Study Notes Anesthesiology

Study Notes – Anesthesiology

James Lamberg

28Jul2010

Textbooks: Miller Anesthesia, Anesthesia Secrets, NMS Clinical Manual of Anesthesia -------------------------------------------------------------------------------------------------------------------------------------------Procedures: NEJM Videos In Clinical Medicine: http://www.nejm.org/multimedia/videosinclinicalmedicine Nerve Block Procedures: NY School of Regional Anesthesia: http://www.nysora.com/ -------------------------------------------------------------------------------------------------------------------------------------------Medical Student’s Anesthesia Primer by Dr. Roy Soto, MD Preoperative History & Physical: * Assess coronary artery disease. What is the patient’s exercise tolerance? How do they feel after walking up three flights of stairs? (poor man’s stress test) * Hypertension controlled? Preop control affects intraoperative control. * Asthma controlled? What triggers it? May be at risk for intraoperative bronchospasm. * Kidney or liver disease? Assess for drug and anesthetic clearance. * Reflux disease? Prone to aspiration. * Smoking? More difficult airway and secretion management. * Alcohol consumption or drug abuse? Hepatotoxicity, drug clearance, and pain tolerance. * Diabetes? Risk of increased blood glucose and aspiration due to gastroparesis. * Medications, allergies, and family history (e.g. malignant hyperthermia). * Last meal to determine induction technique if not on empty stomach. * Assess airway. Have patient open their mouth and stick out their tongue without saying “Ahh.” Give Mallampati classification. Ask about loose teeth, dentures, and cervical range of motion. * Assign physical status classification. ASA-1 is healthy patient, ASA-5 is moribund patient. Preoperative IVs & Medications * Before starting an IV, make sure all your equipment is present (e.g. fluid bag, tape). * Nervous patients may be pre-medicated with a rapidly acting benzodiazepine, such as midazolam. * Metoclopramide and an H2 blocker are also often used if there is a concern that the patient has a full stomach. * Anticholinergics such as glycopyrrolate can be used to decrease secretions. * ASA requirements for patient safety are pulse oximeter, blood pressure monitor, and electrocardiogram. Induction & Intubation (“flight take off”) * Pre-oxygenate with 100% oxygen to achieve >80% end tidal O2. * Administer IV anesthetic until patient is unconscious. Can be checked by loss of eyelash reflex. * Most common IV anesthetics, likely in order of use, Propofol, Thiopental, Etomidate, Ketamine. * Mask ventilate. Administer neuromuscular blocking agent such as succinylcholine (depolarizing agent), or vecuronium (nondepolarizing agent). * Use a twitch monitor to assess when twitch is diminished. Else wait for normal drug onset time. * Most IV induction agents last less than 10 minutes, so you may want to turn on the volatile anesthetic agent. * Keep a tight mask seal so you don’t anesthetize yourself. * Put laryngoscope in your left hand held at the blade base. Use your right hand scissor the mouth open. Advance the blade on the right side of the tongue and sweep. * Advance the blade until you see epiglottis. Place blade (assuming Macintosh) into the vallecula. Life the laryngoscope with your upper arm along the axis of the handle (toward the ceiling, not rocking against the teeth). * When you see vocal cords, insert the tube until you can no longer see the balloon. Remove the stylet, inflate the balloon, and attach the endotracheal tube to the circuit. Keep holding the tube with your left hand. * Assess placement with breath sounds and ETCO2. Tape in place if bilateral rise/fall with sounds. Maintenance (“flight cruising altitude”) * Remain vigilant. Monitor end tidal oxygen, CO2, N20, volatile agents, presence of twitch, and patient position. * Pay attention to blood loss and fluid management. Emergency (“flight landing”) * Re-assess neuromuscular blockade. Ensure the patient is breathing on their own. Ideally, you want the patient following commands. * Ensure suction is close at hand. You should be prepared to re-intubate if necessary. * Extubate, clear airway, move patient, and transfer to post-anesthesia care unit (PACU). * PACU concerns include nausea/vomiting, hemodynamic instability, and pain management. * Follow-up intraoperative procedures, such as a chest x-ray to rule out pneumothorax for an central line. Commonly Used Medications Volatile Anesthetics, Halothane: * Pro: Cheap, Nonirritating so can be used for inhalation induction.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Con: Long time to onset/offset, significant myocardial depression, sensitizes myocardium to catecholamines, association with hepatitis. Volatile Anesthetics, Isoflurane: *Pro: Cheap, excellent renal, hepatic, coronary, and cerebral blood flow preservation. *Con: Long time to onset/offset, irritating so cannot be used for inhalation induction. Volatile Anesthetics, Sevoflurane: * Pro: Nonirritating so can be used for inhalation induction, Extremely rapid onset/offset. * Con: Expensive, Due to risk of “Compound A” exposure must be used at flows >2 liters/minute, Theoretical potential for renal toxicity from inorganic fluoride metabolites. Volatile Anesthetics, Desflurane: * Pro: Extremely rapid onset/offset. * Con: Expensive, stimulates catecholamine release, possibly increases postoperative nausea and vomiting, requires special active temperature controlled vaporizer, irritating so cannot be used for inhalation induction. Volatile Anesthetics, Nitrous Oxide: * Pro: Decreases volatile anesthetic requirement, Dirt cheap, Less myocardial depression than volatile agents. * Con: Diffuses freely into gas filled spaces (bowel, pneumothorax, middle ear, gas bubbles used during retinal surgery), decreases FiO2, increases pulmonary vascular resistance, combustible like oxygen. IV Anesthetics: All have very rapid onset ( 4 METS (can walk a flight of stairs without symptoms). * Decision: Proceed to surgery. Step 5: Clinical Predictors * Ischemic heart disease, compensated or prior HF, cerebrovascular disease (stroke, TIA), diabetes mellitus, renal insufficiency. * Decision: No clinical predictors, Proceed to surgery. * Decision: 1-2 clinical predictors with vascular surgery or immediate-risk surgery, Proceed to surgery with HR control or consider noninvasive testing if it will change management. * Decision: 3 or more clinical predictors with vascular surgery, Consider testing if it will change management. -------------------------------------------------------------------------------------------------------------------------------------------Pre-Operative Anesthesia Equipment Assessment See “Anesthesia Apparatus Checkout Recommendations, 1993” by the U.S. Food & Drug Administration 1) Verify Backup Ventilation Equipment is Available & Functioning. 2) Check Oxygen Cylinder Supply. 3) Check Central Pipeline Supplies.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

4) Check Initial Status of Low Pressure System. 5) Perform Leak Check of Machine Low Pressure System. 6) Turn On Machine Master Switch. 7) Test Flowmeters. 8) Adjust and Check Scavenging System. 9) Calibrate O2 Monitor. 10) Check Initial Status of Breathing System. 11) Perform Leak Check of the Breathing System. 12) Test Ventilation System and Unidirectional Valves. 13) Check, Calibrate, and/or Set Alarm Limits of all Monitors. 14) Check Final Status of Machine. See “Recommendations for Pre-Anesthesia Checkout Procedures, 2008” by the ASA Items to be completed prior to each procedure: 1) Verify patient suction is adequate to clear the airway. 2) Verify availability of required monitors, including alarms. 3) Verify that vaporizers are adequately filled and if applicable that the filler ports are tightly closed. 4) Verify carbon dioxide absorbent is not exhausted. 5) Breathing system pressure and leak testing. 6) Verify that gas flows properly through the breathing circuit during both inspiration and exhalation. 7) Document completion of checkout procedures. 8) Confirm ventilator settings and evaluate readiness to deliver anesthesia care. (ANESTHESIA TIME OUT) -------------------------------------------------------------------------------------------------------------------------------------------Difficult Airway Algorithm by the Difficult Airway Society (DAS) Plan A: Initial tracheal intubation. * If direct laryngoscopy, proceed with tracheal intubation. Plan B: Secondary tracheal intubation. * Use ILMA or LMA, confirm placement, then fiberoptic tracheal intubation through ILMA or LMA. Plan C: Maintenance of oxygenation and ventilation. * Revert to face mask, oxygenate and ventilate, postpone surgery, awaken patient. Plan D: Rescue techniques for “can’t intubate, can’t ventilate” situation. * LMA, if improved oxygenation then awaken patient. * LMA, if increasing hypoxemia then cannula cricothyroidotomy or surgical cricothyroidotomy. -------------------------------------------------------------------------------------------------------------------------------------------Fluid Requirements & Management Estimated Blood Volume, EBV = ABV * kg (ABV = 75mL/kg Male, 65mL/kg Female, 55mL/kg Obese) Allowable Blood Loss, ABL = EBV * (Initial Hgb – Hgb allowable) / Initial Hgb Maintenance Fluid: (4-2-1 Rule) Fluid Deficit: For the first 10kg: 4mL/kg/hr Deficit = preoperative NPO hours * maintenance For the second 10kg: 2mL/kg/hr Preop bowel preparation adds 1 to 1.5L For anything > 20kg: 1mL/kg/hr Replace half of deficit in first hour, half in second Insensible Loss: Blood Loss: Losses: 2-10mL/kg/hr 3mL crystalloid per 1mL blood loss Minimum: 4mL/kg/hr, Extreme: 8mL/kg/hr 1mL colloid or blood products per 1mL blood loss -------------------------------------------------------------------------------------------------------------------------------------------Chapter Highlights – Miller’s Anesthesia (7th, Miller et al) -------------------------------------------------------------------------------------------------------------------------------------------History of Anesthetic Practice * Methods to safely alleviate severe pain are relatively recent discoveries, as viewed within the time span of human history. * The public demonstration of ether anesthesia on October 16, 1846, ranks as one of the most significant events in the history of medicine. * No single individual can be said to have discovered anesthesia. * The specialty of anesthesia rests on discoveries made from several scientific disciplines. * Major discoveries were often made by small groups of curious individuals with diverse backgrounds. * Techniques in common use at any one time often seem dangerous to subsequent generations of anesthesiologists. * Major innovations were sometimes ignored until their rediscovery several decades later.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Developments in anesthesia often arose to meet the needs of patients with severe comorbid conditions that required complex surgical procedures. Consequently, advances within the specialties of surgery and anesthesia are closely integrated. -------------------------------------------------------------------------------------------------------------------------------------------Scope of Modern Anesthetic Practice * With the increase in the elderly population, more of the surgeries performed will be procedures required by elderly patients. * Minimally invasive procedures are increasing; anesthesiologists will be performing more anesthetic procedures outside operating rooms. Anesthesia may be the major risk to patients as the surgical procedures become more minimal. * The mandates for quality, competency, and uniform process will change the way anesthesia is delivered. More standardization and protocols will be used; this will allow more evaluation and research as to what optimal anesthesia is and what competent anesthesiologists are required to do. * The increase in nurses with degrees will change the number of anesthetics delivered by physicians. Team management and relationships between physicians and nurses will become more crucial, and the demand for skills in personnel management will increase. * Not enough research is being done by anesthesiologists. Anesthesiologists will need to engage in research to maintain an academic foothold. Opportunities for multidisciplinary research are increasing, and they need to be embraced to increase the number of research-trained anesthesiologists. -------------------------------------------------------------------------------------------------------------------------------------------The International Scope and Practice of Anesthesia * The Early History of International Anesthesia: India (Deepak K. Tempe), The Middle East (Anis Baraka and Fouad Salim Haddad), Russia (Olga Afonin) * The Cross-Pollination Period: 1920-1980: India (Deepak K. Tempe), The Middle East (Anis Baraka and Fouad Salim Haddad), Russia (Olga Afonin), South America (Guillermo Lema), China (Yuguang Huang), Southeast Asia (Florian R. Nuevo), Europe (Lars I. Eriksson and Peter Simpson), Uganda/Sub-Sharan Africa (D.G. Bogod), Japan (Akiyoshi Namiki and Michiaki Yamakage) * The Modern Period: Essentials of Modern Anesthesia around the World: Roles and Responsibilities of Anesthesia Providers, Facilities and Equipment, Education, Accreditation, and Availability of Practitioners, Subspecialization, Professional and Research Activity -------------------------------------------------------------------------------------------------------------------------------------------Medical Informatics * A computer's hardware serves many of the same functions as those of the human nervous system, with a processor acting as the brain and buses acting as conducting pathways, as well as memory and communication devices. * The computer's operating system serves as the interface or translator between its hardware and the software programs that run on it, such as the browser, word processor, and e-mail programs. * The hospital information system is the network of interfaced subsystems, both hardware and software, that coexist to serve the multiple computing requirements of a hospital or health system, including services such as admissions, discharge, transfer, billing, laboratory, radiology, and others. * An electronic health record is a computerized record of patient care. * Computerized provider order entry systems are designed to minimize errors, increase patient care efficiency, and provide decision support at the point of entry. * Decision support systems can provide providers with best-practice protocols and up-to-date information on diseases or act to automatically intervene in patient care when appropriate. * The Health Insurance Portability and Accountability Act is a comprehensive piece of legislation designed in part to enhance the privacy and security of computerized patient information. * Providers are increasingly able to care for patients at a distance via the Internet, and telemedicine will continue to grow as the technology improves, reimbursement becomes available, and legislation evolves. -------------------------------------------------------------------------------------------------------------------------------------------Quality Improvement * Quality is a characteristic of the system in which care is delivered, and every system is perfectly designed to achieve the results that it achieves. If we want to improve the quality of care that we provide, we need to reorganize the way that we work. * The growing demand for improved quality and safety in health care from patients, providers, insurers, regulators, accreditors, and purchasers calls for anesthesiologists to evaluate the quality of care that they provide.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Improving quality of care entails measuring performance. However, health care providers have limited ability to obtain feedback regarding performance in their daily work, in part because of a lack of information systems and lack of agreement on how to measure quality of care. * The goal of measurement is to learn and improve. The measurement system must fit into an improvement system; caregivers must have the will to work cooperatively to improve, they must have ideas or hypotheses about changes in the current system of care, and the team must have a model for testing changes and implementing those that result in improvements. * Previous efforts to measure performance have focused predominantly on outcome measures, including in-hospital mortality rates. Although important, hospital mortality alone provides an incomplete picture in that it does not provide insight into all domains of quality. A balanced set of structures (how care is organized), processes (what we do), and outcome measures (results we achieve) is needed to obtain a more accurate picture of the quality of care. * Future efforts to improve quality of care in the field of anesthesiology should focus on the development of valid, reliable, and practical measures of quality. * Developing a quality measure requires several steps: prioritize the clinical area to evaluate; select the type of measure; write definitions and design specifications; develop data collection tools; pilot-test data collection tools and evaluate the validity, reliability, and feasibility of measures; develop scoring and analytic specifications; and collect baseline data. * One of the greatest opportunities to improve quality of care and patient outcomes probably will not come from discovering new therapies but from discovering how to better deliver therapies that are known to be effective. * Strategies that have been used successfully in the aviation industry to improve performance include interventions to reduce complexity and the creation of redundancies in the system to ensure that critical processes occur. These strategies have not been fully evaluated in the practice of anesthesia. * Health care providers can organize their patient safety and quality improvement efforts around three key areas: translating evidence into practice, identifying and mitigating hazards, and improving culture and communication. Although each of these areas requires different tools, they all help health care organizations to evaluate progress in patient safety and quality. -------------------------------------------------------------------------------------------------------------------------------------------Human Performance and Patient Safety * Clinical excellence is not achieved by the use of sound medical knowledge alone. Human factors and the interaction of team members, as well as organizational conditions in the system of care, also play major roles. Therefore, the study of human performance and related organizational matters is very important. * The health care system in general and clinical institutions in particular must provide appropriate organizational characteristics to allow and foster safe patient care practices (e.g., improve safety culture, integrate effective incident reporting and analysis systems). * High-reliability organization theory describes the key features of systems that conduct complex and hazardous work with very low failure rates. Errors do occur in such organizations, but their systems make them more impervious to errors and their sequelae (resilience). * In dynamic domains such as anesthesia, continuous decision-making, as described in the cognitive process model, is critical to achieving safe patient care. * Several error mechanisms have been demonstrated through human factors research. Understanding these psychological “traps” (for example, “fixation errors”) can help anesthetists avoid or mitigate them. * The introduction and spread of crisis resource management training, including the application of realistic simulation exercises, is likely to improve patient safety in anesthesia and other acute care domains. * Like all human beings, the performance of individual anesthetists can be adversely influenced by “performanceshaping factors,” including noise, illness, aging, and especially sleep deprivation and fatigue. * A particular technique of human factors research called “task analysis” has been useful in understanding the work of anesthetists. * Observation of anesthetists during routine operations or in the handling of adverse events (using realistic patient simulators) has improved our knowledge of critical decision-making and team interactions. * Future progress on patient safety in anesthesia will require interdisciplinary research and training, improvements in systems safety and organizational learning, and the involvement of all levels of the health care industry. -------------------------------------------------------------------------------------------------------------------------------------------Patient Simulation * Simulators and the use of simulation have become an integral part of medical education, training, and research. The pace of developments and applications is very fast, and the results are promising.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Different types of simulators can be distinguished: computer-based or screen-based microsimulators versus mannequin-based simulators. The latter can be divided into script-based and model-based simulators. * The development of mobile and less expensive simulator models allows for substantial expansion of simulator training to areas where this training could not be applied or afforded previously. The biggest obstacles to providing simulation training are not the simulator hardware but are (1) obtaining access to the learner population for the requisite time and (2) providing appropriately trained and skilled instructors to prepare, conduct, and evaluate the simulation sessions. * Realistic simulations are a useful method to show mechanisms of error development (human factors) and to provide their countermeasures. The anesthesia crisis resource management (ACRM) course model with its ACRM key points is the de facto world standard for human factor–based simulator training. Curricula should use scenarios that are tailored to the stated teaching goals, rather than focusing solely on achieving maximum “realism.” * Simulator training is being adapted by many other fields outside anesthesia (e.g., emergency medicine, neonatal care, intensive care, medical and nursing school). * Simulators have proved to be very valuable in research to study human behavior and failure modes under conditions of critical incidents and in the development of new treatment concepts (telemedicine) and in support of the biomedical industry (e.g., device beta-testing). * Simulators can be used as effective research tools for studying methods of performance assessment. * Assessment of nontechnical skills (or behavioral markers) has evolved considerably and can be accomplished with a reliability that likely matches that of many other subjective judgments in patient care. Systems for rating nontechnical skills have been introduced and tested in anesthesia; one in particular (Anaesthetists' Non-Technical Skills [ANTS]) has been studied extensively and has been modified for other fields. * The most important part of simulator training that goes beyond specific technical skills is the self-reflective (often video-assisted) debriefing session after the scenario. The debriefing is influenced most strongly by the quality of the instructor, not the fidelity of the simulator. * Simulators are just the tools for an effective learning experience. The education and training, commitment, and overall ability of the instructors are of utmost importance. -------------------------------------------------------------------------------------------------------------------------------------------Teaching Anesthesia * Education is an all-encompassing process (not merely a specific activity) that results in a change in behavior on the part of the student/learner. The focus of education is the learner, not the teacher. It is the student who is educated by interacting with an environment that provides experiences. Education is change in behavior based on experiences. * Adult learners learn anesthesiology. Adult learners are those with strong motivation to participate in a set of experiences to learn a specific discipline. The discipline that they want to learn is one that they are interested in or need to know, or both. Adult learners participate in life-centered situational learning in the area or areas in which relevance is most likely. * Adult learners enter the learning activity with a wealth of previous experience and view the current education in light of their background. Adult learners can capitalize on this previous learning; however, the previous learning may color how the current learning takes place. * Adult learners are self-directed and initiate their own activities. Adult learning is goal oriented toward relevant life-centered needs. An adult learner tends to pick and choose some, not necessarily all, of the educational activities available. * Inherent differences among people tend to increase with aging. Adult education must provide for differences in style, time, place, and pace of learning among adult learners. The time factor for learning is especially crucial for adults. Adults perceive that time passes more rapidly; that is, there is less time available to learn—or to do anything for that matter. With time perceived to be in short supply, adult learners tend to be selective in their learning to use what time they have more efficiently. * In 2006, there were 4970 resident anesthesiologists in 131 accredited American core anesthesiology residency programs and 360 subspecialty residents in 213 accredited American subspecialty anesthesiology programs. * Silber and colleagues, in their study of almost 6000 patients undergoing prostate or gallbladder surgery in multiple hospitals, demonstrated that patient recovery or “rescue” from an adverse event correlated with the proportion of board-certified anesthesiologists in the hospital. * The Accreditation Council for Graduate Medical Education has defined six educational areas for which residents and fellows must demonstrate competency. These areas additionally are major components of Maintenance of Certification in Anesthesiology: a. Patient Care: Residents must be able to provide patient care that is compassionate, appropriate, and effective for the treatment of health problems and the promotion of health.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

b. Medical Knowledge: Residents must demonstrate knowledge of established and evolving biomedical, clinical, epidemiologic, and social-behavioral sciences, as well as the application of this knowledge to patient care. c. Practice-Based Learning and Improvement: Residents must demonstrate the ability to investigate and evaluate their care of patients, to appraise and assimilate scientific evidence, and to continuously improve patient care based on constant self-evaluation and lifelong learning. d. Interpersonal and Communication Skills: Residents must demonstrate interpersonal and communication skills that result in the effective exchange of information and collaboration with patients, their families, and health professionals. e. Professionalism: Residents must demonstrate a commitment to carrying out professional responsibilities and adherence to ethical principles. f. Systems-Based Practice: Residents must demonstrate an awareness of and responsiveness to the larger context and system of health care, as well as the ability to call effectively on other resources in the system to provide optimal health care. * Full-time anesthesiology faculty positions in U.S. medical schools in 2006-2007 numbered 5836. Anesthesiologists represent 5.6% of the clinical teachers and 4.7% of all American medical school teaching faculty. The 5836 anesthesia faculty members in medical schools bear the major responsibility for teaching some or all of the 69,028 enrolled undergraduate medical students, the 4970 graduate trainees in anesthesiology residency training programs, the 360 graduate trainees in anesthesiology subspecialty fellowship programs, and many of the approximately 104,879 physician house-staff trainees. * Effective clinical teachers who are able to succeed at the bedside teaching encounter display specific actions noted by their students and themselves. These actions include a. Allocating time for teaching b. Creating a teaching/learning environment of trust and concern c. Demonstrating clinical credibility d. An initial orientation e. A final evaluation f. Learners being able to present a case g. Teachers managing the case presentation h. Didactic sessions being used to enhance clinical case material i. Teaching taking place at the bedside so that students can learn physician-patient relationships j. Teachers and students discussing psychosocial issues k. Attention being paid to transferring the teaching responsibility * Teaching content requires attention to increasingly complex cognitive functions. As described by Bloom, teaching/learning in the cognitive domain for any topic addresses the following: a. Knowledge—recall b. Comprehension—understanding c. Application—use of abstractions d. Analysis—break down; seeing the relationship of parts e. Synthesis—put together; creating a new entity f. Evaluation—judgment of value * A systematic methodology to develop a psychomotor skill lesson includes the following steps: a. Analyze and separate the skill into its component parts and determine which aspects of the skill are most difficult to perform. b. Provide students with a model of the skill, effectively demonstrated in its entirety, that they are expected to perform. c. Make provisions for students to practice until the expected behavior is mastered. d. Provide adequate supervision and an evaluation of the final performance. -------------------------------------------------------------------------------------------------------------------------------------------Ethical Aspects of Anesthesia Care * Anesthesiologists have ethical obligations to promote patients’ abilities to make medical decisions, as well as obligations to respect those decisions. * Competent patients have the right to refuse medical treatments or tests, even if it appears to be a “bad” decision. Coercing or restraining competent patients is unethical. * Children should be involved in medical decision-making to the degree that their abilities allow, and their wishes should usually be respected. * Advance directives and decisions by surrogate decision-makers are legally binding.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Do-not-attempt-resuscitation orders require reconsideration before anesthesia and surgery and cannot be automatically suspended. * Withdrawal or withholding of life-sustaining treatments at the end of life requires specialized training or experience. * Anesthesiologists play a pivotal role in caring for both brain-dead and non–heart-beating organ donors and must be familiar with the medical, legal, and ethical issues involved. * Human and animal research carries special obligations to protect the subjects from inhumane treatment. Whenever possible, alternatives to human and animal research should be sought. * “State-sponsored” activities such as executions (1) are not the practice of medicine, (2) undermine the medical profession, and (3) place the physician on dubious moral grounds. * Although physicians have a right to withdraw from some situations in which patient care presents them with personal moral conflicts, this right is limited, and professionally accepted standards and obligations usually prevail (e.g., well-established standards, such as informed consent). -------------------------------------------------------------------------------------------------------------------------------------------Legal Aspects of Anesthesia Care * The medical malpractice tort system is intended to improve patient care. * Medical negligence occurs when a physician's failure to meet the standard of care directly leads to patient injury. * A fully informed attorney is the physician's best advocate. * Physicians having their medical competence publicly questioned may feel guilt, failure, anger, shame, isolation, depression, fatigue, denial, and physical symptoms. * A detailed, legible anesthesia record strengthens the defense against a malpractice suit. * More than half the states have laws prohibiting the admission of apology or sympathy as evidence of wrongdoing. * The goal of informed consent is to maximize the ability of the patient to make substantially autonomous informed decisions. * Evidence of decision-making capacity (the ability to make a particular decision at a specific time) includes the ability to understand medical problems, proposed treatments, alternatives, options to refuse treatment, and the foreseeable consequences of accepting or refusing proposed treatments, as well as the ability to express a preference based on rational, internally consistent reasoning. * A reasonable person standard of disclosure requires that the extent of the disclosure be based on what a reasonable person would consider material for choosing whether to undergo the proposed intervention. * Anesthesiologists may refuse to provide care when they ethically or morally disagree with the procedure or if they believe that the patient's choice is too inappropriate or likely to result in harm. * Competent patients have a virtually unlimited right to refuse life-sustaining medical treatment. * Anesthesiologists are responsible for negligent acts made within the scope of defined duties by trainees and certified registered nurse anesthetists. * Physicians have been held liable for inadequate pain control. -------------------------------------------------------------------------------------------------------------------------------------------Sleep, Memory, and Consciousness * Sleep is an active process generated in the brain. * Structures in the brainstem, diencephalon, and basal forebrain control the sleep-wake cycle and are directly modulated by general anesthetics. * Sleep and anesthesia are similar states with distinct traits, with each satisfying neurobiologic features of the other. * Distinct memory functions are subserved by distinct neural structures. * Limbic system structures such as the hippocampus and amygdala are critical for memory and play a role in anesthetic-induced amnesia. * Although brainstem, diencephalon, and basal forebrain structures generate wakefulness, the contents of consciousness are thought to be generated by the cortex. * Multiple neural correlates of consciousness are thought to be the targets of general anesthetics. * Consciousness and subsequent explicit recall of intraoperative events—known as “awareness during general anesthesia”—occur in 1 to 2 cases per 1000. * Monitoring anesthetic depth has evolved to electroencephalographic methods, although limitations still exist. -------------------------------------------------------------------------------------------------------------------------------------------The Autonomic Nervous System * The autonomic nervous system works in concert with renin, cortisone, and other hormones to respond to internal and external stresses.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* The hallmark of the sympathetic nervous system is amplification; the hallmark of the parasympathetic nervous system is targeted response. * Inhaled and intravenous anesthetics can alter hemodynamics by influencing autonomic function. * β-Adrenergic blockade has emerged as important prophylaxis for ischemia and as therapy for hypertension, myocardial infarction, and congestive heart failure. * The sympathetic nervous system demonstrates acute and chronic adaptation to stress presynaptically and postsynaptically (e.g., biosynthesis, receptor regulation). * Presynaptic α-receptors play an important role in regulating sympathetic release. * Many therapies for the treatment of hypertension are based on direct or indirect effects of sympathetic function. * The vagus nerve is the superhighway of parasympathetic function; it accommodates 75% of parasympathetic traffic. * Aging and many disease states (e.g., diabetes, spinal cord injury) are accompanied by important changes in autonomic function. -------------------------------------------------------------------------------------------------------------------------------------------Cerebral Physiology and the Effects of Anesthetic Drugs * The brain has a high metabolic rate and receives approximately 15% of cardiac output. Under normal circumstances, cerebral blood flow (CBF) is approximately 50 mL/100 g/min. Gray matter receives 80% and white matter receives 20% of this blood flow. * Approximately 60% of the brain's energy consumption is used to support electrophysiologic function. The remainder of the energy consumed by the brain is involved in cellular homeostatic activities. * CBF is tightly coupled to local cerebral metabolism. When cerebral activity in a particular region of the brain increases, a corresponding increase in blood flow to that region takes place. Conversely, suppression of cerebral metabolism leads to a reduction in blood flow. * CBF is autoregulated and held constant over a mean arterial pressure range conservatively estimated at 65 to 150 mm Hg, given normal venous pressure. There is probably appreciable intersubject variability. CBF becomes pressure passive when mean arterial pressure is either below the lower limit or above the upper limit of autoregulation * CBF is also under chemical regulation. It varies directly with arterial carbon dioxide tension in the Paco2 range of 25 to 70 mm Hg. With a reduction in Pao2 to below 60 mm Hg, CBF increases dramatically. Changes in temperature affect CBF primarily by suppression of cerebral metabolism. * Systemic vasodilators (nitroglycerin, nitroprusside, hydralazine, calcium channel blockers) vasodilate the cerebral circulation and can, depending on mean arterial pressure, increase CBF. Vasopressors such as phenylephrine, norepinephrine, ephedrine, and dopamine do not have significant direct effects on the cerebral circulation. Their effect on CBF is dependent on their effect on systemic blood pressure. When mean arterial pressure is below the lower limit of autoregulation, vasopressors increase systemic pressure and thereby increase CBF. If systemic pressure is within the limits of autoregulation, vasopressor-induced increases in systemic pressure have little effect on CBF. * All modern volatile anesthetics suppress the cerebral metabolic rate (CMR) and, with the exception of halothane, can produce burst suppression of the electroencephalogram. At that level, CMR is reduced by about 60%. Volatile anesthetics have dose-dependent effects on CBF. In doses lower than the minimal alveolar concentration (MAC), CBF is not significantly altered. Beyond doses of 1 MAC, direct cerebral vasodilation results in an increase in CBF and cerebral blood volume. * Barbiturates, etomidate, and propofol decrease CMR and can produce burst suppression of the electroencephalogram. At that level, CMR is reduced by about 60%. Flow and metabolism coupling is preserved and therefore CBF is decreased. Opiates and benzodiazepines effect minor decreases in CBF and CMR, whereas ketamine can increase CMR (with a corresponding increase in blood flow) significantly. * Brain stores of oxygen and substrates are limited and the brain is exquisitely sensitive to reductions in CBF. Severe reductions in CBF (less than 10 mL/100 g/min) lead to rapid neuronal death. Ischemic injury is characterized by early excitotoxicity and delayed apoptosis. * Barbiturates, propofol, ketamine, volatile anesthetics, and xenon have neuroprotective efficacy and can reduce ischemic cerebral injury. Anesthetic neuroprotection is sustained only when the severity of the ischemic insult is mild; with moderate to severe injury, long-term neuroprotection is not achieved. Administration of etomidate is associated with regional reductions in blood flow, and this can exacerbate ischemic brain injury. -------------------------------------------------------------------------------------------------------------------------------------------Neuromuscular Physiology and Pharmacology

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* The neuromuscular junction provides a rich array of receptors and substrates for drug action. Several drugs used clinically have multiple sites of action, and muscle relaxants are not exceptions to the rule that most drugs have more than one site or mechanism of action. The major actions seem to occur by the mechanisms and at the sites described for decades: agonistic and antagonistic actions at postjunctional receptors for depolarizing and nondepolarizing relaxants. This description of neuromuscular drug action is a simplistic one. Neuromuscular transmission is impeded by nondepolarizers because they prevent access of acetylcholine to its recognition site on the postjunctional receptor. * If the concentration of nondepolarizer is increased, another, noncompetitive action—block of the ion channel—is superimposed. The paralysis is also potentiated by prejunctional actions of the relaxant, which prevents release of acetylcholine. The latter can be documented as fade that occurs with increased frequency of stimulation. A more accurate description of the effects of relaxants recognizes that the neuromuscular junction is a complex and dynamic system in which the phenomena produced by drugs are composites of actions that vary with drug, dose, activity in the junction and muscle, time after administration, presence of anesthetics or other drugs, and the age and condition of the patient. * Inhibition of postjunctional acetylcholinesterase by anticholinesterases increases the concentration of acetylcholine, which can compete with and displace the nondepolarizer and thus reverse the paralysis. These anticholinesterases also have other effects, including those on nerve terminals and on the receptor, by an allosteric mechanism. Cyclodextrins are a new class of compounds that reverse paralysis of only steroidal muscle relaxants by directly binding to them. * Depolarizing compounds initially react with the acetylcholine recognition site and, like the transmitter, open ion channels and depolarize the end-plate membrane. Unlike the transmitter, they are not subject to hydrolysis by acetylcholinesterase and therefore remain in the junction. Soon after administration of the drug, some receptors are desensitized and, although occupied by an agonist, they do not open to allow current to flow to depolarize the area. * If the depolarizing relaxant is applied in high concentration and allowed to remain at the junction for a long time, other effects occur, including entry of the drug into the channel to obstruct it or to pass through it into the cytoplasm. Depolarizing relaxants also have effects on prejunctional structures, and the combination of prejunctional and postjunctional effects plus secondary ones on muscle and nerve homeostasis results in the complicated phenomenon known as phase II blockade. * Intense research in the area of neuromuscular transmission continues at a rapid pace. Newer observations on receptors, ion channels, membranes, and prejunctional function reveal a much broader range of sites and mechanisms of action for agonists and antagonists. * Some of the other drugs used clinically (e.g., botulinum toxin) have effects on the nerve and therefore indirectly on muscle. Systemic infection with clostridial toxins (Clostridium tetanus, Clostridium botulinum) can lead to systemic paralysis as a result of decreased release of acetylcholine from the nerve terminal. Nondepolarizing muscle relaxants administered even for 12 hours or for prolonged periods can have effects on the postsynaptic receptor and simulate denervation (chemical denervation). In recognizing these sites and mechanisms, we begin to bring our theoretical knowledge closer to explaining the phenomena observed when these drugs are administered to living humans. * The most recent work seems to be focused on the postjunctional membrane and control of acetylcholine receptor expression in normal and diseased states. The presence or absence of mature and immature isoforms seems to complicate matters further. In certain pathologic states (e.g., stroke, sepsis, burns, immobilization, chronic use of relaxants), acetylcholine receptors are upregulated, usually with expression of the immature isoform. More recently, another isoform of the acetylcholine receptor, previously described in neuronal tissues only, the α7 neuronal acetylcholine receptor, has been identified in muscle. These receptors have different functional and pharmacologic properties than conventional muscle postsynaptic receptors do. The altered functional and pharmacologic characteristics of the immature (γ-subunit) and neuronal (α7-subunit) receptors result in increased sensitivity to succinylcholine with hyperkalemia and resistance to nondepolarizers. * An area of increasing attention is control of the expression of mature versus the other two receptor isoforms. Reexpression of the immature γ and α7 receptors is probably related to aberrant growth factor signaling. Mutations in the acetylcholine receptor that result in prolonged open-channel time, similar to that seen with the immature receptor, can lead to a myasthenia-like state, even in the presence of normal receptor numbers. The weakness is usually related to the prolonged open-channel time. The role of the immature isoform of the receptor in the muscle weakness associated with critical illness such as burns is unknown. * Despite the fact that the neuromuscular junction is the most studied receptor, complete knowledge of its workings has not been achieved. This is an area of continuing interest for many researchers worldwide.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

-------------------------------------------------------------------------------------------------------------------------------------------Respiratory Physiology * Removal of CO2 is determined by alveolar ventilation, not by total, minute ventilation. * Dead space ventilation can be dramatically increased in patients with chronic obstructive pulmonary disease and pulmonary embolism to more than 80% to 90% of minute ventilation in the extreme case. * Breathing at low lung volume increases airway resistance and promotes closure of airways. * Hypoxemia can be caused by alveolar hypoventilation, diffusion impairment, ventilation-perfusion mismatch, and right-to-left shunt. * Almost all anesthetics reduce muscle tone, which in turn lowers functional residual capacity (FRC) to close to awake residual volume. * Lowered FRC during anesthesia together with ventilation with a high O2 concentration causes atelectasis. * Preoxygenation before and during induction of anesthesia is a major cause of atelectasis. * General anesthesia causes ventilation-perfusion mismatch (airway closure) and shunt (atelectasis). * Hypoxic pulmonary vasoconstriction is blunted by most anesthetics, thereby enhancing any ventilation-perfusion mismatch. * Respiratory work is increased during anesthesia, a consequence of reduced respiratory compliance (reduced lung volume available for ventilation?) and increased airway resistance (lowered FRC and subsequent decrease in airway dimensions?). -------------------------------------------------------------------------------------------------------------------------------------------Cardiac Physiology * The cardiac cycle is the sequence of electrical and mechanical events during the course of a single heartbeat. * Cardiac output is determined by the heart rate, myocardial contractility, and preload and afterload. * The majority of cardiomyocytes consist of myofibrils, which are rodlike bundles that form the contractile elements within the cardiomyocyte. * The basic working unit of contraction is the sarcomere. * Gap junctions are responsible for electrical coupling of small molecules between cells. * Action potentials have four phases in the heart. * The key player in cardiac excitation-contraction coupling is the ubiquitous second messenger calcium. * β-Adrenoreceptors stimulate chronotropy, inotropy, lusitropy, and dromotropy. * Hormones with cardiac action can be synthesized and secreted by cardiomyocytes or produced by other tissues and delivered to the heart. * Cardiac reflexes are fast-acting reflex loops between the heart and central nervous system that contribute to regulation of cardiac function and maintenance of physiologic homeostasis. -------------------------------------------------------------------------------------------------------------------------------------------Hepatic Physiology and Pathophysiology * Roughly 25% of cardiac output flows through the liver via a dual blood supply. The portal vein conveys 75% of total hepatic blood flow; the hepatic artery provides the rest. Each vessel, however, delivers about 50% of the total hepatic oxygen supply. * Hepatic sinusoids are the capillaries of the liver. Blood reaches the sinusoids via terminal branches of the portal vein and hepatic artery; it exits the sinusoids via hepatic venules (i.e., central veins) and travels through a venous network before draining in the inferior vena cava. Postsinusoidal vessels are a major source of total hepatic vascular resistance. * The acinus is the functional microvascular unit of the liver. It has three circulatory zones, defined by hepatocellular proximity to the portal axis. Blood perfusing zone 1 hepatocytes (periportal) is rich in oxygen and nutrients. By contrast, zone 3 hepatocytes (centrilobular) are perfused with effluent blood from zones 1 and 2, which is relatively oxygen poor. * Hepatocytes of zone 3, which have the highest density of cytochrome P450 proteins, are the most susceptible to injury from drug metabolism, oxidative stress, severe hypotension, or hypoxia. * The hepatic arterial buffer response (HABR) is the main intrinsic regulator of liver blood flow. Since the liver lacks pressure-flow autoregulation (in the fasted state), low systemic arterial pressure leads to low portal venous flow. HABR induces a compensatory increase of hepatic arterial flow, thereby preserving hepatic oxygen delivery despite decreases of total hepatic blood flow. Pathologic disruptions of HABR increase the susceptibility of the liver to hypoxic injury. * The liver is integral to the splanchnic blood reservoir, which can transfer up to 1 L of whole blood to the systemic circulation within 30 seconds of sympathoadrenal activation in healthy, euvolemic adults. If this reservoir is dysfunctional, abrupt, yet mild losses of intravascular volume (10% to 15%) may cause severe hypotension.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* The liver regulates the pathways of intermediary metabolism. When hepatic glycogen is depleted (e.g., due to prolonged fasting), the body depends on hepatic gluconeogenesis to supply blood glucose. Stress induces catabolic changes, including increased lipolysis, fatty acid oxidation, and hepatic ketone production. Ketosis develops. But ketosis triggers insulin release, thereby decreasing substrate (fatty acids) availability for ketogenesis. Thus, stressinduced ketosis tends to be self-limited, except in insulin-deficient states, when diabetic ketoacidosis may occur. * Hepatocytes play a central role in nitrogen metabolism. They remove nitrogen from various molecules, incorporate it into ammonia, and convert ammonia to urea. If liver failure occurs (without severe renal dysfunction), blood urea nitrogen levels typically remain low, while nitrogenous wastes accumulate in blood and other tissues. * Albumin is the most abundant hepatic protein. It is the main determinant of plasma oncotic pressure and an essential plasma transporter of exogenous substances and endogenous compounds, such as unconjugated bilirubin and free fatty acids. * Liver produces most of the molecular participants in coagulation pathways (besides factors III, IV, VIII). Hepatic proteins—such as factors II, VII, IX, X, proteins C and protein S—require vitamin K–dependent, posttranslational modifications, which enables their extrahepatic activation and subsequent involvement in the coagulation cascade. * Hepatocytes make, and regulate production of, bile salts. These natural ionic detergents have many physiologic roles, including enteric absorption, transport, and secretion of lipids. Disruption of biliary circulation predisposes to vitamin K deficiency; hepatocytes continue to synthesize procoagulants but cannot γ-carboxylate them. Parenteral vitamin K therapy should therefore correct the coagulopathy of cholestasis, unless liver failure has supervened. * The liver is the main site of xenobiotic biotransformation. Multifarious, complex chemical reactions of hepatic drug disposition fit in at least one of three broad metabolic categories (or phases): Phase 1 oxidizes drugs via cytochrome P450-mediated redox reactions; phase 2 produces conjugates of endogenous polar molecules and drugs (or their metabolites); phase 3 uses adenosine triphosphate transport proteins to facilitate biliary elimination of endogenous and exogenous substances. * The liver is the largest reticuloendothelial organ in the human body. Kupffer cells (macrophages) account for nearly 10% of the liver's mass. These macrophages filter the venous effluent of the gastrointestinal tract and in the process phagocytose microbes, destroy toxins, process antigens, modulate immunity, and regulate inflammatory responses. Kupffer cells, activated by such processes, release nitro-radicals, reactive oxygen species, proteases, chemokines, and cytokines, which recruit neutrophils to the liver and intensify the hepatic inflammation. If uncontrolled, these activated macrophages can damage normal hepatic parenchyma. * Portosystemic shunting (as occurs with cirrhosis-induced portal hypertension) circumvents the hepatic filtering mechanism and thereby allows drugs, nitrogenous waste, and toxins to enter the central circulation. Some of these substances are putative mediators of hepatic encephalopathy. * Standard liver function tests are used to screen for hepatobiliary diseases and identify categories of pathologic events within the hepatobiliary system, such as hepatocellular injury or biliary dysfunction. * The onset of portal hypertension signals depletion of the normal physiologic reserve of the liver. At this stage, severe pathophysiologic derangements develop and can give rise to life-threatening complications such as variceal hemorrhage, hepatic encephalopathy, and renal failure. * The cardiovascular hallmark of cirrhosis and portal hypertension is a hyperdynamic circulation in which cardiac output increases, total peripheral resistance decreases, and systemic blood pressure is slightly below normal. The hemodynamic profile is reminiscent of a large arteriovenous fistula because of extensive arteriovenous communications within the splanchnic vasculature and in organs throughout the body. Splanchnic vasculature may be engorged with blood even though effective plasma volume is perilously low. Cardiovascular responses to physiologic and pharmacologic vasoconstrictors are attenuated because of a plethora of endogenous vasodilators, dysfunction of the splanchnic reservoir, and occasionally, cardiac failure (e.g., cirrhotic cardiomyopathy). -------------------------------------------------------------------------------------------------------------------------------------------Renal Physiology * To cross the filtration barrier between plasma and tubular fluid, a molecule must pass in succession through the endothelial fenestrations, the glomerular basement membrane, and the epithelial slit diaphragm. The capillary endothelium restricts the passage of cells, but the basement membrane filters plasma proteins. All three layers contain negatively charged glycoproteins, which retard the passage of other negatively charged proteins. Thus, the filtration barrier is size selective and charge selective. * A primary determinant of glomerular filtration rate (GFR) is the glomerular filtration pressure, which depends not only on the renal artery perfusion pressure but also on the balance between afferent and efferent arteriolar tone. In the presence of decreased afferent arteriolar pressure or blood flow, low levels of catecholamines, angiotensin, and arginine vasopressin (AVP) induce preferential efferent arteriolar constriction, which maintains glomerular filtration pressure. This is reflected by an increase in calculated filtration fraction (FF), which is the GFR expressed as a

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- 13 -

Study Notes – Anesthesiology

James Lamberg

28Jul2010

fraction of the renal plasma flow (RPF), that is, FF = GFR/RPF. High levels of catecholamines and angiotensin (but not AVP) increase afferent arteriolar tone and decrease glomerular filtration pressure (and GFR) out of proportion to RPF, and FF decreases. * Tubuloglomerular feedback may be a primary mechanism in renal autoregulation. When GFR is increased, distal tubular NaCl delivery is enhanced. The increase in chloride is sensed by the macula densa, which triggers the release of renin from the adjacent afferent arteriole. Angiotensin is elaborated and arteriolar constriction ensues, which decreases GFR. When the thick ascending loop becomes ischemic, reabsorption of NaCl ceases, the ability of the tubule to concentrate urine is lost, and, theoretically, intractable polyuria should result. Thurau and Boylan suggested that the increased delivery of NaCl to the macula densa triggers angiotensin-mediated arteriolar constriction, which decreases GFR, induces oliguria, conserves intravascular volume, and protects the organism from dehydration—so-called acute renal success. * Autoregulation enables the kidney to maintain solute and water regulation independently of wide fluctuations of arterial blood pressure. It is noteworthy that urinary flow rate is not subject to autoregulation. Tubular water reabsorption determines urinary flow rate and is closely related to the hydrostatic pressure in the peritubular capillaries. Hypotension, whether induced or inadvertent, results in decreased urinary flow rate that may be correctable only when the arterial blood pressure is restored toward normal. * The tubule has an enormous capacity for reabsorption of water and NaCl. Each day, 180 L of protein-free glomerular ultrafiltrate is formed, of which almost 99% of the water and 99% of the sodium is reabsorbed. Many other filtered substances are completely reabsorbed, but some, such as glucose, have a maximum rate of tubular reabsorption (tubular maximum). Tubular reabsorption of glucose increases at a rate equal to that of the filtered load. * The ability of the kidney to concentrate urine is dependent on the interaction of at least three processes: (1) the generation of a hypertonic medullary interstitium by the countercurrent mechanism and urea recycling, (2) concentration and then dilution of tubular fluid in the loop of Henle, and (3) the action of antidiuretic hormone (now known as arginine vasopressin [AVP]) in increasing water permeability in the last part of the distal tubule and collecting ducts. * Serum creatinine reflects the balance between creatinine production by muscle and creatinine excretion by the kidney, which is dependent on the GFR. Creatinine generation rate varies with muscle mass, physical activity, protein intake, and catabolism. However, when these processes are in equilibrium and renal function is stable, serum creatinine is a useful marker of GFR. The relationship between serum creatinine and GFR is inverse and exponential. A doubling of the serum creatinine implies a halving of the GFR. An increase in serum creatinine from 0.8 to 1.6 mg/dL may not generate much attention, but it indicates a 50% decrease in GFR. A much larger increase from 4 to 8 mg/dL also represents a 50% decrease in GFR, but by this time renal insufficiency is well established. After a transient renal insult (e.g., suprarenal aortic cross-clamping), serum creatinine may increase for a few days while GFR is actually recovering. * The juxtaglomerular apparatus consists of three groups of specialized tissues. In the afferent arteriole, modified fenestrated endothelial cells produce renin; in the juxtaposed distal tubule, cells of the macula densa act as chemoreceptors; and in the glomerulus, mesangial cells have contractile properties. Together these provide an important regulating system for blood pressure, salt, and water homeostasis. * Hypothalamic osmoreceptors are sensitive to increases in serum osmolality of as little as 1% above normal. The threshold for AVP secretion (and the sensation of thirst) is between 280 and 290 mOsm/kg. When this is exceeded, the secretion rate has a very steep gain. Even mild dehydration results in a rapid antidiuresis, and urine osmolality can increase from 300 to 1200 mOs/kg as plasma AVP levels rise from 0 to 5 pg/mL. Decreases in intravascular volume also stimulate AVP secretion, mediated by stretch receptors with vagal afferents in the left atrium and pulmonary veins. Hypovolemia-induced secretion of AVP overrides osmolar responses and contributes to the perioperative syndrome of inappropriate antidiuretic hormone secretion (SIADH): fluid retention, hypo-osmolality, and hyponatremia. The situation is exacerbated by administration of large volumes of hypotonic solutions that decrease serum osmolality. Psychic stress, via cortical input, also induces AVP release and can override osmotic and volume sensors. * All anesthetic techniques and drugs tend to decrease GFR and intraoperative urine flow. Some drugs also decrease renal blood flow (RBF), but filtration fraction is usually increased, which implies that angiotensin-induced efferent arteriolar constriction limits the decrease in GFR. However, these effects are much less significant than those caused by surgical stress or aortic cross-clamping and after emergence from anesthesia usually resolve promptly. Any anesthetic technique that induces hypotension will result in decreased urine flow because of altered peritubular capillary hydrostatic gradients, even if renal autoregulation is preserved (as it usually is during anesthesia). Permanent injury seldom results, unless the kidneys are abnormal to begin with or the hypovolemic insult is prolonged and exacerbated by nephrotoxic injury.

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- 14 -

Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Clinically significant renal injury with the use of low-flow sevoflurane anesthesia has not been reported in patients, even with moderate preexisting renal dysfunction. The relationship between compound A formation, biochemical injury, and clinically relevant renal dysfunction remains unclear and unproven. Nonetheless it appears prudent to follow current FDA guidelines, which recommend a fresh gas flow of at least 2 L/min to inhibit compound A formation and its rebreathing and to enhance its washout. * Regardless of the position of the aortic cross-clamp, RBF is decreased to 50% of normal during surgical preparation of the aorta, presumably due to direct compression or reflex spasm of the renal arteries. After release of the suprarenal cross-clamp, RBF increases above normal (reflex hyperemia), but GFR remains depressed to one third of control for up to 2 hours. After 24 hours, GFR is still only two thirds of control. Tubular functions (concentrating ability, sodium, and water conservation) are markedly impaired, but urine flow is maintained. Myers and Moran observed that these changes resemble an attenuated form of acute tubular necrosis. In the above study all patients received mannitol pretreatment, which probably limited the tubular insult because oliguria was uncommon and recovery was relatively rapid. Cross-clamp times longer than 50 minutes are associated with prolonged depression of GFR and transient azotemia. * In contrast to dopamine, there does appear to be increasing evidence to support a renoprotective effect for infusion of low-dose fenoldopam infusion (0.1-0.3 µg/kg/min) during cardiac surgery. A meta-analysis of 13 randomized and case-matched studies on 1059 patients found that fenoldopam infusion is associated with a significant decrease in dialysis requirement, intensive care unit length of stay, and in-hospital mortality. Most studies have been relatively small and identified improved serum creatinine and creatinine clearance rather than renal outcome. The most convincing evidence thus far comes from a randomized, double-blinded study in 193 high-risk patients by Cogliati and associates. Risk factors included elevated preoperative serum creatinine (>1.5 mg/dL), age older than 70 years, diabetes, and previous cardiac surgery. Patients who received fenoldopam had a decreased incidence of acute kidney injury (12.6 versus 27.6%, P = .02) and requirement for dialysis (0 versus 8.2%, P = .004). * The beneficial effect of AVP on renal function in sepsis may in part be due to its ability to increase low renal perfusion pressure back into the autoregulatory range. Another important factor is that, unlike norepinephrine, even at high local concentrations AVP preferentially constricts the efferent arteriole, thereby improving filtration fraction and GFR. However, in a large, prospective, randomized, blinded trial in 778 patients with severe septic shock, lowdose AVP (0.01-0.03 unit/min) did not provide a mortality benefit or decrease the requirement for dialysis when compared with an infusion of norepinephrine (5-15 µg/min). -------------------------------------------------------------------------------------------------------------------------------------------Basic Principles of Pharmacology * The fundamental pharmacokinetic processes are dilution into volumes of distribution and clearance. These processes are governed by the physical properties of the drug and the metabolic capacity of the patient. Anesthetic drugs tend to be highly bound to protein in plasma and highly bound to lipid in peripheral tissues. Most anesthetic drugs are metabolized in the liver. * The pharmacokinetics of anesthetic drugs are typically described by mathematical models with a central compartment and one or two peripheral compartments. These compartments do not directly correspond to any anatomic or physiologic structures. Computer simulations can be used to predict the time course of plasma concentration and drug effect after any dose. * Drugs exert their effects through binding to receptors. The fraction bound is determined by the law of mass action, which yields a sigmoidal relationship between fractional occupancy and drug concentration. * Drugs can be agonists, partial agonists, neutral antagonists, or inverse agonists. Receptors can exist in many states, but for simplicity, one can think of them as having just two states: activated and inactivated. The intrinsic efficacy of a drug is determined by the extent to which it stabilizes the active form of the receptor (agonists) or the inactive form (inverse agonists) or simply displaces agonists from the binding site without favoring either form (neutral antagonists). * A fraction of receptors are in the activated state when drug is present. Thus, a “baseline effect” in the absence of drug does not represent the true baseline if all receptors are inactivated. This can be observed only by giving an inverse agonist that forces nearly all receptors into the inactivated state. * Four main receptor types of relevance in anesthesia are G protein–coupled receptors (opioids, catecholamines), ligand-gated ion channels (hypnotics, benzodiazepines, muscle relaxants, ketamine), voltage-gated ion channels (local anesthetics), and enzymes (neostigmine, amrinone, caffeine). The first three are located in cell membranes. Enzymes can be located anywhere. * Many drugs act through second messengers, which amplify drug action. Common second messengers are G proteins, which can release stimulating or inhibitory subunits in response to drug binding at the receptor; cyclic

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- 15 -

Study Notes – Anesthesiology

James Lamberg

28Jul2010

adenosine monophosphate, which is frequently a target of G protein stimulation or inhibition; inositol 1,4,5triphosphate and diacylglycerol, also targets of G-protein regulation; and intracellular ions, especially calcium. * Advances in molecular pharmacology are helping identify the specific function of individual receptors, the role of individual amino acids in mediating receptor action, and the specific sites of action of many anesthetic drugs. Tools to explore the mechanism of drug action include site-directed mutagenesis to create “designer” receptors and knockout/knock-down (underexpressed) or transgenic (overexpressed) murine models to understand the physiologic action of individual receptors. * The fundamental properties of the concentration-versus-response relationship are potency and efficacy. Potency is the concentration associated with a 50% drug effect. Efficacy is the maximal possible drug effect. * Drugs can interact both pharmacokinetically, through enzymatic induction or inhibition, or pharmacodynamically, through synergy or antagonism. Anesthetic techniques typically take advantage of the synergy between hypnotics and opioids to produce the anesthetic state at far lower doses of each drug than would be required if they were used alone. * Pharmacogenetics is gradually explaining some of the variability in response to drugs. Genetic variability in pharmacokinetics can be attributed to variability in hepatic cytochromes (e.g., CYP2D6, CYP2C19), circulating enzymes (e.g., pseudocholinesterase), or transporters. Genetic variability in pharmacodynamics can be attributed to alterations in receptors, as has been demonstrated for multiple adrenergic receptor variants. Malignant hyperthermia has been clearly linked to variability in the ryanodine receptor. * Variability in response to drugs can also be attributed to nongenetic causes, such as aging, disease, exposure to environmental toxins, and the pharmacokinetic or pharmacodynamic influence of other drugs. Variability is also introduced through continuous exposure to a single drug, which can trigger desensitization (tolerance) or, if the drug is an antagonist, increased receptor sensitivity to the agonist. -------------------------------------------------------------------------------------------------------------------------------------------Inhaled Anesthetics: Mechanisms of Action * Anesthesia consists of separable and independent components or substates, each of which involves distinct, but possibly overlapping, mechanisms at different sites in the central nervous system. * The potency of general anesthetics correlates with their solubility in oil, indicating the importance of their interaction with hydrophobic targets. * General anesthetics act by binding directly to amphiphilic cavities in proteins. Binding sites are being identified by a combination of site-directed mutagenesis and high-resolution structural analysis of anesthetic binding. * The effects of inhaled anesthetics cannot be explained by a single molecular mechanism. Rather, multiple targets contribute to the effects of each agent. * The immobilizing effect of inhaled anesthetics involves a site of action in the spinal cord, whereas sedation/hypnosis and amnesia involve supraspinal mechanisms. * Volatile inhaled anesthetics enhance inhibitory synaptic transmission postsynaptically by potentiating ligand-gated ion channels activated by γ-aminobutyric acid (GABA) and glycine, extrasynaptically by enhancing GABA receptors and leak currents, and presynaptically by enhancing basal GABA release. * Inhaled anesthetics suppress excitatory synaptic transmission presynaptically by reducing glutamate release (volatile agents) and postsynaptically by inhibiting excitatory ionotropic receptors activated by glutamate (gaseous agents). * No comprehensive theory of anesthesia describes the sequence of events leading from the interaction between an anesthetic molecule and its targets to the behavioral effects. -------------------------------------------------------------------------------------------------------------------------------------------Inhaled Anesthetics: Uptake and Distribution * During induction and maintenance of anesthesia, ventilation, the first of five factors that govern the pulmonary inhaled anesthetic concentration, delivers anesthetic to the lung and thereby increases the alveolar concentration. * Uptake of anesthetic by blood passing through the lung opposes the effect of ventilation by drawing anesthetic from the lung. * An increased inspired concentration of anesthetic decreases the effect of uptake (the concentration effect), and at 100% inspired concentration, uptake no longer opposes the effect of ventilation. * Metabolism of anesthetics can increase uptake. * Anesthetic uptake may be enhanced by movement of anesthetic between tissues (intertissue diffusion), especially from highly perfused tissues (e.g., intestine) to poorly perfused tissues with a great capacity for anesthetic (e.g., mesenteric fat).

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Three factors determine uptake by blood: solubility (the blood-gas partition coefficient), pulmonary blood flow (cardiac output), and the difference in anesthetic partial pressure between the lungs and venous blood returning to the lungs. * Solubility differentiates one anesthetic from another in that lower solubility translates to faster recovery from anesthesia. * Changes in ventilation and the distribution of ventilation, cardiac output (and its distribution), and inflow rate each influence anesthetic concentration in predictable ways. -------------------------------------------------------------------------------------------------------------------------------------------Pulmonary Pharmacology * Inhaled anesthetics affect every facet of pulmonary physiology, from the variety of forces controlling ventilation and pulmonary blood flow to surface tension, secretion of mucus, airway smooth muscle tone, and lung inflammatory responses. * The bronchodilatory actions of volatile anesthetics occur through several complex mechanisms that involve both a decrease in intracellular calcium concentration and a reduction in calcium sensitivity. Volatile anesthetics increase baseline pulmonary dynamic compliance, but these agents are more effective at attenuating increases in pulmonary airway resistance caused by chemical or mechanical stimuli. Inhaled anesthetics preferentially dilate the distal airways rather than the proximal airways. * Inhaled anesthetics diminish the rate of mucus clearance by decreasing ciliary beat frequency, disrupting metachronism, or altering the characteristics of mucus. * Pulmonary surfactant decreases the work of breathing by reducing alveolar surface tension. Volatile anesthetics cause progressive, yet reversible reductions in phosphatidylcholine, the main lipid component of surfactant. The roles of depressed mucociliary function and alterations in type II alveolar cell function in postoperative pulmonary complications after the administration of a volatile agent are unknown. * The multiple sites of actions of inhaled anesthetics on the pulmonary parenchyma and vasculature complicate direct assessment of anesthetic-induced alterations in pulmonary vascular resistance. Volatile anesthetics cause a biphasic contraction-relaxation response in pulmonary vascular smooth muscle that is mediated at multiple sites through a Ca2+-mediated signaling pathway. Overall, the net effect of inhaled anesthetic–induced changes in pulmonary vascular resistance is relatively small. * Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism by which pulmonary blood is preferentially redistributed away from poorly ventilated lung regions to those with adequate alveolar ventilation. Most inhaled anesthetics attenuate HPV in vitro and exert relatively modest inhibitory effects on HPV, shunting, or oxygenation in vivo. * Inhaled anesthetics (with the exception of xenon) reduce tidal volume and minute ventilation and cause tachypnea in a dose-related fashion. The relative effect of inhaled anesthetics in increasing arterial carbon dioxide tension (as an index of respiratory depression) is enflurane > desflurane = isoflurane > sevoflurane = halothane > nitrous oxide. * Inhaled anesthetics affect the inspiratory and expiratory respiratory muscles to varying degrees, possibly as a result of the differential sensitivity of bulbospinal inspiratory and expiratory neurons. * All inhaled anesthetics depress the ventilatory responses to hypercapnia and hypoxia by altering central and peripheral chemoreceptor function in a dose-dependent fashion. The effects of subanesthetic concentrations of inhaled agents on hypercapnic responses are controversial. Inhibition of hypoxic responses by subanesthetic concentrations of volatile agents depends on the agent used and perhaps the baseline state of central nervous system arousal. These findings may have important clinical implications during the perioperative period. * Volatile anesthetics may exhibit proinflammatory actions and worsen acute lung injury. Alternatively, volatile anesthetics have been shown to reduce inflammation and improve both chemical and physiologic pulmonary function in acute lung injury. -------------------------------------------------------------------------------------------------------------------------------------------Cardiovascular Pharmacology * In a normal heart, volatile anesthetics produce dose-related depression in left ventricular, right ventricular, and left atrial myocardial contractility; left ventricular diastolic function; and left ventricular–arterial coupling. * The negative inotropic effects of volatile anesthetics are related to alterations in intracellular Ca2+ homeostasis within the cardiac myocyte. * Volatile anesthetics affect the determinants of left ventricular afterload to varying degrees in the presence of normal and dysfunctional myocardium. * The systemic hemodynamic effects of volatile anesthetics are complex and determined by the interaction of myocardial effects, direct actions on the arterial and venous vasculature, and alterations in autonomic nervous system activity.

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- 17 -

Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Volatile anesthetics sensitize myocardium to the arrhythmogenic effects of epinephrine to varying degrees and may prevent or facilitate the development of atrial or ventricular arrhythmias during myocardial ischemia or infarction, depending on the concentration of the agent, the extent of the injury, and the location affected within the conduction pathway. * Volatile anesthetics are relatively weak coronary vasodilators that are not capable of producing coronary steal at typically used clinical concentrations, even in patients with steal-prone coronary artery anatomy. * Volatile anesthetics exert important cardioprotective effects against reversible and irreversible myocardial ischemia in experimental animals and humans when administered before, during, or immediately after the onset of coronary artery occlusion and reperfusion. * Volatile anesthetics depress baroreceptor reflex control of arterial pressure to varying degrees. * Nitrous oxide causes direct negative inotropic effects, does not substantially affect left ventricular diastolic function, and produces modest increases in pulmonary and systemic arterial pressure via a sympathomimetic effect. These actions are dependent to some degree on the baseline anesthetic. * Xenon is essentially devoid of cardiovascular effects but has been shown to protect myocardium against infarction in experimental animals. -------------------------------------------------------------------------------------------------------------------------------------------Inhaled Anesthetics: Metabolism and Toxicity * The liver is the major site of endogenous and exogenous drug metabolism. The primary result of drug metabolism is the production of more water-soluble and therefore more easily excreted drug metabolites. Drugs are sometimes biotransformed into more reactive metabolites that may lead to toxicity. * Most drug metabolism is catalyzed by phase 1 or phase 2 enzymes. The predominant phase 1 enzymes are the cytochrome P450 (CYP) monooxygenases. Approximately 50 of the more than 1000 CYP isoforms are functionally active in humans. The predominant isoform catalyzing the metabolism of inhaled anesthetics is CYP2E1. The major phase 2 enzyme is uridine diphosphate glucuronosyltransferase. * Many factors affect drug metabolism. Perhaps the most important are pharmacogenetic factors. Genetics ultimately determines absorption, distribution, metabolism, and excretion. Other important determinants are environmental factors, age, gender, disease states, and other drugs or medications. Induction and inhibition of CYP enzymes because of concurrent medications can have an important impact on therapeutic drug levels and pharmacologic effects. * Pharmacogenomics, or the influence of DNA sequence variation on the effect of a drug, provides a basis for understanding the interindividual variation observed in drug responses. * Nitrous oxide and xenon are both nonhalogenated anesthetics. Xenon is not currently approved for clinical use; however, aside from the expense associated with its use, it may be the most ideal and environmentally friendly anesthetic agent. * The combination of drug-related antibodies, the apparent need for prior sensitization, and the association of fever and eosinophilia all support an immune basis for anesthetic-induced hepatitis. * Halothane, enflurane, isoflurane, and desflurane are all metabolized to trifluoroacylated hepatic protein adducts that have been reported to induce liver injury in susceptible patients. The propensity to produce liver injury appears to parallel metabolism of the parent drug; thus, halothane (20%) >>> enflurane (2.5%) >> isoflurane (0.2%) > desflurane (0.02%). The incidence of halothane hepatitis in the adult population is roughly 1 in 10,000. Sevoflurane does not produce acylated protein adducts. * Halothane hepatitis has been reported in the pediatric population. The incidence appears to be approximately 1 in 200,000. * Toxicity and liver injury have been reported after repeat exposure on subsequent occasions to different fluorinated anesthetics. This phenomenon of cross-sensitization has also been reported with hydrochlorofluorocarbons, the chlorofluorocarbon replacement agents. * Sevoflurane is metabolized to hexafluoroisopropanol, formaldehyde, inorganic fluoride, and carbon dioxide. Although very high fluoride levels have been reported after sevoflurane anesthesia, fluoride-associated renal injury has not been reported. * The major base-catalyzed breakdown product of sevoflurane is compound A. Compound A is a nephrotoxic vinyl ether that induces both dose- and time-dependent renal injury. The threshold for renal injury in rats and humans appears to be approximately 150 ppm-hours of exposure to compound A (i.e., 50 ppm for 3 hours). The toxic threshold appears to be reached only under clinical conditions of prolonged sevoflurane anesthesia, and changes in glucosuria and enzymuria are observed. Blood urea nitrogen and creatinine levels remain unchanged. To date, no significant clinical renal toxicity has been associated with the use of sevoflurane.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Desiccated carbon dioxide absorbent and inhaled anesthetic interactions can lead to the production of carbon monoxide in the anesthesia circuit (desflurane ⋙ enflurane > isoflurane). Negligible amounts of carbon monoxide are formed from halothane and sevoflurane. * New calcium hydroxide–based CO2 absorbents, such as Amsorb and DragerSorb Free, contain neither NaOH or KOH and thus are chemically inert and do not degrade inhaled anesthetics to carbon monoxide or degrade sevoflurane to compound A. * The interaction of inhaled anesthetics with CO2 absorbents is an exothermic reaction resulting in the production of heat. The temperature of CO2 canisters during routine clinical use averages 25°C to 45°C but increases inversely with decreased fresh gas flow, and sevoflurane is associated with the greatest production of heat. Hydrogen is an important by-product of this reaction. The high yield of hydrogen, ease of ignition, and low tissue solubility make hydrogen the most likely fuel in anesthesia machine fires because of its reactions with desiccated CO2 absorbents and sevoflurane. This reaction can be significant and result in fire, toxic gas, and patient injury. * There appears to be no risk associated with brief periods of low-level occupational exposure to waste anesthetic gases (operating room, postanesthesia care unit, intensive care unit). Occupational exposure to high concentrations (103 ppm) may be correlated with an increased incidence of abortions and decreased fertility. Individuals with vitamin B12 deficiency may be at risk for neurologic injury from nitrous oxide. * Fluorinated inhaled anesthetics containing bromine and chlorine deplete ozone (halothane ⋙ enflurane > isoflurane) and contribute to the greenhouse gas effect and global warming. N2O does not deplete ozone, but it does contribute to the greenhouse gas effect and global warming. -------------------------------------------------------------------------------------------------------------------------------------------Inhaled Anesthetic Delivery Systems * The low-pressure circuit (LPC) is the “vulnerable area” of anesthesia machines because it is most subject to breakage and leaks. The LPC is located downstream from all safety features of anesthesia machines except the oxygen analyzer, and it is the portion of the machine that is missed if an inappropriate LPC leak test is performed. * It is mandatory that the LPC be checked for leaks before administering an anesthetic because leaks in the LPC can cause delivery of a hypoxic mixture or patient awareness during anesthesia (or both). * Because many GE/Datex-Ohmeda anesthesia machines have a one-way check valve in the LPC, a negativepressure leak test is required to detect leaks in the LPC. A positive-pressure leak test will not detect leaks in the LPC of most GE/Datex-Ohmeda products. * Internal vaporizer leaks can be detected only with the vaporizer turned on. * Before administering an anesthetic, the circle system must be checked for leaks and for flow. To test for leaks, the circle system is pressurized to 30 cm H2O, and the circle system airway pressure gauge is observed (static test). To check for appropriate flow to rule out obstruction and faulty valves, the ventilator and a test lung (breathing bag) are used (dynamic test). * Some new anesthesia workstation self-tests do not detect internal vaporizer leaks unless each vaporizer is individually turned on during the self-test. * In the event of pipeline crossover, two actions must be taken. The backup oxygen cylinder must be turned “on,” and the wall supply sources must be disconnected. * Fail-safe valves and proportioning systems help minimize delivery of a hypoxic mixture, but they are not foolproof. Delivery of a hypoxic mixture can result from (1) the wrong supply gas, (2) a defective or broken safety device, (3) leaks downstream from the safety devices, (4) administration of an inert gas, and (5) dilution of the inspired oxygen concentration by high concentrations of inhaled anesthetics. * Because of desflurane's low boiling point and high vapor pressure, controlled vaporization of desflurane requires special sophisticated vaporizers such as the Datex-Ohmeda Tec 6 and the Aladin cassette vaporizer. * Misfilling a conventional variable-bypass vaporizer with desflurane could theoretically be catastrophic and result in delivery of a hypoxic mixture and a massive overdose of inhaled desflurane anesthetic. * Inhaled anesthetics can interact with carbon dioxide absorbents and produce toxic compounds. During sevoflurane anesthesia, compound A can be formed, particularly at low fresh gas flow rates, and during desflurane anesthesia, carbon monoxide can be produced, particularly with desiccated absorbents. * Desiccated strong-base absorbents (particularly Baralyme) can react with sevoflurane and produce extremely high absorber temperatures and combustible decomposition products. In combination with the oxygen- or nitrous oxide– enriched environment of the circle system, these effects can produce fires within the breathing system. * Anesthesia ventilators with ascending bellows (bellows that ascend during the expiratory phase) are safer than descending bellows because disconnections will be readily manifested by failure ascending bellows to refill.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* With ascending bellows anesthesia ventilators, fresh gas flow and oxygen flushing during the inspiratory phase contribute to the patient's tidal volume because the ventilator relief valve is closed. Oxygen flushing during the inspiratory phase can cause volutrama and/or barotrauma, (particularly in pediatric patients). Therefore, the oxygen flush should never be activated during the inspiratory phase of mechanical ventilation. * New ventilators that use fresh gas decoupling technology virtually eliminate the possibility of barotrauma from oxygen flushing during the inspiratory phase because fresh gas flow and oxygen flush flow are diverted to the reservoir breathing bag. However, if the breathing bag has a leak or is absent, patient awareness under anesthesia and delivery of a lower than expected oxygen concentration could occur because of entrainment of room air. * With newer GE/Datex-Ohmeda anesthetic ventilators such as the 7100 and 7900 SmartVent, scavenging of both the patient gas and the drive gas results in substantially increased volumes of scavenged gas. Thus, the scavenging systems must be set appropriately to accommodate the increased volume or pollution of the operating room environment could result. -------------------------------------------------------------------------------------------------------------------------------------------Intravenous Anesthetics * The introduction of thiopental into clinical practice in 1934 marked the advent of modern intravenous (IV) anesthesia. Today, IV anesthetics are used for induction of anesthesia, maintenance of anesthesia, and provision of conscious sedation. * The most commonly used IV anesthetic is propofol, an alkylphenol presently formulated in a lipid emulsion. Propofol provides rapid onset and offset with context-sensitive decrement times of approximately 10 minutes when infused for less than 3 hours and less than 40 minutes when infused for up to 8 hours. Its mechanism of action is thought to be potentiation of γ-aminobutyric acid (GABA)–induced chloride currents. At therapeutic doses, propofol produces a moderate depressant effect on ventilation. It causes a dose-dependent decrease in blood pressure primarily through a decrease in cardiac output and systemic vascular resistance. A unique action of propofol is its antiemetic effect, which remains present at concentrations less than those producing sedation. The induction dose is 1 to 2 mg/kg for loss of consciousness with a maintenance infusion of 100 to 200 µg/kg/min. For conscious sedation, rates of 25 to 75 µg/kg/min are usually adequate. * Until more recently, the most commonly used IV induction agents were the barbiturates. Thiopental provides rapid onset and offset when used as a single dose, but it accumulates rapidly with prolonged administration and leads to slow recovery. Methohexital has a rapid onset and offset similar to propofol for procedures lasting less than 2 hours. The barbiturates are administered as sodium salts diluted in a water base at an alkaline pH. Similar to propofol, the barbiturates are thought to provide their hypnotic effects largely through action on the GABAA receptor. Barbiturates provide cerebral protection and are output from induction of anesthesia used primarily for this purpose. They cause a moderate dose-dependent decrease in blood pressure (primarily as a result of peripheral vasodilation) and respiratory drive. The barbiturates are contraindicated in patients with porphyria. The induction dose of thiopental is 4 mg/kg, and the induction dose for methohexital is 2 mg/kg. Methohexital can be used for maintenance of anesthesia at 100 to 200 µg/kg/min or for conscious sedation at 25 to 75 µg/kg/min. * The benzodiazepines are used primarily for anxiolysis and amnesia or for conscious sedation. The water-soluble benzodiazepine midazolam is the most frequently used intravenously because of its rapid onset and offset and lack of active metabolites compared with other benzodiazepines (e.g., diazepam). The onset of midazolam is slower than that of propofol and barbiturates, and its offset, especially when used at higher doses or in a prolonged infusion, is considerably longer than that of propofol or methohexital. The benzodiazepines act through the GABA receptor. Flumazenil is a specific benzodiazepine antagonist. It can be used to reverse the effects of benzodiazepines. The benzodiazepines generally produce only a mild decrease in blood pressure and mild-to-moderate respiratory depression. The dose of midazolam for anxiolysis and mild sedation is 0.015 to 0.03 mg/kg intravenously and is generally repeated in 30 to 60 minutes as needed. * Ketamine is a phencyclidine derivative that is uniquely different from the above-mentioned hypnotics. It produces a dissociative state of hypnosis and analgesia. It has been used for induction and maintenance of anesthesia. Ketamine acts primarily, but not entirely, through the N-methyl-d-aspartate (NMDA) receptor. Ketamine is associated with significant adverse psychological effects at higher doses and several other side effects. It is used now primarily for its analgesic properties. It has rapid onset and relatively rapid offset, even after an infusion of several hours. It has sympathomimetic action that preserves cardiac function. Ketamine has minimal effect on respiration and tends to preserve autonomic reflexes. The induction dose is 2 to 4 mg intravenously. An infusion of ketamine provides analgesia and can be given with propofol in a total IV anesthesia technique. A dose of 10 to 20 mg preoperatively has been shown to provide preemptive analgesia. * Etomidate is an imidazole derivative used primarily for induction of anesthesia, especially in elderly patients and patients who have cardiovascular compromise. It has a rapid onset of effect and a rapid offset even after a

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- 20 -

Study Notes – Anesthesiology

James Lamberg

28Jul2010

continuous infusion. Prolonged infusion results in inhibition of adrenocortical synthesis and potential mortality in intensive care unit (ICU) patients. The major advantage of etomidate is its minimal effect on the cardiovascular and respiratory systems. It is associated with a high incidence of burning on injection, thrombophlebitis, and postoperative nausea and vomiting (PONV), limiting its popularity. The induction dose is 0.2 to 0.3 mg/kg. * Dexmedetomidine is the most recently released IV anesthetic. It is a highly selective α2-adrenergic agonist that produces sedation, hypnosis, and analgesia. Dexmedetomidine is presently approved only for brief (35%) and bilateral knee replacement (41%). * PACU Standards of Care require that a physician accept responsibility for the discharge of patients from the unit (Standard V). This is the case even when the decision to discharge the patient is made at the bedside by the PACU nurse in accordance with hospital-sanctioned discharge criteria or scoring systems. -------------------------------------------------------------------------------------------------------------------------------------------Postoperative Nausea and Vomiting * Postoperative nausea and vomiting (PONV) may be triggered by various pathways through peripheral and/or centrally located receptors; however, the exact etiology is unknown. * Numerous patient-, anesthesia-, and surgery-related risk factors are associated with a high incidence of PONV, but this association may not be causal. For example, the high incidence of PONV after gynecologic surgery is likely observed because the surgery is conducted in women, who are more susceptible to PONV, and not because of the surgery itself. * Instead of assessing a wide range of associated risk factors, a patient's risk for PONV is best predicted by a simplified risk score using independent predictors (statistically corrected for confounders). * In adult inpatients undergoing a general inhaled anesthesia, Apfel's simplified risk score includes female gender, nonsmoking status, history of PONV/motion sickness, and the use of postoperative intravenous opioids as the main independent predictors. When 0, 1, 2, 3, or 4 of these factors are present, the risk for PONV is about 10%, 20%, 40%, 60%, or 80%, respectively. * In children, a similar simplified risk score exists for postoperative vomiting (POV) with duration of surgery greater than or equal to 30 minutes, age older than or equal to 3 years, strabismus surgery, and a positive patient history of POV or POV/PONV in relatives as the main predictors. * Because main triggers for PONV appear to be inhaled anesthetics and opioids, strategies to avoid or reduce exposure (e.g., regional or total intravenous anesthesia) are effective means to reduce the risk for PONV. * A PONV prophylaxis strategy should be tailored based on a patient's baseline risk, which can be determined using a simplified risk score. Patients at greatest risk will experience the greatest absolute risk reduction from interventions (absolute risk reduction = baseline risk x relative risk reduction). * Effective antiemetics to reduce PONV are cyclizine, dimenhydrinate, droperidol, dexamethasone, metoclopramide, ondansetron, dolasetron, tropisetron, and granisetron. The relative risks (RR) of these antiemetics versus placebo for nausea and for vomiting vary between approximately 0.60 and 0.80. * Neurokinin (NK1) antagonists are similarly effective against nausea compared with other antiemetics but are considerably more effective against postoperative vomiting.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* While the minimally effective dose for prophylaxis with ondansetron is 4 mg, the minimally effective dose for rescue treatment with ondansetron is only 1 mg. Based on this observation, it has been generalized that about a quarter of the prophylactic dose is needed for rescue treatment. * Patient who suffer from PONV in spite of intraoperative prophylaxis with ondansetron do not respond to rescue treatment with a second dose of ondansetron or granisetron in the postanesthesia care unit. It is therefore concluded that rescue treatment targeting an already blocked receptor is ineffective so that an antiemetic strategy using a different mechanism should be used instead. -------------------------------------------------------------------------------------------------------------------------------------------Acute Postoperative Pain * The process of nociception is not a hard-wired characteristic but a plastic and dynamic process (i.e., neuroplasticity) with multiple points of activation and modulation. Persistent noxious input may result in relatively rapid neuronal sensitization and possibly chronic pain. * Postoperative pain, especially when poorly controlled, results in harmful acute effects (i.e., adverse physiologic responses) and chronic effects (i.e., delayed long-term recovery and chronic pain). * By preventing central sensitization, preemptive analgesia may reduce acute and chronic pain. Although experimental studies overwhelmingly support the concept of preemptive analgesia, the evidence from clinical trials is equivocal because of methodologic issues. * By allowing individual titration of analgesic agents, use of patient-controlled anesthesia (intravenous or epidural) may provide several advantages over traditional provider-administered analgesia (e.g., intramuscular injections) in the management of postoperative pain. * The incidence of respiratory depression from opioids does not appear to be significantly different among the various routes of administration (i.e., intravenous versus intramuscular versus subcutaneous versus neuraxial). Appropriate monitoring of patients receiving opioid analgesics is essential to detect those with opioid-related side effects such as respiratory depression. Whether patients receiving neuraxial opioid analgesics require monitoring in an intensive care unit is debatable, although there is literature demonstrating the relatively safe use of single-dose and continuous-infusion neuraxial opioids on routine surgical wards under appropriate monitoring conditions. * Judicious use of adjuvant agents, such as nonsteroidal anti-inflammatory drugs, may improve postoperative analgesia and diminish analgesic-related side effects. * When compared with systemic opioids, perioperative epidural analgesia may confer several advantages, including a facilitated return of gastrointestinal function and decrease in the incidence of pulmonary complications, coagulation-related adverse events, and possibly cardiovascular events, especially in higher-risk patients or procedures. However, the risks and benefits of epidural analgesia should be evaluated for each patient, and appropriate monitoring protocols should be used during postoperative epidural analgesia. * Epidural analgesia is not a generic entity because different catheter locations (catheter-incision congruent versus catheter-incision incongruent), durations of postoperative analgesia, and analgesic regimens (local anesthetics versus opioids) may differentially affect perioperative morbidity. * Postoperative pain management should be tailored to the needs of special populations (e.g., ambulatory surgical, elderly, opioid-tolerant, pediatric, and obese patients, as well as those with obstructive sleep apnea) who may have different anatomic, physiologic, pharmacologic, or psychosocial issues. -------------------------------------------------------------------------------------------------------------------------------------------Postoperative Intravascular Fluid Therapy * Water is the most abundant component in the body: total body water accounts for approximately 50% of the lean body weight in women and 60% in men. Derangements in the fluid homeostasis are common in the postoperative period. * The goal of fluid management in the postoperative period is to provide the optimal amount and type of fluid to the patient. Thus, patients should remain euvolemic with a normal electrolyte distribution. * Besides physical examination and routine patient monitoring, different devices are available for advanced hemodynamic monitoring. They can be clinically used in a stepwise escalating approach—from invasive blood pressure measurement, to central venous cannulation, to less invasive, advanced hemodynamic monitoring, to pulmonary artery catheterization, to transesophageal echocardiography. * For adequate assessment of a patient's fluid balance, all available variables (i.e., cardiac filling, heart function, or end-organ perfusion) have to be considered like the “pieces of a puzzle.” * Maintenance fluid therapy in the postoperative period aims at preserving the water and electrolyte balance. It should replace the ongoing losses of water and electrolytes under normal physiologic conditions. * Replacement fluid therapy in the postoperative period corrects any existing and additionally occurring water and electrolyte deficits. These deficits result from bleeding, third space sequestration, evaporative losses (e.g.,

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- 50 -

Study Notes – Anesthesiology

James Lamberg

28Jul2010

mechanical ventilation without humidifier, surgical field if wound is left open), profuse sweating, and additional gastrointestinal as well as other fluid losses. * Fluid therapy must be individualized to each patient and balanced according to the benefits and risks of intravascular fluid administration. Therefore, the patient's characteristics and the type of procedure that has been performed should determine whether to choose a more liberal or a more restrictive fluid regimen. * To optimize the fluid status and to avoid fluid overload, frequent re-evaluations are required, especially during a “fluid trial,” which is the intravenous administration of a specified amount of fluid over a short period of time. * A variety of manufactured fluid formulations exist for intravenous fluid therapy that differ in two fundamental ways: the component electrolyte solution and the suspended material providing colloid osmotic (oncotic) pressure. -------------------------------------------------------------------------------------------------------------------------------------------Cognitive Dysfunction and Other Long-Term Complications of Surgery and Anesthesia * The selection, measurement, and analysis of neuropsychological tests (NP tests) will influence findings with postoperative cognitive dysfunction (POCD). * Patients’ subjective reports after surgery are unrelated to assessed neuropsychological change and appear to be driven by mood. * There is good evidence of POCD after cardiac surgery where the mechanism is multifactorial but includes microemboli. * POCD after noncardiac surgery is evident in larger studies with good methodology although the mechanisms are less clear than after cardiac surgery. * Increased age is a risk factor for POCD. -------------------------------------------------------------------------------------------------------------------------------------------Postoperative Visual Loss * Visual loss after anesthesia is a rare but devastating injury that appears more frequently after cardiac, spine, and head and neck surgery. * The causes of perioperative visual loss include central or branch retinal artery occlusion, anterior and posterior ischemic optic neuropathy, cortical blindness, and acute glaucoma. Transient visual loss may be experienced after transurethral resection of the prostate. Retinal vascular occlusion in patients who receive nitrous oxide–containing gas mixtures after a vitrectomy procedure with vitreal gas bubble tamponade is caused by acute expansion of the gas bubble and increased intraocular pressure. * Signs and symptoms of visual loss in the postoperative period may be subtle and can be incorrectly attributed to the residual effects of anesthetic agents. Any patient complaining of eye pain, an inability to perceive light or motion, complete or partial loss of visual fields, decreased visual acuity, or loss of pupil reactivity must be evaluated immediately by an ophthalmologist. * The most common causes of central and branch retinal artery occlusion are emboli from the operative site and compression of the eye. External pressure on the eyes must be scrupulously avoided. * The causes of ischemic optic neuropathy have not been clearly determined. This disease may be related to, among other factors, hypotension, blood loss, fluid replacement, patient positioning, emboli, the use of vasopressors, disturbed autoregulation in the optic nerve circulation, anatomic variation in the optic nerve, and systemic patient factors such as hypertension and atherosclerosis. * Patients who undergo prolonged operative procedures in the prone position with anticipated large blood loss are at higher risk for the development of ischemic optic neuropathy. There is controversy with respect to the appropriate level of blood pressure and hemoglobin, fluid replacement, and use of vasopressors in these patients. The anesthesiologist should consider the potential risk for ischemic optic neuropathy in the design of the anesthetic plan and weigh the risks versus benefits of interventions that decrease blood pressure and hemoglobin concentration perioperatively. Anesthesiologists should consider informing patients of the risk of visual loss accompanying lengthy surgical procedures with the patient positioned prone and with anticipated large blood loss. Because surgeons may be in a better position to discuss this complication with their patients, anesthesiologists should consider asking surgeons to mention the risk of visual loss at their preoperative visit with the patient. * Perioperative visual loss in the presence of focal neurologic signs or the loss of accommodation reflexes or abnormal eye movements suggests a diagnosis of cortical blindness. Neurologic consultation should be obtained. -------------------------------------------------------------------------------------------------------------------------------------------Overview of Anesthesiology and Critical Care Medicine * By the year 2030, only 35% of the intensivists needed will be available to staff intensive care units. * Mandatory intensivist consultation may reduce intensive care unit mortality by as much as 29%. * Cortisol replacement, tight glycemic control, and activated protein C are actively being studied in randomized controlled trials as therapy for sepsis.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Patients with acute lung injury or acute respiratory distress syndrome should be mechanically ventilated with tidal volumes of 6 mL/kg of ideal body weight. * Without liver transplantation, mortality from acute liver failure is high and mainly due to multisystem organ failure, sepsis, and cerebral edema. * Earlier institution of dialysis and higher filtration volumes appear to be associated with reduced mortality among patients with acute renal failure. * Quality improvement initiatives can reduce nosocomial infections, mortality, and cost. * Proposals to prevent ventilator-associated pneumonia include maintenance of gastric pH with sucralfate, positioning the head of the bed at 30 degrees, and subglottic aspiration of secretions. * A comprehensive approach to central venous catheter insertion, including ultrasound guidance, maximum sterile barrier precautions, and antibiotic-coated catheters, can reduce the rate of catheter-related bloodstream infections. -------------------------------------------------------------------------------------------------------------------------------------------Critical Care Protocols * Protocols allow for standardization of research protocols and minimization of confounding variables. * A multidisciplinary team is required and a specific educational plan is necessary to properly implement all facets of a protocol. * Protocols must be devised with the intention of not only improving the quality of patient care but also improving patient outcome and the efficiency of care, while at the same time decreasing practice variation and costs. * The ability to measure the effect of a particular protocol and adapt appropriately is the key to successful protocol application. * Quality measures that were found to be valuable (based on effect, feasibility, and strength of evidence) included: (a) percentage of patients with ventilator-associated pneumonia, (b) percentage of patients with resistant infections, (c) percentage of patients with central venous catheter infections, (d) number of complications per patient, (e) average days of mechanical ventilation, (f) rate of gastrointestinal bleeding, (g) average intensive care unit (ICU) length of stay, and (h) patient satisfaction. * With appropriate standards, definitions, defined pathways, and explicit interventions, the interpretation of research findings, whether prospective randomized or observational, will enhance clinical equipoise. -------------------------------------------------------------------------------------------------------------------------------------------Respiratory Care * Acute respiratory failure requiring ventilatory support occurs if a pathologic process, or a pharmacologic intervention (a) impairs the capacity of the respiratory muscles to generate sufficient Pmus; (b) increases the ventilatory requirements above the muscle capacity; (c) increases the workload associated to the act of breathing. * Ventilator-induced lung injury (VILI) acts as the “engine” of multiple organ dysfunction syndrome (MODS). * In normal subjects at rest, the end-expiratory lung volume (EELV) closely corresponds to the elastic equilibrium point of the respiratory system (functional residual capacity [FRC]). Whenever the time available for expiration is shorter than the time required for passive emptying back to FRC, air trapping will develop. Consequently, alveolar pressure will remain positive at the end of expiration, which generates a “dynamic hyperinflation,” that is, a positive end-expiratory alveolar pressure, called intrinsic PEEP (PEEPi) or auto-PEEP. * Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by abnormal mechanical properties of the respiratory system with the hallmark features of a reduced FRC and a reduced static compliance of the respiratory system. Measurements of the inspiratory volume-pressure curves of the respiratory system have been used in mechanically ventilated patients with ALI/ARDS as a means of assessing their status and progress and to optimize the use of PEEP and mechanical ventilation. * The ARDSNet study was to enroll up to 1000 patients, but accrual was stopped at 861 patients when an interim analysis revealed that the mortality rate in the lung protective group was 22% lower than in the control group. The beneficial results using 6 mL/kg ventilation (predicted body weight) occurred in all patient groups, including septic and nonseptic patients, and those with different degrees of lung dysfunction as assessed by respiratory system compliances. * At present the optimal level of PEEP and the best method used to set PEEP have not been definitively established for ARDS and ALI patients. Prone positioning has been demonstrated to improve oxygenation in patients with acute hypoxic respiratory failure but does not improve mortality, so that this therapeutic option might be considered useful only for ARDS patients with refractory hypoxemia. Similarly, inhaled nitric oxide led to improvements in oxygenation in ARDS patients but there was no beneficial effect on mortality. Thus, inhaled nitric oxide cannot be recommended for the routine treatment of ALI/ARDS but it may be useful as a rescue therapy in patients with refractory hypoxemia.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Applying noninvasive pressure support ventilation (PSV) (to unload inspiratory muscles and to increase tidal volume [Vt]) and PEEP (to counterbalance the inspiratory threshold load for the inspiratory muscles posed by PEEPi) in the early course of exacerbations of chronic obstructive pulmonary disease (COPD) reduces intubation rates, the frequency of complications, the in-hospital mortality, and the length of stay. * Noninvasive techniques, both continuous positive airway pressure (CPAP) and noninvasive positive-pressure ventilation (NIPPV), have been shown to reduce the need of intubation and improve outcomes in patients with acute cardiogenic pulmonary edema (ACPE). Some authors suggest that CPAP should be considered as the first-line treatment in patients with ACPE because it is less expensive and easier to implement and as efficacious as NIPPV. However, it might be better to use NIPPV in hypercapnic patients with ACPE. -------------------------------------------------------------------------------------------------------------------------------------------Neurocritical Care * Critical care of the nervous system is based on support of cerebral and spinal cord physiology and the prevention of secondary insult. This, in turn, depends on the comprehensive maintenance of cardiopulmonary, gastrointestinal, renal, and endocrine functional adequacy. * Cerebral function is critically dependent on perfusion and oxygenation. Increased intracranial volume beyond the capacity of compensatory mechanism will increase intracranial pressure (ICP) and may diminish perfusion adversely. Resulting cellular energy failure will both initiate and propagate edema and inflammation. * The resolution of cerebral edema depends on hydrostatic and osmolar forces applied to the blood-brain barrier. Excesses of perfusion pressure or intravascular hypotonicity will worsen edema and must be avoided. Blood-brain barrier disruption will vary over time and will markedly affect the ability of hypertonic agents to exert an osmotic effect. * Fever is frequently overlooked in the neurocritical care unit but significantly affects outcome across a range of pathologic processes. * Neurologic monitoring comprises placement of appropriate monitoring devices as well as prompt response and institution of therapy to changes detected. The goal is to optimize the physiologic environment, despite the current lack of level 1 evidence to support the majority of monitors in common use. Clinical examination of neurologic function remains a crucial part of monitoring and care. * Incidence of traumatic brain injury has declined but remains a disease of the young, with enormous long-term socioeconomic impact. Prompt surgical appraisal is mandatory; and although hypothermia remains controversial, decompressive craniotomy may be lifesaving in patients with elevated ICP refractory to medical treatment. Corticosteroids are contraindicated. * After the initial hemorrhage, mortality and morbidity from subarachnoid hemorrhage (SAH) arise chiefly from subsequent vasospasm. Medical therapy for this complication involves augmentation of perfusion pressure, maintenance of blood volume, and optimization of oxygen delivery. Endovascular therapy with angioplasty with or without chemical vasodilation plays an increasingly important role. SAH may be accompanied by significant pulmonary, cardiovascular, or endocrine effects. * Successful therapy for ischemic stroke is contingent on a time window of viability. Urgent appraisal and rapid treatment is crucial to good outcome. * Injury to the spinal cord necessitates careful observation of respiratory adequacy, because conditions may deteriorate before any observed improvement. Fatigue is frequently a factor. * Infectious disease of the central nervous system demands an aggressive approach to resuscitation, cerebrospinal fluid sampling, and early empirical antibiotic therapy, similar to that in the patient with septic shock. -------------------------------------------------------------------------------------------------------------------------------------------Nutrition and Metabolic Control * Sepsis, trauma, and surgery activate complex metabolic and inflammatory responses that affect all body systems. * The metabolic response to stress response is characterized by catabolism, hypermetabolism, hyperglycemia (diabetes of injury), and enhanced lipolysis. * The counterregulatory hormones (cortisol, glucagon, catecholamines) along with the cytokines (e.g., IL-1, TNF) are major mediators of this response. * Certain intraoperative anesthetic and postoperative analgesic techniques can modulate the stress response. * During the acute phase of illness, patients unable to eat should receive parenteral or enteral nutritional support. * Nutritional support during the acute phase of critical illness is a supplementary therapy designed to provide patients suffering from underlying metabolic disarray with sufficient nutrients to aid cellular biochemical functions and attenuate further loss of body mass. * Only once the ravages of the stress response have abated can lost lean and fat mass be repleted. * Overfeeding or aggressive refeeding should be avoided.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

-------------------------------------------------------------------------------------------------------------------------------------------Renal Replacement Therapies * The removal of sodium and water cannot be dissociated when using diuretics or in certain renal replacement techniques. Diuretics lead to a natriuresis, whereas dialysis may result in hypotonia or hypertonia, depending on the effect of dialysis on the diffusion and on the removal of molecules, including urea and other electrolytes. * Slow continuous ultrafiltration (SCUF) produces an ultrafiltration (UF) that varies from plasma water minimally due to Donnan effects. The UF from SCUF is iso-osmotic and isonatremic because sodium elimination is linked to the sodium concentration in plasma. * The ultrafiltrate composition produced from continuous venovenous hemofiltration (CVVH) and from hemofiltration in general is similar to plasma water, but the sodium concentration in the UF can be significantly affected by the sodium concentration in the replacement solution. * Sodium removal can be dissociated from water removal in CVVH, thus obtaining a real change of the sodium pool in the body. This effect on sodium cannot be achieved with any other technique. * The best evidence to date supports a renal replacement therapy dose of at least 35 mL/kg/hr—spKt/V 1.4—for CVVH, continuous venovenous hemodiafiltration (CVVHDF), or daily intermittent hemodialysis (IHD). * There is evidence that, when the circuit set-up is perfectly optimized, anticoagulants are only a relatively minor component of circuit patency: in fact, when patients have bleeding disorders (i.e., prolonged clotting times, thrombocytopenia), renal replacement therapy can be safely performed without the utilization of any anticoagulant. * The UNLOAD trial is the first randomized comparison of intravenous diuretic therapy alone against an alternative therapy, ultrafiltration, in hypervolemic patients. The principal findings of this trial were (a) in hypervolemic patients with congestive heart failure (CHF), ultrafiltration led to greater weight and fluid loss than intravenous diuretics at the doses used in this trial; (b) volume removal with ultrafiltration at the index hospitalization was associated with significant reductions in the rate and durations of subsequent hospitalizations and fewer unscheduled medical visits for CHF; and (c) the benefits from the short-term use of ultrafiltration over 90 days was achieved without significant adverse effects. * It is now possible to generate ultrapure replacement fluid and administer it in the intensive care unit (ICU) with a lower cost than continuous renal replacement therapy (CRRT), in greater amounts and for shorter periods of time. The choices are now almost limitless; 3 or 4 hours of IHD with standard settings or CRRT at 35 mL/kg/hr of effluent flow rate can be selected. Slow low-efficiency extended daily dialysis (SLEDD) at blood and dialysate flow rates of 150 mL/min for 8 hours during the day or SLEDD for 12 hours overnight can be considered as an alternative. -------------------------------------------------------------------------------------------------------------------------------------------Cardiopulmonary Resuscitation: Basic and Advanced Life Support * Chest compressions performed with minimal interruption are critically important in improving the chance of survival from sudden cardiac arrest. * Thirty chest compressions followed by two rescue breaths is the recommended ratio for single rescuers resuscitating children and adults. * Chest compressions should be performed at a rate of 100/min for children and adults. * The American Heart Association 2005 guidelines recommend that a single shock be delivered when a shockable dysrhythmia exists, followed by resumption of chest compressions as soon as the shock is delivered. Two minutes of chest compressions and ventilation should be performed before reassessing the underlying cardiac rhythm. * Automated external defibrillators (AEDs) may follow an outdated defibrillation protocol (e.g., three defibrillation shocks before resumption of cardiopulmonary resuscitation [CPR]). In this circumstance, the rescuer should allow the AED to function as programmed until a manual defibrillator becomes available. * When a rescuer is unfamiliar with the type of manual defibrillator used during resuscitation, a default energy of 200 J is a reasonable energy level for defibrillation. * In an unwitnessed cardiac arrest or in situations in which initiation of CPR has been delayed, 2 minutes of CPR before the first defibrillation has been shown to have survival benefit. * Hyperventilation during resuscitation increases intrathoracic pressure, impairs venous return to the heart, and has a negative impact on survival from cardiac arrest. The resuscitation team leader must ensure that only 8 to 10 breaths per minute are being delivered during resuscitation attempts. * Therapeutic hypothermia has demonstrated benefit in improving the neurologic outcomes of victims resuscitated from out-of-hospital ventricular fibrillation who remain comatose on hospital admission. This therapeutic intervention should be considered for victims of in-hospital ventricular fibrillation cardiac arrest with decreased neurologic function after resuscitation.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Resuscitation knowledge declines rapidly, even in anesthesia providers. Review of advanced cardiac life support (ACLS) resuscitation protocols may be necessary in the interim between ACLS certification. ACLS protocols should be made available on resuscitation carts to ensure that more uniform and accepted resuscitation interventions are followed during resuscitation attempts. -------------------------------------------------------------------------------------------------------------------------------------------Brain Death * The first description of cessation of brain functions using a concept similar to the modern definition of brain death appeared in 1959, although the subject became more controversial after the development of organ transplantation. Criteria for brain death were first published in 1968, a year after the first heart transplantation. Although cultural and religious diversity may lead to great differences in attitudes toward brain death and there is no global consensus in diagnostic criteria, the concept of brain death as defining the death of the individual is widely accepted, and many countries have published recommendations or legal requirements for the diagnosis of brain death, in particular, as a necessary prerequisite for organ donation. * The traditional concept of death has used the cessation of cardiac and respiratory functions as its basis because of the acceptance of simple and nonmedical concepts: that life begins with the first inspiration after birth, that death comes with the last expiration, and that cardiac activity ceases within a few minutes of the last expiration. In contrast, the modern concept of brain death adopts the conclusions of modern biologic science (central integrator theory of the brain): that the central nervous system (CNS), including the brainstem, is the control center for the living organism; that cessation of CNS functions represents cessation of the harmony of life; and that without CNS control, the living organism is nothing more than an aggregation of living cells. However, this notion has become controversial, because not all brain-dead patients inevitably deteriorate to cardiovascular collapse in a short time and they can assimilate nutrients, fight infections, heal wounds, and carry out a pregnancy. * Trauma to the brain or cerebrovascular injury produces brain edema. Because the brain is covered by a rigid bony skull, edema is accompanied by an increase in intracranial pressure, which, if sufficiently high, exceeds arterial blood pressure. When cerebral circulation ceases, aseptic necrosis of the brain ensues. Within 3 to 5 days, the brain becomes a liquefied mass. Such increased intracranial pressure compresses the entire brain, including the brainstem, and total brain infarction follows. * Clinical studies indicate that hypothalamic and anterior pituitary functions are preserved to some degree for a certain period after the onset of brain death. The response of the immune system to stimulation is modified considerably after total and irreversible loss of CNS functions. Hormonal changes and inflammatory responses after brain death are the theoretical and scientific basis of hormonal therapy for hemodynamic stabilization of brain-dead organ donors. * During the process of brain death after head injury or intracranial bleeding, intracranial pressure increases and compression of the brainstem leads to marked hypertension and bradycardia (i.e., Cushing phenomenon). At the onset of brain death by tonsillar herniation, sudden decrease of arterial blood pressure occurs, but the arterial pressure gradually returns to normal with the spinal cord gaining automaticity. * Determination of brain death confirms the irreversible cessation of all functions of the entire brain, including the brainstem. Irreversibility means that no treatment may be reasonably expected to change the condition. Although testing all functions of the brain is conceptually impossible, the cessation of all functions of the brain is practically determined by loss of consciousness, loss of brainstem responses, apnea, and confirmatory tests. * Cerebral death, the so-called persistent vegetative state, refers to cessation of the functions of the cerebral cortices. It is not the equivalent of death. * It is true that cultural and religious diversities may affect the notion of death, but there is a significant variability in policies and practices for determining brain death internationally and even among states and hospitals. * Tests to confirm brain death include an electroencephalogram, evoked responses, and measurement of blood flow. * Because of their intact spinal cord and the presence of somatic and visceral reflexes, brain-dead patients require special anesthetic management, including use of muscle relaxants, vasodilators, and perhaps sedation and analgesia. Anesthesiologists should understand the medical and legal definitions of death, as well as the ethical concepts behind them. -------------------------------------------------------------------------------------------------------------------------------------------Operating Room Management * Reorganizing the governance structure of the OR to consolidate control and authority into one position, such as the OR medical director, has many advantages in making the OR function at an optimal level. * Improvement in the OR scheduling process may lead to the biggest gains in OR efficiency. Block time scheduling allows better predictability and satisfaction for OR personnel.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* On-time OR starts, surgical case performance benchmarks, and room turnover are all critical elements in making an OR run efficiently. * Traditional OR utilization assessments may not reflect how well an OR is working. Newer methods that focus on OR productivity are increasingly being used to determine allocation of OR resources. * Managing the daily surgical schedule requires careful planning, as well as frequent re-evaluation, to deal with the variability in case times, add-ons, and cancellations. * The OR director must create a professional environment in the OR and not allow disruptive behavior patterns to exist. * A detailed OR information system is essential in tracking OR activity and creating reports for assessment and improvement projects. OR cost accounting is essential to the OR director in guiding decisions for resource application. -------------------------------------------------------------------------------------------------------------------------------------------Electrical Safety in the Operating Room Fire Safety Issues * When setting up the anesthesia machine and drug cart before a case, be sure to know about the operation and the location of emergency equipment. Questions to ask oneself include the following a) Where is the nearest fire extinguisher—there should be one in every operating room? b) Where are the oxygen shut-off valves and how do I operate them to stop oxygen flow to the operating room? c) Where is the nearest fire alarm should it be impractical to call the hospital's equivalent of “911” (fire alarms are often recessed in the wall near fire hoses)? d) Where is the nearest escape passage? e) Where is the nearest defibrillator and code cart? * Recall that electrical fires, particularly those that involve the electric panel, require a special approach. If possible, quickly cut all electric power that feeds an electrical fire (which then converts it into an ordinary fire). In fighting a fire, the proper type of fire extinguisher must be used. The most common type of fire extinguisher sprays water. However, water must never be thrown or sprayed onto an electrical fire or onto burning flammable liquids. Electrical fires require a dry chemical extinguisher, but CO2 extinguishers, which are optimal for control of burning oils and liquids, may also be used. * Avoid use of high “blow-by” oxygen flow from an open facemask if after “blowing by” the patient, the flow ends up providing oxygen enrichment at a site of electrosurgery. Macroshock Electrical Issues * All electrical equipment used in the operating room should be grounded (although internally such equipment can contain ungrounded circuits). If the power cord for a piece of equipment has a plug with only two prongs (i.e., no grounding prong to go in the third hole in the outlet), the equipment should not be in the operating room. When connecting or disconnecting plugs from outlets, do not yank the plug by the cord. Similarly, do not use equipment whose power plugs have been damaged, and do not let heavy equipment crush power cords by rolling over them. * Patients should not be directly connected to the operating room's electrical ground. * When electrosurgery is in use, a grounding pad should be used that connects the patient to the ground connection provided on the electrosurgery machine. The grounding pad should be well gelled and placed in contact with the patient across a large area. The grounding pad should be inspected during lengthy operations and gelled again or replaced if necessary. The electrosurgical grounding pad should be placed as near the operative site as reasonably possible and as far as possible from any pacemaker wires and ECG wires. When grounding pads are removed, the underlying skin should be inspected for burns. * The anesthesiologist should be concerned if increasing current levels are required for electrosurgery and take it as a cue to check for faulty connection of the electrosurgical grounding pad. In the event of very “wet” operations, with or without increasing current levels for electrical surgery, the physician should beware of errant current paths that include the grounding pad and other electrical contacts (e.g., ECG electrodes). For example, saline and body fluids in an abdominal procedure can extend under the drapes beyond the operative site and potentially form an electrical connection to a grounding pad or ECG electrodes. * If the line isolation monitor (LIM) sounds an alarm after someone activates equipment, the offending piece of equipment should be unplugged immediately. Plugging in that equipment has allowed the secondary side of the main isolation transformer to be coupled to the ground. It is also possible that so many items were plugged in simultaneously that the secondary side of the main transformer was coupled to ground by their combined capacitance. The anesthesiologist can try various combinations of unplugging one piece of equipment and plugging in another. However, if it is found that one piece of equipment causes the LIM to sound an alarm under several

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

combinations, that piece of equipment should be removed from the operating room and examined for an unwanted connection to the ground contact. * All electrical equipment should be tested periodically by experienced personnel, usually a clinical bioengineering group associated with the operating rooms. Anesthesiologists should verify that equipment has been maintained properly, that standards of performance have been met, and that the entire electrical environment also meets National Fire Protection Association standards. Microshock Electrical Issues with Pacemakers * Patients with an automated implanted cardioverter-defibrillator (AICD) need to have the AICD turned off before surgery starts after first having established Zoll pad connections. Turning off the AICD feature is commonly done by magnet placement but can also be done by reprogramming. It should be appreciated that magnets do not change the pacing program that is in an AICD. Thus, preoperative cardiac electrophysiology consultation is essential for establishing appropriate pacing. * If possible, bipolar electrocautery units should be used instead of unipolar electrocautery. * All programmable pacemakers should be interrogated preoperatively to ensure proper function. * Pacemaker-dependent patients need to have asynchronous pacing programmed along with all rate-sensing features disabled. A conventional defibrillator should be available. * Other pacemaker patients should have a pacing strategy established by preoperative cardiac electrophysiology consultation. * A plan for pharmacologic treatment of complete heart block should be in place, particularly for pacemakerdependent patients, and isoproterenol should be readily available on the anesthesia drug cart. * If electrophysiologic monitoring is being done, the anesthesiologist should review the locations of grounding pads that will be placed by the electrophysiologist. MRI Issues * When using a pulse oximeter to monitor the oxygen saturation of patients in an MRI scanner, the connection between the oximeter console and the patient must take place through a long fiberoptic cable having no wires or conducting segments. * Items with internal wires should not be present during an MRI examination, including pulmonary artery catheters that have a wire for determination of temperature and certain epidural catheters with wires. * Because of missile danger, ferromagnetic anesthesia equipment may not be brought into the magnet room. * Essential anesthesia equipment that can be sucked into a magnet must be bolted to a wall and tested before entry of the patient into the scanner. * Anesthesiologists who stay in the magnet room during examinations must wear ear plugs to avoid permanent hearing loss from high-decibel acoustic noise. Common to All Issues If the cause of an electrical burn or incident is uncertain, the relevant equipment or areas should be secured until experienced biomedical personnel mount a thorough investigation that may include simulation of patient conditions. -------------------------------------------------------------------------------------------------------------------------------------------Environmental Safety Including Chemical Dependency * Escape of anesthetic vapors into the operating room atmosphere is unavoidable. In the United States, the limits of exposure to atmospheric waste gases are set by NIOSH, which recommends a time-weighted average of 25 ppm for nitrous oxide and a ceiling of 2 ppm for volatile anesthetics. * No definitive evidence has shown that trace concentrations of anesthetics in the ambient air of the operating room present a health hazard. * Occupational exposure to radiation comes primarily from x-rays scattered by the patient and surrounding equipment. A distance of 6 feet from the patient provides the same protection as 2.5 mm of lead. A distance of 3 feet from the patient is recommended to minimize occupational exposure. * Occupational exposure to HIV is most often the result of a percutaneous injury. The risk of transmission is greatest from hollow-bore needles, needles contaminated with visible blood, and a source patient with high viral titer. * Post-exposure prophylaxis is recommended after occupational exposure to HIV or hepatitis B virus. The U.S. Public Health Service–recommended guidelines for post-exposure prophylaxis are available on the Centers for Disease Control and Prevention (CDC) website. The National Post-Exposure Prophylaxis Hotline is open 24 hours a day for expert advice (1-888-448-4911). * To minimize occupational exposure to blood-borne pathogens, standard precautions should be practiced at all times. The appropriate barrier precautions for anticipated contact with blood or body fluids are published by the CDC. Whenever possible, needleless systems should be used.

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Study Notes – Anesthesiology

James Lamberg

28Jul2010

* Sleep deprivation has an adverse effect on physician mood, cognitive function, reaction time, and vigilance. Although it is clear that sleep deprivation and fatigue adversely affect clinical performance, their full impact on patient outcome has not yet been determined. * Anesthesiologists are overrepresented in drug treatment centers. The preference for and access to potent opioids contribute to the prevalence of drug addiction among anesthesiologists. * The rate of drug-related deaths is more than twice as high in anesthesiologists as internists. * Although many recovered anesthesiologists return to the practice of anesthesia, there is a significant relapse rate. The chance of relapse is highest in physicians who become addicted to potent narcotics early in their career. Successful recovery requires a lifelong commitment to treatment. In some cases, a change in specialty is the only solution. -------------------------------------------------------------------------------------------------------------------------------------------Statistical Methods in Anesthesia * Always plot your data. Significant trends should be visible to the eye. * Know your statistics program well enough to be sure that it is calculating what you want. * Interval data should not be treated like categorical data—the mathematics is different. * Many statistical methods assume that the data are distributed “normally,” that is, in a symmetric bell-shaped curve; these methods can be misleading if the data are not normally distributed. * Standard deviation (SD) is used to describe the spread of data, and standard error of the mean (SEM) is used to compare data sets. * Multivariate regression, which relates the outcome variable to more than one other factor, requires more data but will probably pick up correlations that may be missed if only univariate regression is used. * When using multivariate regression, if two variables correlate closely with each other, the statistical package may miss reporting one as correlating with the outcome. * In hypothesis testing, a negative result may indicate no real difference or may just mean that the study was underpowered to pick up a true, but small difference. * A P value is the probability that the observed result will occur, assuming no true difference between the tested hypotheses, which is not the same as the probability of the difference being true. * A bayesian approach to diagnostic testing recognizes the fact that the value of a test depends on the patient population: if the test is almost always truly positive in the population, false-negative results will outnumber truenegative ones and make the test less useful. This is also the situation if the test is almost always truly negative, in which case false-positive results cause the confusion. * Selection biases make many real-life clinical studies difficult to interpret. Randomized clinical trials are the best way to minimize this problem. * Beware of the error of “data dredging.” Applying too many tests to insufficient data will probably find something that, misleadingly, seems significant. --------------------------------------------------------------------------------------------------------------------------------------------

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