with the anesthesia reservoir bag to allow expulsion or secretions out of the glottis. • Immediately following deep extubation: – Oxygen should be administered to the patient in the form of a facemask for adults, and either a facemask or blow-by oxygen for pediatric patients. – Laryngospasm can occur especially when extubation is performed during Stage 2. Laryngospasm is the prolonged, intense glottis closure in response to direct glottis or supraglottic stimulation from inhaled agents, secretions, or foreign bodies. Patients usually produce sounds that range from high-pitched and squeaky to complete absence. Treatment of laryngospasm consists of recognizing this condition and then treating it appropriately; partial laryngospasm may be managed with 100% oxygen administration, CPAP, and jaw thrust whereas complete laryngospasm (or unremitting partial laryngospasm) requires propofol or muscle relaxation (most commonly succinylcholine). – Obstruction from the tongue or redundant tissue may be relieved with repositioning of the head, jaw thrust, insertion of an oral airway or nasal trumpet, or positive pressure ventilation with a facemask. • Recovery room care following deep extubation: – The “no-touch” technique for pediatric and adult patients involves not touching or manipulating the airway until the patient is fully awake. – Patients must be fully monitored for the duration of their stay in PACU.

REFERENCES

1. Daley MD, Norman PH, Coveler LA. Tracheal extubation of adult surgical patients while deeply anesthetized: A survey of U.S. anesthesiologists. J Clin Anesth. 1999;11(6):441–444.

2. Ma HN, Li HL, Che W. Effect of exchange of tracheal tube for laryngeal mask airway (LMA) on intratracheal extubation stress response under deep anesthesia level after surgery in elderly patients with hypertension. Zhonghua Wai Ke Za Zhi. 2010;48(23):1811–1814. 3. Valley RD, Freid EB, Bailey AG, et al. Tracheal extubation of deeply anesthetized pediatric patients: A comparison of desflurane and sevoflurane. Anesth Analg. 2003;96(5):1320– 1324. 4. Koga K, Asai T, Vaughan RS, et al. Respiratory complications associated with tracheal extubation. Anesthesia. 1998;53(6):540–544.

5. Suzuki A, Ogawa H. A new technique of extubation using laryngeal mask in the neurosurgical anesthesia. Masui. 1997;46(7):994–996.

6. Smith I, Taylor E, White PF. Comparison of tracheal extubation in patients deeply anesthetized with desflurane or isoflurane. Anesth Analg. 1994;79(4):642–645.

7. Valley RD, Ramza JT, Calhoun P, et al. Tracheal extubation of deeply anesthetized pediatric patients: A comparison of isoflurane and sevoflurane. Anesth Analg. 1999;88(4):742–745. 8. Higuchi H, Ura T, Taoda M, et al. Minimum alveolar concentration of sevoflurane for tracheal extubation in children. Acta Anaesthesiol Scand. 1997;41(7):911–913. 9. Forestner JE, McGraw SA, Norman PF. Laryngeal papillomatosis: Anesthetic management. South Med J. 1979;72(9):1107–1112. See Also (Topic, Algorithm, Electronic Media Element) • Laryngospasm • Superior laryngeal nerve • Recurrent laryngeal nerve • Aspiration

CLINICAL PEARLS

• Deep extubation is a technique that can be used in certain circumstances when minimal hemodynamic change is advantageous, or where avoidance of coughing and bucking would be beneficial. • The major drawback is that the anesthetist is relinquishing a known secured airway for an unsecured one. • Deep extubation does have uses, but serious negative complications can result if not vigilant about the technique.

DEFIBRILLATION Jochen Steppan, MD Nanhi Mitter, MD

BASICS DESCRIPTION

• Defibrillation is the application of electricity during cardiac arrest either to the chest wall or directly to the heart muscle to restore a coordinated cardiac rhythm and a spontaneous circulation. • The first scientific work on defibrillation was published by a team of researchers at the Johns Hopkins University in 1933. Funding was provided from an electrical company as a result of an increase in the rate of sudden death among utility workers who were rewiring American homes with electricity. This work was followed by the development of closed chest cardiac massage by the same team and publication in 1960. PHYSIOLOGY PRINCIPLES

• Adequate current flow through the heart is required for successful defibrillation: I = V/R, where I = current, V = voltage, and R = resistance. Therefore, for the same voltage (V) applied, the current (I) delivered to the patient varies depending on the transthoracic impedance (R). • Transthoracic impedance (70–80 Ohm) is influenced by: – Electrode surface area: Electrodes should be 8–12 cm in diameter for adults. Large electrode pads result in smaller transthoracic impedance. – Pressure on the electrodes: As per the American Heart Association guidelines, a force of 8 kg applied to paddles results in an optimal reduction of transthoracic impedance. – Body habitus and tissue properties of the rib cage, muscle, subcutaneous fat and skin contribute to transthoracic impedance. In order to further reduce transthoracic impedance, a conductive material such as gel pads or electrode paste should be used. • There is no direct relationship between the energy applied (Energy = Power × Time) and current flow. • Theories about mechanisms of defibrillation: – Critical mass theory (original): The delivery of current to a critical mass of myocardium can stun and make the muscle unexcitable. The uncoordinated waveforms of excitation that perpetuate ventricular fibrillation would then be extinguished and a normal cardiac excitation will resume. Tissue in close proximity to the shocking electrodes produces virtual electrodes that either hyperpolarize or depolarize the surrounding cardiac tissue. – Vulnerability theory (newer): Defibrillation is mediated by depolarizing fully excitable cells and also by depolarizing cells in the relative refractory period by a stimulus that exceeds the upper limit of vulnerability. • Defibrillator waveforms: – Monophasic defibrillators deliver current in one direction (one polarity).

– Biphasic defibrillators deliver current in 2 directions. The current flows in one direction during the first phase of the waveform and in the opposite direction during the second phase. Therefore, lower energy levels can be used during defibrillation for equivalent or higher success rates. – No specific waveform has shown to be consistently associated with a greater incidence of return of spontaneous circulation or higher survival to hospital discharge. – All newer defibrillators deliver biphasic shocks, but monophasic shocks are still acceptable and currently in clinical use.

ANATOMY

• Physiological cardiac excitation is initiated in the sinus node. It travels through atrial tissue to the AV node and is then conducted through the bundle of His to the bundle branches over the Purkinje fibers and finally to the myocardium. • Ventricular fibrillation (Vfib) is a state of disorganized electrical activity that leads to uncoordinated contraction of the myocardium, making its ejection ineffective.

DISEASE/PATHOPHYSIOLOGY

Cardiac arrest is a leading cause of death in many parts of the world. • In the US and Canada, approximately 350,000 people suffer a cardiac arrest per year and require resuscitation (half of the cases occur in-hospital). • The incidence of in-hospital cardiac arrests is estimated at 3–6/1,000 admissions. • For every minute that elapses between collapse and defibrillation, the chance of survival from ventricular fibrillation diminishes by 7–10% every minute if no CPR is provided and by 3–4% with CPR. • Defibrillation is the only effective treatment of Vfib and should be performed within 10 minutes after sudden onset cardiac arrest (90% of reported instances of dental damage. • Airway devices: Endotracheal tubes, laryngeal mask airways, bite blocks, and oral airways can cause damage during insertion, removal, or biting during emergence. • Pre-existing dental conditions increase the risk of dental injury. – Cavities or caries consist of a bacterial process that causes rotting of the root. – Periodontal disease consists of gingival inflammation, alveolar bone loss, and tartar buildup. • Restorations and prosthetics increase the risk of dental injury: – Bridges: Replacement of one or more missing teeth. A pontic is fused between 2 porcelain crowns to fill in the space left by the missing teeth. – Bonding: Restoration of decaying teeth or cosmetically improving teeth (discoloration,

abnormal shapes, small gaps). A composite resin filling is applied to the anterior face of the tooth, followed by a bonding material that can be shaped or colored to achieve the desired result. – Veneers: Improvement cosmetically of discolored, worn, chipped, or misaligned teeth – Crowns: Coverage of the visible surface of a decayed or worn-down tooth in order to reduce further wearing down • Pulmonary aspiration of foreign body: Detection requires identification of the event. Any missing tooth should be assumed to have been aspirated until proven otherwise. A chest radiograph can identify the presence and location.

PREVENTATIVE MEASURES

• Preoperative evaluation and assessment of the airway should include the dentition: – Loose teeth – Chips – Fractures – Restoration or prosthetics (crowns, bridges, veneers, bonding) – Periodontal disease • Documentation preoperatively: If pre-existing dental disease is present, the patient should be informed and findings should be confirmed with the patient. Documentation should include a careful description of the preoperative evaluation record. • Consent: Anesthesia consent should include a verbal discussion, followed by a written consent that is signed by the patient or their designated caretaker/power of attorney regarding the possibility of dental injury. More time or attention should be given to those with pre-existing dental disease or anticipated difficult intubation. • Alternative airway management: – Anticipated difficult intubation: May be prudent to preemptively utilize special airway management tools such as fiberoptic bronchoscopy, indirect laryngoscopy tools (GlideScope, etc.), laryngeal mask airway guided intubation, etc. If laryngoscopy is to be attempted, consider special angulated blades (McCoy, Belscope), plastic blades, or blades with soft heels. – Unexpected difficult airways: Consider alternative devices early to avoid repeated laryngoscopy attempts and fulcruming the laryngoscope. • Standard and routine laryngoscopy: Should avoid teeth with gentle insertion and advancement. Proper patient positioning (head, neck, shoulder rolls, ramps), preoxygenation (“buys time” before desaturation), and avoidance of “cranking” the wrist should always be performed. • Tooth guards: Routine use is controversial. They may impair visualization, insertion of the endotracheal tube, or increase apneic time. One study demonstrated that insertion increased intubation time by 7 seconds (statistically significant) (4). • Insertion and removal of airway devices and bite blocks should always be done gently. Laryngeal mask airways have a thicker diameter and are less compliant than endotracheal tubes. Avoid forceful pulling and removal of items while the patient is biting (downward movement). • Soft bite blocks constructed from gauze may reduce damage from biting of the endotracheal tube. Consider utilizing when motor evoked potentials are being performed.

• Dental consultation and treatment prior to surgery for dentition “at risk” for avulsion or further damage may prevent or reduce the incidence of damage. If this is not feasible, one technique that has been suggested is the wrapping of suture around the gingival margins several times and taping the other end to the cheek. • Studies have suggested that despite careful attention to poor dentition, the risk of dental lesions cannot be completely eliminated.

DIAGNOSIS • Visual inspection after routine intubation with documentation in the anesthetic record may reduce ambiguity postoperatively. • Visual inspection following a difficult or traumatic intubation, suctioning, insertion or removal of other airway devices is always suggested (1). • Missing teeth should be assumed to have been aspirated until proven otherwise. A chest radiograph can easily rule out this possibility.

DIFFERENTIAL DIAGNOSIS

Pre-existing chips, fractures, missing teeth (a careful preoperative evaluation will remove any doubts or confusion)

TREATMENT • Dental consultation • Avulsed and retrieved. Transport medium of choice is Hanks Balanced Salt Solution, followed by cool milk, saliva, and cool saline. In the operating room, cool saline may be the most easily available. • Avulsions may require repositioning and splinting with non-rigid fixation (wire) for 7–10 days. • Tooth fractures can range from composite bonding, to root canal therapy (with coronal restoration), to dental extraction, depending on the size/depth/location of the fracture. • Alveolar fractures require segmental arch bar placement. • Consider antibiotics and Peridex oral rinse in the event of any dental or intraoral injury. If the damage extends extraorally, check for tetanus status and vaccinate if indicated.

FOLLOW-UP • A discussion with the patient and family should inform them of the situation as well as the immediate efforts that will be taken to remedy the situation (dental consultation). • Dental consultation may be coordinated while an inpatient if appropriate. • Reimbursement may be considered as per department, group, or hospital policy.

CLOSED CLAIMS DATA

• Reported to the National Practitioner Data Bank • Estimated to be as high as 1/3rd of all claims against anesthesiologis (3)

REFERENCES

1. Yasny JS. Perioperative dental considerations for the anesthesiologist. Anesth Analg. 2009;108(5):1564–1573. 2. Rosa Maria G, Paolo F, Stefania B, et al. Traumatic dental injuries during anaesthesia. Part 1: Clinical evaluation. Dental Trauma. 2010;26(6):459–465. 3. Warner ME, Benenfeld SM, Warner MA, et al. Perianesthetic dental injuries. Anesthesiology. 1990;90:1302–1305. 4. Brosnan C, Radford P. The effect of a toothguard on the difficult of intubation. Anaesthesia. 1997;52:1011–1012.

ADDITIONAL READING

• Gasier RR, Castro AD. The level of anesthesia resident training does not affect the risk of dental injury. Anesth Analg. 1998;87:255–257. • Givol N, Gershtansky Y, Halamish-Shani T, et al. Perianesthetic dental injuries: Analysis of incidence reports. J Clin Anesth. 2004;16:173–176. • Newland MC, Ellis SJ, Peters KR, et al. Dental injury associated with anesthesia: A report of 161,687 anesthetics given over 14 years. J Clin Anaesth. 2007;19:339–345.

See Also (Topic, Algorithm, Electronic Media Element) • Difficult airway

CODES ICD9 • 525.11 Loss of teeth due to trauma • 525.63 Fractured dental restorative material without loss of material • 525.64 Fractured dental restorative material with loss of material ICD10 • S03.2XXA Dislocation of tooth, initial encounter • S02.5XXA Fracture of tooth (traumatic), init for clos fx • S02.5XXB Fracture of tooth (traumatic), init encntr for open fracture

CLINICAL PEARLS

• A preoperative exam of dentition should be performed on every patient receiving an anesthetic. Additionally, in the event of pre-existing disease, it should be confirmed with the patient and appropriately documented in the preoperative evaluation. • Routine examination following airway management may reduce the ambiguity of preexisting or postoperative incidents that can be misconstrued or mislabeled as intraoperative dental damage. In patients in whom injury may have occurred (difficult intubation, traumatic insertion or removal of airway devices or oral airway, biting down on the suction

catheter) it is prudent to do so. • Identification of dental damage should be discussed with the patient, and appropriate follow-up should be determined and coordinated.

DEPRESSION

Dmitri Souzdalnitski, MD, PhD Samuel Samuel, MD

BASICS DESCRIPTION

• Major depressive disorder (also known as “depression”) can be diagnosed on the basis of one or more major depressive episodes. The symptoms cause significant distress as well as impairment in social, occupational, and/or other important areas of functioning. • Symptoms persist for longer than 2 months and are characterized by distinct functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. • The diagnostic criteria for a depressive episode requires that 5 (or more) of the following symptoms have been present during a 2-week period and represent a change from previous function (1)[A] and that at least one of the symptoms has to be either a depressed mood or (2) loss of interest or pleasure: – Depressed mood – Noticeably diminished interest or pleasure – Significant weight loss (when not dieting) or weight gain, or decrease/increase in appetite – Insomnia or hypersomnia – Psychomotor agitation or retardation – Fatigue or loss of energy – Feelings of worthlessness or excessive/inappropriate guilt – Diminished ability to think or concentrate, indecisiveness – Frequent thoughts of death or suicide

EPIDEMIOLOGY Incidence

2.0–4.5 per 1,000 persons per year (2)[B]

Prevalence

• Lifetime prevalence rates for significant depressive symptoms are 11–21% and 3–7% for major depressive disorder. • Rates in women and men are highest in the 25–44 year-old age group. • Major depressive disorder is about 2–3 times as common in adolescent and adult females as in adolescent and adult males. • In children, boys and girls are affected equally.

Morbidity

Rather than producing its own morbidity, depression commonly influences the morbidity resulting from other medical conditions. For example, it complicates the management of

patients with chronic back pain. 9% of these patients take anti-anxiety medications, and 25% take antidepressants (3)[B]. Mortality

• One in 7 patients with major depressive disorder eventually dies by suicide. • Major depression accounts for about half of suicides, which are the 8th leading cause of death in the US.

ETIOLOGY/RISK FACTORS

• Various genetic, biological, or psychosocial models have been implicated in the etiology of depression. However, the exact cause of major depressive disorder is not known. • The traditional thinking that depression follows a triggering event, such as emotional trauma, has been observed in fewer than 20% of patients. The following risk factors have also been observed: – Alcohol or drug abuse – Loneliness – Inadequate social support – Remote significant emotional trauma – Recent negative life events – Financial problems – Unemployment or underemployment – History of depression in the family – Medical problems, chronic pain – Early childhood trauma or abuse – Marital or relationship problems – Terminally or severely ill children – Insecure

PATHOPHYSIOLOGY

• The exact mechanism of development of major depressive disorder is unknown. Commonly discussed mechanisms are: – Biological: Genetically mediated neurotransmitter misbalance of norepinephrine, serotonin, dopamine, acetylcholine, gamma-aminobutyric acid, melatonin, glycine, histamine, etc. – Neuroendocrine and hormonal mechanisms: Corticotropin-releasing hormone, endorphins, enkephalins, vasopressin, cholecystokinin, substance P, thyroid and adrenal hormones, and others – Psychoanalytic, psychodynamic, and behavioral mechanisms

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Literature recommends that anesthetist be more sensitive to the psychological concerns in depressed patients who are undergoing surgery. • Antidepressants are important elements in the treatment of depression and should be continued in the perioperative period with certain exceptions (discussed in the “Medications” section).

PREOPERATIVE ASSESSMENT SYMPTOMS

• Commonly reported symptoms are: – Depressed mood – Feelings of helplessness and hopelessness – Anhedonia – Irritability or restlessness – Change in appetite • Weight changes • Unexplained aches and pains • Change in sleep • Change in body activity • Loss of interest in daily activities • Loss of energy • Feelings of worthlessness • Excessive or inappropriate guilt • Indecisiveness or decreased concentration • Suicidal ideation

History

• Clues to potential depression also include the general appearance and manners of communication of the patient. • Review relevant medical records, including history of suicide, emotional trauma, domestic violence, abuse, etc. • Family history may be helpful as well. For example there is a high risk for clinical depression in families with history of depression (7%) or alcoholism (8%).

Signs/Physical Exam

• Physical exam findings may demonstrate poor eye contact, malnutrition, disheveled appearance, or other evidence of poor personal hygiene. • A further exam may reveal certain personality changes. They might be worried, introverted, stress sensitive, obsessive, unassertive, very dependent.

TREATMENT HISTORY

• Outpatient counseling • Psychiatric admissions • Electroconvulsive therapy

MEDICATIONS

• Selective serotonin reuptake inhibitors (SSRIs) • Serotonin/norepinephrine reuptake inhibitors (SNRIs) • Tricyclic antidepressants (TCAs) • Monoamine oxidase inhibitors (MAOIs) • Lithium

• Antipsychotics

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

Not applicable to the anesthetist

CONCOMITANT ORGAN DYSFUNCTION

It is not uncommon to have concurrent chronic pain problems. If this is the case, the perioperative pain management should be carefully planned and discussed with the patient in details. CIRCUMSTANCES TO DELAY/CONDITIONS

Typically, cases are not delayed because of depression. CLASSIFICATIONS

• Major depression (one or more episodes) • Melancholic subtype • Atypical depression • Seasonal affective disorder

TREATMENT PREOPERATIVE PREPARATION Premedications

Benzodiazepines to decrease preoperative anxiety Special Concerns for Informed Consent

No special concerns for informed consent INTRAOPERATIVE CARE Choice of Anesthesia

General or regional, or MAC anesthesia for routine cases Monitors

Standard ASA monitors

Induction/Airway Management

• Serum cholinesterase activity may decrease in patients treated with phenelzine; thus, the dose of succinylcholine may need to be reduced. • Ketamine should be avoided in patients taking MAOIs since it may exaggerate the sympathetic stimulation. Maintenance

• Any volatile anesthetic with or without nitrous oxide is acceptable for maintenance of

general anesthesia. • The MAC may be higher in patients with depression because of the medications they are on (MAOIs, SSRIs, SNRIs, TCAs). • The epinephrine used for spinal anesthesia should be limited in patients taking MAOIs because of the potential of an exaggerated sympathetic response.

Extubation/Emergence

No special considerations in extubation or emergence in patients with depression

POSTOPERATIVE CARE BED ACUITY

No special considerations

MEDICATIONS/LAB STUDIES/CONSULTS

• Brief psychological screening. Also, if needed, a comprehensive assessment and assistance from mental health professionals to improve the depressed patient’s and his/her family’s experience during the acute postoperative period. • The analgesic potency has been demonstrated for some of the antidepressant medications. TCAs, duloxetine, milnacipran, and several others are approved for the treatment of chronic neuropathic or myofascial pain. These medications, therefore, may contribute to the overall effects of postoperative pain management. • SSRIs and SNRIs should be continued at preoperative dosages. • TCAS should be continued at their regular dose in the perioperative period. – Adverse effects are common, and patients should be re-evaluated if there is evidence of sedation and delirium, or other anticholinergic effects, particularly in elderly patients. – Cardiovascular risks at regular doses are extremely low.

COMPLICATIONS

• Meperidine should be avoided in combination with SSRIs (paroxetine, fluoxetine, sertraline, citalopram, and others), MAOIs, and certain other antidepressant medications (phenelzine, selegiline, tranylcypromine) since these combinations may produce somatic, autonomic, and neuropsychiatric derangements (including hyperreflexia, myoclonus, ataxia, fever, shivering, diaphoresis, diarrhea, anxiety, salivation, confusion and others, termed “serotonin syndrome”). • Less than 1% of all patients treated with antipsychotic drugs may develop a neuroleptic malignant syndrome (presenting as hyperthermia, hypertonicity of the skeletal muscles, fluctuating levels of consciousness and autonomic nervous system instability), and it is therefore advisable that patients taking antipsychotics should be very closely monitored in the perioperative period.

REFERENCES

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed., text revision. Washington, DC: American Psychiatric Association, 2000.

2. Kruijshaar ME, Barendregt J, Vos T, et al. Lifetime prevalence estimates of major depression: An indirect estimation method and a quantification of recall bias. Eur J Epidemiol. 2005;20(1):103–111. 3. Walid MS, Robinson JS, 3rd, Robinson ER, et al. Comparison of outpatient and inpatient spine surgery patients with regards to obesity, comorbidities and readmission for infection. J Clin Neurosci. 2010;17(12):1497–1498.

ADDITIONAL READING

• Ebert TJ, Schid PG. Inhaled anesthetics. In: Barash PG, et al., eds. Clinical anesthesia, 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2009:424. • Hines RL, Marschall KE. Psychiatric disease/substance abuse/drug overdose. In: Hines RL, Marschall KE, eds. Stoelting’s anesthesia and co-existing disease, 5th ed. Philadelphia: Churchill Livingstone, 2008:533–538.

See Also (Topic, Algorithm, Electronic Media Element) • Electroconvulsive therapy • Complex regional pain syndrome type I • Complex regional pain syndrome type II

CODES ICD9 • 296.20 Major depressive affective disorder, single episode, unspecified • 296.30 Major depressive affective disorder, recurrent episode, unspecified • 311 Depressive disorder, not elsewhere classified ICD10 • F32.9 Major depressive disorder, single episode, unspecified • F33.9 Major depressive disorder, recurrent, unspecified

CLINICAL PEARLS

• Earlier recommendations suggested discontinuation of MAOIs 14 days prior to elective operations, to permit the restoration of normal enzyme activity. The current literature suggests that anesthesia can be safely administered to patients being treated with MAOIs. However, excessive sympathetic stimulation or use of sympathomimetic drugs should be limited. • Patients with a history of bipolar disorder may be on lithium. It is important to be aware of signs of acute lithium intoxication: Vomiting, profuse diarrhea, tremor, confusion, hyperreflexia, ataxia, coma, convulsions, and seizures. The toxicity can be triggered by drugs that reduce lithium excretion or increase reabsorption, such as NSAIDs, ACE inhibitors, thiazide diuretics, and metronidazole. Cardiac toxicity can be presented as sinus dysfunction, T-wave flattening, ventricular arrhythmia, and myocarditis. Lithium potentiates depolarizing and non-depolarizing neuromuscular blocking drugs causing

potentially dangerous reactions with ECT.

DIABETES INSIPIDUS Keren Ziv, MD Linzy Fitzsimons, MD

BASICS DESCRIPTION

• Diabetes insipidus (DI) describes a disease process defined by polyuria and polydipsia resulting from either: – Decreased or absent secretion of antidiuretic hormone (ADH) – Resistance to the action of ADH at the level of the kidneys • There are multiple etiologies: – Neurogenic – Nephrogenic – Dipsogenic – Gestational EPIDEMIOLOGY Incidence

• Occurs during the postoperative course in ∼30% of pituitary surgeries, although the course is usually transient • Overall incidence is difficult to obtain due to the various etiologies of DI.

Prevalence

• 1 in 25,000 • Equal prevalence in males and females

Morbidity

• Severe dehydration resulting in hypernatremia • Fever and cardiovascular collapse can occur in patients with coexisting illnesses, the elderly, or children. Mortality

Rare, especially in adults without coexisting illness. However, may occur if treatment is delayed in children or the elderly in which the disease progresses to complete cardiovascular collapse. ETIOLOGY/RISK FACTORS

• Neurogenic: Decreased production of ADH by the hypothalamus in the brain. Risk factors include: – Trauma – Tumor in the region of the pituitary or hypothalamus

– Surgery in the region of the pituitary or hypothalamus • Nephrogenic: Decreased sensitivity to ADH by the kidneys. The most common cause in children is hereditary; 90% are associated with mutations in the AVPR2 gene that encodes for a dysfunctional vasopressin receptor (V2R). In adults, acquired nephrogenic DI is usually secondary to medications such as lithium, foscarnet, cidofovir, amphotericin B, demeclocycline, as well as a result of chronic hypercalcemia and hyperkalemia. • Dipsogenic: Defect in the thirst trigger (located in the hypothalamus) which causes increased thirst and fluid intake that subsequently suppresses vasopressin secretion and increases urine output. • Gestational: During pregnancy, all women produce vasopressinase by the placenta, which breaks down ADH. When excess vasopressinase is produced, gestational DI will occur. This etiology is the most common and can be treated by desmopressin. – In a small subset of patients, the thirst mechanism is disrupted, causing DI; it is not improved with desmopressin. – DI is also associated with other diseases of pregnancy, such as preeclampsia and HELLP syndrome. In these disease processes, hepatic vasopressinase is activated, and the only treatment is delivery of the fetus.

PATHOPHYSIOLOGY

• Hypothalamus: Produces ADH in the supraoptic and paraventricular nuclei. ADH is then transported to the posterior lobe of the pituitary gland where it is stored for later use. It is released when the body senses that electrolyte and/or fluid status are unbalanced. • Kidney: The primary target for ADH and water retention; the hormone acts on the collecting ducts and distal convoluted tubules (DCT) to allow more water to be reabsorbed into the systemic circulation and therefore create a more concentrated urine. • Thirst sensation: Also regulated by the hypothalamus when it senses decreases in serum osmolarity. • In DI, either ADH secretion is deficient or the renal response to ADH is abnormal. This results in the following pathology: – Increased urine output; water remains in the urine (polyuria) – Decreased body water (dehydration) – Increased serum [Na+] – Increased serum osmolality – Decreased urine osmolality or specific gravity – Decreased urine [Na+] – No change in total body sodium – No change in urine sodium excretion

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The possibility of DI should be evaluated in patients who present perioperatively with hypernatremia or excessive urine output; in particular, those who have had traumatic injury, tumor, status post surgery in the region of the pituitary or hypothalamus, or are pregnant. • In patients with known DI, electrolyte abnormalities may be present perioperatively. It is important to have recent chemistry labs done prior to anesthesia. Treatment may need to be

administered perioperatively by the anesthetist.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Polyuria (4–18 L/day) with acute onset, usually within 24–48 hours of neurosurgery • Polydipsia, often with a craving for cold fluids • Hypovolemia: Depending on whether thirst mechanism is intact • Nocturia, enuresis in children, anorexia, fatigue

History

• Central DI usually presents abruptly in patients with pituitary/hypothalamic surgery, head trauma, or malignancy. • Familial nephrogenic DI presents in early childhood. • Psychogenic polydipsia may have a long history.

Signs/Physical Exam

• Minimal typically • Dehydration • In rare cases, there may be bladder enlargement

TREATMENT HISTORY

When patients are awake, they can usually drink enough fluids to replace their urine losses. Patients with inadequate thirst, however, may be treated with dextrose and water or IV fluid that is hypoosmolar with respect to the patient’s serum. Serum sodium should not be reduced too quickly, ideally only 0.5 mEq/L/hr. MEDICATIONS

• ADH therapy: Desmopressin (DDAVP) is a synthetic analog to endogenous vasopressin but with greater platelet and antidiuretic effects and decreased blood pressure effects. It binds to V2 receptors in the renal collecting duct, causing increased water reabsorption in the

kidney (increased urine osmolality, decreased urine output, and no effect on sodium, potassium, or creatinine reabsorption. – Intravenous: 1–2 mcg BID, onset 15–50 minutes – Oral: 0.05 mg BID, onset 60 minutes – Nasal: 5–40 mcg BID – The duration of action is highly variable and lasts from 5 to 21 hours. Additionally, it is renally excreted; thus, renal failure will prolong its action and dosage adjustments should be considered.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Urine specific gravity 200–250 mL/hr for ≥2 hours with a urine specific gravity pulmonary venous pressure > pulmonary alveolar pressure).

– Waveforms: Left atrial tracings are similar to central venous pressure (CVP) tracing from the right atrium, with “a”, “c”, and “v” waves.

PHYSIOLOGY PRINCIPLES

• During an ideal ventricular diastole, the pressures in all cardiac chambers equilibrate: CVP = RVEDP = PADP = PAWP = LAP = LVEDP; where CVP is central venous pressure, RVEDP is right ventricular end diastolic pressure, PADP is pulmonary artery diastolic pressure, PAWP is pulmonary artery wedge pressure, and LAP is left atrial pressure. • Frank Starling principle states that the force of cardiac contraction is directly proportional to end-diastolic muscle fiber length at any given level of intrinsic contractility or inotropy. – Increasing the venous return of the left ventricle increases the volume and preload and thereby LVEDP (increases stroke volume). – Flat portion of diastolic filling: A significant increase in filling volume or preload results in a small increase in filling pressure. – Steep portion of diastolic filling: In comparison, there is a significant increase in filling pressure with the same volume towards the end of diastole. – Left-shifting describes abnormal decreases in compliance (e.g., sepsis, shock, myocardial ischemia, or fibrotic chambers). Additionally, there is a paradoxical increase in filling pressures with a decrease in filling volume.

FIGURE 2. The ventricular diastolic pressure-volume relationship forms a curvilinear line and the slope reflects wall compliance. Compliance is dynamic and changes with chamber volume, thus affecting the ability of using the LVEDP to approximate the LVEDV. Curve A represents normal compliance. Curve B represents a right shift or increased compliance, as can occur with dilated cardiomyopathy, where a change in the volume (x) results in a smaller increase in pressure.

FIGURE 3. Frank Starling curve. Changes in venous return correlate to changes in LVEDP/LVEDV that affect the stroke volume (SV). The inotropic state affects the stroke volume at a given preload (dashes–higher inotropy, dots–decreased inotropy).

ANATOMY

• PAWP is taken at the pulmonary artery (distal tip of pulmonary artery catheter) with the balloon inflated and occluding the branch of the pulmonary artery. • The ability of proximal pressures (CVP, PAWP, etc.) to accurately reflect the LVEDP is dependent on unobstructed continuity of blood flow during diastole. Any anatomical or physiological condition that impairs this will result in inaccurate downstream pressure estimation.

DISEASE/PATHOPHYSIOLOGY

• Conditions in which PAWP underestimates LVEDP: – Decreased left ventricular compliance (e.g., MI, LVH). The mean left atrial pressure (LAP) is less than LVEDP, and there is an increased end-diastolic “a” wave. – Aortic regurgitation (AR): The mitral valve closes before the end of diastole due to run-off from the aorta (LAP < LVEDP). – Pulmonary regurgitation: Bidirectional run-off of the pulmonary artery flow (PADP < LVEDP). – Decreased pulmonary vascular bed • Conditions in which PAWP overestimates LVEDP: – Positive end-expiratory pressure (PEEP): The pulmonary artery catheter may become lodged in lung zone 1 or 2. Pulmonary venous pressure readings are actually lower than airway pressure, leading to a falsely elevated PAWP. – Pulmonary hypertension: Increases in the pulmonary vascular resistance will record a higher PADP which does not reflect left ventricular pressures (PADP > mPAWP). – Mitral stenosis: There is obstruction to the flow of blood through the mitral valve, which results in a higher mean LAP and thereby overestimation of the LVEDP. – Mitral regurgitation: A retrograde systolic “v” wave or regurgitant systolic flow raises the mean atrial pressure. • Increased compliance. In dilated cardiomyopathy, the left ventricle is very dilated without any appreciable increase in ventricular wall thickness. This will result in increased compliance and even though the LVEDV may be very high, the corresponding LVEDP elevation might not be significant.

PERIOPERATIVE RELEVANCE

• Elevated LVEDP is an independent risk factor of mortality in cardiac surgery, independent of left ventricular ejection fraction (2,3). • Atrial kick: Normally provides 20% contribution to the LVEDV. In LVH, this may increase to 50% and the “a” wave may be prominent and provide a better estimate of LVEDP than PAWP (4). • Mitral valve: Both stenosis and regurgitation can overestimate the LVEDP. • Perioperative presentation of cardiogenic versus hypovolemic shock can be differentiated by using the LVEDP (CVP/PAWP) as a surrogate marker of preload. A low CVP, or PAWP, is

consistent with hypovolemia, and a high CVP/PAWP would indicate cardiogenic shock (e.g., MI, CHF). This can be clinically important in deciding when to give fluids versus other interventions. – The goal of all-fluid resuscitation is to increase preload and “recruit” stroke volume to increase end-organ perfusion, as per the Starling mechanism. – Markers of LVEDP (CVP/PAWP) can be trended over time with improvement or worsening of cardiac output. – Clinically, signs of increased cardiac output changes would relate to increased urine output, decreased capillary refill time, improvement in mental status and blood pressure. – Other more sophisticated monitors which can measure cardiac output changes with preload changes are esophageal Doppler monitor, echocardiography, and systolic pressure variations. • Myocardial compliance: PAWP measurements are dependent on myocardial compliance. Multiple studies on ICU patients have shown the failure of PAWP in acute illness to correlate with LVEDV (5). • Clinical use: CVP or PAWP alone is rarely used to guide therapy. In situations of shock, after the patient has been given IV fluids to raise the CVP to around 12 mm Hg (adequate preload), without improvement in blood pressure or cardiac output, other methods of assessment such as bedside echocardiography may be used for cardiac assessment. – The American Society of Anesthesiologist Practice Guidelines recommends PAC for highrisk surgical patients only (6). – Suggested clinical indications for monitoring LVEDV and LVEDP are severe sepsis and trauma, high-risk cardiac surgery, pulmonary hypertension, abdominal compartment syndrome, and therapy with PEEP.

REFERENCES

1. Braunwald E, Fishman AP, Cournand A. Time relationship of dynamic events in the cardiac chambers, pulmonary artery and aorta in man. Circ Res. 1956;4:100–107. 2. Salem R, Denault AY, Couture P, et al. Left ventricular end-diastolic pressure is a predictor of mortality in cardiac surgery independently of left ventricular ejection fraction. Br J Anaesth. 2006;97:292–297. 3. Apostolakis EE, Baikoussis NG, Parissis H, et al. Left ventricular diastolic dysfunction of the cardiac surgery patient: A point of view for the cardiac surgeon and cardioanesthesiologist. J Cardiothorac Surg. 2009;4:67. 4. Falicov RE, Resnekov L. Relationship of the pulmonary artery end-diastolic pressure to the left ventricular end-diastolic and mean filling pressures in patients with and without left ventricular dysfunction. Circulation. 1970;42:65–73. 5. Fontes ML, Bellows W, Ngo L, et al. Assessment of ventricular function in critically ill patients: Limitations of pulmonary artery catheterization. Institutions of the McSPI Research Group. J Cardiothorac Vasc Anesth. 1999;13:521–527. 6. American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Practice guidelines for pulmonary artery catheterization: An updated report. Anesthesiology. 2003;99:988–1014.

ADDITIONAL READING

• Miller RD. Miller’s anesthesia, 7th ed. Philadelphia: Churchill Livingstone, 2009.

See Also (Topic, Algorithm, Electronic Media Element) • Cardiac output • Mitral stenosis • Mitral regurgitation • Left ventricular hypertrophy • Dilated cardiomyopathy • Positive end expiratory pressure (PEEP)

CLINICAL PEARLS

• LVEDP (pressure) is a surrogate measurement for LVEDV (volume). • The assumption that the pulmonary artery catheter is in continuity with the left ventricle during diastole is only valid when the catheter is in the West zone 3 of the lungs (e.g., where the pulmonary venous pressure is greater than the airway pressure). • In using CVP and PAWP as a marker of LVEDP, it is important to be aware of the caveats of interpreting the readings. Any situation which anatomically or physiologically interrupts the continuity of blood in the heart during diastole will alter the CVP or PAWP readings. Conditions, such as mitral stenosis or regurgitation, pulmonary regurgitation, and aortic regurgitation, will all cause an overestimation or underestimation of the LVEDP by the CVP and PAWP. • The pressure volume curve in the heart is curvilinear and shifts to the right with increased LV compliance or the left with decreased compliance.

LIVER FUNCTION TESTS Jason Han Chua, MD Anahat Dhillon, MD

BASICS DESCRIPTION

• “Liver function tests” (LFTs) is the common vernacular for the standard biochemistry profile provided by most laboratories. It typically includes: – Aspartate aminotransferase (AST or SGOT) – Alanine aminotransferase (ALT or SGPT) – Alkaline phosphatase – Bilirubin (total, unconjugated, conjugated) – Albumin • LFTs are more accurately described as tests of overall liver health (metabolic and synthetic function) or inflammation (necrosis). • True, specific tests of liver function (galactose clearance, aminopyrine clearance) are not widely used. PHYSIOLOGY PRINCIPLES

• Aspartate transaminase (also known as serum glutamic oxaloacetic transaminase [SGOT]) is an enzyme found in liver parenchymal cells, brain, heart, kidneys, muscle, and red blood cells. It is responsible for transferring the aspartate amino group to ketoglutaric acid. Elevated levels may indicate tissue damage or inflammation. • Alanine aminotransferase (also known as serum glutamic pyruvic transaminase [SGPT]) is an enzyme found primarily in liver parenchymal cells and, to a lesser extent, in the heart, kidneys, and muscle. It is responsible for transferring the alanine amino group to ketoglutaric acid. Values provide a measure of hepatic damage or inflammation and are considered more specific than AST values. • Alkaline phosphatase is an enzyme that catalyzes hydrolysis of phosphate esters at an alkaline pH. More than 80% is found in the liver and bone; minor sites include the placenta, intestine, and kidney. Measurements indicate inflammation, particularly in the biliary tract. • Bilirubin is the byproduct of heme catabolism. When hemoglobin is released from red blood cells (normal breakdown, damaged or old cells), the globin is turned into amino acids. In reticuloendothelial cells, the heme is converted into unconjugated bilirubin which is waterinsoluble and binds to albumin. The liver conjugates it with glucuronic acid to form conjugated bilirubin, which is water-soluble. Bilirubin values can, thus, provide a measure of hepatic metabolic function. • Albumin is synthesized by the liver and comprises 60% of plasma proteins. It has a serum half-life of approximately 20 days. Measurements indicate hepatic synthetic function, but do not necessarily reflect acute processes. Normal adult values: 3.4–5.4 g/dL. PHYSIOLOGY/PATHOPHYSIOLOGY

• As many as 1/3rd of patients screened may have a nonspecific abnormality in LFTs. Incidence of clinically significant disease is ∼1%. • Differential diagnosis can be broken down into: – Hepatocellular inflammation or dysfunction: Inflammation and necrosis of hepatocytes result in the release of AST and ALT (e.g., hepatitis A). Normal levels of AST and ALT do not fall within a Gaussian distribution. Instead, distribution is skewed rightward, meaning levels up to 1.5 the upper limits of “normal” do not necessarily suggest liver disease. Hepatic dysfunction results in decreased metabolic and/or synthetic function. – Cholestatic disease: Includes intrahepatic and extrahepatic processes and is usually accompanied by an elevation in bilirubin (direct or indirect) and/or alkaline phosphatase. – Infiltrative disease such as amyloidosis can result in the release of AST and ALT as well as decreased metabolic and synthetic function. • Clinical history is important to help differentiate between causes: – Family history is relevant since many genetic disorders can affect liver function (Gilbert’s and Dubin Johnson, Wilson’s disease, etc.). – Sexual and social history, travel, and work exposure can also point to causes such as viral hepatitis. – Systemic conditions affecting LFTs include cardiac disease, inflammatory bowel disease, diabetes, arthritis, hypogonadism, and thyroid disease. • Transaminases: – Since AST is less specific for liver disease, an isolated elevation can suggest cardiac or muscular disease. – An elevated AST/ALT ratio >2 is more likely to be associated with alcoholic hepatitis. When it is 3 weeks duration, or in rapidly progressive liver disease, where albumin is consumed rapidly – Lower in parturients – In the absence of other liver test abnormalities, low albumin is usually due to non-hepatic causes such as proteinuria or malnutrition. • Prothrombin time: – Measures activity of vitamin K-dependent clotting factors which are synthesized in the liver – Cholestasis prevents absorption of vitamin K; hepatocellular disease prevents synthesis of factors. • Miscellaneous: – IgM, ANA: Elevated in autoimmune disease – Low serum copper, uric acid, and ceruloplasmin indicate Wilson’s disease. – Transferrin saturation >60% suggests hemochromatosis.

PERIOPERATIVE RELEVANCE

• Preoperative LFTs can aid with diagnosing disease/hepatic insults and assessing severity. • Associated disease: – Infectious diseases (Hepatitis B, C): Care must be taken to minimize practitioner exposure. – Hepatorenal syndrome: Renal failure associated with hepatic failure. May be reversible or irreversible. Increased morbidity/mortality due to risk of fungemia, uremia, etc. – Hepatopulmonary syndrome: Elevated pulmonary arterial pressure and increased extracardiac shunting leading to hypoxemia • Severity-dependent considerations: – Encephalopathy: Increased risk in the presence of portocaval shunt – Ascites, increased intra-abdominal pressure: Increased risk of aspiration and desaturation – Coagulopathy: Transfusion may be indicated in procedures that may not otherwise require blood; patients requiring transfusion are more prone to citrate toxicity. – Vasoplegia, low SVR: Higher cardiac output required to maintain blood pressure • Postoperative abnormal LFTs can occur in up to 25–75% of patients without liver disease, and mild elevations are considered typical. Postoperative jaundice typically presents within 2 weeks following surgery and is unusual in patients without liver disease. It is commonly the result of a combination of hypotension, hypoxemia, pigment overload, and sepsis.

EQUATIONS

Child-Pugh score: • Class A = 0–1 point, good prognosis • Class B = 2–4 points • Class C = ≥5 points, limited life expectancy Table 1 Relevant Child-Pugh Scores

REFERENCE

1. Faust TW, Reddy KR. Postoperative jaundice. Clin Liver Dis. 2004;8:151–166.

2. Kamath PS. Clinical approach to the patient with abnormal liver test results. Mayo Clin Proc. 1996;71:1089–1096.

3. Kaplan MM. Laboratory tests. In: Schiff L, Schiff ER, eds. Diseases of the liver, 7th ed. Philadelphia, PA: Lippincott, 1993:108–144. 4. Quinn PG, Johnston DE. Detection of chronic liver disease: Costs and benefits. Gastroenterologist. 1997;5:58–77. See Also (Topic, Algorithm, Electronic Media Element) • Postoperative jaundice • End-stage liver disease • Prothrombin time

CLINICAL PEARLS

• Of the routine LFTs, only albumin, bilirubin, and PT are actual indicators of liver function. • Patients with cirrhosis can have “normal LFTs.” • Mildly elevated ALT can be due to normal age and gender variability or muscle injury.

LIVER RESECTION Michelle Braunfeld, MD

BASICS DESCRIPTION General

• Liver resections are performed to remove diseased liver parenchyma: Tumors (primary and secondary), cysts, and adenomas. It is not suitable for severely cirrhotic livers because of the risk of postoperative hepatic failure. • Outcome and, hence, the decision to resect, are dependent on the location, number, and distribution of the mass, as well as the amount of liver that will remain. The liver has significant reserve capacity that allows a large portion to be excised. Additionally, it has the capability to regenerate; occasionally portal vein embolization may be performed to facilitate this. • Modalities prior to resection: – Tumor shrinkage may be achieved with chemotherapy; it can either be systemic or directed. Intra-arterial therapies can be utilized to decrease whole-body adverse effects. It involves threading a catheter through the femoral artery in the groin to the feeding vessels. – Radiofrequency ablation (RFA): May be performed percutaneously with the aid of imaging modalities or direct visualization during open procedures (or laparoscopic surgery). The tip of a needle probe is heated utilizing alternating electric current to destroy tumors. Alternatively, microwave ablation may be performed, particularly for tumors near largediameter vessels. – Portal vein embolization: Blood vessels to the tumor are embolized, and nutrients and flow are diverted to the other side with the goal of facilitating growth/regeneration. Repeat imaging to assess hypertrophy is recommended 3–4 weeks after embolization. • Following dissection, hepatic resection is either: – Anatomic: Margins defined by segmental liver anatomy – Non-anatomic: Margins defined by tumor • Surgical maneuvers to decrease bleeding include portal triad clamping (Pringle’s maneuver) and selective hepatic venous occlusion. Pringle’s maneuver is generally without hemodynamic consequence to the patient. Hepatic tolerance of this maneuver is enhanced by intermittent clamping for 15 minutes followed by unclamping for 5 minutes. Selective hepatic venous occlusion (occlusion of the hepatic venous branches without caval compromise) has been shown to be as effective as a low CVP (central venous pressure) technique for reducing blood loss in patients who are unable to tolerate a CVP Sciatic > Spinal. – Type of local anesthetic: More potent, longer-acting LAs tend to be more toxic. The S(–) isomers (levobupivacaine and ropivacaine) seem to be less toxic than R(+) isomers or racemic bupivacaine.

– Technique and dosage Dose = volume × concentration Unnecessarily high dosing can increase the risk of serious toxicity if intravascular uptake occurs. Studies on ultrasound-guided regional blockade have indicated that with proper placement, smaller doses can provide adequate blockade. • Individual patient risk factors: – Patients at extremes of age (70 years) – History of cardiac conduction defects or ischemic heart disease – Cardiac, renal, and hepatic dysfunction are important predictors of local anesthetic plasma levels after a specific dose rather than body weight or BMI.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The mechanism of LA toxicity is highly controversial. Due to ethical concerns, no human randomized controlled trials exist. Data on this topic relies on animal studies and case reports. • In general, the CNS is more sensitive to LA toxicity than the CV system. For most local anesthetics, CV toxicity does not occur until 3 times the concentration necessary to produce seizures. This CV/CNS ratio tends to be lower with bupivacaine. • Hypoxia and hypercarbia can decrease the convulsive threshold and predispose to myocardial toxicity. • CNS toxicity: 2-phase pathophysiologic process: – First, preferential blockade of the inhibitory CNS pathways leaves the excitatory pathways unopposed. This can manifest as shivering/muscle tremors and proceed to tonic–clonic seizures. – With increasing plasma levels, both inhibitory and excitatory pathways are blocked. Generalized CNS depression ensues with potential respiratory arrest. • CV toxicity: One of the primary mechanisms of CV toxicity is thought to be from binding and inhibition of Na+ channels by LAs. At higher concentrations, it is believed that cardiac Ca2+ and K+ channels are also inhibited. LAs are also thought to antagonize betaadrenergic receptors. 2-phase pathophysiologic process: – In the CNS excitatory phase, activation of the sympathetic nervous system results in tachycardia and hypertension. – With increasing plasma levels, bradycardia, hypotension, and ventricular arrhythmias occur.

PREVENTATIVE MEASURES

According to the 2010 American Society of Regional Anesthesia (ASRA) practice advisory: • Use lowest effective dose of LA • Incremental dosing: Pause 15–30 seconds between each 3–5 mL dosing. • Aspirate for blood prior to each injection. • Consider using a pharmacologic marker/test dose to identify inadvertent intravascular injection: – Epinephrine 15 μg produces a greater than 10 beat increase in heart rate or a greater than

15 mm Hg increase in systolic blood pressure. – Note that beta-blockers, advanced age, labor, and general/neuraxial anesthesia may inhibit this response. – Fentanyl 100 μg produces sedation in laboring patients. • Ultrasound guidance: Reportedly decreases the incidence of intravascular injection. Whether it decreases actual incidence of LA systemic toxicity still remains to be answered.

DIAGNOSIS • Classically in LA systemic toxicity, CNS symptoms are followed by CV symptoms. However, in review of case reports, there is extreme variability in presentation. • Particularly with potent local anesthetics, cardiac toxicity may occur simultaneously or precede seizures. Sometimes CV toxicity is the only manifestation. • CNS toxicity: – Classic early symptoms: Circumoral numbness, metallic taste, lightheadedness, visual/auditory disturbances, agitation/tremors – Later symptoms: Seizure, coma, respiratory arrest • CV toxicity: – First, cardiac excitation: Tachycardia, hypertension, ventricular arrhythmias – Later, CV depression: Bradycardia, hypotension, decreased contractility, asystole

DIFFERENTIAL DIAGNOSIS

Pain during uterine contraction may also produce increased heart rate.

TREATMENT • Airway management is of utmost importance. Prevention of hypoxia and hypercarbia/acidosis can halt progression of LA toxicity to seizures and/or CV collapse, as well as aid in successful resuscitation. • For seizures, the first-line therapy is benzodiazepines. Small doses of thiopental or propofol may also be used, realizing this may worsen hypotension/CV depression. Avoid propofol when there are signs of CV compromise. Future studies may support lipid infusion as the initial treatment. • If seizures persist, consider small doses of neuromuscular blockers to halt muscle contractures, thus preventing further oxygen consumption and CO2 production. Seizures

(electrical function) may continue despite a lack of tonic–clonic muscle activity. • For cardiac arrest, perform standard ACLS with the following modifications: – Small doses of epinephrine (30 minutes after injection. • Consider LA toxicity in any patient with altered mental status, neurologic symptoms, or CV instability following a regional anesthetic. • Note that >40% of cases do not follow the classic presentation of local anesthetic systemic toxicity. Cardiovascular signs may be the only manifestation in severe cases.

LOWER EXTREMITY AMPUTATION Menelaos Karanikolas, MD, MPH

BASICS DESCRIPTION General

• Lower extremity (LE) amputation is one of the oldest known surgical procedures. It can be classified as: – Minor: Removal of a toe or part of the foot – Major: Removal of part of the leg. It is further described as a below-the-knee amputation (BKA) or an above-the-knee amputation (AKA). • Indications for LE amputation include: End-stage peripheral vascular disease (PVD), trauma, tumor, infection, congenital limb deficiency, and painful, non-functional limbs. In recent years, as prosthesis technology has advanced, the indications for elective amputation have expanded. • Surgical technique is important for long-term functional outcome. Use of a pneumatic tourniquet reduces blood loss and the need for transfusion (1)[B]. After incision, the muscle compartments are isolated, and the main arteries, veins, and nerves are identified. Arteries and veins are ligated separately, in order to avoid arteriovenous fistula formation. Nerves are transected under tension as proximally as possible, and are then allowed to retract in the soft tissues, in an attempt to avoid neuroma formation. • The bone is cut and the bony edges are smoothed, to minimize postoperative soft-tissue trauma and pain with application of a prosthesis. Several techniques (myoplasty or myodesis) can be used to place muscle over the cut end of the bone. Enough skin should be preserved to cover the muscle and achieve a symmetric, smooth, tension-free closure. At the end of surgery, drains are placed to avoid formation of wound hematoma. • A guillotine (or open) amputation is a quicker procedure, and is reserved for cases with infection, contaminated trauma, or uncertain survival; it leave an open wound at the end of the stump. Blood vessels are ligated and nerves are cut as described above, but the wound is not closed. Instead, the stump is dressed with gauze and application of bandages. Later, when the risk of infection is reduced, the amputation can be revised higher or grafted. • Postoperative pain, depression, need for rehabilitation, and appropriate application of prosthesis are important long-term considerations. Position

Supine: A bump under the hip is often used to limit limb rotation. Incision

Anterior and posterior, above the line of ischemic tissue demarcation Approximate Time

1–2 hours

EBL Expected

• BKA: 200 mL • AKA: >250 mL

Hospital Stay Up to 7 days

Special Equipment for Surgery

• Saw or guillotine • Pneumatic tourniquet • Vascular and orthopedic instruments

EPIDEMIOLOGY Incidence

In the US: 30,000–40,000 procedures per year (2)[B] Prevalence

In the US in 2005, 1.6 million people lived with loss of a limb; this number is projected to double by 2050 (2)[B].

Morbidity

Cardiac, respiratory (most patients are smokers), infection (most patients have diabetes), nonhealing wound, re-amputation, acute pain, phantom limb pain (PLP), and stump pain Mortality

Very high given the comorbidities of the patient population. Median survival is 20–27 months after AKA and 52 months after BKA (3)[B]. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintain hemodynamic stability: These patients are at high risk for coronary artery disease; thus, hypotension and tachycardia should be avoided. Tourniquet pain can cause tachycardia and hypertension, which can be treated with beta-blockers, opioids, or increasing the anesthetic depth. Depending on preoperative hemoglobin and surgical blood loss, transfusion of RBCs may be needed. • Use of an epidural or regional block has the advantage of avoiding general anesthesia and mechanical ventilation, and may decrease intraoperative and immediate postoperative pain. It is not clear, however, if it decreases the incidence of PLP (4)[B].

PREOPERATIVE ASSESSMENT SYMPTOMS

• Severe ischemic and/or neuropathic LE pain • Symptoms of coronary artery disease or ischemic cardiomyopathy

History

Inquire about diabetes, smoking, hypertension, chronic obstructive pulmonary disease, symptoms of coronary artery disease or congestive heart failure. Confirm the timing of hemodialysis in patients with renal failure. Signs/Physical Exam

No special considerations MEDICATIONS

• Beta-blockers should be continued perioperatively. • Antiplatelet agents: Generally should be discontinued for 7–14 days before surgery. However, the risk of discontinuation (e.g., thrombosis to coronary or cerebral vasculature) should be discussed with the surgeon and primary care physician. Additionally, it is not always feasible when the amputation is urgent. • Oral antihyperglycemics should be held on the morning of surgery to avoid hypoglycemia while the patient is NPO. Blood glucose can be checked perioperatively, and insulin can be administered to treat hyperglycemia. • Antihypertensive medications should generally be continued throughout the perioperative period. ACE inhibitors, however, have been associated with severe hypotension and should perhaps be discontinued 24–48 hours before surgery. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• EKG (coronary artery disease) • Hemoglobin: Values >10 g/dL are recommended to ensure adequate oxygen delivery for wound healing. • Blood glucose in diabetic patients: Hyperglycemia is associated with increased risk of infection. • Serum albumin: Values 50% regurgitant volume • Effective regurgitant orifice area >0.4 cm2 • Color Doppler vena contracta >0.7 cm • Pulmonary vein flow reversal on ventricular systole • Severe LA enlargement • MR jet ‘V’ wave and PCWP cannon “V” wave

TREATMENT PREOPERATIVE PREPARATION Premedications

Midazolam to prevent anxiety and increased sympathetic tone. Special Concerns for Informed Consent

Risk for intraoperative stroke, myocardial infarction, and death should be discussed.

INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on the procedure; sedation, general (endotracheal tube or laryngeal mask airway), and regional anesthesia may be utilized. • Neuraxial techniques can result in a sympathectomy and facilitate forward flow (reduce regurgitation), but may reduce coronary perfusion pressure.

Monitors

• Standard ASA monitors. • Invasive monitors may be chosen based upon the severity of MR and the surgical procedure: 5 lead EKG, arterial line, central venous catheter, pulmonary artery catheter, transesophageal echocardiogram or less invasive cardiac output monitors.

Induction/Airway Management

• Smooth controlled induction to maintain vital signs within normal limits. • Anticholinergic medications may be administered to maintain high-normal heart rate.

Maintenance

• Volatile anesthetics, intravenous, or a combination may be utilized. Reductions in systemic vascular resistance are desirable to facilitate forward flow; however, adequate cerebral and coronary perfusion should be ensured. Total intravenous techniques may be associated with bradycardia, particularly if utilizing high doses of remifentanil. • Fluid balance includes maintaining normal preload and a hematocrit >24–30% to optimize forward flow and myocardial oxygen balance. Excessive preload may add to regurgitant volume and cause LV failure.

Extubation/Emergence No additional concerns

POSTOPERATIVE CARE BED ACUITY

Depends on surgical procedure and severity of underlying disease. MEDICATIONS/LAB STUDIES/CONSULTS

Standard postoperative fluid and electrolyte management and related laboratory studies. COMPLICATIONS

Perioperative arrhythmia

REFERENCES

1. Moustafa SE, et al. Global left atrial dysfunction and regional heterogeneity in primary chronic mitral insufficiency. Eur J Echocardiogr. 2011; 12(5):384–393. 2. Rusinaru D, et al. Left atrial size is a potent predictor of mortality in mitral regurgitation

due to flail leaflets: Results from a large international multicenter study. Circ Cardiovasc Imaging. 2011; 4(5):473–481. 3. Lai HC, et al. Mitral regurgitation complicates postoperative outcome of noncardiac surgery. Am Heart J. 2007;153(4):712–717. 4. Grigioni F, et al. Ischemic mitral regurgitation: Long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103:1759–1764.

ADDITIONAL READING

• 2006 American College of Cardiology/American Heart Association guidelines.

CODES ICD9 • 394.1 Rheumatic mitral insufficiency • 424.0 Mitral valve disorders • 746.6 Congenital mitral insufficiency ICD10 • I05.1 Rheumatic mitral insufficiency • I34.0 Nonrheumatic mitral (valve) insufficiency • Q23.3 Congenital mitral insufficiency

CLINICAL PEARLS

• Etiologies of mitral regurgitation are either: – Organic from intrinsic valvular causes such as myxomatous, rheumatic, or calcific disease. – Functional from non-valvular causes such as dilated cardiomyopathy that result in incomplete closure. • Mitral regurgitation is described based upon onset: – Acute: life-threatening and may require immediate surgical management. – Chronic: requires medical or surgical management and may be asymptomatic until late stages. • Severity is classified by echocardiographic criteria. Severe MR will have a regurgitant volume that is >60 mL or >50%, or an effective regurgitant orifice area >0.4 cm2. Significant signs and symptoms are present (shortness of breath, systolic and diastolic congestive heart failure).

MITRAL STENOSIS Brian L. Marasigan, MD

BASICS DESCRIPTION

• Mitral valve stenosis (MS) is a narrowing of this area at the valve itself. New criteria for diagnosis of severe mitral stenosis includes an open area of 10 mm Hg, although symptoms may begin at much earlier stages of stenosis. EPIDEMIOLOGY Incidence

Most common after rheumatic fever with a latency period of 10–25 years in under-developed countries to 20–40 years in developed countries. Prevalence

• Women: 1.6% • Men: 0.4% (1)[B]

Morbidity

• Risk for congestive heart failure, atrial fibrillation, thromboembolism, stroke, pulmonary hypertension, right-sided heart failure, and pulmonary edema. • Mitral stenosis with atrial fibrillation increases the risk of stroke 7–15% per year (2)[B]. • Mild to moderate MS may be asymptomatic except during exertion, while severe MS symptoms occur at rest. • LV dysfunction may occur in 30% of MS patients. Mortality

2-year mortality for infants with severe congenital MS is 40% (3)[B].

ETIOLOGY/RISK FACTORS

• Majority of cases are due to rheumatic fever and resultant rheumatic heart disease. • Severe mitral calcification and congenital mitral stenosis are uncommon causes.

PATHOPHYSIOLOGY

• The basic pathophysiology of MS stems from obstruction of left ventricular filling with a highly resistant valve opening. The disease process progresses as follows: – Initially, the resistance to left ventricular filling is compensated by left atrial hypertrophy (enhanced atrial kick). – With time, the left atrium begins to dilate to handle the increase in volume – However, the volume overload eventually overwhelms the left atrium and LV filling

becomes impaired. Fluid backs up into the pulmonary vasculature leading to pulmonary congestion, left congestive heart failure, and resultant right heart failure. • Left atrial enlargement increases the risk for developing atrial fibrillation. In addition, the decreased flow state increases the risk for thrombus formation. • Normal sinus rhythm and a slow rate are desired to allow time for forward flow and filling of the left ventricle

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Primary goals are the maintenance of: – Cardiac output – Coronary perfusion (diastolic perfusion pressure) – Normal and slow sinus rhythm – Volume status – Prevention of cardiac decompensation • Inotropic support may be necessary to prevent cardiovascular overload or collapse. Vasopressor support and fluid maintenance may help maintain preload and coronary perfusion pressure. • Pulmonary hypertension is a major concern and may persist after mitral valve repair. Resulting right ventricular (RV) dysfunction may be a greater concern than left ventricular (LV) dysfunction.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Severity of symptoms may be classified by NYHA I–IV. • Exertional shortness of breath, orthopnea, fatigue, palpitations, and rarely chest discomfort. • Severe symptoms occur from pulmonary edema, pulmonary hypertension, and decreased cardiac output with resultant dyspnea, angina, cough, and hemoptysis.

History

Commonly diagnosed after symptomatic exercising, during work up for diastolic or systolic CHF, or new onset atrial fibrillation. Signs/Physical Exam

• Mid-diastolic murmur with opening S2 snap. • Congestive heart failure (jugular venous distention, pitting edema, shortness of breath) and increased sympathetic tone (cool extremities, hypertension, etc.). • In infants: Cyanosis, poor growth, shortness of breath.

TREATMENT HISTORY

• Balloon mitral valvuloplasty or valve replacement • Atrial fibrillation: Ablation

MEDICATIONS

• Beta blockers to maintain a slow normal sinus rhythm.

• Heart failure treatments including digoxin and ACEI/ARBs, diuretics, nitrates. • Anticoagulants to prevent or treat thrombus. • Atrial fibrillation: Amiodarone, beta blockers, calcium channel blockers.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Basic metabolic profile: Electrolytes and kidney function aid with perioperative management and risk stratification (renal failure carries an increased risk of mortality). • Complete blood count: Preoperative infection, hematocrit, and platelet counts adequate for surgery. • Basic coagulation studies • Chest X-ray: Active congestive heart failure. • Transesophageal echocardiogram: Diagnosis and classification of disease severity and ventricular function. • Cardiac catheterization: Cardiac function and pulmonary pressure evaluation.

CONCOMITANT ORGAN DYSFUNCTION

• Cardiac: Left ventricular dysfunction, hypertension; mitral regurgitation (due to poor valve closure); aortic stenosis or regurgitation in rheumatic heart disease. • Pulmonary: Hypertension, congestion, and pleural effusion.

CIRCUMSTANCES TO DELAY/CONDITIONS • Decompensated congestive heart failure • Sepsis or infection

CLASSIFICATIONS

• Based upon echocardiographic or cardiac catheterization measurements of valve area and transvalvular pressure gradients. • Mitral stenosis severity by valve area. – Normal: 4–6 cm2 – Mild stenosis: 5 mm: Classic prolapse • O2 delivered. An increase in demand

(increased metabolic requirement) is met by an increase in CO (increased HR, SV) or oxygen extraction (75% reserve). However, after the compensatory mechanisms are exhausted, demand > consumption, the tissue/cell resorts to anaerobic metabolism (without oxygen) in order to maintain cellular function. • Low MvO2 states: Potential increase in O2 demand/consumption, or reduced CO, Hg, or arterial saturation – Increased O2 demand/consumption: Fevers, seizures, shivering, fighting ventilator,

malignant hyperthermia, thyroid storm. If the patient has adequate cardiac reserve, the body will compensate by increasing CO, to preserve tissue oxygenation. With increasing demand above that, the body will compensate by increasing O2 extraction from the

arterial blood. – Reduced CO: Ischemia, infarction, negative inotropes, increased afterload, acute failure, reduced SV or hypovolemia, shock, arrhythmias, tamponade. When this occurs, the only available mechanism is to increase O2 extraction. Poorly tolerated compared to other causes of reduced MvO2.

– Reduced Hg: Hemorrhage, anemia, surreptitious blood loss. Mild reductions can often be met by increased CO in a patient with adequate cardiac reserve. Significant blood loss is met by an increase in CO and O2 extraction from the arterial blood. If the patient has

reduced cardiac reserve, they are at risk of tissue/cell hypoxia. – Arterial desaturation: Atelectasis causing reduction in FRC from positioning, insufflations, fluid overload, retractors, or other V/Q mismatch such as pulmonary embolism. Met by increased CO, followed by O2 extraction and does not necessarily result in anaerobic

metabolism or lactic acidosis if compensated for. • High MvO2 states: Potential reduced O2 demand/consumption, increased O2 sat%, Hg, or CO; arterialized venous sample. – Reduced O2 demand/consumption: Hypothermia, anesthesia, pharmacologic paralysis.

– Sepsis results in inappropriate shunting of blood away from cells/tissues that need O2, leaving them poorly oxygenated and resorting to anaerobic metabolism. This is a maladaptation, given that the shunted blood returns to the heart highly oxygenated or

unused (increased MvO2) (2,3).

– AVMs and other large shunts can also create a similar clinical scenario (increased MvO2

despite oxygen deprivation, secondary to inappropriate shunting of blood away from tissues). – Cyanide poisoning prevents utilization of O2 at the cellular level because oxidative enzymes are blocked or only partially functional; prevents Hgb unloading from capillary blood. Blood returns highly oxygenated, (increased MvO2), despite cell hypoxia.

– Increased arterial saturation: Increased FIO2, increased FRC (alveolar recruitment from PEEP, larger tidal volumes, positioning such as reverse Trendelenburg, removal of abdominal retractors), improved V/Q matching. – Increased Hg: Blood transfusion. – Increased CO: Increased inotropy from medication, sympathetic stimulation, reduced afterload, increased preload (Starling curve), resolution of arrhythmia, increased heart rate (4). – A wedged PAC samples blood from surrounding alveoli that has been oxygenated; referred to as “arterialized” sample.

PERIOPERATIVE RELEVANCE

• When there is an imbalance of O2 supply to demand, the body mobilizes its compensatory mechanisms to ensure adequate availability; increased O2 extraction and CO.

• Intraoperatively, O2 is usually at steady state consumption, and a reduction should prompt a search for reduced tissue delivery, often from reduced CO, but also from low Hg or O2 sat%

(4). Reduced CO is problematic, as it removes one of the body’s compensatory mechanisms for tissue/cell oxygenation. • Studies have demonstrated that a decrease in MvO2 generally precedes or indicates

imminent cardiac failure (10–15 minutes prior) as well as poor overall prognosis. In addition, consequent lactic acidosis is presumptive evidence of tissue hypoxia and is also associated with a poor prognosis. • In the ICU, it can be utilized to monitor, assess, and guide therapy during sepsis. • ScVO2 may be utilized, as it is less invasive and is more routinely inserted in critically ill patients. Values should be evaluated with caution as it reflects the degree of O2 extraction

from the brain and upper body (1). • PAC migration often occurs in cardiac surgery when the heart is being manipulated. Deflate the balloon and pull the catheter back 1–3 cm.

EQUATIONS •

13.9 = K factor (derived from 1.39 × 10, see below) • MvO2 normal values: – Mixed venous oxygen saturation = 60–80%

– Mixed venous partial pressure = 35–45 mm Hg • Venous oxygen content; CvO2 = 15.5 mL/dL

– O2 dissolved + O2 bound to Hg {Hg × 1.39 × MvO2) + PvO2(0.003) = 15.5 mL/dL. – 1.39 = mL of O2 that can bind to 1 g of Hb

– 0.003 = solubility coefficient of O2 in plasma

– (15 × 1.39 × 0.75) + 40(0.003) = 15.5 mL/dL • Venous O2 transport = DvO2 = 775 mL O2/min. – CvO2 × CO × 10 = 775 mL O2/min

– 15.5 mL/dL × 5 L/min × 10 = 775 mL O2/min

– Multiplying by 10 allows to convert from dL to mL • Arterial oxygen content; CaO2 = 20.1 mL/dL – Arterial O2 Saturation = SaO2-95–98%

– Arterial O2 partial pressure = 80–100 mm Hg

– O2 dissolved + O2 bound to Hg

– [Hg × 1.39 × SaO2] + [PaO2(0.003)] = 20.1 mL/dL

– (15 × 1.39 × 0.97) + 100(0.003) = 20.1 mL/dL • Arterial O2 transport = DO2 = 1005 mL O2/min – CaO2 × CO × 10 = 1005 mL O2/min

– 20.1 mL/dL × 5 L/min × 10 = 1005 mL O2/min

• VO2 = Arterial O2 transport – Venous O2 transport – = (CO × CaO2 × 10) – (CO × CvO2 × 10)

– = CO (CaO2 – CvO2) × 10

– = CO × [(Hg × 1.39 × SaO2)−(Hg × 1.39 × SvO2)] ×10

– = CO × Hg ×1.39 × (SaO2−SvO2) × 10 – = CO × Hg × 13.9 × (SaO2 – SvO2)

– = (5 L/min × 15 g/dL × 13.9) × (0.97−0.75) – Note that the O2 dissolved in plasma is excluded because it is miniscule – = 230–250 mL O2/minute

– Extraction = 250/1005 mLO2 = 25%

REFERENCES

1. Ho KM, Harding R, Chamberlain J, Bulsara M. A comparison of central and mixed venous oxygen saturation in circulatory failure. J Cardiothoracic Vasc Anesth. 2010;24(3):434– 439. 2. Edwards JD. Oxygen transport in cardiogenic and septic shock. Crit Care Med. 1991;19(5):658–663.

3. Shoemaker WC, Appel PL, Kram HB, Bishop M, Abraham E. Hemodynamic and oxygen transport monitoring to titrate therapy in septic shock. New Horiz. 1993;1(1):145–159. 4. Cariou A, Monchi M, Dhainaut JF. Continuous cardiac output and mixed venous oxygen saturation monitoring. J Crit Care. 1998;13(4):198–213.

ADDITIONAL READING

• Kelly KM. Does increasing oxygen delivery improve outcome? Yes. Crit Care Med. 1996;12(3):635–644. • Yu M, Levy MM, Smith P, Takiguchi SA, Miyasaki A, Myers SA. Effect of maximizing oxygen delivery on morbidity and mortality in critically ill patients: A prospective, randomized controlled study. Crit Care Med. 1993;21(6):830–838.

See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary artery catheter • Cardiac output • Sepsis

CLINICAL PEARLS

• Mixed venous oxygenation saturation provides a measurement and tool to assess tissue oxygenation in the perioperative and intensive care unit period. Most of the current monitors of perfusion are on a global level. • The venous oxygen saturation is directly measured and inferences about the contributing factors can be made (hemoglobin levels, oxygen consumption, and cardiac output).

MULTIPLE MYELOMA Keyuri Popat, MD

BASICS DESCRIPTION

• Multiple myeloma describes the abnormal, excessive growth of a single clone of plasma cells with a resultant monoclonal immunoglobulinopathy. • These abnormal plasma cells grow in the bone marrow resulting in extensive skeletal destruction with osteolytic lesions, osteopenia, and/or pathologic fractures. • Patients with multiple myeloma may present for interventional pain therapy, spinal cord decompression, bone marrow transplant, pathological fracture repair, or other non-related procedures. EPIDEMIOLOGY Incidence

Approximately 1% of all cancers. Prevalence

• Approximately 10% of all hematologic malignancies • Age adjusted incidence has remained stable at 4 per 100,000 persons • Median age of onset 66 years • Men > women • African Americans > Caucasians

Morbidity

Incurable disease Mortality

Responsible for approximately 20% of deaths from hematologic malignancies; 2% of deaths from all cancers ETIOLOGY/RISK FACTORS

• First degree relatives have a 3.7-fold increase in incidence • More common in farmers, miners and those with wood dust exposure

PATHOPHYSIOLOGY

• Multiple myeloma is a clonal B cell malignancy. While some steps of replication of the malignant clone have been discovered, many remain unknown. Almost all myeloma cases are preceded by a premalignant plasma cell proliferative disorder known as monoclonal gammopathy of undertermined significance (MGUS). MGUS is present in over 30% of the population above the age of 50 years, and progresses to myeloma or a related malignancy at

a rate of 1% per year. • The disease is characterized by the aberrant expansion of plasma cells within the bone marrow as well as extramedullary sites. The most common sites are the back and chest; extramedullary plasmacytomas can be found in the oronasopharynx and paranasal sinuses and rarely throughout the gastrointestinal system, lung, and central nervous system. • Bone lesions: The abnormal proliferation of the plasma cell line results in overcrowding and encroachment of normal progenitor cells. This results in classic bone pain with lytic lesions that can present on routine skeletal films. • Hypercalcemia may be either symptomatic or discovered incidentally. This is due to increased bone resorption, which in turn is due to the release of osteoclast activating factors such as lymphotoxin, interleukin-6, hepatocyte growth factor, and receptor activator of nuclear factor kappa B ligand (RANK ligand). • Immune system: Patients with myeloma are prone to infection due to a combination of immune dysfunction and physical factors. Immune dysfunction results from impaired lymphocyte function, suppression of normal plasma cell function, and hypogammaglobulinemia (due to suppression of normal gamma globulin). Physical factors that predispose to pulmonary infection include hypoventilation secondary to pathologic fractures and pain involving the rib cage. • POEMS syndrome (osteosclerotic myeloma): Polyneuropathy, Organomegaly, Endocrinopathy (hypogonadism, adrenal insufficiency), Monoclonal protein, Skin changes is a rare presentation of monoclonal cell disorder due to chronic overproduction of proinflammatory and other cytokines (e.g., vascular endothelial growth factor). Microangiopathy, edema, effusions, increased vascular permeability, neovascularization, polyneuropathy, and pulmonary hypertension are also features of this syndrome.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assessment of concomitant organ dysfunction should be performed, with the anesthetic tailored as needed (e.g., renal disease requiring adjustments to medication doses). • Patients may have significant pain and be on chronic analgesia; appropriate pain management should be provided. • Careful patient positioning should be performed given the possibility of skeletal destruction, radiculopathy, and cord compression. • Macroglossia can result from amyloid deposition in approximately 15% of patients and may present difficulty with airway management.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Pain • Fatigue • Paralysis/paraparesis

History

• Bone pain

• Neuropathy secondary to chemotherapy • Thrombosis secondary to thalidomide • Renal failure • Anemia • Infection • Spinal cord compression

Signs/Physical Exam

• Fracture • Kyphosis • Motor and sensory neurologic deficit • Macroglossia

MEDICATIONS

• Thalidomide, bortezomib, and lenalidomide (are at higher risk for thrombosis and rarely of interstitial lung disease) • Vincristine, doxorubicin, and dexamethasone • Analgesics • Erythropoietin

TREATMENT • Stem cell transplantation • Blood, platelet, plasma transfusions • Plasma exchange (patient’s plasma is removed on a cell separator and replaced with transfusions of human albumin or synthetic plasma)

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, including calcium level • BUN/Creatinine • Complete blood count • Urinalysis for proteinuria: Plasma cell proliferation increases total serum proteins and results in “spillage” into the urine.

CONCOMITANT ORGAN DYSFUNCTION

• Nervous system: Most commonly includes radiculopathy and cord compression. This can occur due to direct plasma cell proliferation in the spinal cord or due to bone collapse. Rarely, peripheral neuropathy due to amyloidosis and central nervous system plasmacytoma is also seen. Hyperviscosity from monoclonal immunoglobulins may result in stroke or confusion. • Cardiovascular: Amyloid deposition can result in restrictive cardiomyopathy and reduce chamber filling and contractility, as well as cause capillary fragility. • Renal disease can be glomerular (amyloidosis, immunoglobulin deposition), tubular (cast

nephropathy), or interstitial (interstitial nephritis, plasma cell infiltration). This can be the presenting feature of myeloma. • Skeletal destruction commonly involves the spine and can cause vertebral collapse or cord compression. • Anemia is due to the involvement of the bone marrow which replaces normal hematopoietic tissue and by the disruption of the bone marrow microenvironment. • Airway: Macroglossia may result from amyloid deposition and can occur in 15% of patients. • Hypercoagulability occurs due to the disease itself, as well as from treatment with thalidomide. There is increased risk of both venous and arterial thrombosis.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Acute infection due to poor immunity as discussed above • Acute thrombosis • Need for plasmapheresis

CLASSIFICATIONS

• Based on bone marrow biopsy and cytogenetics. • Broadly classified as: – Monoclonal gammopathy of unknown origin (MUGUS); asymptomatic. – Multiple myeloma (MM): End organ damage maybe present. – Smoldering multiple myeloma (SMM); asymptomatic

TREATMENT PREOPERATIVE PREPARATION Premedications

Analgesics as needed; patients may have developed a tolerance and require higher dosages. INTRAOPERATIVE CARE Choice of Anesthesia

• General: Be aware of possible renal failure and thus the choice of agents used for induction and maintenance of anesthesia. Use of certain muscle relaxants cleared by the kidney may have a longer than desired duration of action. • Regional anesthesia as the sole technique or for postoperative pain may also be used. If a neuraxial technique is considered, evaluate the spine carefully for fractures and any anticoagulation issues that may contraindicate placement. • Thromboprophylaxis should be discussed with the surgeon and appropriately planned.

Monitors

• Standard ASA monitors • Consider arterial line placement in patients with concomitant organ failure

Induction/Airway Management

• Any neck manipulation should be done cautiously due to the possibility of lytic spine

lesions. • Macroglossia may make ventilation or intubation challenging. • Pharmacokinetics of anaesthetic drugs may be unpredictable due to an altered volume of distribution, drug clearance, and plasma albumin/globulin ratio. The possibilities of change in protein binding have been alluded to in the past but no studies have proven this to be clinically significant (3). Maintenance

• Analgesia may be challenging as patients may be on high dose or chronic narcotics. Requirements should be increased accordingly. • Adequate hydration is important to avoid the precipitation of hyperviscosity syndrome and renal failure. • Careful and meticulous positioning and padding of pressure points should be performed.

Extubation/Emergence

No special consideration; routine extubation criteria apply.

POSTOPERATIVE CARE BED ACUITY

• Consider supplemental oxygen (nasal cannula, face mask). • Pain management may be challenging in opioid tolerant patients; consider an acute pain consultation or the placement of regional/neuraxial blocks if appropriate.

COMPLICATIONS

• Inadequate analgesia • Fluid overload • Perioperative thrombosis

REFERENCES

1. Rajkumar SV. Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol. 2011;86(1):57–65. 2. Mahindra A, Hideshima T, Anderson KC. Multiple myeloma. Blood Rev. 2010;24(Suppl 1):S5–11. 3. Walder AD. Failure of anaesthesia with etomidate. Eur J Anaesthesiol. 1995;12(3):325– 327. 4. Dabrowska DM, Gore C, Griffiths S, et al. Anaesthetic management of a pregnant patient with multiple myeloma. Int J Obstet Anesth. 2010;19(3):336–339.

ADDITIONAL READING

• Falanga A, Marchetti M. Venous thromboembolism in the hematologic malignancies. J Clin Oncol. 2009;27(29):4848–4857.

See Also (Topic, Algorithm, Electronic Media Element)

• Bone marrow harvest • Intrarenal failure • Epidural hematoma • Vertebroplasty/kyphoplasty • Pulmonary embolism

CODES ICD9

• 203.00 Multiple myeloma, without mention of having achieved remission • 203.01 Multiple myeloma, in remission ICD10 • C90.00 Multiple myeloma not having achieved remission • C90.01 Multiple myeloma in remission

CLINICAL PEARLS

• Assess for the severity of disease in order to appropriately formulate an anesthetic plan. • Pain control may be a challenge due to multiple lytic lesions. Consider acute pain consult, regional block. • Adequate hydration can reduce the occurrence of hypercalcemia and possible renal damage. • Careful patient positioning to avoid nerve injury. • Rarely, abnormal pharmacokinetics may be present secondary to changes in the albumin/globulin ratio. • If a transfusion is needed or anticipated perioperatively, a discussion with the surgeon and possibly a hematologist should be conducted.

MULTIPLE SCLEROSIS

Christine E. Goepfert, MD, PhD, DESA

BASICS DESCRIPTION

• Multiple sclerosis (MS) is a polygenic, organ specific autoimmune disease of unknown etiology. There exist evidentiary signs of tissue destructive activity of humoral and/or cellular immune system in the myelin components of the central nervous system (CNS). • It was first described by Dr. J. M. Charcot (1825–1893) and named in accordance with the widespread “scars” seen in the CNS. • MS is the most common demyelinating disorder of the CNS and is the leading cause of acquired neurological disability in young adults. EPIDEMIOLOGY Incidence

Female > males in a 2.3:1 ratio. Prevalence

• In the US, it is present in 30–80 per 100,000 persons. • Peaks around the age of 30. • Regional differences exist. In the north–south gradient, there is a higher risk in northern, industrialized countries. It is rare in Asians and Africans. • There appears to be a genetic component, with a 10- to 50-fold greater occurrence in relatives of MS patients. Morbidity

In 20–40% of patients, it is considered benign with minimal permanent disability Mortality

• Survival is linked to the extent of disability/secondary complications (lungs, renal). • Life-expectancy is slightly shortened in most patients. • Higher risk for suicide.

ETIOLOGY/RISK FACTORS

• Complex interaction of genetic and environmental factors: Related to certain HLA types and over-expression of human endogenous retroviruses (HERVs), resulting in an altered immune response. • Multiple genetic loci have been identified; however, the penetrance of risk only has a maximum of 25%. • Involvement of infectious factors include: Viruses (EBV, HHV-6), hepatitis B vaccination, chlamydia pneumonia.

• Hygiene related factors, low levels of vitamin D, production of melanoma-like melanin.

DISEASE/PATHOPHYSIOLOGY

• MS is a neurodegenerative, primary inflammatory disease that affects both white and gray matter. It is classically considered a disease of demyelination; however, histopathology also demonstrates neuroaxonal damage. • There is a proliferation of CD4 helper T-cells with the formation of cytokines resulting in blood brain barrier (BBB) damage, production of antibodies, and perforins. • Exacerbations are dependent on oxidative/nitrosative stress mitochondrial alterations, and stressful life-events.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Decrease perioperative stress and maintain body homeostasis to avoid exacerbations. • The response to non-depolarizing muscle relaxants is variable. Succinylcholine should be avoided. • Medications for the treatment of multiple sclerosis may result in co-morbidites with anesthetic implications as well as interactions with anesthetic medications.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Depression • Paresthesias • Paresis • Ataxia, dystonia, vertigo (cerebellar symptoms) • Pain (in 30–50%): Neuropathic and neurogenic pain, trigeminal neuralgia • Chronic fatigue (>75%), emotional changes

History

• Remissions and relapses: Determine course of disease and neurological function. • Determine the effects of heat • Determine if there are side effects of therapies

Signs/Physical Exam

• Nystagmus • Spasticity with dysfunctional reflexes • Muscle atrophy • Respiratory distress, use of accessory muscles, small tidal volumes, one-sided diaphragm impairment • Hypotonia, bradycardia (autonomic nervous system)

TREATMENT HISTORY

• Stem cell transplantation • Plasmapheresis

MEDICATIONS

• General principle: Anti-inflammatory and neuroprotective therapy targeting neuronal processes and cell bodies. • Medications for the prevention of relapse: – First-line treatment: Interferon-β1α: May be administered IM or SC depending on the formulation. Can result in hepatic failure/elevated LFTs, leukopenia. Glatiramer acetate can result in a self-limited, post-injection systemic reaction with chest tightness, flushing, anxiety, dyspnea, and palpitations in 15% of patients. This may be mistaken for cardiac ischemia or hives. – Second-line agents: Mitoxantrone is an immunosuppressive, chemotherapeutic agent. May result in AML, leukopenia, congestive heart failure and decreased LVEF, nausea/vomiting. Natalizumab is a specific mAb. Side-effects include infections (e.g., UTIs, URIs), arthralgias. Fingolimod is an immunomodulator. • Medications for exacerbation: – High dose methylprednisolone (5–15 mg/kg/d for3–10 days). – Immunosuppressants: Azathioprine, cyclophosphamide • Symptom-oriented medication – Baclofen for spasticity (intrathecal, oral) – Amantadine for fatigue – Antidepressants for depression – Carbamazepine and phenytoin for pain syndromes – Anticholinergics for neurogenic bladder

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• When significant respiratory insufficiency is present, consider pulmonary function testing and an arterial blood gas. • Imaging studies: MS is primarily a clinical diagnosis. An MRI (T2-weighted) can show multifocal lesions involving periventricular white matter, optic nerve, brainstem, and spinal cord white matter. • CSF analysis: Intrathecal IgG synthesis and oligoclonal bands with lymphocytic pleocytosis. • Evoked potentials: Visual evoked potentials (VEP) and somatosensory evoked potentials (SSEPs). • Plasma: Endothelial microparticles.

CONCOMITANT ORGAN DYSFUNCTION

• Depression, emotional changes, optic neuritis (70%), nystagmus, paresthesias, spasticity with dysfunctional reflexes, and atrophy. Cerebellar symptoms include ataxia, dystonia, and vertigo. • Autonomic nervous system dysfunction may manifest as hypotonia or bradycardia. • Respiratory: Muscle weakness can result in a decreased FRC, as well as maximal inspiratory

and expiratory efforts. Diaphragmatic palsy may be seen in cervical cord involvement. If central control of ventilation is impaired, there may be a decreased response to PaCO2.

• Pain (in 30–50%): neuropathic and neurogenic pain, trigeminal neuralgia. • Chronic fatigue (>75%) • GERD

CIRCUMSTANCES TO DELAY/CONDITIONS • Current exacerbation • Acute cardiotoxic effects of mitoxantrone

CLASSIFICATIONS

• McDonald criteria: Diagnostic criteria with clinical findings to prove dissemination in time and space of lesions supported by MRI, VEP, and CSF • Relapsing-remitting (RRMS): 80% • Secondary progressive (SPMS): 50% of RRMS after 10–15 years • Primary progressive (PPMS): 15% and carries the worst prognosis • Progressive relapsing (PRMS): 5%

TREATMENT PREOPERATIVE PREPARATION Premedications

• Consider high-dose glucocorticoids above the antiemetic dose after discussion with a neurologist. • In patients with respiratory dysfunction at baseline, benzodiazepines and opioids should be cautiously titrated if needed. Patients should be monitored with pulse oximetry. Special Concerns for Informed Consent

• Patients should be informed about the potential for postoperative exacerbations. • Depression might make informed consent difficult. • Pregnancy may cause partial remission; however, in the postpartum period, there is an increased risk of exacerbation. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia is considered safe. • Regional anesthesia is possible after carefully weighing the risks and benefits. – Respiratory dysfunction may be decreased. Avoid intubation, ventilation, and sedation; beneficial in patients with central nerve involvement or respiratory muscle weakness. – “Double-crush” phenomenon due to involvement of the peripheral nervous system, which may be subclinical. Peripheral nerve damage has been reported after peripheral nerve blocks. – Epidural anesthesia may be preferred over spinal anesthesia, which is associated with

exacerbations as well as profound hypotension that is resistant to vasopressors. – Because neurons are demyelinated, they may be more susceptible to local anesthetic neurotoxicity, which can aggravate conduction blockade. To that extent, consider lower concentrations and decreased exposure.

Monitors

• Standard ASA monitors; careful attention to temperature • Neuromuscular monitoring when neuromuscular blocking agents are utilized

Induction/Airway Management

• Good pre-oxygenation • Consider a rapid sequence induction if the patient has dysphagia. There is an increased risk of aspiration if the cranial nerves are involved (decrease in pharyngeal and laryngeal reflexes). However, avoid succinylcholine, because up-regulation of acetylcholine (ACh) receptors may lead to hyperkalemia. The response to non-depolarizing drugs is variable. The patient may be resistant due to upregulation of ACh receptors or co-medication with anticonvulsants. However, muscle atrophy and baclofen can render the patient more sensitive to its effects.

Maintenance

• No studies exist that demonstrate a benefit with any particular technique. However, inhalational agents have been shown to increase the risk of hypotension due to defects in the autonomic nervous system. • Maintain at a “deep” level of anesthesia to avoid stress (MAC-BAR). • Neuromuscular blockade has an unpredictable response. Utilization of a nerve stimulator can aid with dosing • Temperature: Meticulously avoid increases in body temperature as this can slow nerve conduction in demyelinated nerves.

Extubation/Emergence

• Goals include reducing stress/distress while ensuring sufficient respiratory function. • Consider administering pre-emptive analgesia to minimize postoperative pain (needs to be balanced against its respiratory effects).

POSTOPERATIVE CARE BED ACUITY

Depends on the surgery and baseline condition. The patient should be placed in an ICU if they have respiratory muscle weakness, diaphragmatic palsy and hypoventilation, or dysphagia due to cranial nerve involvement. MEDICATIONS/LAB STUDIES/CONSULTS

Neurological assessment by the anesthesia team, and in the event of any uncertainties, by a formal neurologic consult. COMPLICATIONS

• Respiratory failure/aspiration • Exacerbations of MS, primarily due to inappropriate pain management, hyperthermia, and psychological distress • Potential drug interactions of anesthetics with immunosuppressants, antispasticity and antiepileptic drugs, and anticholinergics

REFERENCES

1. Dickerman RD, Schneider SJ, Stevens QE, et al. Prophylaxis to avert exacerbation/relapse of multiple sclerosis in affected patients undergoing surgery. Surgical observations and recommendations. J Neurosurg Sci. 2004;48(3):135–137.

2. Dorotta IR, Schubert A. Multiple sclerosis and anesthetic implications. Curr Opin Anaesthesiol. 2002;15:365–370.

3. Koff MD, Kohen JA, McIntyre JJ, et al. Severe brachial plexopathy after an ultrasoundguided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis. Anesthesiology. 2008;108(2):325–328. 4. Krone B, Grange JM. Paradigms in multiple sclerosis: Time for a change, time for a unifying concept. Inflammopharmacology. 2011;19(4):187–195. 5. Stadelmann C. Multiple sclerosis as a neurodegenerative disease: Pathology, mechanisms and therapeutic implications. Curr Opin Neurol. 2011;24:224–229. 6. Vercauteren M, Heytens L. Anaesthetic considerations for patients with pre-existing neurological deficit: Are neuroaxial techniques safe? Acta Anaesthesiol Scand. 2007;51(7):831–838. See Also (Topic, Algorithm, Electronic Media Element)

• Postoperative pulmonary complications • Epidural

CODES ICD9 340 Multiple sclerosis ICD10 G35 Multiple sclerosis

CLINICAL PEARLS

• The primary goal is to avoid any perioperative stress, especially hyperthermia. • Monitor neuromuscular blockade closely or consider alternatives such as topicalization with lidocaine or deep anesthesia with remifentanil. • Interestingly, in patients with MS, there are no exacerbations seen during pregnancy. However, there is a threefold increase in exacerbations postpartum; this is independent of whether the patient had anesthesia or not. It may be explained by infection, emotional

lability, and hyperpyrexia.

MYASTHENIA GRAVIS Fabrizio Racca, MD Elena C. Capello, MD Federica Manfroi, MD V. Marco Ranieri, MD

BASICS DESCRIPTION

• Myasthenia gravis (MG) is an autoimmune postsynaptic neuromuscular junction (NMJ) transmission disorder. In the majority of cases (85%), MG is associated with auto-antibodies against the acetylcholine (ACh) receptor. • The hallmark of the disorder is weakness and fatigability in ocular, bulbar, limb, and respiratory muscles. EPIDEMIOLOGY Prevalence

In the US, 10–20 new cases of MG per million annually Prevalence

• In the US, 150–200 cases of MG per million population • Bimodal distribution of MG tending to affect: – Young woman: 20–40 years of age – Older men: 50–70 years of age Morbidity

• Intermittent impairment of muscle strength, which may cause aspiration and increased incidence of pneumonia and falls. • Medications used to control the disease may produce adverse effects.

Mortality

• In the past, untreated MG had a mortality rate of 30–70%; now most patients have a nearnormal life expectancy. • Myasthenic crisis: Even with prompt diagnosis and treatment, the mortality rate of a myasthenic crisis is 50% of patients with MG) • Bulbar symptoms including dysarthria, dysphagia, fatigable chewing (about 15% of patients with MG) • Proximal limb weakness • Facial muscles are frequently involved and make the patient appear expressionless • On physical examination, the findings are limited to the motor system, without loss of reflexes or alteration of sensation or coordination. • Careful assessment of respiratory function, ability to cough, and bulbar function

MEDICATIONS

Evaluate the adequacy of drug therapy • Anticholinesterases • Immune suppression (steroids, azathioprine, cyclosporine) • Thymectomy (for patients with generalized MG with thymoma or who are less than age 60 without thymoma) • Plasmapheresis and intravenous immune globulin. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Pulmonary function tests (negative inspiratory pressure and forced vital capacity) • Arterial blood gasses (ABGs): The paCO2 and paO2 can help to predict the need for postoperative MV. • Chest x-ray may be indicated to rule out aspiration or other pneumonias.

CONCOMITANT ORGAN DYSFUNCTION

• Thymoma: The majority of patients with AChR antibody-positive MG have thymic abnormalities; hyperplasia in 60–70% and thymoma in 10–15%.

• Other autoimmune disorders that may be present include systemic lupus erythematous, rheumatoid arthritis, pernicious anemia, thyrotoxicosis.

CIRCUMSTANCES TO DELAY/CONDITIONS THAT NEED OPTIMIZATION

If the patient is poorly controlled, a course of plasmapheresis may be of benefit in the preoperative period. There should a 24-hour delay between the last plasmapheresis and surgery to restore clotting factors. CLASSIFICATIONS

• Grades – Grade I: Only eyes affected – Grade IIa: Mild generalized MG responding well to therapy – Grade IIb: Moderate generalized MG responding less well – Grade III: Severe generalized disease – Grade IV: Myasthenic crisis requiring MV • Preoperative factors associated with need for prolonged postoperative MV include: FVC 6 years, major surgery, co-existing lung disease, and grades III and IV MG

TREATMENT PREOPERATIVE PREPARATION Premedications

• Continue all the doses of medications preoperatively to avoid aggravation of symptoms and muscle weakness. • Steroid-dependent patients will require steroid stress dose (hydrocortisone up to 100 mg IV bolus before induction, then 100 mg q8h × 24h). • Avoid sedatives as they can cause respiratory compromise.

Special Concerns for Informed Consent

Inform the patient of the potential requirement for prolonged MV. INTRAOPERATIVE CARE Choice of Anesthesia

• Use of regional or local anesthesia should be utilized, whenever possible. • Since local anesthetic agents may block neuromuscular transmission, it is better to use techniques which involve the use of small quantities of these agents; therefore, subarachnoid block is preferable to the use of epidural or caudal anesthesia. Monitors

• Standard ASA monitors • Consider an arterial line in high-risk patients and for thymectomy (ABGs, electrolyte analysis, and invasive arterial pressure monitoring): Monitoring of neuromuscular transmission (nerve stimulator).

Induction/Airway Management

• Airway should be secured with an appropriate size ET tube using a non-paralyzing technique. Sevoflurane often provides adequate relaxation for tracheal intubation. • When muscle relaxant use is indicated, it is better to use small doses (1/10th of the usual dose) of non-depolarizing rather than depolarizing relaxant drugs. • The presence of a thymoma (anterior mediastinal mass) can result in intrathoracic airway or vascular obstruction and may occur upon the induction of anesthesia.

Maintenance

• Several general anesthetic techniques have been proposed (balanced anesthetic technique or TIVA), although none has been proven to be superior to the other. • Avoid muscle relaxants, if possible. Volatile anesthetics may provide adequate relaxation during surgery; however, intermediate and short-acting non-depolarizing agents can be used. It is best to use small doses with careful monitoring of neuromuscular transmission. • Preferentially utilize ultra-short–acting anesthetics (propofol, sevoflurane, remifentanil). • Avoid factors which can enhance neuromuscular blockade (hypothermia, hypokalemia, hypophosphatemia, and certain drugs).

Extubation/Emergence

• Criteria for extubation include: – Head lift (5 sec) – Negative inspiratory force of >25 cm of H2O

– Tidal volume >5 mL/kg – Adequate muscle power evidenced by nerve stimulator • Adequate postoperative pain control, pulmonary toilet, and the avoidance of drugs that interfere with neuromuscular transmission facilitate tracheal extubation. • Anticholinesterases therapy should be restarted in the immediate postoperative period. The dose is based on the preoperative pyridostigmine dose (2 mg IV neostigmine is equivalent to 60 mg PO pyridostigmine) and titrated to effect.

FOLLOW-UP BED ACUITY

• Postoperative care should take place in the ICU with monitoring of respiratory function as well as chest physiotherapy for 12 hours. • Meticulous attention to pulmonary toilet is required, particularly since respiratory secretions may be increased by anticholinesterase drugs • Good pain control, especially after thymectomy • Avoid drugs that may exacerbate MG.

COMPLICATIONS

• Weakness after surgery presents a special problem in MG patients. The differential diagnosis includes myasthenic crisis, residual effects of anesthetic drugs, non-anesthetic drugs interfering with neuromuscular transmission, and cholinergic crisis. For these reasons, many

clinicians prefer to avoid the use of muscle relaxants, or if they use muscle relaxants, allow the neuromuscular block to recover spontaneously. Tensilon (edrophonium) challenge test is useful in distinguishing myasthenic crisis from cholinergic crisis. • Aspiration, pneumonia, inadequate cough, atelectasis • Need of ventilatory assistance in the postoperative period due to respiratory failure • Rule out pneumothorax and phrenic nerve damage in case of thymectomy.

REFERENCES

1. irsch NP. Neuromuscular junction in health and disease. Brit J Anaesth. 2007;99(1):132– 138. 2. O’Neill GN. Acquired disorders of the neuromuscular junction. Int Anesthesiol Clin. 2006;42(2):107–121. 3. Tripathi M. The effect of the use of pyridostigmine and requirement of vecuronium in patients with myasthenia gravis. Journal of Postgraduate Medicine. 2003;49:311–315. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary function tests • Functional residual capacity • Anterior mediastinal mass • Flow volume loops

CODES ICD9 • 358.00 Myasthenia gravis without (acute) exacerbation • 358.01 Myasthenia gravis with (acute) exacerbation ICD10 • G70.00 Myasthenia gravis without (acute) exacerbation • G70.01 Myasthenia gravis with (acute) exacerbation

CLINICAL PEARLS

• Assess severity of the disease. • Evaluate the adequacy of drug therapy and optimize the patient’s condition. • Use of regional or local anesthesia, whenever possible • Avoid muscle relaxants and use ultra-short–acting anesthetics. • Avoid postoperative ventilation, whenever possible. • Admission to ICU for postoperative monitoring. • MG may worsen during the course of pregnancy. The first trimester and the month postpartum are the periods of highest risk of exacerbation.

MYASTHENIC SYNDROME Fabrizio Racca, MD Elena C. Capello, MD Federica Manfroi, MD V. Marco Ranieri, MD

BASICS DESCRIPTION

• Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune presynaptic neuromuscular junction (NMJ) disorder. It results from antibodies against voltage-gated calcium channels which are involved with acetylcholine (ACh) release. • The clinical picture is characterized by: – Weak proximal limb muscles – Depressed tendon reflexes – Respiratory failure – Abnormal autonomic function such as dry mouth, gastrointestinal slowing, postural hypotension – Oropharyngeal and ocular muscles are usually spared. – Weakness that improves with sustained contraction • Approximately one-half of LEMS cases are associated with a malignancy, mainly small-cell lung cancer. EPIDEMIOLOGY Incidence

• The true incidence of LEMS is unknown, but the condition is uncommon and occurs much less frequently than myasthenia gravis. • In a population-based study from a region of Holland with 1.7 million inhabitants, 220 cases of myasthenia gravis and 10 of LEMS were identified over a 9-year period. Prevalence

• Cancer is present or later found in ∼40% of patients; clinical manifestations frequently precede cancer identification. • LEMS is most commonly seen with small-cell lung cancer (∼3%). • More common in middle aged patients. • Male:female 2:1 ratio.

Morbidity

• Respiratory failure • Mostly associated with the underlying disease or cancer

Mortality

Mostly associated with the underlying disease or cancer ETIOLOGY/RISK FACTORS

• Cancers: Small-cell lung cancer, as well as non-SCLC, lymphosarcoma, malignant thymoma, cancer of the breast, stomach, colon, or prostate. • Drugs that may worsen the muscular weakness include aminoglycosides, fluoroquinolones, macrolides, beta blockers, diuretics, procainamide, magnesium salts, calcium channel blockers, intravenous iodinated contrast.

PATHOPHYSIOLOGY

• LEMS is an autoimmune disorder that reduces ACh release from the presynaptic nerve terminals. Antibodies directed against the voltage-gated calcium channel interfere with the release of Ach, resulting in muscle weakness. ACh binding and its effect on the postsynaptic membrane are not impaired, neither is the ACh receptor. • In patients with cancer, antigens that mimic voltage-gated calcium channels are believed to induce antibodies. In patients without cancer, antibodies to voltage-gated calcium channels are believed to result from an autoimmune state. • Consequently, muscle weakness improves with use as more Ach becomes available in the NMJ. This phenomenon is referred to as postexercise or postactivation facilitation.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess severity of disease and evaluate pulmonary function. • Patients show extreme sensitivity to both depolarizing and nondepolarizing blocking drugs and these should be avoided if possible. • Other non-anesthetic medications may worsen the muscular weakness by inhibiting neuromuscular transmission (see risk factors). • Postural hypotension may be exacerbated by anesthetic induction agents and mechanical ventilation (MV). • Whenever possible, the use of ultra-short acting anesthetics should be administered to avoid postoperative respiratory depression and hypoventilation.

PREOPERATIVE ASSESSMENT SYMPTOMS

Weakness that improves with activity History

• Clinical course • Hospitalizations • Intubations and ICU admissions

Signs/Physical Exam

• Proximal limb motor weakness • Depressed tendon reflexes

MEDICATIONS

• 3,4-diamimopyridine increases ACh release • Guanidine hydrochloride increases ACh release • Pyridostigmine decreases ACh metabolism and resultantly increases the amount of ACh that is available. • Immune suppressors (steroids, azathioprine, cyclosporine) • Plasmapheresis and intravenous immune globulin

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Pulmonary function tests to help predict the need for postoperative mechanical ventilation; specifically, the negative inspiratory pressure and forced vital capacity (FVC). • Arterial blood gases to assess the pCO2 and pO2. • Chest radiograph if aspiration or pneumonia is suspected.

CONCOMITANT ORGAN DYSFUNCTION • Cancer; see risk factor section • Other autoimmune disorders: – Systemic lupus erythematosus – Rheumatoid arthritis – Pernicious anemia – Thyrotoxicosis

CIRCUMSTANCES TO DELAY/CONDITIONS THAT NEEDED OPTIMIZATION

If the patient is poorly controlled, a course of plasmapheresis may be of benefit in the preoperative period. There should be a 24-hour delay between the last plasmapheresis and surgery in order to restore clotting factors.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Continue medications preoperatively to avoid aggravation of symptoms and muscle weakness. • Steroid-dependent patients may require steroid stress dose (hydrocortisone up to 100 mg IV bolus before induction, then 100 mg q8h × 24h). • In general, sedation is avoided as it may cause respiratory compromise.

Special Concerns for Informed Consent

Inform the patient of the potential requirement for prolonged MV. INTRAOPERATIVE CARE Choice of Anesthesia

• Use of regional or local anesthesia should be warranted whenever possible. • Because local anesthetic agents may block neuromuscular transmission, it is better to use techniques which involve the use of small quantities of these agents; therefore, a subarachnoid block is preferable to the use of epidural or caudal anesthesia.

Monitors

• Standard ASA monitors • Monitoring of neuromuscular transmission (nerve stimulator)

Induction/Airway Management

• The airway should be secured with an appropriate size ET tube using a non-paralyzing technique (i.e., without the use of muscle relaxant and after adequate topical analgesia of the pharynx and larynx). Sevoflurane often provides adequate relaxation for tracheal intubation. • When muscle relaxant use is indicated, it is better to use small doses (1/10th of the usual dose) of non-depolarizing drugs.

Maintenance

• Several general anesthetic techniques have been proposed (balanced anesthetic technique or TIVA), although none have been proven to be superior to the other. • Avoid muscle relaxants and use ultra-short acting anesthetics (propofol, sevoflurane, remifentanil) or volatile agents to achieve the relaxation required for surgery. If using nondepolarizing agents, it is best to use small doses with careful monitoring of neuromuscular transmission. • Avoid drugs that can enhance neuromuscular blockade (beta blockers, diuretics, magnesium, calcium channel blockers).

Extubation/Emergence

• Criteria for extubation include: – Head lift (5 seconds) – Negative inspiratory force of >25 cm of H2O

– Tidal volume > 5 mL/kg – Adequate muscle power evidenced by nerve stimulator • Adequate post-operative pain control, pulmonary toilet, and the avoidance of drugs that interfere with neuromuscular transmission facilitate tracheal extubation.

POSTOPERATIVE CARE BED ACUITY

• Post-operative care should be done in the ICU with monitoring of respiratory function as well as chest physiotherapy. • Avoid drugs that may exacerbate motor weakness (see risk factors).

COMPLICATIONS

• Aspiration, pneumonia, inadequate cough, atelectasis

• In addition to postoperative pulmonary complications, laryngeal and respiratory muscle weakness may warrant ventilatory assistance in the post-operative period.

REFERENCES

1. Hirsch NP. Neuromuscular junction in health and disease. Br J Anaesth. 2007;99(1):132– 138. 2. O’Neill GN. Acquired disorders of the neuromuscular junction. Int Anesthesiol Clin. 2006;42(2):107–121. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary function tests • Functional residual capacity • Myasthenia gravis

CODES ICD9 • 358.1 Myasthenic syndromes in diseases classified elsewhere • 358.30 Lambert-Eaton syndrome, unspecified ICD10 • G70.80 Lambert-Eaton syndrome, unspecified • G73.3 Myasthenic syndromes in other diseases classified elsewhere

CLINICAL PEARLS

• Assess severity of the disease. • Evaluate the adequacy of drug therapy and optimize the condition of the patients. Patients may require plasmapheresis or stress dosing of steroids. • Use of regional or local anesthesia, whenever possible. • Avoid muscle relaxants and use ultra-short acting anesthetics. • Avoid post-operative ventilation, whenever possible. • Admission to ICU for post-operative monitoring.

MYOCARDIAL CONTUSION Kenneth F. Kuchta, MD

BASICS DESCRIPTION

• Myocardial contusion is an injury that usually results from blunt trauma. • It does not have a standardized diagnostic criteria; clinical presentation is variable and can range from minor cardiac bruises to severe insults such as cardiac rupture and death. • Unlike much of cardiac disease managed by anaesthetists, the right ventricle tends to be predominantly affected due to its anterior location. Thus right-sided failure takes a predominant place in the pathophysiology of myocardial contusions. EPIDEMIOLOGY Incidence

• The lack of clear clinical diagnostic criteria makes determining the exact incidence difficult. • A very wide range has been reported across the literature following blunt chest trauma: 9.4– 76%. Morbidity

Associated with a higher incidence of perioperative hypotension, arrhythmias, and death. This risk may persist for one month post trauma, but the magnitude of risk has not been clearly defined. Mortality

• Overall mortality is approximately 15%. • One study found that a myocardial contusion in patients with thoracic trauma was associated with a higher operative mortality (e.g., 54% vs. 4.6%), but this seemed to be related to more severe injuries as most of the deaths were attributed to non-cardiac causes (1).

ETIOLOGY/RISK FACTORS

Blunt trauma can result in myocardial contusions due to a variety of mechanisms:

• Energy transfer to the underlying heart from direct impact to the thorax. • An injury due to deceleration of the heart. • Compression of the heart within the thorax (e.g., between the spine and sternum). • Trauma to the abdomen or lower extremities (without direct thoracic trauma) has been implicated via upward displacement of the viscera. PATHOPHYSIOLOGY

• Histopathology of the affected heart muscle can show hemorrhage, edema, necrosis, and polymorphonuclear infiltrates.

• Animal models suggest that the pathogenesis is distinct from ischemic heart disease. Although there is an initial fall in coronary arterial blood flow, it recovers quickly (over a 20-minute period), and the extent of ventricular dysfunction appears to be proportional to direct myocyte injury and necrosis. • The most common complication is arrhythmia and can occur even after mild trauma (leading to the dilemma as to the need for, and the duration of, cardiac monitoring in many trauma patients). • As the right heart lies anterior, it is most commonly involved. As a result, frank cardiac failure from left ventricular failure is less common. Increased pulmonary artery pressure (from lung contusions, ARDS, etc.) may occur concurrently in this setting and can complicate a right ventricular contusion, resulting in right ventricular failure. • Commotio cordis is a cardiac arrest as a result of a low energy impact, often during sports, resulting in a cardiac arrest. – Distinct from a myocardial contusion, as there are no histological findings of trauma to the heart. – Also called a myocardial concussion. – If the impact occurs shortly before the peak of the T wave, the result can be ventricular fibrillation. – Impact during the QRS complex can result in complete heart block.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Anesthetic management should take into account the manifestations of myocardial contusions (which may have presented preoperatively or declare themselves during the case). – Arrhythmias may need to be treated pharmacologically or via cardioversion/ defibrillation. – Recognition that cardiac failure is likely to be right sided: Adequate preload is essential, and thus TEE may be more useful than PA catheter measurements, especially in the setting of concomitant pulmonary contusions, mechanical ventilation, and elevated pulmonary artery pressures.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Often masked by other injuries or intubation in the severely injured. • Chest pain and shortness of breath (though this may be secondary to chest wall trauma or CPR). • Palpitations. • Evidence indicating high impact injuries: – Rib fractures (especially upper) and clavicle fractures – Pulmonary contusions – Pneumothorax and/or hemothorax – Flail chest – Great vessel injuries

History

Any trauma history consistent with the possibility of myocardial injury should prompt further investigation. Myocardial contusion should be considered in high-speed motor vehicle accidents with blunt force trauma (especially chest trauma), auto versus pedestrian trauma, falls, and other deceleration injuries as well as after cardiopulmonary resuscitation. Signs/Physical Exam

• Irregular pulse indicating arrhythmias. • Distended neck veins may indicate right ventricular failure or tamponade. • Muffled heart tones, pulsus paradoxus may further indicate tamponade. • Cardiovascular deterioration (decreased blood pressure, poor peripheral perfusion). • Respiratory failure could represent further deterioration.

TREATMENT HISTORY

• Intubation and mechanical ventilation • Increased oxygen requirement • Temporary pacing for complete heart block

MEDICATIONS

• Antiarrhythmics • Pharmacologic support of cardiac failure

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• EKG, though as the right ventricle is the most commonly affected, this test may have very limited utility (low negative predictive value). – ST and T wave changes are frequent, Q waves are rare. – Sinus tachycardia is the most common arrhythmia, as would be expected in trauma (i.e., low specificity). – Arrhythmias, right bundle branch block (RBBB), and interventricular conduction defects should be sought. – Ventricular tachycardia is very concerning, but may not be captured on a 12-lead EKG (continuous cardiac monitoring is suggested). • Creatinine kinase MB is generally not considered helpful due to frequent concurrent skeletal muscle injuries. • Troponin levels: Troponin I is more specific than troponin T. However, – Injury, especially small areas that may predispose to arrhythmia, may occur without release of troponin. – Hemorrhage or shock without myocardial contusion can result in troponin release. • Echocardiography. – Transthoracic method may be limited by mechanical ventilation, pneumothorax, and difficulty in positioning the patient. – Transesophageal might have some difficulty in imaging the right ventricle (the chamber most often involved) but is still useful for the diagnosis of myocardial contusions and its

complications as well as to assist with cardiovascular management of the patient. • Cardiac catheterization is indicated in the very few cases where coronary lesions are suspected.

CONCOMITANT ORGAN DYSFUNCTION

• Other blunt force injuries: Rib and clavicle fractures, flail chest. • Pulmonary injuries such as pulmonary contusions, ARDS, aspiration, and pneumothorax and/or hemothorax can potentially complicate the diagnosis and management of myocardial contusions, particularly if pulmonary hypertension occurs. • Associated cardiac injuries include: – Myocardial infarction as either a complication, or the cause, of the trauma is a definite and increasing possibility, given the changing population demographics. This can further complicate the diagnosis and management of myocardial contusion. – Coronary artery injury. – Myocardial rupture: The right ventricle is most commonly involved. – Ventricular and atrial septal defects. – Valvular lesions: Most often affects the aortic and mitral valves due to the higher intracavitary pressures. – Pericardial effusion or hemopericardium. – Pericardial rupture with the potential for myocardial herniation. – Aortic rupture.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Ideally the diagnosis of myocardial contusion should be established, including the extent of the lesion and the related complications prior to surgery. The nature of much of trauma injuries and surgery, however, does not frequently allow this luxury. Diagnostic effort may need to occur in the operating room (e.g., via TEE), although this may prove difficult due to the demands of merely caring for an unstable trauma patient. • Further workup, however, may be possible in the more elective subsequent procedures that are often part of the care of the trauma patient.

CLASSIFICATIONS Not established

TREATMENT PREOPERATIVE PREPARATION Premedications

In the setting of confirmed or suspected myocardial contusion, caution with any premedication may be warranted to avoid compromising the patient’s hemodynamic status. Special Concerns for Informed Consent

If applicable, informing the patient and/or their family of the increased risk due to a possible or confirmed myocardial contusion may be warranted. This might include possible additional

monitors that might be needed during the surgery. INTRAOPERATIVE CARE Choice of Anesthesia

• Usually dictated by concomitant injuries and necessary surgery. • In rare circumstances, sedation may be utilized to avoid general anesthesia and positive pressure ventilation, if right ventricular function is compromised.

Monitors

Depending upon the extent of the contusion and its complications, additional monitoring might be considered, including arterial, central, and pulmonary pressure monitoring as well as cardiac output monitoring and TEE. Induction/Airway Management

Careful consideration with regard to hemodynamic changes may dictate a “slow careful induction”; however, a full stomach and potentially unstable cervical spine may complicate this consideration. Maintenance

• While no specific anesthetic is indicated, the goal should be to optimize hemodynamics in a setting of potentially impaired cardiac function. • Increased FIO2 is often administered. • Consider the use of an ICU ventilator to allow for additional modes of ventilation (high frequency, etc).

Extubation/Emergence

As per the extent of injury and the course of the surgery.

POSTOPERATIVE CARE BED ACUITY

• Dependent upon the acuity of the patient’s overall condition and extent of the injury. • Strongly consider a monitored setting if there is a suspicion of a myocardial contusion in an otherwise stable (lower acuity) patient due to the potential for developing arrhythmias.

MEDICATIONS/LAB STUDIES/CONSULTS

• Continued surveillance for, and support of, the manifestation of myocardial contusion as outlined above may be indicated. • Cardiology consult, if not already obtained, should be considered.

COMPLICATIONS

• Pericardial effusions and hemopericardium can occasionally lead to late constrictive pericarditis (at times with significant calcifications) and may require pericardiectomy. • Ventricular aneurysms are also occasionally seen as a late complication with variable significance.

REFERENCES

1. Devitt JH, McLean RF, McLean BA. Perioperative cardiovascular complications associated with blunt thoracic trauma. Can J Anesth. 1993;40:197–200. 2. Baxter BT, Moore EE, Synhorst DP, Reiter MJ, Harken AH. Graded experimental myocardial contusions: impact on cardiac rhythm coronary artery flow, ventricular function, and myocardial oxygen consumption. J Trauma. 1988;28(10):1411–1417.

ADDITIONAL READING

• Orliaguet G, Ferjani M, Riou B. The Heart in Blunt Trauma. Anesthesiology. 2001;95:544– 548. • Schultz JM, Trunkey DD. Blunt cardiac injury. Critical Care Clinics. 2004;20:57–70.

See Also (Topic, Algorithm, Electronic Media Element) • Pneumothorax • Trauma • Ventricular septal defect

CODES ICD9 • 861.01 Contusion of heart without mention of open wound into thorax • 861.11 Contusion of heart with open wound into thorax ICD10 • S26.91XA Contusion of heart, unsp w or w/o hemopericardium, init • S26.91XD Contusion of heart, unsp w or w/o hemopericardium, subs • S26.91XS Contusion of heart, unsp w or w/o hemopericardium, sequela

CLINICAL PEARLS

• While most of our thinking about the heart (diagnosis and treatment) relates to the left ventricle, much of the pathophysiology of myocardial contusions relates to the right side. This is due to the orientation of the heart in the chest; the heart lies rotated, thus the right ventricle is closest to the sternum and is most vulnerable to blunt trauma. • In at least two scenarios, trauma patients may present with more traditional appearing cardiac events (with coronary-based pathophysiology) that would dictate angiography with possible stenting or bypass. – A young trauma patient with classic findings of a myocardial infarction (on EKG, enzymes and possibly echo) should be considered for the possibility of having a coronary injury. – Older patients may have suffered atherosclerotic-related myocardial infarction as either the cause of the trauma or as a result of the injury. With the aging trauma population, this added consideration only indicates how much more complex the differential diagnosis will become in the future.

MYOCARDIAL OXYGEN DEMAND Emily Gordon, MD

BASICS DESCRIPTION

• The balance between myocardial oxygen supply and demand is critical to the proper function of the heart. If myocardial oxygen demands are not met, myocardial ischemia, infarction, arrhythmias, or death may result. • Oxygen demand is not equivalent to oxygen consumption. Demand is related to need. Consumption is the actual amount of oxygen used per unit time. • The myocardium uses oxygen primarily for effective contraction. Requirements for basal metabolism comprise only 10–20% of total O2 consumption. Requirements of the electrical conduction system are even less. • The major determinants of myocardial oxygen demand are: – Heart rate – Contractility – Myocardial (systolic) wall tension

PHYSIOLOGY PRINCIPLES

• Myocardial oxygen consumption (VO2): Large amounts of ATP are needed for the proper

function of the myocardium. Aerobic metabolism (most efficient source) of fatty acids is the primary mechanism by which ATP is regenerated at rest. • Oxygen extraction: The myocardium is a tightly regulated tissue which excels in its ability to extract oxygen from the blood that enters the coronary arteries. In the non-stressed state, the myocardium extracts 70–75% of the oxygen from the red blood cells/hemoglobin that flow through the coronary arteries. Venous saturation thus equals ∼25–30%. • Coronary blood supply is comprised of coronary blood flow and blood oxygen carrying capacity. Furthermore, because coronary oxygen extraction is near maximal under resting conditions, the primary mechanism to meet increased oxygen demand is through enhanced delivery; thus, it is a dynamic process that is modulated by multiple parameters. – Autoregulation is the intrinsic mechanism to maintain a constant blood flow over a range of perfusion pressures (60–160 mm Hg); changes in pressure are met by reciprocal changes in resistance. Local metabolic and myogenic factors appear to play a role. Myogenic factors describe the response of smooth muscles to the shear forces of perfusion pressure. Metabolic factors (e.g., oxygen and carbon dioxide tension and adenosine) affect vascular smooth muscle tone as their concentrations vary. In other words, an increase in the PaCO2 would stimulate vasodilation and “washout.”

– Humoral factors include circulating agents such as angiotensin II, serotonin, thromboxane, prostacyclin, and bradykinin that effect coronary resistance. – Neural control describes autonomic innervation such as alpha, beta, and parasympathetic

activity. – Diastolic time: The left ventricle’s systolic pressures exceed the coronary artery’s diastolic perfusion pressure; thus extravascular compressive forces prevent perfusion during systole. – Blood oxygen–carrying capacity is the sum of oxygen bound to hemoglobin and dissolved in blood. It is primarily determined by the hemoglobin level (capable of binding 1.39 mL of oxygen per gram); dissolved oxygen is poorly soluble in blood (0.003), thus, its contribution is minimal. This serves as the physiologic basis for blood transfusions. • Oxygen demand: Heart rate has the greatest effect on myocardial work and oxygen demand. – Heart rate: For every heartbeat, the myocardium undergoes electrical depolarization and repolarization, generates contractility, ejects blood against the wall tension (preload or volume work and afterload or pressure work), and undergoes relaxation. Note: Tachycardia will decrease the diastolic perfusion time which primarily affects the left ventricle’s blood supply. – Cardiac contractility or inotropy is the intrinsic ability of the cardiomyocyte to shorten from its individual resting fiber length; it is independent of preload and afterload. Contraction results from myosin and actin filament binding and is dependent upon intracellular calcium ion concentration. Increases in sympathetic tone or catecholamine state, calcium levels, heart rate, as well as inotropic drugs (beta agonists, calcium, glucagon, phosphodiesterase inhibitors) have a positive effect on contractility. – Myocardial wall tension: The law of LaPlace states that wall tension is directly proportional to the chamber radius and pressure; it is inversely proportional to the wall thickness. Radius is primarily determined by preload (changes in blood volume or chamber size). Pressure is primarily determined by the afterload which is a function of systemic vascular resistance, the aortic valve, and blood viscosity. Myocardial wall thickness is responsible for long-axis function secondary to endocardial and midwall fractional shortening. However, wall thickness is not responsible for shortaxis function. Tension is dynamic (aside from wall thickness) and can vary with each heartbeat and throughout the contraction (chamber size decreases with ejection).

ANATOMY

• Coronary arteries: The presence of a stenotic lesion results in a pressure drop that is proportional to the fourth power of the radius, the length of the plaque, and the magnitude of flow. • The subendocardium (inner one-third to one-fourth of the myocardium) is most susceptible to the effects of CAD or to a reduction in perfusion pressure. This is secondary to: – Adjacent intraventricular pressures (left ventricular end-diastolic pressure) – Limited maximal vasodilator response – Blood flow only occurs during diastole; during systole, extravascular compressive forces (mechanical forces that compress coronary vasculature) are greatest

PHYSIOLOGY/PATHOPHYSIOLOGY • Heart rate is increased by: – Pain or inadequate anesthesia

– Postoperative shivering – Catecholamines – Hypovolemia – Anemia – Hypoxia – Fever – Hyperthyroidism – Administration of vagolytic drugs (e.g., atropine, glycopyrrolate) • Cardiac contractility is increased by: – Catecholamines – Increased heart rate: The Treppe or Bowditch effect describes an autoregulatory method by which myocardial contractility increases with an increase in heart rate. This mechanism is believed to result from an inability of the sodium–potassium ATPase (moves sodium extracellularly) to keep up with the sodium–calcium exchanger (moves sodium intracellularly) during tachycardia. This results in increased intracellular levels of calcium. • Myocardial wall tension is increased by: – Increased ventricular diameter (volume overload, impaired ejection fraction, dilated cardiomyopathy). – Increased aortic pressure: Hypertension, aortic stenosis, and hemoconcentration increase the pressure that needs to be generated in order to eject blood from the left ventricle.

PERIOPERATIVE RELEVANCE

• Induction of anesthesia – Laryngoscopy and airway instrumentation can result in excessive catecholamine release. The goal is to pre-empt with opioid or anti-hypertensive administration, decrease laryngoscopy time, ensure an adequate depth of anesthesia (and time for onset), and be prepared to treat hemodynamic perturbances (esmolol, nitroglycerin, additional anesthetic agents such as propofol or volatile agents). • Maintenance of anesthesia – Pain and awareness under anesthesia can result in tachycardia; ensure an adequate depth of analgesia and anesthesia. This may become challenging in the hypotensive patient. Consider the use of nitrous oxide and decrease of volatile agent, volume administration, or phenylephrine infusion to maintain adequate mean arterial pressures. – Perioperative beta-blockade may be titrated to a heart rate of 50–80 beats/min or bolused during catecholaminergic states. – Changes to desflurane concentrations can result in sympathetic discharge and tachycardia. – Normothermia may be maintained with blankets or warming devices (convective blankets, warming fluids, etc.) – Optimize volume status: Hypovolemia can result in a reflex tachycardia, whereas hypervolemia increases the myocardial chamber radius (preload). • Postoperative/PACU care – Provide adequate pain control: A multimodal approach may include anti-inflammatory medications, regional nerve blocks, and opioids, as appropriate. – Optimize volume status: The postoperative period may be marked by fluid flux between the intracellular and extracellular compartments as well as continued bleeding.

– Treat postoperative shivering (warming techniques, meperidine, clonidine). – Ensure adequate oxygenation: Residual sedatives or narcotics can decrease the functional residual capacity and result in hypoxia (increased sympathetic state). Consider nasal cannula, facemask, deep breathing, coughing or CPAP/BIPAP when indicated.

EQUATIONS

• MVO2 = CBF × (CaO2 – CvO2); where MVO2 is mixed venous oxygen saturation, CBF is cerebral blood flow, CaO2 is the arterial blood oxygen content, and CvO2 is the venous

blood oxygen content • A-VO2 = (CaO2 – CvO2) is the arterial-venous oxygen content difference (mL O2/mL blood) • CO = O2 consumption/A-VO2 difference

• Law of LaPlace: T = ΔPr/2h, where T is tension, ΔP is change in pressure, r is radius, and h is myocardial wall thickness

REFERENCES

1. DeFily DV, Chilian WM. Coronary microcirculation: autoregulation and metabolic control. Basic Res Cardiol. 1995;90(2):112–118. 2. Duncker DJ, Bache RJ. Regulation of coronary blood flow during exercise. Physiol Rev. 2008;88(3):1009–1086. 3. Duncker DJ, Merkus D. Regulation of coronary blood flow. Effect of coronary stenosis. Arch Mal Coeur Vaiss. 2004;97(12):1244–1250. 4. Ardehali A, Ports TA. Myocardial oxygen supply and demand. Chest. 1990;98(3):699–705. See Also (Topic, Algorithm, Electronic Media Element) • Coronary arteries • Intraoperative myocardial ischemia • Chronic angina • Hypothermia • Myocardial oxygen supply • Preload • Afterload

CLINICAL PEARLS

• The myocardial oxygen demand cannot be easily measured in the perioperative period. To that extent, a clear understanding of the various factors that affect demand, as well as supply, are critical to optimize an adequate balance and avoid ischemia.

NARCOTIC WITHDRAWAL Angela T. Hsu, MD

BASICS DESCRIPTION

• Sudden opioid abstinence or administration of an opioid antagonist in a narcotic-dependent individual may induce a traumatic reaction in the body, collectively characterized as opioid withdrawal syndrome. • Opioid withdrawal is rarely life-threatening, but is highly unpleasant and may complicate care in the perioperative period. EPIDEMIOLOGY Incidence

• Narcotic pain medications are the most frequent class of medications that are misused or abused; they accounted for 397,160 ED visits in 2009. • In a 2009 US survey of ER departments, heroin accounted for 213,118 visits.

Prevalence

• In 2002, the prevalence of heroin dependence was estimated at 0.14% of the US population. • Although ED visits from heroin usage has not changed significantly from 2004 to 2009, narcotic painkiller related visits have risen dramatically. • According to recent estimates, >2 million people in the US are abusing prescription opioids.

Morbidity

• Narcotic withdrawal is uncomfortable and associated with sympathetic nervous system hyperactivity. • Patients with underlying cardiac risk factors may be predisposed to arrhythmias, ischemia, and subsequent cardiovascular collapse during withdrawal. Mortality

Fatality is rare.

ETIOLOGY/RISK FACTORS

In chronic opioid-dependent patients, withdrawal may be precipitated by:

• Abrupt cessation or a significant decrease in the regular dosing of opioids • Administration of an opioid antagonist: Nalmefene, naltrexone, naloxone • Administration of an opioid agonist–antagonist: Pentazocine, butorphanol, nalbuphine, buprenorphine PHYSIOLOGY/PATHOPHYSIOLOGY

• Opioid receptors were once thought to be found exclusively in the CNS, but recent studies

show that they are found in virtually all organ systems. • Endogenous opioids not only modulate the perception of pain, but also help regulate many other physiologic functions, including: – Respiration – Blood pressure – Shock and stress states – Vasopressin release and free water clearance by the kidneys • Neuroadaptation results from the regular use of opioids. – There is a downregulation of opioid receptors with the continuous presence of high levels of opioid agonists. – At the cellular level, there are changes in several components of cyclic adenosine monophosphate (cAMP) signal transduction cascades. – Physical dependence usually occurs 1–4 weeks after continuous opioid usage. • Withdrawal from opioids can result in a sudden increase in cAMP levels in many organ systems. The sympathetic nervous system is one of the most prominent systems affected by opioid withdrawal. – Epinephrine levels increase ∼30 times and norepinephrine levels increase ∼3 times, leading to restlessness, rhinorrhea, lacrimation, diaphoresis, myosis, piloerection, and CV changes. – Explains the benefit of clonidine in attenuating withdrawal symptoms

PREVENTATIVE MEASURES

Management of heroin abusers and chronic opioid-dependent patients • Maintain opioids during the perioperative period to avoid withdrawal. Long-acting opioids such as methadone or buprenorphine formulations may be used in combination with shortacting opioids to decrease troughs in opioid levels and treat breakthroughs, respectively. • Avoid opioid antagonists and opioid agonist–antagonists in these patients since they can precipitate acute withdrawal.

DIAGNOSIS • History: As narcotic withdrawal is not associated with altered mental status (AMS), patients can often tell you if they are undergoing withdrawal secondary to opioids. They can also tell you their usual opioid dosing schedule and the timing of their last dose. • Signs and symptoms – Manifest between 5 and 24 hours from the last dosing. Methadone withdrawal may take longer to present, but is usually between 24 and 48 hours. – Peak withdrawal is 36–72 hours after the last dose. For methadone, it is 72–96 hours after the last dose. – Duration is usually 5–10 days. Methadone withdrawal typically lasts 2–3 weeks, sometimes longer. – Signs: Pupillary dilation, sweating, piloerection, tachycardia, ventricular dysrhythmias, vomiting, diarrhea, hypertension, yawning, fever, rhinorrhea – Psychological withdrawal symptoms, such as dysphoria and insomnia, may last weeks to

months. – Symptoms: Craving for opioids, restlessness, irritability, increased sensitivity to pain, nausea, abdominal cramps, myalgia, dysphoria, insomnia, anxiety • Labs: Urine or blood toxin screen confirms opioids and/or other illicit substances.

DIFFERENTIAL DIAGNOSIS

• Other substances that cause autonomic instability. AMS, disorientation, hallucinations, and seizures are not found in narcotic withdrawal but may be found when withdrawing from: – Alcohol – Benzodiazepines – Barbiturates • Other sedatives/hypnotics

TREATMENT For patients undergoing anesthesia for emergency procedures: • Abort withdrawal symptoms by administering opioid agonists. • Check electrolytes, BUN, and creatinine if there has been significant dehydration, vomiting, or diarrhea. Give fluids or replete electrolytes, as indicated. • Consider regional anesthesia when possible. • For general anesthesia, a balanced technique with volatile anesthetics +/– nitrous is recommended. • Beware of perioperative hypotension as intravascular volume depletion is common, given the fevers, malnutrition, chronic infection, and adrenocortical deficiency often associated with opioid addiction and withdrawal. • Clonidine, a central acting alpha-2 agonist, may be given orally or applied via a transdermal patch to help with sympathetic nervous system hyperactivity found in narcotic withdrawal. • NSAIDs, such as ibuprofen, are given to attenuate muscle aches. • Benzodiazepines are sometimes used for anxiety, insomnia, and muscle cramps. However, given the potential for abuse and high risk of physical dependence, this is not considered first-line therapy. • For patients undergoing procedures or for acute pain consultation where narcotic detoxification is desired: – Consider administering the original opioid dosing and planning a gradual taper. – Alternatively switch to long-acting methadone or buprenorphine for gradual detoxification. Note: Patient must be in full withdrawal prior to starting buprenorphine. As an agonist/antagonist, buprenorphine can precipitate more severe withdrawals if given prematurely. • Ultra-rapid opiate detoxification in which patients are given large doses of opioid antagonist and placed under general anesthesia for the most severe stages of withdrawal, has become popular. However, compared to buprenorphine- or clonidine-assisted opioid detoxification, it is not as effective or safe. Several serious adverse events, including possibly fatal cardiac and pulmonary complications, have been linked to ultra-rapid opioid detoxification. • Instead of detoxification, consider lifelong maintenance on methadone or buprenorphine

since these have been associated with much higher rates of long-term program retention. Studies on methadone maintenance programs have shown decreased medical comorbidity, transmission of HIV, mortality, and increased social functioning.

FOLLOW-UP The relapse rate for opioid addiction is high. Significant psychosocial support is needed beyond the withdrawal period to prevent relapse.

REFERENCES

1. Administration SAaMHS. Results from the 2007 National Survey of Drug Use and Health: National Findings. Rockville, MD: Administration SAaMHS, 2008. 2. Collet BJ. Opioid tolerance: The clinical perspective. Br J Anaesth. 1998;81:58–68. 3. Collins ED, Kleber HD, Whittington RA, et al. Anesthesia-assisted vs. buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction: A randomized trial. JAMA. 2005;294:903–913. 4. Kaye AD, Gevirtz C, Bosscher HA, et al. Ultra-rapid opiate detoxification: A review. Can J Anaesth. 2003;50(7):663–671. 5. Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348:1786–1795. 6. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. The DAWN Report: Highlights of the 2009 Drug Abuse Warning Network (DAWN)—Findings on Drug-Related Emergency Department Visits. Rockville, MD, December 28, 2010. See Also (Topic, Algorithm, Electronic Media Element) • Drug abuse in pregnancy • Alcohol withdrawal syndrome

CODES ICD9 292.0 Drug withdrawal ICD10 F11.23 Opioid dependence with withdrawal

CLINICAL PEARLS

• Opioid withdrawal is rarely life-threatening, but may complicate care in the perioperative period. • Clonidine may attenuate the sympathetic nervous system hyperactivity found in withdrawal.

• Consider the possibility of abuse of other illicit substances in patients who abuse opioids. • Consider comorbid psychiatric conditions in narcotic withdrawal patients. • When caring for opioid addicts, particularly the intravenous abuser, beware that these patients often have associated infectious problems: hepatitis, HIV, endocarditis, septic thrombophlebitis, cellulitis, abscesses, aspiration pneumonitis, malnutrition.

NEGATIVE PRESSURE PULMONARY EDEMA Agnes Miller, MD Kalpana Tyagaraj, MD

BASICS DESCRIPTION

• Negative pressure pulmonary edema (NPPE) is an uncommon, but well-recognized clinical entity that results from the negative intrathoracic pressure generated during spontaneous ventilation with concurrent upper airway obstruction. • The pulmonary edema results from either: – “Pulling” of fluids from the pulmonary capillary bed into the alveoli (Starling forces), or – Injury to the pulmonary microvascular membranes from severe mechanical stress that results in capillary “leaking” of fluid. • NPPE can result from laryngospasm or biting, commonly at induction or extubation, as well as from epiglottitis, tumors, obesity, hiccups, or obstructive sleep apnea. • Clinical manifestations result from ventilation and perfusion difficulties (V/Q mismatching or shunt) with a frequent need for reintubation and temporary ventilatory support. EPIDEMIOLOGY Prevalence

• All anesthetic practices: 0.05–0.1%. • Laryngospasm post-extubation or biting of the endotracheal tube (ETT): 74% • Initial airway management secondary to laryngospasm or obstruction from large head and neck tumors: 26%. Prevalence

Development of pulmonary edema following active intervention for acute upper airway obstruction: 11% Morbidity/Mortality

• In undiagnosed cases it can range between 11% and 44%. • If diagnosed and treated promptly, it is less than 1%.

ETIOLOGY/RISK FACTORS • Etiology – Laryngospasm – ETT biting – Airway trauma – Upper airway collapse – Bronchial obstruction – Foreign body aspiration

– Postoperative residual curarization (impairs the upper airway dilator muscle strength while preserving inspiratory muscle function) • Patient characteristics – Young, healthy, athletic (capable of generating large negative intrathoracic pressures during an obstructive event) – Obstructive sleep apnea • Surgical procedures – Oropharyngeal surgery, particularly for tumors or other potentially obstructing masses

PHYSIOLOGY/PATHOPHYSIOLOGY

• The pathogenesis of NPPE is related to the development of high negative intrapleural pressure by vigorous inspiratory efforts against an obstructed upper airway. • 2 different mechanisms may explain the development of pulmonary edema during airway obstruction: – Starling forces: High negative intrathoracic pressures draw fluid out of micro-vessels into the peri-microvascular interstitium. Cardiogenic pulmonary edema states (CHF, fluid overload) have a similar presentation but result from positive capillary pressures that “push" fluid out of micro-vessels. During upper airway obstruction and forceful inspiration, pressure in the trachea and lower airways will decrease markedly (become more negative). The pressure in the pleural space decreases (becomes more negative) by exactly the same amount. The pressure in the pulmonary vessels decreases by much less, thus increasing the pressure difference between the inside and the outside of the capillaries and accelerating the formation of interstitial fluid. – Disruption of the alveolar epithelium and pulmonary microvascular membranes from severe mechanical stress occurs, leading to increased pulmonary capillary permeability and protein-rich pulmonary edema (this resembles non-cardiogenic pulmonary edema states such as acute respiratory distress syndrome). – Starling equation: Q = K [(Pmv − Ppmv) − (πmv − πpmv)], where Q = Net transcapillary flow of fluid K = Transcapillary permeability Pmv = Hydrostatic pressure in microvessels Ppmv = Perimicrovascular interstitium

πmv = Plasma protein osmotic pressure in the peripheral vessels

πpmv = Protein osmotic pressure in the perimicrovascular interstitium

• Respiratory dynamics: – Pulmonary edema is the pathologic accumulation of fluid in the lung interstitium, and later alveoli, producing impairment in gas exchange. – Pulmonary edema leads to V/Q mismatching since less alveoli are participating in gas exchange. The severity of V/Q mismatch correlates with the severity of the pulmonary edema. – Lung edema leads to decreased lung compliance, which leads to an increased work of breathing.

PREVENTATIVE MEASURES

• Bite block to prevent biting on the ETT • In patients prone to upper airway obstruction, consider prophylactic placement of an oral airway or nasal trumpet. • Treat laryngospasm aggressively with positive pressure ventilation or succinylcholine.

PREOPERATIVE ASSESSMENT • History: Acute upper airway obstruction in spontaneously ventilating patients • Signs and symptoms: Onset can occur within minutes after the relief of obstruction. Can present as stridor, wheezing, decreased SaO2%, or frothy or pink sputum. • Studies: EKG is typically normal, but may demonstrate right heart strain. • Laboratory findings: None that are specific • Radiographic findings: Peripheral or central asymmetric peribronchial infiltrates

DIFFERENTIAL DIAGNOSIS

• Cardiogenic pulmonary edema • Neurogenic pulmonary edema • Fluid overload • Acute respiratory distress syndrome • Non-cardiogenic pulmonary edema (e.g., acute respiratory distress syndrome).

TREATMENT • The goal is to maintain a patent upper airway and administer supplemental oxygen. • Consider a trial of CPAP or pressure support as an alternative to intubation. The aim of noninvasive respiratory support is to: – Partially compensate for the increased work of breathing – Improve alveolar recruitment with better gas exchange – Reduce left ventricular afterload – Increase cardiac output and improve hemodynamics • In severe cases, consider re-intubation. Ventilation mode should be similar to the mode used during acute lung injury (i.e., small tidal volumes [6 mL/kg], increased respiratory rate [14–18 breaths/minute], and attempt to keep peak pressures 5–8 mm▒Hg, maintain the same tidal volume; otherwise, decrease tidal volume so that the airway pressure is maintained within the above-mentioned range. – Increase the respiratory rate as needed to maintain normocarbia; keep in mind that this

can indirectly increase airway pressures. • Collapsing the non-dependent lung: Exposure of the pleural cavity to atmospheric pressure on the surgical side will initiate collapse of the lung. – Accelerated by a higher FIO2 before lung isolation, clearing the airway of secretions, and

applying gentle suction to the non-ventilated lung – Slowed or hampered by small airway diseases, secretions in the airway, tumor pressure on the airway, malpositioning of the DLT, and pleural adhesion and fibrosis • Factors that aid with diverting blood flow and maintaining a PaCO2 in an acceptable range during surgery: – Passive: Gravity (lateral decubitus), pre-existing lung disease (mass), surgical manipulation and interventions (ligation of vessels) – Active (more effective): HPV • Hypoxia: – DLT malposition (major cause): Fiberoptic examination of the tube position is necessary in any patient with OLV and hypoxia; confirm that the tube is not too deep (endolobar) or that the cuff is not herniating upwards into the carina (8)[B]. – Shunting: Interventions to decrease shunting depend upon the severity of hypoxia. If mild, consider starting with continuous positive airway pressure (CPAP) to the non-dependent lung followed by positive end expiratory pressure (PEEP) to the dependent lung (may “shunt” blood to the non-dependent lung and worsen hypoxia). When acute or severe, temporary re-expansion of the non-dependent lung and/or clamping of the pulmonary artery to the non-dependent lung (if surgical conditions permit). – Secretions: Can cause localized hypoventilation, which can be improved by suctioning – Decreased cardiac output: Can impair oxygen delivery to tissues. Increasing the CO may improve hypoxia by improving mixed venous O2. GRAPHS/FIGURES

FIGURE 1. Left-sided double lumen tube. The endobronchial lumen sits in between the carina and left upper lobe. There is an increased margin for error while positioning, and even for right sided lung surgeries and procedures, a left DLT is commonly placed (with ventilation to the left lung/dependent lung through the endobronchial lumen).

FIGURE 2. Right-sided double lumen tube. The endobronchial lumen sits below the carina. However, because of the

shorter distance between the carina and right upper lobe takeoff, there is little margin for error while positioning. In order

to avoid occlusion and shunting of the right upper lobe, a Murphy’s eye is embedded into the endobronchial cuff to allow ventilation. Ventilation also occurs through the endobronchial lumen.

FIGURE 3. Fiberoptic view of a properly positioned left double lumen tube via the tracheal lumen. The carina should be

visualized along with the endobronchial cuff slightly above the bronchial lumen. The posterior tracheal rings can aid with identifying that the view is of the trachea, and not endobronchial.

REFERENCES

1. Koshy T, Nair SG. Positioning of double-lumen endobronchial tubes: Correlation between clinical and bronchoscopic findings. Indian J Anaesth. 2003;47(2):116–119. 2. Campos JH. Current techniques for perioperative lung isolation in adults. Anesthesiology. 2002;97(5):1295–1301. 3. Campos JH. An update on bronchial blockers during lung separation techniques in adults. Anesth Analg. 2003;97:1266–1274. 4. Ransom ES, Carter L, Mund GD. Univent tube: A useful device in patients with difficult airways. J Cardtothorac Vasc Anesth. 1995;9(6):725–727. 5. Campos JH, Kernstine KH. A comparison of a left-sided Broncho-Cath with the torque: Control blocker Univent and the wire-guided blocker. Anesth Analg. 2003;96:283–289. 6. Takenaka I, Aoyama K, Kadoya T. Use of the Univent bronchial-blocker tube for unanticipated difficult endotracheal intubation. Anesthesiology. 2000;93(2):590–591.

7. Kernstine KH. The incidence of right upper-lobe collapse when comparing a right-sided double-lumen tube versus a modified left double-lumen tube for left-sided thoracic surgery. Anesth Analg. 2000;90:535–540. 8. Uwe K, Karzai W, Bloos F, et al. Role of fiberoptic bronchoscopy in conjunction with the use of double lumen tubes for thoracic anesthesia: A prospective study. Anesthesiology. 1998;88:346–350.

9. Campos JH, Massa C, Alliaume B, et al. Reliability of auscultation in positioning of doublelumen endobronchial tubes. Can J Anaesth. 1992;39(7):687–690. 10. Brodsky JB, Lemmens HJ. Left double-lumen tubes: Clinical experience with 1,170 patients. J Cardiothorac Vasc Anesth. 2003;17(3):289–298.

11. Swift J. Placement of double lumen tubes—time to shed light on an old problem. Br J Anaesth. 2000;84(3):308–310. See Also (Topic, Algorithm, Electronic Media Element) • Double lumen tube • Hypoxic pulmonary vasoconstriction

CLINICAL PEARLS

• Correct positioning of a DLT can be confirmed clinically by auscultation of the lungs during manual ventilation; breath sounds should be absent distally when clamping the desired lumen (tracheal, bronchial) (9)[B]. Visualization with a fiberoptic scope is the gold standard for confirming positioning. • Patients with severe restrictive lung disease, very low cardiac output, or pneumonia in nonventilated lung may be less capable of handling the shunt created in the non-dependent lung.

OPERATING ROOM FIRES Jeanna Blitz, MD Shawna Dorman, MD

BASICS DESCRIPTION

• An operating room fire is any fire that ignites in the operating or procedure room. • Anesthesia providers should be aware of the treatment and prevention of surgical and airway fires. – Surgical fires are defined as those that occur on or around a patient. – Airway fires are defined as surgical fires that ignite within the patient’s airway or breathing circuit. • All fires require the triad of an ignition, oxidizer, and fuel. Thus, prevention in high-risk scenarios should aim at reducing or eliminating one of these elements. EPIDEMIOLOGY Incidence

• Difficult to accurately assess because there is no FDA mandate requiring operating room staff to report a fire • In the US, there are approximately 550–650 surgical fires per year. • 21% of surgical fires involve the airway.

Morbidity

Disfiguring or disabling injuries from operating room fires is estimated to occur in 20–30 patients per year (1).

Mortality

Death from operating room fires occur in ~1–2 patients per year (mostly airway fires) ETIOLOGY/RISK FACTORS

• Fire triad – Ignition: Electrocautery, lasers, fiberoptic light source, defibrillators, high-speed burrs – Oxidizers (gases that can support combustion): Oxygen and nitrous oxide – Fuel: Alcohol-based surgical preps, ETT, breathing circuits, drapes, body hair, nasal cannula, face masks, intestinal gases • High-risk surgical procedures are defined as anytime an ignition source may come in close proximity to an oxygen-rich environment. – Procedures above the xiphoid, sedation with open oxygen source (face mask, nasal cannula) Cataract Carotid endarterectomy (cervical block)

Removal of skin lesions Face lifts Blepharoplasty – Procedures that “enter" the airway Tracheostomy Biopsy (vocal cords, tracheal) Removal of lesions Oropharyngeal procedures

PHYSIOLOGY/PATHOPHYSIOLOGY

• Oxygen lowers the temperature at which a fuel will ignite. – Even materials that will not burn in room air will do so in an oxygen-enriched environment. – Oxygen-enriched fires are hotter, more intense, and spread more rapidly. • Oxygen-enriched environments are defined as any atmosphere in which the oxygen concentration is >21% or the partial pressure is >160 mm Hg (2). – Drapes promote trapping or pooling of oxygen from open sources (blow by, face mask, nasal canula). – Airway procedures enter an enclosed, oxygen-enriched environment • Nitrous oxide supports combustion by dissociating and releasing heat and oxygen.

PREVENTATIVE MEASURES

• Most, if not all, operating room, surgical, and airway fires are preventable. • Deliver safe room air sedation. – Select patients with normal pulmonary function – Judiciously administer hypnotics, sedative, and opioids – Use of a pulse oximeter AND end-tidal CO2 to monitor the patient’s oxygenation and

ventilation can decrease hypoxic events by allowing earlier diagnosis of hypoventilation. – Oxygen saturations of 92% can be safe and acceptable; 65 years, intrapericardial or extrapleural pneumonectomy, right-sided procedure, and any major complication are factors associated with an increased risk of dysrhythmias (p < 0.05) (2)[B]. • Others: Pulmonary embolism, myocardial infarction (MI), bronchopleural fistulas, chylothorax, subcutaneous emphysema, phrenic and recurrent laryngeal nerve injury.

Mortality

• Overall 30-day mortality ranges from 5–13% (5)[B]. • Increased with low predicted postoperative FEV1 (ppo-FEV1), high perfusion fraction of the resected lung (3)[B], and postoperative acute lung injury (30–50%) (4)[B].

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperative evaluation of lung and cardiac function along with discussion with the surgeon can help decrease factors leading to pulmonary complications. • One lung ventilation physiology and management • Judicious intraoperative fluid management can decrease acute lung injury (ALI).

PREOPERATIVE ASSESSMENT SYMPTOMS

Dyspnea, cough, hemoptysis History

• Extensive evaluation of pulmonary disease and cardiac status; exercise tolerance, cigarette smoking • Myasthenic syndrome (Eaton–Lambert)

Signs/Physical Exam

• Cyanosis, clubbing • Auscultation: Crackles, wheezes, distant sounds. • Pulmonary hypertension: Split or increased second sound • Heart failure: Peripheral edema, jugular venous distention, hepatomegaly

MEDICATIONS

• Radiation therapy and chemotherapy • Inhaled beta agonists, anticholinergics, or steroids • Antibiotics • Diuretics • Home oxygen • Antiarrhythmics

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• EKG – COPD: Right atrial and ventricular hypertrophy, low voltage QRS, and poor R wave progression across the precordial leads – Cor pulmonale: Enlarged P waves in lead II. • Arterial blood gas: Baseline hypoxia or CO2 retention • Imaging: Chest x-ray (CXR), CT scan, MRI to identify airway anatomy, masses, obstruction to flow and narrowing of airway, lung lesions/disease, lung hyperinflation, effusions, abscesses and hematomas • Pulmonary function tests: Performed to establish a baseline, to determine the ability to tolerate lung resection, and to risk stratify. • Split-lung function tests: Predicts the function of the lung tissue that will remain after resection CONCOMITANT ORGAN DYSFUNCTION

• Cardiac failure due to pulmonary disease • Right ventricular straining and hypertrophy • Arrhythmias • Hepatic congestion

TREATMENT PREOPERATIVE PREPARATION Premedications

• Minimize use of benzodiazepines and narcotics (may worsen hypercarbia). Benzodiazepines may contribute to postoperative delirium, especially in elderly patients. • Nebulizers: Beta agonists and anticholinergics.

Special Concerns for Informed Consent

• Possibility of prolonged postoperative intubation and mechanical ventilation • Blood and blood product transfusion • Invasive monitoring: Central line, arterial line, transesophageal echocardiography (TEE) • Regional anesthesia: Epidural, paravertebral blocks(6)[B]

Antibiotics/Common Organisms

Third generation cephalosporin for skin organisms INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia with thoracic epidural placement or ipsilateral paravertebral blocks with catheter placement for continuous infusion (6,7)[B]

Monitors

• Standard ASA monitors • Arterial line • Central line for CVP tracing and SvO2 monitoring • TEE

Induction/Airway Management

• Induction agent (often based on cardiac status) along with IV lidocaine, narcotics, and muscle relaxation are most commonly used. Introduction of volatile agent during bag mask ventilation will bronchodilate prior to laryngoscopy and intubation. • Double lumen tube (DLT), bronchial blocker, or main-stemmed single lumen tube. A fiberoptic scope is used to confirm proper placement.

Maintenance

• Ventilation – During OLV, implement an FiO2 of 1.0, low tidal volumes 5–6 mL/kg, and limit peak and plateau pressures to 46 mm Hg

– PaO2 0.3 mg/dL or 1.5–2-fold increase from baseline, or urine output (UOP) 0.5 mg/dL in patients with a baseline SrCr >4 mg/dL, or UOP 0.5 mg/dL in hospitalized patients is associated with a 6.5-fold increase in the odds of inhospital death. ETIOLOGY/RISK FACTORS

• High risk surgical procedures include: Cardiac and vascular surgery, heart and liver transplant, hepatobiliary surgery, and procedures utilizing radiocontrast • High risk patients include: – Renal insufficiency, both mild and moderate – Ascites – Active congestive heart failure – Emergency surgery – Age >56 years – Diabetes mellitus – Hypertension – Male sex

PHYSIOLOGY/PATHOPHYSIOLOGY

• Total renal blood flow (TRBF) is about 20% of the cardiac output with an oxygen delivery of 80 mL/min/100 g of tissue. • The renal cortex receives most of the TRBF and has a low oxygen extraction ratio (∼20%). • The renal medulla has a smaller blood flow and a high oxygen extraction ratio (∼80%), consequent to the high metabolic demand of tubular reabsorptive function. Thus, the renal medulla is susceptible to ischemic insults. • In acute tubular necrosis (ATN), ischemia and/or direct toxicity result in apoptosis and shedding of tubular cells as well as recruitment of vasoactive and inflammatory mediators that worsen ischemic injury. Loss of tubular cells allows leakage of glomerular filtrate into the interstitium which results in edema that may progress to chronic inflammation and fibrosis, ultimately leading to chronic kidney disease. • Perioperatively, a combination of factors contribute to renal dysfunction: – Preoperatively: Hypovolemia due to preoperative fasting, bowel preparation – Intraoperatively: Effect of anesthetics on hemodynamics and renal perfusion, effect of surgical technique on renal blood flow (e.g., laparoscopic procedures), blood loss, neuroendocrine response to anesthesia and surgery, excessive fluid resuscitation – Use of nephrotoxins such as contrast media, antibiotics, NSAIDs, etc.

PREVENTATIVE MEASURES

• The cornerstone of treatment is prevention.

• Pharmacologic interventions have been controversial, and as of yet, no pharmacologic interventions have definitively been beneficial in the prevention of renal failure in the perioperative period with the exception of mannitol administration prior to renal transplant reperfusion. • Maintain adequate blood pressure. – Autoregulation maintains a constant renal blood flow between mean arterial pressures (MAPs) of 80–160 mm Hg. – Improved renal hemodynamics has been shown with MAPs around 75 mm Hg. – The autoregulation curve may be shifted to the right in chronic hypertensives, so higher pressures may be needed. • Ensure euvolemia. – Oxygen delivery to the kidneys may be reduced in hypovolemia, resulting in ischemic ATN. – Excessive fluid resuscitation may lead to abdominal compartment syndrome (intraabdominal hypertension [IAH]) and impaired renal perfusion. – Normal saline given in volumes >30 mL/kg can cause a non-gap hyperchloremic metabolic acidosis and hyperkalemia. Hyperchloremia may result in a decrease in renal blood flow, glomerular filtration rate, and urine output. – Albumin may not be more beneficial than crystalloids except in specific situations such as in cirrhotic patients with spontaneous bacterial peritonitis. – There is conflicting evidence on the renal safety of hydroxyethyl starch. • Optimize the oxygen delivery to the kidneys by maintaining an adequate hemoglobin level and cardiac output. • Avoid nephrotoxins. – Iodinated contrast agents are being used with increasing frequency and can cause contrast induced-acute kidney injury (CI-AKI). In addition to being directly toxic to tubular cells, they can cause renal vasoconstriction. Unfortunately at this time, no definitive technique has been shown to consistently decrease or eliminate this risk. The following may be considered: Adequate hydration to a goal of 100–150 mL/hr of UOP to potentially “wash off” the agent and minimize contact time with tubular cells; antioxidants such as N-acetyl cysteine, statins, and urine alkalinizers such as sodium bicarbonate may reduce free radical-related tubular cell apoptosis; the use of low osmolar agents (approximately twice the osmolarity of plasma) in normal patients and iso-osmolar agents in patients at risk of CI-AKI; avoid concomitant use of other nephrotoxins as well as repeat exposure (within 72 hours) of receiving a contrast medium load. – NSAIDs inhibit vasodilatory prostaglandins and can result in decreased glomerular filtration pressure by vasoconstricting afferent arterioles. Consider avoiding in high-risk patients. However, in one study, no long-term impairment in renal function was found when given postoperatively to kidney donors. – ACEI and ARBs: Decrease glomerular filtration pressure by vasodilating efferent arterioles. Avoid in hypovolemia. – Antibiotics such as aminoglycosides can cause ATN by accumulating in the proximal tubules. – Other nephrotoxins include antifibrinolytics such as aprotinin, immunosuppressants such

as cyclosporine and tacrolimus, and chemotherapeutic agents such as cisplatin.

PREOPERATIVE ASSESSMENT • History and physical examination including medication review, perioperative exposure to nephrotoxins, volume and hemodynamic assessment. • On urinalysis, hyaline casts suggest prerenal azotemia, whereas pigmented casts are seen in ATN. • Concentration of urine solutes and avid sodium retention is seen in prerenal azotemia. This will result in a specific gravity >1.015, osmolality >350 mOsm/kg, and urine sodium 53 years: 50% • ASA 3–5: 45% • Intraoperative oliguria or anuria: 31% • Emergency surgery (ASA classification): 29% • Vascular surgery: 16% • Cardiac surgery: 3% • Perioperative events leading to renal dysfunction/failure: – Patient condition or surgical cause: 17% – Wrong blood administered: 15% – Electrolyte imbalance or inappropriate fluid therapy: 13% – Medication error: 12% – Excessive blood loss: 8% • Outcome and liability: – Mortality: 47% – Substandard anesthesia care: 48% – Payments/settlement to patient: 56% – Median payment: $255,000 (range: $4,000–$3,625,000)

REFERENCES

1. agshaw SM, et al. Review article: Acute kidney injury in critical illness. Canadian J Anesth. 2010;57:985–998. 2. Kheterpal S, Tremper K, Heung M, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery. Anesthesiology. 2009;110:505– 515. 3. Crowley ST, Pexioto AJ. Acute kidney injury in the intensive care unit. Clin Chest Med. 2009;29–43. 4. Jones D, Lee H. Perioperative Renal Protection. Best Pract Res Clin Anesthesiol. 2008;22(1):193–208. 5. Khalil P, Murty P, Palevsky P. The patient with acute kidney injury. Prim Care Clin Office Pract. 2008;35:239–264. 6. Posner KL. Personal communication. ASA Closed Claims Project N8954, March 1, 2011.

ADDITIONAL READING

• Chertow MG, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365–3370. • Friedwald VE, Goldfarb S, Laskey W, et al. The editor’s roundtable: contrast-induced nephropathy. Am J Cardiol. 2007;100(3):544–51. • Jarnberg P. Renal protection strategies in the perioperative period. Best Pract Res Clin Anesthesiol. 2004;18(4):645–660. • Sear JW. Kidney dysfunction in the postoperative period. Brit J Anesth. 2005;95(1):20–32. • Tang I, Murray P. Prevention of perioperative acute renal failure: what works? Best Pract Res Clin Anesthesiol. 2004;18(1):91–111.

CODES ICD9 • 584.9 Acute kidney failure, unspecified • 997.5 Urinary complications, not elsewhere classified ICD10 • N17.8 Other acute kidney failure • N99.89 Oth postprocedural complications and disorders of GU sys

CLINICAL PEARLS

• With the exception of maintaining adequate renal perfusion pressures and fluid hydration, there are not many interventions that can actively prevent renal failure postoperatively. • Low intraoperative urinary output is not always correlated with postoperative renal failure. • Oliguria during laparoscopic procedures is due to compression of the kidneys and their vessels by the pneumoperitoneum. It usually resolves after desufflation. Avoid insufflations pressures >15 mm Hg.

POSTOPERATIVE SHIVERING Jose M. Soliz, MD

BASICS DESCRIPTION

Postoperative shivering is involuntary, oscillatory muscle activity that augments heat production; it is common upon emergence from anesthesia. EPIDEMIOLOGY Prevalence

• Up to 40% of patients shiver during recovery after undergoing a general anesthetic (1) • Up to 30% of patients shiver during epidural anesthesia • The incidence of shivering is affected by the core body temperature: – At 35.5°C, up to 50% of patients shiver. – Between 34.5–35.4°C: Up to 90% of patients shiver. Morbidity

• Increases O2 consumption by up to 300%; as a result, it may increase the incidence of adverse myocardial events in high-risk patients. • Increases CO2 production

• Increases plasma catecholamine levels • Increases intraocular and intracranial pressures • Increases postoperative pain and discomfort • Hypothermia may exacerbate postoperative bleeding, prolong neuromuscular blockade, delay emergence, delay wound healing, and increase the risk of surgical site infection (1).

Mortality

May indirectly increase due to adverse cardiovascular events and increased risk of infection. Data is not currently available. ETIOLOGY/RISK FACTORS

• Most commonly occurs as a complication of hypothermia (2) • Normothermic shivering can also occur in: – Younger patients – Prolonged surgery – Orthopedic surgery

PHYSIOLOGY/PATHOPHYSIOLOGY

• The preoptic region of the hypothalamus is the dominant autonomic thermoregulatory center. When this region is cooled, shivering is believed to be mediated via recurrent inhibition of a group of inhibitory neurons called Renshaw cells. Shivering thus serves as a

normal, physiologic, protective mechanism to create warmth by energy expenditure. • Perioperative hypothermia – During general peripheral vasodilation results in redistribution of heat from the core to the periphery; this typically occurs over the first hour. – Heat loss from the patient to the environment/surroundings occurs via radiation, conduction, convection, and evaporation. • Anesthetic agents and shivering. During surgery, anesthetic medications increase the shivering threshold and protect against intraoperative shivering. However, as plasma concentrations decrease in the postoperative period, shivering can occur (8). • Neuraxial anesthesia and shivering. Spinal and epidural anesthetics produce sympathetic blockade with resultant vasodilation and heat loss. The mechanism of postoperative shivering is not fully understood. – Shivering is a function of motor activity; thus dermatomes that have motor blockade will not produce oscillatory muscle activity. – Spinal blocks initially decrease core temperature faster than epidural anesthesia; thus, the shivering threshold is achieved faster. • Non-thermoregulatory shivering: Shivering is not isolated to hypothermic states; the pathogenesis is not completely understood. Potential causes include: – The release of pyrogenic mediators elicited by surgical tissue damage – Anesthetic drugs – Postoperative pain – Decreased sympathetic activity – Uninhibited spinal reflexes/loss of descending control – Adrenal suppression – Fever – Respiratory alkalosis

Pediatric Considerations

• Neonates have an increased body surface area and are susceptible to hypothermia in the perioperative period. In addition, neonates cannot respond to cold stress by shivering; these mechanisms do not develop until the age of 6 months to 1 year. Measures to decrease heat loss and generate heat include: – Peripheral vasoconstriction via norepinephrine release: This can lead to pulmonary artery constriction and right-to-left shunting (hypoxia, cyanosis), as well as decreased tissue perfusion with subsequent tissue hypoxia and metabolic acidosis. – Non-shivering thermogenesis (NST): Describes the metabolism of brown fat which increases oxygen consumption and carbon dioxide production. The increased oxygen requirements may lead to hypoxia and metabolic acidosis; the increased carbon dioxide production may lead to tachypnea (if unable to adequately exhale the increased load, can result in respiratory acidosis). Furthermore, inhalational anesthetics inhibit brown fat metabolism, further increasing neonatal susceptibility to hypothermia in the operating room.

Pregnancy Considerations

Epidural meperidine, fentanyl, alfentanil, and morphine have been used to treat shivering in

the obstetric patient. Intravenous propofol has also been used to decrease cold responses. Shivering can also occur in the laboring patient who did not receive neuraxial anesthesia, which suggests a non-thermoregulatory mechanism for shivering during labor. PREVENTATIVE MEASURES

• Prevention of hypothermia is preferred to rewarming in the postoperative period (3). This can be facilitated by: – Intraoperative temperature monitoring: Core body temperature is measured in the distal esophagus, nasopharynx, tympanic membrane, or pulmonary artery. – Blankets and drapes to decrease radiation of heat into the cooler environment. – Forced air warming decreases the radiation of heat into the cooler environment as well as actively warms the patient. It is considered the most effective method. – Increasing the ambient temperature of the surgical suite decreases the radiation of heat into the environment – Warm intravenous fluids and blood products – Humidify anesthesia circuits

PREOPERATIVE ASSESSMENT Visualized cutaneous muscle contractions DIFFERENTIAL DIAGNOSIS

• Seizure • Muscle spasms from hypocalcemia, hypokalemia • Rigors in patients developing fever • Extrapyramidal symptoms in patients with Parkinson’s disease or Parkinson-like syndrome.

TREATMENT • Hypothermic shivering: Cutaneous warming with blankets or forced air in the recovery room. • Non-thermoregulatory (and hypothermic shivering, while simultaneously rewarming) can be treated with pharmacologic agents: – Meperidine 12.5 mg or 25 mg IV; via kappa receptor effects. – Granisetron 40 mcg/kg IV (5); via 5-HT3 activity. – Tramadol 0.1 mg/kg IV; via a modulatory effect on central monoaminergic pathways. It has the benefit of decreased sedation compared to meperidine (6). – Opioids (morphine, fentanyl); likely via analgesic effects. – Physostigmine 0.04 mg/kg IV; crosses the blood–brain barrier and is a cholinesterase inhibitor. Cholinergic stimulation of the hypothalamic–pituitary–adrenal axis and the adrenal medulla enhance the secretion of arginine vasopressin, epinephrine, and norepinephrine; these neurotransmitters are believed to be involved in body temperature control. Physostigmine is associated with bradycardia and gastrointestinal upset. – Ketamine 0.5 mg/kg IV prophylactically (7); mechanism via antagonism of the NMDA

receptor. – Clonidine 75 mcg IV; a centrally acting alpha-2 receptor agonist. May decrease blood pressure. – Chlorpromazine 10–20 mg IV; exact mechanism to reduce shivering is unknown. It may possibly occur via antidopaminergic or anticholinergic activity. – Doxapram 100 mg IV (3); centrally acts to increase the shivering threshold, may also have weak opioid receptor activity. – Dexmedetomidine 1 mcg/kg; likely via reduced central adrenergic flow.

FOLLOW-UP • If patients are hypovolemic, rewarming may cause vasodilatation leading to hypotension, reflex tachycardia, and myocardial ischemia. Replacing intravascular volume while rewarming may be necessary. • Opioid-related side effects can occur when used for the treatment of shivering. Monitor for respiratory depression, drowsiness, altered mental status, nausea, vomiting, and pruritus.

CLOSED CLAIMS DATA

Devices used to warm the patient’s skin resulted in 28 burns (N = 3000 total claims). 18 of the 28 were from IV fluid bags or water bottles applied directly to the patient’s skin. 5 of the 28 burns resulted from circulating water mattresses (4).

REFERENCES

1. Bhattacharya PK, Bhattacharya L, Jain R, et al. Post anesthesia shivering (PAS): a review. Indian J Anaesth. 2003;47(2): 88–93. 2. Leopold H, Eberhart J, Doderlein F, et al. Independent risk factors for postoperative shivering. Anesth Analg. 2005;101:1849–1857. 3. Kranke P, Eberhart LH, Roewer N, et al. Pharmacological treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials. Anesth Analg. 2002;94:453–460. 4. Cheney FW, Posner KL, Caplan RA, et al. Burns from warming devices in anesthesia. Anesthesiology. 1994;80:806–810. 5. Sajedi P, Yaraghi A, Moseli HA. Efficacy of graniesetron in preventing postanesthetic shivering. Acta Anaesthesiol Taiwan. 2008;46(4):166–170. 6. Tsai YC, Chu KS. A comparison of tramadol, amitryptyline, and meperidine for postepidural anesthetic shivering in parturients. Anesth Analg. 2001;93(5):1288–1292. 7. Sagir O, Guthas N, Toprak H, et al. Control of shivering during regional anesthesia: Prophylactic ketamine and granisetron. Acta Anaesthesiol Scand. 2007;51(1):44–49.

8. Horn EP. Postoperative shivering: Aetiology and treatment. Curr Opin Anaesthesiol. 1999;12(4):449–453.

ADDITIONAL READING

• Hypothermia • Surgical site infection • Chronic angina

CODES ICD9

995.89 Other specified adverse effects, not elsewhere classified ICD10

T88.51XA Hypothermia following anesthesia, initial encounter

CLINICAL PEARLS

• Prevention of hypothermia is key. • Intraoperative forced air warming is the most effective method of preventing hypothermia. • Various pharmacologic agents can be used as treatment. Meperidine (12.5 mg or 25 mg IV) is the most consistently effective.

POSTRENAL ACUTE KIDNEY INJURY Jonathan Anson, MD

BASICS DESCRIPTION

• Acute kidney injury (AKI) is a sudden decrease in kidney function causing acid–base imbalance along with fluid and electrolyte disturbances. • AKI causes can be divided into: – Prerenal – Intrarenal – Postrenal: Accounts for just 5–10% of all AKI, but is often easily reversible. • In the perioperative period, patients may present: – For temporary or definitive surgical treatment to relieve a pre-existing urinary obstruction – For pre-emptive stent placement prior to abdominal or pelvic surgeries – With anuria, oliguria, or signs and symptoms of AKI secondary to mechanical obstruction • The reversible nature of postrenal disease makes a prompt diagnosis essential.

PHYSIOLOGY PRINCIPLES

• Nephrons are the functional units of the kidney. – Afferent arterioles form glomerular capillaries within the Bowman’s capsule (cup-like structure). They exit via efferent arterioles after filtering into the nephron via hydrostatic forces. – Urine ultrafiltrate passes from the proximal convoluted tubule to the loop of Henle to the distal convoluted tubule and finally to the collecting ducts. • Glomerular filtration rate (GFR) is the plasma volume filtered by the kidneys per unit of time and is used to assess the kidney function. GFR can be estimated by calculating a patient’s creatinine clearance. Additionally, trends in creatinine clearance can be used to predict perioperative outcomes. ANATOMY

• Gross anatomy of the kidney: – Consists of an outer cortical layer and inner medulla. – Renal artery, renal vein, and ureter enter/exit the kidney at the hilus on the midportion of the concave side. – At the hilus, the ureter dilates into the renal pelvis. The renal pelvis further divides into many tube-like calyces that combine to form the renal parenchyma. – Sympathetic innervation is via the T8-L1 preganglionic fibers. – Parasympathetic input is from the vagus nerve. • Gross anatomy of the ureter: – Muscular tubes propel urine from the renal pelvis to the bladder. – The lumen is lined with transitional epithelium.

– Descends anterior to the psoas muscle and crosses the pelvic brim at the bifurcation of the iliac arteries. – Ureters enter the bladder at the vesicoureteric junction. – Ureterovesical valves prevent backflow of urine. • Gross anatomy of the bladder: – Hollow, muscular, elastic organ that collects urine excreted by the kidney. – The bladder wall is composed of a smooth muscle called detrusor. – Internal surface consists of the transitional epithelium, cuboidal cells that can expand and contract to support volume fluctuations. – Sympathetic innervation is via T11-L2 – Parasympathetic innervation is from S2–S4. Bladder stretching induces the parasympathetic nervous system to contract the detrusor muscle and expel urine to the urethra

PHYSIOLOGY/PATHOPHYSIOLOGY

• Postrenal failure occurs when urine flow from both kidneys is obstructed. This can result from obstruction of a single kidney in the presence of a diseased contralateral kidney or partial or complete obstruction of the bladder or urethra. Specific instances where this can occur are: – Urethral obstruction bilaterally, such as stones or strictures – Bladder obstruction – Neurogenic bladder – Prostatic hypertrophy – Obstruction of the renal pelvis – Blood clots – Cancer of the bladder, prostate, or cervix – Mechanical obstruction of a Foley catheter • Urinary obstruction increases renal intraluminal pressure with resultant: – Decreased renal blood flow – Decreased glomerular filtration rate – Decreased tubular function; distal tubule injury impairs sodium reabsorption with accompanying hyperkalemic renal tubular acidosis – Systemic hypertension via an unknown mechanism, but possibly involving renin– angiotensin activation and volume overload – Pain from distension of the renal capsule, collecting system, or bladder. More common with acute complete obstruction such as ureteral calculus; slow-developing obstructions such as tumors tend to cause less pain – Prolonged obstruction leads to tubular atrophy and irreversible injury

Pediatric Considerations

Anatomic abnormalities are the most common cause of urinary obstruction in children. They include urethral strictures and stenosis of the ureteropelvic or ureterovesical junctions. Geriatric Considerations

The incidence of benign prostate hypertrophy (BPH) increases with age. Eighty percent of

men over the age of 80 years have BPH and therefore are at a higher risk for urinary obstruction and postrenal failure Pregnancy Considerations

• Hydronephrosis and hydroureter without evidence of obstruction is a normal finding present in 80% of pregnancies • More likely to occur on the right side • A dilated collecting system is a risk factor for pyelonephritis

PERIOPERATIVE RELEVANCE

• Patients at increased risk for postrenal dysfunction: – Anticholinergic drugs (acute or chronic): Decreased detrusor contractility places patients at increased risk postoperatively. – Narcotics: Decreased detrusor contractility and ureteral colic. – Benign prostatic hypertrophy: Risk is increased with intraoperative narcotics and missed doses of chronic alpha blockade. – Neuraxial blocks: Blocking the S2–S4 nerve roots can lead to decreased bladder contractility. Advanced age, history of BPH, and neuraxial narcotics can further increase this risk. A urinary catheter should always be used intra-operatively with a neuraxial block. – Preoperative renal impairment: The stress response to surgery can induce a decrease in RBF and GFR, ultimately leading to ischemic damage. This can exacerbate a co-existing postrenal disorder. • Postrenal AKI in the intraoperative period: Usually noticed as a decrease or cessation of urinary output in patients with a bladder catheter. Kinks, clots, or other reversible obstructions should be ruled out prior to presumptively assuming that there is a prerenal or intrarenal cause. It may also present as hypertension or hypervolemia. • Postrenal AKI in the Post Anesthesia Care Unit (PACU) typically presents as an inability to void. Tachycardia, hypertension, and abdominal pain are also common. Bladder ultrasound scan may be considered and can avoid the placement of a catheter. A catheter should be placed if there is evidence of bladder distension on ultrasound. Ability to void is not a criterion for discharge at all institutions (some may use it for urologic or laparoscopic procedures or if neuraxial anesthesia is used). • Postrenal AKI on the floor or ICU: Presents with signs of fluid overload (tachycardia, hypertension, or pulmonary edema in severe cases) as well as decreased or absent urine output. Electrolyte disturbances such as hyperkalemia and metabolic acidosis can be present as well. • Diagnosis – A serum BUN:Cr >15 can result from increased tubular pressure causing BUN reabsorption. However, this is not a marker of acute change. Trends can be monitored to track progression of renal impairment over time. – Fractional excretion of sodium (FENa) may initially be 45 years old. – Continuous epidural infusion can block sympathetic nerve fibers and may assist with BP control. • Magnesium sulfate (first line): 4–6 g IV bolus over 15 minutes, followed by 1–2 g/hr for seizure, prophylaxis. Therapeutic level ∼6–8 mEq/mL • Ergot alkaloids (e.g., Methergine) should be avoided as it may cause a hypertensive crisis.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• 24-hour urine protein • Urine protein: urine creatinine ratio • Hgb/Hct/platelet count • Liver enzymes to assess for HELLP syndrome • Blood type and screen or cross-matching, as appropriate • Fetal ultrasound • Echocardiogram if suspicion for cardiomyopathy

CONCOMITANT ORGAN DYSFUNCTION

• CNS: Visual disturbance, headache, eclamptic seizures, or cortical blindness may be due to cerebral edema. • CV: Vasoconstriction due to endothelial dysfunction and consequent hypertension. • Respiratory: Increased risk of pulmonary edema due to lower colloid oncotic pressures and increased capillary permeability • Renal: Proteinuria due to increased permeability of albumin and other plasma proteins. • Hematologic: Microconsumption coagulopathy, and/or thrombocytopenia. • GI: Hepatic edema causing RUQ pain; rupture of Glisson’s capsule in severe disease may lead to hepatic hemorrhage; elevated liver enzymes in HELLP syndrome. CIRCUMSTANCES TO DELAY/CONDITIONS

• Appropriate BP control is necessary before induction of general anesthesia, even in emergent cases. • Coagulopathy may preclude the use of neuraxial anesthesia.

CLASSIFICATIONS

• Mild preeclampsia: Systolic >140 mm Hg or diastolic >90 mm Hg with proteinuria (>300 mg/24 hrs) • Severe preeclampsia: Systolic >160 mm Hg or diastolic >110 mm Hg and/or end-organ damage. – Renal involvement defined as proteinuria >3 g/24 hrs, 3+ on urine dipstick, or sudden oliguria – CNS involvement – Pulmonary edema – Liver dysfunction – RUQ/epigastric pain – Thrombocytopenia – HELLP syndrome – Evidence of fetal compromise • Eclampsia: New onset of grand mal seizures occurring during or after pregnancy that do not have another identifiable cause.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Avoid benzodiazepines and limit narcotics. • Nonparticulate antacid (i.e., bicitrate) • MgSO4 infusion for seizure prophylaxis Special Concerns for Informed Consent

• Regional anesthesia and coagulopathy • Possible need for blood transfusion • Possible need for invasive monitoring

INTRAOPERATIVE CARE Choice of Anesthesia

• ACOG and ASA recommend regional anesthesia in patients without evidence of coagulopathy. • Early placement of epidural should be considered to avoid general anesthesia. • Spinal anesthesia is a suitable alternative to epidural for Cesarean section even in severe preeclampsia. Monitors

• Standard ASA monitors • Consider arterial line for better hemodynamic monitoring. • CVP and PAP monitoring is rarely necessary.

Induction/Airway Management

• Neuraxial techniques: Consider supplemental O2 via facemask or nasal canula for patients

with neuraxial anesthesia/analgesia. • General endotracheal anesthesia (GETA) – Rapid sequence induction, along with aspiration precautions. – Difficult airway: There is an increased risk of failed intubation due to pharyngolaryngeal edema. Be prepared for a difficult airway, including having a supraglottic device available. – Careful attention to BP management with induction and intubation; intracranial hemorrhage, secondary to severe hypertension, is the leading cause of morbidity and mortality in preeclamptic women. Consider having esmolol and nitroglycerin available. – Hypotension with induction may lead to fetal compromise/distress. Maintenance

• Neuraxial. In the OR, intermittent boluses with high concentration local anesthetics (possibly without epinephrine) for surgical anesthesia/analgesia. • GETA. Less than 0.5 MAC of volatile anesthetic supplemented by nitrous oxide after delivery of the fetus. All inhalational agents cause uterine relaxation and can contribute to postpartum hemorrhage. – MgSO4 causes prolonged duration of non-depolarizing neuromuscular blockade. • Gentle fluid resuscitation with caution to avoid fluid overload

Extubation/Emergence

• The patient is considered to have a full stomach. • Avoid severe hypertension.

FOLLOW-UP BED ACUITY

• ICU admission may be indicated if there is evidence of severe end-organ damage, including renal failure, cerebral hemorrhage, hepatic rupture, and/or pulmonary edema. • Routine postpartum ward may be appropriate in a patients without pulmonary edema or hemodynamic derangements. • Preeclampsia and all of its associated complications may present de novo after delivery. • IV MgSO4 should continue for 24 hours postpartum. COMPLICATIONS

• HELLP, DIC, eclampsia, pulmonary edema, cerebral hemorrhage, placental abruption. • MgSO4

– Toxicity: Decreased deep tendon reflexes, EKG changes, respiratory depression (10–15 mEq/L), cardiac arrest (25 mEq/L) – Fetal depression

REFERENCES

1. Turner JA. Diagnosis and management of pre-eclampsia: An update. Int J Womens Health. 2010;2:327–337. 2. Steegers EA, von Dadelszen P, Duvekot JJ, et al. Lancet. 2010;376(9741):631–644. 3. Gogarten W. Preeclampsia and anaesthesia. Curr Opin Anaesthesiol. 2009;22:347–351.

4. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice Guidelines for Obstetric Anesthesia. Anesthesiology. 2007;106:843–863. 5. Visalyaputra S, Rodanant O, Somboonviboonvv W, et al. Spinal versus epidural anesthesia for cesarean delivery in severe preeclampsia: A prospective randomized, multicenter study. Anesth Analg. 2005;101:862–868.

ADDITIONAL READING

• American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin: Diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol. 2002;99 (1):159–167. • Lewis G , ed. 2007. The confidential enquiry into maternal and child health (CEMACH). Saving mothers’ lives: Reviewing maternal deaths to make motherhood safer-2003–2005. 6. The Seventh Report on Confidential Enquiries into Maternal Deaths in the United Kingdom. London: CEMACH. • www.preeclampsia.org

See Also (Topic, Algorithm, Electronic Media Element) • HELLP syndrome • Pregnancy-induced hypertension • Eclampsia

CODES ICD9 • 642.40 Mild or unspecified pre-eclampsia, unspecified as to episode of care or not applicable • 642.50 Severe pre-eclampsia, unspecified as to episode of care or not applicable ICD10 • O14.00 Mild to moderate pre-eclampsia, unspecified trimester • O14.10 Severe pre-eclampsia, unspecified trimester • O14.90 Unspecified pre-eclampsia, unspecified trimester

CLINICAL PEARLS

• Preeclampsia is a relatively common, transient multi-organ system disease diagnosed after 20 weeks gestation. • Early placement of a epidural should be considered to assist with BP control and as a preferred alternative to general anesthesia. Rule out coagulopathy and thrombocytopenia before neuraxial anesthesia is attempted. • When a GETA is indicated, be prepared for a difficult tracheal intubation and have back-up airway equipment, including supraglottic devices, if available.

PREGNANCY INDUCED HYPERTENSION Richard C. Jensen, MD Judith A. Turner, MD, PhD

BASICS DESCRIPTION

• Pregnancy-induced hypertension (PIH) is a spectrum of hypertensive disorders of pregnancy including gestational hypertension (GH), chronic hypertension, preeclampsia, and eclampsia. • GH is defined as systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg in a woman without preexisting hypertension or signs of preeclampsia. It manifests after 20 weeks gestation and resolves by 12 weeks postpartum. • Chronic hypertension involves either pre-pregnancy hypertension (SBP >140 mm Hg or DBP >90 mm Hg) or failure of hypertension to resolve within 12 weeks postpartum. • Preeclampsia is the onset of hypertension and proteinuria after 20 weeks gestation with remission by 6–12 weeks postpartum. Eclampsia is new onset of seizures or unexplained coma in a woman with signs and symptoms of preeclampsia. EPIDEMIOLOGY Prevalence

• Hypertension complicates ∼20% of pregnancies • GH is encountered in ∼5% of pregnancies. • Chronic hypertension is present in 1–2% of pregnancies. • Preeclampsia–eclampsia develops in ∼5% of pregnancies in the US; nearly 20% of women with chronic hypertension develop preeclampsia. Morbidity

• Sustained hypertension can result in end-organ damage such as renal failure, left ventricular hypertrophy, and/or cerebrovascular accident. • Maternal morbidity associated with preeclampsia–eclampsia includes pulmonary edema, disseminated intravascular coagulation, hepatic rupture, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), and seizures. • Fetal morbidity is due to increased incidence of placental abruption, intrauterine growth restriction, and preterm delivery. Mortality

• PIH is the third leading cause of maternal mortality in the US behind pulmonary embolus and hemorrhage. It accounts for ∼10% of all deaths, with intracranial hemorrhage as the primary cause. • Approximately 10% of neonatal deaths occur in the presence of PIH.

ETIOLOGY/RISK FACTORS

• GH risk factors: History of GH in a previous pregnancy. • Chronic hypertension risk factors – Essential chronic hypertension: Obesity, African American ethnicity, increased salt intake, hyperlipidemia, family history – Secondary chronic hypertension: Oral contraceptive use, renal disease, aortic coarctation, endocrine disorders • Preeclampsia-eclampsia risk factors – Maternal: Age >40 years, African American ethnicity, obesity, hypertension, diabetes, thrombotic vascular disease (interestingly, smoking decreases the risk) – Pregnancy-associated: Nulliparity, multiple gestations, molar pregnancy – Fetal: Gestational age 14% may also suggest volume responsiveness (2)[B]. Aortic blood flow velocity variation >12% (measured by echocardiography or esophageal Doppler) is similarly highly predictive of volume responsiveness (3)[B]. – Looking at the venous system via bedside ultrasound, an inferior vena cava (IVC) distensibility index >12% predicts volume responsiveness (4)[B]. IVC engorgement occurs as positive pressure ventilation inhibits blood return to the right heart. • In spontaneously ventilating patients, IVC collapse of >50% suggests a CVP 24 weeks gestation) would otherwise be positioned supine. • Uterine compression of the IVC may impair venous return and decrease preload, resulting in up to a 30% reduction of cardiac output.

DISEASE/PATHOPHYSIOLOGY

• Volume overload. Upon gross overdistention of the chamber, microscopic myofibrils (myosin and actin) are stretched beyond their ability to optimally overlap, decreasing their strength/contractility and heart failure ensues (Figure 1). • Diastolic dysfunction results in increased filling pressures as a compensatory mechanism to maintain adequate/minimal EDV. Such compensated patients often appear more sensitive to filling pressure/volume decreases and are relatively “preload dependent.” • Myocardial ischemia. Filling of a cardiac chamber during diastole involves both the active (early) relaxation by the myocytes and the passive compliance of chamber’s wall. Active relaxation of a cardiac chamber is decreased during myocardial ischemia. Relaxation (diastolic) abnormalities occur in the ischemic tissue before contraction (systolic) dysfunction is seen. Impaired active relaxation (during ischemia) will result in reduced ventricular filling during diastole, contributing to the appearance of decreased compliance (decreased ventricular volume for same filling pressure). • Left ventricular hypertrophy (LVH). As the ventricular wall thickens, it becomes less compliant. LVH can develop with: – Increased afterload: Hypertension, morbid obesity, and aortic stenosis that result in a chronic increase in work. – Reduced compliance: Infiltrative diseases such as amyloidosis or cardiac tumors where there is an increase in myocardial stiffness. • Rhythm disturbances (tachycardia, heart block, atrial fibrillation, or atrial flutter) may impair filling by decreasing coordinated active relaxation or by simply decreasing the total filling time. • Tricuspid stenosis and mitral stenosis result in increased measured CVP and PAOP, respectively, while RVEDP and LVEDP may remain normal (valvular stenosis creates a pressure gradient and violates the assumptions required for CVP and PAOP approximate RVEDP and LVEDP, respectively). • External compression from pericardial effusion, positive end-expiratory pressure (PEEP), tension pneumothorax, pleural effusions, or greatly increased abdominal pressures may reduce passive ventricular compliance. • Intraventricular filling defects (tumors and clots) and septal shifts causing ventricular

interdependence (severe pulmonary hypertension, high levels of PEEP, and RV infarction) may restrict diastolic filling of cardiac chambers. • Surrogate filling pressures (CVP and PAOP) cannot reliably discern diastolic dysfunction from systolic dysfunction. In several studies in critically ill patients, volume assessment via transesophageal echocardiography disagreed with static pulmonary artery catheter pressure assessments in up to 55% of patients and significantly altered medical management in 32– 44% of those patients (5)[B].

PERIOPERATIVE RELEVANCE

• Volume responsiveness refers to the ability of an increase in preload (volume challenge) to produce a clinically significant increase in stroke volume (resulting in increased blood pressure and cardiac output). – Ongoing volume responsiveness suggests that the LV is still on the upslope of the Frank– Starling curve (increased LVEDP generates the expected increased ventricular contractility). – Lack of volume responsiveness suggests that the LV has “fallen off” the Frank–Starling curve (meaning increased LVEDP no longer generates increased contractility). • Many pathophysiologic processes disrupt the normal relationship between measured filling pressures and actual preload volumes, making appropriate interpretation of filling pressures difficult.

EQUATIONS

• SV = EDV – ESV; where SV is stroke volume, EDV is end diastolic volume, and ESV is end systolic volume • Ejection fraction = [(EDV – ESV)/EDV] • Stroke volume variation (SVV) = [(SVmax − SVmin)/SVmean] where SV is proportional to the area under the pulse contour curve

REFERENCES

1. Hofer CK, Senn A, Weibel L, et al. Assessment of stroke volume variation for prediction of fluid responsiveness using the modified FloTrac and PiCCOplus system. Critical Care. 2008;12:R82. 2. Cannesson M, Desebbe O, Rosamel P, et al. Pleth variability index to monitor the respiratory variations in the pulse oximeter plethysmographic waveform amplitude and predict fluid responsiveness in the operating theatre. Br J Anaesth. 2008;101:200–206. 3. Michard F, Boussat S, Chemla D, et al. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med. 2000;162:134–138. 4. Feissel M, Michard F, Faller JP, et al. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med. 2004;30:1834–1837. 5. Beaulieu Y. Bedside echocardiography in the assessment of the critically ill. Crit Care Med. 2007;35:S235–S249.

ADDITIONAL READING

• Bar-Yosef S, Schroeder RA, Mark JB. Hemodynamic Monitoring. In: Longnecker et al., eds. Longnecker DE, Brown DL, Newman MF, et al. Anesthesiology. New York, NY: McGraw-Hill Medical; 2008:519–551. • Chappell D, Jacob M, Hofman-Keifer K, et al. A rational approach to perioperative fluid management. Anesthesiology. 2008;109:723–740.

See Also (Topic, Algorithm, Electronic Media Element) • Positive end expiratory pressure (PEEP) • Left ventricular end diastolic pressure

CLINICAL PEARLS

• Echocardiographic assessment of EDV is the gold standard for preload determination. When echocardiography is performed to optimize preload, the filling pressures required to achieve that desired preload should be noted and maintained (although compliance may still change over time). • Dynamic pressure changes (both arterial and venous) in response to fluid challenges are better guides to ongoing fluid resuscitation than static preload pressure surrogates (CVP/PAOP). • During positive pressure mechanical ventilation, the SVV induced by the heart–lung interaction is a more reliable assessment of volume responsiveness than static filling pressure. – CVP/PAOP should always be measured during the passive exhalation phase of the respiratory cycle to avoid artifactual changes due to active inspiratory forces (PEEP transmitted during this exhalation will still elevate the measured filling pressures). – Due to higher intrathoracic pressures, positive pressure ventilation (especially with higher PEEP) impedes diastolic ventricular filling, so higher filling pressures (CVP/PAOP) are then required to maintain the normal preload. • Measures of preload or volume responsiveness do not necessarily indicate volume need. If a patient is normotensive with presumed normal cardiac output as measured by the end organ function (e.g., urine output), conservative fluid management is likely appropriate regardless of SVV or CVP. • Expect the need for higher filling pressures to maintain normal/adequate EDV in patients suspected of LVH. In the absence of echocardiography, LVH may be clinically suspected in hearts that have been working against high afterload over many years (e.g., chronic poorly treated hypertension or morbid obesity) or when high voltage changes are seen on the electrocardiogram. • While low filling pressures (CVP/PAOP) are generally associated with suboptimal filling volumes (i.e., additional volume responsiveness), high filling pressures often correlate poorly with filling volumes (due to coexisting pathophysiology or measurement difficulties). Confidence in the presumed pressure–volume relationships should decrease as measured filling pressures increase (echocardiography or dynamic preload measures should be considered for confirmation of preload status when deciding to restrict further fluids due to

high CVP/PAOP measurements).

PREMATURE ATRIAL CONTRACTIONS Dwayne E. McClerklin, MD

BASICS DESCRIPTION

• Premature atrial contractions (PACs) describe the initiation of a discordant atrial contraction by an ectopic atrial pacemaker focus. • In the perioperative period, PACs are seen – In patients with a chronic, baseline occurrence (most common) – In response to hypoxia, hypercarbia, or metabolic derangements (e.g., hypokalemia, hypomagnesemia). EPIDEMIOLOGY Prevalence

Information not available Prevalence

Very common and often asymptomatic; therefore, difficult to quantify with any accuracy. Morbidity

• In isolation, PACs usually do not indicate heart disease. • Under certain circumstances, premature atrial depolarizations may trigger re-entrant tachycardias or atrial fibrillation. Atrial fibrillation is the most common secondary dysrhythmia associated with premature atrial depolarizations. Mortality

Not fatal intrinsically; however, death can occur from the secondary arrhythmia. ETIOLOGY/RISK FACTORS

• Extremes of age • Excessive caffeine consumption • Hyperthyroidism • Alcohol abuse • Tobacco abuse • Chronic lung disease • Ischemic heart disease • Digitalis toxicity • Anxiety • Pregnancy • Perioperative causes – Hypoxia

– Hypercarbia – Sympathetic stimulation – Metabolic abnormalities Hypokalemia Hypomagnesemia Hypercalcemia • Following cardioversion

PHYSIOLOGY/PATHOPHYSIOLOGY

• Pacemaker cells: Spontaneous (phase 4) diastolic depolarization conveys the property of automaticity (pacemaking) that is characteristic of cells in the following: – Sinoatrial (SA) node: Action potentials are characterized by a membrane potential of –40– 60 mV (vs. –85 mV in the ventricular myocyte), slow and spontaneous phase 4 upstroke, and rapid phase 0 depolarization after the threshold potential is reached. – Atrioventricular (AV) nodes – His–Purkinje system – Cells surrounding the coronary sinus – Cells surrounding the pulmonary veins • Hierarchy: The intrinsic rates of depolarization in cardiac pacemakers are greatest in atrial pacemakers, followed by AV junctional pacemakers, followed by ventricular pacemakers. – The sinoatrial node (SA), located at the junction of the right atrium and superior vena cava, functions as the primary pacemaker of the heart. It displays the highest intrinsic rate of action potential discharge at 80–100 bpm. – Packemaker cells in the AV node may initiate an action potential if the SA node is not functioning properly. Consequently, pacemaker cells in the ventricle may initiate an action potential in the event that the SA and the AV node do not fire. • P wave: The action potential generated by the SA node is transmitted rapidly through the atria, to the AV node, and is the source of the P wave seen on the ECG. • Autonomic nervous system: Dynamically regulates the rate of phase 4 depolarization and, therefore, the firing rate of pacemaker cells. • Premature atrial depolarization and contraction: A known or unknown eliciting factor results in an ectopic atrial depolarization that occurs prior to SA node depolarization; it fires early and out of turn, subverting the hierarchy. The premature depolarization can then, in a domino-like fashion, depolarize adjacent cells in the atrium, travel to the AV node, and produce a normal ventricular depolarization. Consequently, a premature mechanical contraction will result. • Premature atrial depolarization and abnormal accessory tracts: A circus rhythm may result in patients with abnormal pathways that connect the atria and ventricles (normally, the AV node is the only connection between the atria and ventricles). – If the accessory pathway is still refractory when the premature atrial depolarization encounters it, then the impulse will conduct normally through the AV node. – However, if the premature atrial depolarization impulse encounters the accessory pathway when it is out of its refractory period, it can result in a self-sustaining “circus rhythm.” Antidromic tachycardia: When the accessory tract is excited in the atria, conduction to the ventricles is via the accessory node. Subsequent atrial depolarization occurs from

retrograde transmission (ventricles to the atria) via the AV node. A widened QRS complex is seen on the EKG. Orthodromic tachycardia (more common): When the accessory tract is excited in the ventricles, retrograde transmission (ventricles to the atria) is via the accessory tract and subsequent atrial depolarization occurs through the AV node. A normal width QRS is seen on the EKG.

PREVENTATIVE MEASURES

• Maintenance of physiologic acid-base status as well as avoidance of hypoxia, hypercarbia, electrolyte derangements, and sympathetic stimulation. • Anxiolysis • Treatment of underlying chronic condition • Avoidance of alcohol use, tobacco use, and caffeine consumption.

PREOPERATIVE ASSESSMENT • Intraoperatively: – Early P wave of different sizes, shapes, or axes than the patient’s sinus P wave complex. However, if the ectopic focus occurs near the atrial pacemaker, the P wave may appear identical to the patient’s normal sinus P wave. – The P–R interval varies. Premature atrial depolarizations that originate near the AV node may feature a shortened PR interval due to the proximity of the ectopic focus to the AV node. A longer P–R interval may be seen if the premature atrial depolarization reaches the AV node during the relative refractory period. If the premature atrial depolarization reaches the AV node during the absolute refractory period, it is not conducted. It appears as an isolated P wave. – QRS complexes are normal and narrow; they are conducted normally via the AV node and through the right and left bundle branches. – Aberrant, wide QRS complexes may be seen when the premature atrial depolarization is conducted to ventricular tissue before complete repolarization has occurred. – Compared to premature ventricular depolarizations, premature atrial depolarizations are not associated with a full compensatory pause. • Awake or outpatient setting. – Symptoms: Often asymptomatic; patients who are symptomatic endorse a “wavering” heartbeat or a “skipped” beat. – Holter monitoring is the most sensitive method of diagnosing PACs.

DIFFERENTIAL DIAGNOSIS

• Premature ventricular depolarizations: Lack an associated P wave complex and feature a full compensatory pause prior to initiation of the successive depolarization. • Sinus arrhythmia: Features normal sinus P waves and P–R intervals and 1:1 AV conduction. Sinus arrhythmia may be associated with inspiration and expiration. • Digitalis effect: The ECG demonstrates ST segment sloping and a regular rhythm.

TREATMENT • Rule out hypoxia, hypercarbia, myocardial ischemia, sympathetic stimulation (pain, awareness), and metabolic abnormalities. If present or suspected, therapy should be aimed at the underlying cause. • Determine hemodynamic stability. – Stable: No treatment is required. – Unstable: Beta-blockade and calcium channel blockers may be necessary. • Chronic therapy: Ranolazine is a novel antianginal agent that alters the trans-cellular Na+ current and has been shown to be effective in terminating premature atrial depolarizations.

FOLLOW-UP • For intraoperative PACs, inform the patient’s family if the PACs were associated with hemodynamic instability or anesthetic cause. • Hemodynamic causes: If from hypoxia, hypercarbia, hypotension, hypertension, or ischemia, ensure that the underlying cause has been treated and resolved. • If the intraoperative PACs were secondary to an anesthetic cause, careful examination of the intraoperative anesthetic record may provide information regarding the potential triggering agents or conditions. Documentation of the findings is warranted to prevent recurrence or replication of the onset of PACs. • Consider a telemetry bed, particularly if associated with hemodynamic instability.

REFERENCES

1. Perez MV, Dewey FE, et al. Electrocardiographic predictors of atrial fibrillation. Am Heart J. 2009;158:622–628.

2. Sosalla S, Wagner S, et al. Altered Na+ currents in atrial fibrillation: Effects of ranolazine on arrhythmias and contractility in human atrial myocardium. J Am Coll Cardiol. 2010;55:2330–2342. 3. Narayan SM, Kazi D, et al. Repolarization and activation restitution near human pulmonary veins and atrial fibrillation initiation: Mechanisms separating persistent from paroxysmal atrial fibrillation. J Am Coll Cardiol. 2008;52: 1222–1230. 4. Stein PK, Barzilay JI, et al. Heart rate variability and its changes over 5 years in older adults. Age Ageing. 2009;38:212–218. 5. Folkeringa RJ, Hartgers J, et al. Atrial extrasystoles after exercise predict atrial fibrillation in patients with left ventricular hypertrophy. Heart. 2006;92:545–546. See Also (Topic, Algorithm, Electronic Media Element) • Premature ventricular contractions • Pacemaker cells of the heart

CODES

ICD9

427.61 Supraventricular premature beats ICD10

I49.1 Atrial premature depolarization

CLINICAL PEARLS

• Premature atrial depolarizations are commonly benign dysrhythmias. They can, however, trigger a circus rhythm via an accessory tract or atrial fibrillation (rare). • Intervention is warranted only if there is an associated compromise in hemodynamic stability. • Beta blockers and calcium channel blockers are the most commonly used agents to terminate PACs in the event of hemodynamic compromise.

PREMATURE VENTRICULAR CONTRACTIONS J. Aaron Williams, MD

BASICS DESCRIPTION

• Premature ventricular contractions (PVCs) describe a discordant ventricular contraction that is caused by an ectopic ventricular pacemaker focus. PVCs are also referred to as ventricular premature beats (VPBs) and ventricular extrasystoles. • Although PVCs can be a common, non-pathologic occurrence, the new onset or an increased frequency in the perioperative period should alert the anaesthetist to the possibility of ominous underlying pathology: – Hypoxia – Hypercarbia – Acidosis – Myocardial ischemia EPIDEMIOLOGY Prevalence

• True incidence is hard to ascertain secondary to most being asymptomatic at onset and over time. • Increases primarily with age. • Predilection toward males, and African Americans (vs. Caucasians).

Prevalence

• Numbers vary greatly with the length of the monitoring period; longer periods result in a much higher detection rate (e.g., single EKG versus 2 minute EKG versus 24-hour Holter monitoring). • PVCs are detected in at least 50% of young men and women (on 24-hour Holter monitoring) (1,2). • Elderly patients in one study had a nearly 30% incidence of >30 PVCs/hr (Lown classification 2) (3). Morbidity

• Palpitations causing distress, or uncommonly, pre-syncopal or syncopal episodes. • Related to underlying condition. • Bigeminy, over time, can lead to cardiomyopathy irrespective of other disease processes (4).

Mortality

• Related to the underlying condition or progression to more malignant arrhythmias. • Increased mortality has been associated with: – Increased frequency/number

– Multiform waves – Runs of PVCs (couplets, NSVT) – Complex arrhythmias during exercise, and particularly after exercise (5).

ETIOLOGY/RISK FACTORS

• Perioperative – Normal variant – Hypoxemia – Hypercarbia/acidosis – Myocardial ischemia/infarction – Pulmonary embolism – Electrolyte imbalance: Hypokalemia, hypomagnesemia, and hypercalcemia (can result from intraoperative furosemide, mannitol, and IV contrast dye) – Any high-catecholamine state – Medications: Epinephrine, norepinephrine, dopamine, digoxin, tricyclic antidepressants, aminophylline, other anti-arrhythmic agents (flecainide, etc.) – Bradycardia – Anxiety – Localized irritation/mechanical factors: Central venous line introducer wire or catheter, pulmonary artery catheter, surgical tools or hands in the operative field (particularly in open heart surgery as well as in thoracic surgery, Nuss procedures, etc.) • Chronic conditions: Hypertension, left ventricular hypertrophy, prior myocardial infarction, cardiomyopathy, and valvular heart disease • Provocative events: Exercise, smoking/nicotine exposure, caffeine and chocolate ingestion

PHYSIOLOGY/PATHOPHYSIOLOGY

• Three mechanisms in general: – Enhanced automaticity: Electrolyte disturbances and elevated-catecholamine states can affect the membrane resting potential/automaticity of ventricular pacemakers – Triggered activation: Ischemia, digoxin – Re-entrant phenomenon: Ischemic pathways or old infarcts can delay normal impulse conduction and cause delayed firing that is “off-cycle” or “out-of-sync.” • May originate from one focus or multiple foci within one or both ventricles (i.e., outside the SA–AV-nodal or His–Purkinje systems) • Hemodynamic concerns: – Can cause hemodynamic instability; the lack of an atrial kick during ventricular diastole can decrease the stroke volume and cardiac output (particularly with bigeminy or frequent PVCs). – Although commonly benign in nature, may signify a more sinister underlying disorder. – May progress to malignant dysrhythmias in certain conditions (6).

PREVENTATIVE MEASURES

• In the operating room, avoid hypoxemia, hypercarbia/acidosis, hypotension or tachycardia (myocardial ischemia), and other above-mentioned causes. – Chronic beta-blocker therapy may be appropriate in certain settings (i.e., symptomatic,

post-MI arrhythmias, etc.) (7). • Outpatient setting: Avoid caffeine, nicotine, alcohol, and chocolate, as well as herbals and diet pills containing stimulants (pseudoephedrine, etc.).

PREOPERATIVE ASSESSMENT Intraoperatively

• Primarily an EKG diagnosis: Level 1A (7) – Premature ventricular depolarization – No P wave (as seen with a premature atrial depolarization/contraction) – Irregular, wide-complex QRS – Compensatory pause takes place prior to the next normal beat. – R–R interval of surrounding beats is usually constant – If multifocal, it will show various QRS morphologies. • Pulse oximeter or arterial line waveform can be observed to rule out electrical artifact, patient movement, or movement around the patient. If it is “real” one would see an irregularly placed pulsation/beat with a smaller waveform (amplitude). • Initial diagnostic tests – 12-lead EKG would be helpful if new-onset ischemia is suspected – Arterial blood gas to check for acidosis, hypoxia, hypercarbia – Electrolyte studies – Initial cardiac enzymes if ischemia is suspected • Other diagnostic tests: – CXR if a central venous line or retained wire is suspected – Digoxin level (if applicable) – Urine drug screen – Echocardiogram Awake or outpatient setting: • History – Many are asymptomatic – Can be associated with palpitations (from the augmented beat after the PVC) or a “pause” in the heartbeat from non-sustained ventricular tachycardia (NSVT) or ventricular tachycardia (VT) – Previous presyncopal or syncopal episodes from bigeminy or progression to NSVT/VT – Presence on the preoperative EKG; however, it is more likely to be detected on intraoperative EKG (longer duration of monitoring than preoperative 10-second EKG) • Diagnostic tests – 24-hour Holter monitoring: Level 1A (7) – Cardiac stress testing – Coronary angiography – Electrophysiologic testing • Lown classification system: (8) – 0 = No PVCs – I = 36°C) – In a 1996 study of patients undergoing colorectal surgery, patients randomized to hypothermia were three times more likely to develop a SSI compared to patients randomized to normothermia. Additionally, the duration of hospitalization was prolonged by 2.6 days in the hypothermia group. • Control of hyperglycemia – In patients undergoing cardiac surgery, perioperative hyperglycemia is strongly associated with SSIs. That said, the risks of aggressive glucose control must be measured against the significant risks associated with hypoglycemia. Recommendations may be patient-specific and disease-specific; however, most data suggests that glucose should be controlled with an IV insulin infusion to keep levels below 180 mg/dL. • Hyperoxia – The use of normobaric hyperoxia (∼80%) has been shown to decrease the risk of SSI during surgery and the immediate postoperative period. Of note, in all trials demonstrating efficacy, hyperoxia was continued for a minimum of 2 hours after the conclusion of surgery. – It is unknown if normobaric hyperoxia used only during the intraoperative period is associated with decreases in the risk of SSI. A meta-analysis of the results found it reasonable to conclude that hyperoxia has a beneficial, albeit limited, effect on the incidence of SSI.

PREOPERATIVE ASSESSMENT • CDC criteria, revised in 1992, for incisional SSI are an infection at the incision site within 30 days after surgery as defined by any of the following items: – Purulent drainage from the incision or drain located above the fascial layer – Organism isolated from a fluid culture in a closed wound – Surgeon deliberately opens wound (unless the wound culture is negative) – Surgeon’s or attending physician’s diagnosis of infection • The CDC criteria for deep surgical wound infections are an infection related to surgery occurring at the operative site within 30 days of surgery involving tissues or spaces at or beneath the fascial layer and any of the following:

– Purulent drainage from the drain placed beneath the fascial layer – Wound spontaneously dehisces or is deliberately opened by the surgeon when the patient has a fever (>38°C) and/or localized pain or tenderness, unless the wound culture is negative – An abscess or other evidence of infection seen on direct examination, during surgery, or by histopathologic examination – Surgeon’s diagnosis of infection

TREATMENT SSIs are typically treated with a combination of antibiotic and/or surgical drainage.

FOLLOW-UP • Scheduled antibiotics are often necessary • Return to the operating room for a “wash out” in certain incidences.

REFERENCES

1. Haley RW, Culver DH, Morgan WM, et al. Identifying patients at high risk of surgical wound infection. A simple multivariate index of patient susceptibility and wound contamination. Am J Epidemiol. 1985;121(2):206–215. 2. Houbiers JG, et al. Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal surgery: A prospective study. Transfusion. 1997;37(2):126–134. 3. Jonsson K, Jensen JA, Goodson WH III, et al. Assessment of perfusion in postoperative patients using tissue oxygen measurements. Br J Surg. 1987;74(4):263–267. 4. Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of wound infection and temperature group. N Engl J Med. 1996;334(19):1209–1215. 5. Mauermann WJ, Nemergut EC. The anesthesiologist’s role in the prevention of surgical site infections. Anesthesiology. 2006;105(2): 413–421. 6. Mauermann WJ, Sampathkumar P, Thompson RL. Sternal wound infections. Best Prac Res Clin Anaesthesiol. 2008;22(3):423–436. 7. Murray BW, Huerta S, Dineen S, et al. Surgical site infection in colorectal surgery: A review of the nonpharmacologic tools of prevention. J Am Coll Surg. 2010;211(6):812–822. 8. Nichols RL. Preventing surgical site infections: A surgeon’s perspective. Emerg Infect Dis. 2001;7(2): 220–224. See Also (Topic, Algorithm, Electronic Media Element) • Hypothermia • Hyperglycemia

CODES ICD9

998.59 Other postoperative infection ICD10 • T81.4XXA Infection following a procedure, initial encounter • T81.4XXD Infection following a procedure, subsequent encounter • T81.4XXS Infection following a procedure, sequela

CLINICAL PEARLS

• Although generally thought to be a surgical complication, the incidence of SSIs is lower when anaesthetists take an active role in infection prevention. Studies have shown that when anaesthetists administer antibiotics, on time administration occurs 92% of the time. • Keep patients warm. • Check and control blood glucose in patients prone to hyperglycemia. • Consider normobaric hyperoxia if there is no contraindication.

SYNCHRONIZED ELECTRICAL CARDIOVERSION Susan Kaplan, MD

BASICS DESCRIPTION General

• Synchronized electrical cardioversion is the delivery of a brief pulse of external electrical direct current (DC) across the chest wall to convert certain abnormal rhythms to a normal sinus rhythm (NSR) in elective or emergent scenarios. It is utilized for (1): – Atrial fibrillation (elective treatment is the most common indication). – Reentry supraventricular tachycardia (SVT) – Atrial tachycardia – Monomorphic ventricular tachycardia (VT) with pulses • Elective cardioversion (CVN) is generally performed by a cardiologist or electrophysiologist in a controlled setting. • Urgent or emergent CVN may be performed in the perioperative period by the anaesthetist. • A biphasic, synchronized discharge is delivered via paddles or self-adhesive electrodes (pads or patches). – Current flow is either in the anterolateral (AL) or anteroposterior (AP) direction. – Electrode positioning: Parasternal and inferoapical for AL, parasternal and left infrascapular for AP. – Electrodes should be firmly adherent to chest wall with sufficient conductive gel to prevent skin burns or improper current dispersion. – If a pacemaker or internal cardioverter defibrillator (ICD) is present, electrodes should be positioned 15 cm from the device (2), preferably in the AP position • Energy requirements for DC CVN vary depending on the underlying rhythm (Biphasic mode). – Atrial fibrillation: 120–200 J; if initial shock fails, increase sequentially (200 J then 360 J) (1) – Atrial flutter: 50–100 J (2) – Monomorphic VT with pulse: 100 J; if initial shock fails, increase sequentially (200 J then 360 J) (1) • Synchronization and discharge occur with the R or S wave of the QRS complex to avoid energy delivery during the relative refractory period of the myocardium (apex of T wave) that can result in malignant ventricular arrhythmias • Common surgical problems – Inadequate anticoagulation (international normalized ratio (INR) 0.1 seconds). The PR interval is also shortened (2 years): 90 mg/m2/day in 3 divided doses, up to 180 mg/m2 /day • Pregnancy risk B • Enters breast milk

Mechanism of Action

• Impairs conductance at potassium channels and prolongs action potential duration and repolarization • Has nonspecific beta-blocking activity

Uses

• Treatment/prevention of VT and VF, atrial fibrillation/flutter • IV form indicated for monomorphic, hemodynamically stable VT

Onset

1–2 hours Duration

8–16 hours

Metabolism

Excreted unchanged by kidney Adverse Effects

Proarrhythmia, QT prolongation and Torsade, bradycardia, worsening CHF, bronchospasm, fatigue, dyspnea, dizziness

CLINICAL PEARLS

Has same concerns/adverse effects as beta-blockers, including withdrawal phenomena, avoid

sudden discontinuation of drug. Additive cardiac depression with anesthetic agents Table 2 Class IC antiarrhythmic agents

ANTIBIOTICS

Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Vancomycin (Vancocin®) • Usual dose is based on actual body weight (approximately 12–15 mg/kg): 50–65 kg 750 mg IV, 66–82 kg 1000 mg IV, 83–99 kg 1250 mg IV, >100 kg 1500 mg IV over 1–2 hours. Subsequent doses may be given every 12–24 hours; adjustments need to be made to dosing interval for impaired renal function • Pediatric dosing 20 mg/kg IV; subsequent doses every 6 hours • Pregnancy risk C • Breastfeeding not recommended/enters breast milk

Mechanism of Action

Glycoprotein antibiotic, bacteriocidal, inhibits cell wall synthesis in Gram-positive bacteria by blocking glycopeptide polymerization Uses

• Perioperative antibiotic prophylaxis in neurosurgery and orthopedic surgery • Infections due to susceptible organisms—Staphylococci (including methicillin-resistant S. aureus [MRSA], Streptococci, Enterococci

Onset

IV: Time to peak immediately at end of infusion Duration

Half life 5–12 hours, highly dependent on renal function Metabolism

80–90% excreted unchanged via kidney Adverse Effects

Nephrotoxicity, ototoxicity, “red man syndrome”—flushing, hypotension, tachycardia, transient rash/hives, pruritus, chills

CLINICAL PEARLS

• Red man syndrome is not a true allergy. It is due to non-immunogenic histamine release and is related to rapid infusion; it can be decreased with slow infusion and/or antihistamines • May be used for preoperative surgical prophylaxis in patients with true allergies to penicillins or cephalosporins

• Trough levels should be 15–20 mcg/mL • Additive nephrotoxicity may be seen with aminoglycosides/other nephrotoxins • Extravasation may cause severe tissue injury

TREATMENT DRUGS

Linezolid (Zyvox®) • Usual dose: IV/PO 600 mg every 12 hours • Pediatric (age 20 hours in renal failure Metabolism

30–60% hepatic via CYP3A4, 2C6, to a somewhat active metabolite; metabolites are mostly excreted in the urine, some in bile/feces Adverse Effects

Dizziness, peripheral or optic neuropathy, nausea, flu-like symptoms, disulfiram-like reactions, rash, hypersensitivity reactions

CLINICAL PEARLS

Less frequently used for surgical prophylaxis as it is a moderate inhibitor of CYP3A4 (affects drug metabolism)

TREATMENT DRUGS

Clindamycin phosphate (Cleocin®) • Usual dose: 900 mg IV over 10–20 minutes, 30–60 minutes prior to procedure; may be repeated in 8 hours. Dose adjustments need to be made in hepatic disease, but not for renal disease • Pediatric dosing 20 mg/kg IV

Mechanism of Action

Bacteriostatic or bacteriocidal (dependent on target organism, infection site, drug concentration), binds to 50S ribosomal subunit and reversibly inhibits bacterial protein synthesis Uses

• Surgical prophylaxis in patients with risk of anaerobic infections, mostly as an alternative in patients truly allergic to penicillins or cephalosporins • Effective against Streptococcus, Staphylococcus, Pneumococcus Onset

Time to peak: 1 hour (if given PO or IM) Duration

Half life 2–3 hours Metabolism

Hepatic, to variably active metabolites Adverse Effects

Pruritus, rash, eosinophilia, agranulocytosis, neutropenia, jaundice, abnormal liver function tests, rare cardiac arrest/hypotension, abdominal pain, diarrhea, pseudomembranous colitis

CLINICAL PEARLS

• Usually combined with a fluoroquinolone or an aminoglycoside when used for prophylaxis • May enhance/prolong neuromuscular blockade produced by non-depolarizing neuromuscular blockers • Inducible resistance to clindamycin may occur

TREATMENT DRUGS

Aminoglycosides: Gentamicin (Garamycin®), Tobramycin (Nebcin®) • Usual dose: 1.5–2.0 mg/kg IV (may be given IM) based on ideal body weight; usually infused over 30 minutes. May be repeated every 8 hours. Doses and interval need to be adjusted in renal insufficiency and based on peak/trough levels • Pregnancy risk D • Breastfeeding not recommended/enters breast milk

Mechanism of Action

Bacteriocidal, irreversible binding to 30S and 50S ribosomal subunits in susceptible bacteria, causing inhibition of protein synthesis and defects in bacterial cell membranes Uses

• Surgical prophylaxis in GI or GU surgery • Infections caused by aerobic Gram negatives, including Pseudomonas, some Gram positives • Ineffective against anaerobes

Onset

Peak at end of 30-minute infusion Duration

Half life of 1.5–3 hours, progressively prolonged if renal function declines Metabolism

Excreted unchanged by kidneys Adverse Effects

Nephrotoxicity, ototoxicity (vestibular and/or auditory), muscle weakness

CLINICAL PEARLS

• May prolong/intensify neuromuscular blockade produced by non-depolarizing neuromuscular blockers • Exhibits concentration-dependent killing of micro organisms • Usually used in combination with a beta-lactam antibiotic to enhance efficacy • Ototoxicity may be worsened by diuretics. Peak and trough levels must be followed if used beyond immediate perioperative period, especially if renal function deteriorates. May cause hearing loss in fetus/newborn if given to mother during pregnancy • A nebulized version of tobramycin may be given via aerosol to cystic fibrosis patients infected with Pseudomonas aeruginosa

TREATMENT DRUGS

Fluoroquinolones: Ciprofloxacin (Cipro®), Levofloxacin (Levaquin®) • Ciprofloxacin 400 mg IV, may also be given PO; can be repeated every 8–12 hours, as indicated • Levofloxacin 500 mg IV every 24 hours. Should be administered over 1 hour. Doses need to be adjusted for renal dysfunction • Pregnancy risk C • Breastfeeding not recommended/enters breast milk

Mechanism of Action

Bacteriocidal, inhibits bacterial DNA gyrase and subsequent DNA uncoiling, promotes breakage of double-stranded DNA Uses

• Surgical prophylaxis in GU/prostate surgery

• In patients with a true beta-lactam allergy may be given concomitantly with clindamycin for head and neck, gastric, or biliary surgery • Infections due to enteric Gram-negative organisms; active against some Gram-positive cocci

Onset

Peak levels occur at the end of infusion Duration

Ciprofloxacin half life 3–5 hours, levofloxacin half life 6–8 hours Metabolism

• Ciprofloxacin is hepatically metabolized, to 4 partially active metabolites. 30–50% excreted in urine as unchanged drug. Potent CYP1A2 inhibitor • Levofloxacin is excreted unchanged (87%) in urine with little metabolism

Adverse Effects

Polyneuropathy, tendon rupture, QT prolongation/Torsades de Pointes, convulsions, dizziness, confusion, hypoglycemia, muscle weakness

CLINICAL PEARLS

• Caution when given to patients on other agents that prolong QT interval • Tendon rupture more common in patients on corticosteroids, anti-rejection agents, and those aged 60 and older • Should be avoided in myasthenia gravis (increases muscle weakness) • Should not be used in children unless multidrug-resistant pathogens show sensitivity to fluoroquinolones

TREATMENT DRUGS

Aztreonam (Azactam®) • Usual dose: 1–2 grams IV every 6–12 hours • Surgical prophylaxis dose 2 grams IV • Adjust for renal insufficiency • IM administration may also be performed • Pediatric dosing 30 mg/kg every 8 hours • Pregnancy risk B • Breastfeeding not recommended/enters breast milk

Mechanism of Action

Bacteriocidal, similar to beta-lactam, inhibits cell wall cross-linkage Uses

• Alternative surgical prophylaxis in penicillin-allergic patients for neurosurgery via

nasal/sinus approaches • Limited to use for Gram-negative infections

Onset

Time to peak: 60 minutes IV or IM Duration

Half life 2–3 hours, prolonged in renal failure Metabolism

Renal excretion 60–70% as unchanged drug, some hepatic metabolism Adverse Effects

Rash, nausea, vomiting, diarrhea

CLINICAL PEARLS

• Is a monobactam agent without cross-allergenicity to penicillins or cephalosporins • Increased risk of enterococcal superinfection and Clostridium difficile associated diarrhea/infection with prolonged use

TREATMENT DRUGS

Ertapenem (Invanz®) • Usual dose: 1 gram IV, infuse over 30 minutes (decrease to 500 mg if CrCl 6: 15–60 mg/kg/day • Pregnancy Category: D • Breastfeeding contraindicated

Mechanism of Action

• Exact mechanism is unknown • Alters cation transport across the cell membranes of nerve and muscle cells • Alters reuptake of serotonin and norepinephrine in nerve cells • Reduces sensitivity of certain CNS dopamine receptors

Uses

• Treatment of acute mania in bipolar disorder; mood stabilizer • Chronic pain adjunct

Onset

Time to peak 4–12 hours with extended release product Duration

Half-life 18–24 hours Metabolism

• Primarily excreted in the urine (95%) • Increased sodium intake and osmotic diuretics increase renal excretion (may necessitate increased dosing) Adverse Effects

• Acute intoxication (correlates with serum levels >1.5 mEq/L) usually manifests as vomiting, profuse diarrhea, confusion, hyperreflexia, coma, and seizures. Mild toxicity can usually be managed with supportive measures (sodium and fluid repletion) whereas severe toxicity can require hemodialysis. Co-administration of drugs that increase reabsorption or decrease excretion in the kidneys include NSAIDs, ACE-inhibitors, thiazide diuretics, and metronidazole • Nausea, fatigue, dizziness, tremor, thirst, polyuria, edema, weight gain, confusion, ataxia,

seizures, renal toxicity, nephrogenic diabetes insipidus, hypothyroidism, leukocytosis • Hypothermia may result when co-administered with diazepam • Prolongs effects of neuromuscular blocking drugs • Increases risk of serotonin syndrome if given with other agents that modulate CNS serotonin levels

CLINICAL PEARLS

• Most effective drug for treatment of bipolar disorder • Therapeutic serum levels are 0.6–1.2 mEq/L for acute mania, and 0.8–1.0 mEq/L for chronic maintenance therapy • Careful monitoring of fluid status, electrolytes, and lithium levels are required if the patient needs to maintain use of this drug in the perioperative period Table 1 Atypical antipsychotic agents

TREATMENT DRUGS

Atypical antipsychotic agents Some agents require alteration of dosage in patients with renal or hepatic dysfunction. In general, lower doses are used in the elderly Mechanism of Action

• Antagonists at dopamine-2 receptors in the brain • They also produce some modulation of serotonin receptors

Uses

• Psychoses • Schizophrenia • Agitation • Acute mania • Bipolar disorder • Adjuncts in treatment of depression

Adverse Effects

• Tardive dyskinesia, extrapyramidal muscle movements, hyperglycemia, diabetes, weight gain, hyperlipidemia, impaired temperature regulation, QT interval prolongation/risk of Torsades, elevation of prolactin levels, somnolence, orthostatic hypotension • Lower risk of anticholinergic side effects than older agents

CLINICAL PEARLS

• In general, the newer generation of antipsychotics have the same efficacy as older agents but with a lower incidence of tardive dyskinesia, extrapyramidal muscle movements, and neuroleptic malignant syndrome • The most effective agent is clozapine; however, it is not commonly used due to its ability to cause agranulocytosis, seizures, and myocarditis • Parenteral forms (IM use only) of aripiprazole, olanzapine, and ziprasidone are available • Impaired temperature regulation is a concern intraoperatively • May hold these agents perioperatively (long half-lives) unless there is a high risk of exacerbation of psychiatric disease present • There are many potential drug interactions • There exists an increased risk of death in elderly patients with dementia • If taken during the 3rd trimester of pregnancy, there is an increased risk of EPS and withdrawal symptoms in the newborns

COCAINE

Nabil Elkassabany, MD

TREATMENT DRUGS

• Usual dose: – Topical use 1–10% concentration, applied to desired mucosal area, not to exceed 1 mg/kg – Reduce dose in children and the elderly – Pregnancy class C, X for non-medical use – Breastfeeding contraindicated, excreted in breast milk Mechanism of Action

• Esteratic local anesthetic agent • Blocks voltage-gated sodium channels and inhibits depolarization, initiation, and conduction of nerve impulses • Blocks neuronal reuptake of norepinephrine resulting in CNS stimulation, tachycardia, hypertension, and vasoconstriction • Blocks neuronal reuptake of dopamine and serotonin in the midbrain, with resulting euphoria and arousal Uses

• Local anesthetic with vasoconstrictor activity, used on mucosal surfaces of the respiratory tract for otorhinolaryngology procedures and bronchoscopy • Used in combination with other agents (tetracaine-adrenaline-cocaine) for the repair of minor head and neck lacerations • Commonly abused CNS stimulant in the US (National Institute of Drug Abuse NIDA)

Onset

1 minute when applied to mucosa, peak effect in 5 minutes Duration

Serum half-life of cocaine is 30–90 minutes Metabolism

• Non-enzymatic hydrolysis to benzoylecgonine, via hepatic esterases, or plasma pseudocholinesterases to ecgonine methylester, and minimal amounts by CYP3A4 to norcocaine, all of which are active and excreted in urine • Benzoylecgonine has the highest concentration in urine and can be detected for 2–3 days after exposure Adverse Effects

Hypertension, tachycardia, dysrhythmias, myocardial ischemia, CNS stimulation, euphoria,

hallucinations, paranoia, seizures, fever, agitation, restlessness, tremor, stroke, mydriasis, rhinitis, tachypnea, vasculitis, Raynaud’s phenomenon

CLINICAL PEARLS

• Should not be applied to inflamed or traumatized mucosa • Other vasoconstrictors should not be used within 2 hours of cocaine exposure • Avoid using with other drugs that can result in tachycardia and hypertension, such as pancuronium or ketamine • Caution in use of beta-blockade for treatment in cocaine toxicity, due to risk of unopposed alpha-induced vasoconstriction/ischemia • Concern regarding prolonged action of succinylcholine used simultaneously with cocaine has been refuted in clinical studies • Toxicity has occurred in infants breastfed by cocaine-abusing mothers • Medical use is generally declining, due to adverse effects, abuse liability, and availability of effective alternatives

DIURETICS/COLLOIDS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Furosemide (Lasix®) • Adult IV (or IM) 20–40 mg initially, may repeat or increase dose by 20 mg in 2 hours. IV infusion not to exceed 4 mg/minute may also be used. Single maxi- mum doses of 200 mg may be used, as appropriate • Pediatric IV/IM 1 mg/kg/dose • Pregnancy Category: C, caution with breastfeeding

Mechanism of Action

• Inhibits chloride binding co-transport of sodium and chloride in the ascending loop of Henle and distal renal tubule • Results in sodium, chloride, potassium, calcium, and magnesium excretion in the urine • Increases venous capacitance and decreases cardiac output

Uses

Acute pulmonary edema, CHF, edema. May also be used for hypercalcemia (with saline administration), hyperkalemia, ascites, during renal transplant to invoke diuresis Onset

IV 5 minutes, IM 30 minutes, PO 30–60 minutes Duration

IV 2 hours, PO 6–8 hours Metabolism

Hepatic—minimal. Excretion of unchanged drug 80% renal for parenteral dose, oral dosing 50% renal, 50% fecal Adverse Effects

Hypokalemia, hypomagnesemia, hypotension, hyperglycemia, hyperuricemia, volume depletion, metabolic alkalosis, ototoxicity (especially if >4 mg/minute IV administered)

CLINICAL PEARLS

• Other loop diuretics (with dose equivalents to furosemide 40 mg) include bumetanide 1 mg, torsemide 10 mg, and ethacrynic acid 50 mg • Close monitoring of renal function and electrolytes is required • Caution with use in patients with an allergy to sulfonamides

• If used for the treatment of ascites in cirrhotics, should be carefully dosed and monitored to avoid severe hypokalemia and intravascular volume depletion Table 1

TREATMENT DRUGS

Hydrochlorothiazide (HCTZ)

• Adult PO 12.5–100 mg/daily • Pediatric PO 1–3 mg/kg/day • Pregnancy Category: B; breastfeeding not recommended

Mechanism of Action

• Inhibits sodium reabsorption in distal tubule of the nephron, causing increased excretion of sodium and water, as well as hydrogen and potassium ions

Uses

Diuresis, hypertension, edema Onset

2 hours, peak effect 4–6 hours Duration

6–12 hours

Metabolism

Into urine, unchanged Adverse Effects

Dehydration, hypovolemia, hypotension, hyponatremia, hypochloremic hypokalemia, hypomagnesemia, hyperuricemia, hyperglycemia, hypercalcemia

CLINICAL PEARLS

alkalosis,

• Component in many antihypertensive drug combinations, given to counteract fluid/sodium retention induced by other agents • Ineffective at CrCl