38642877 Anesthesiology Notes

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Study Notes – Anesthesiology James Lamberg 25May2010 DO NOT DISTRIBUTE - 1 - Textbooks: Miller Anesthesia, Anesthesia Secrets, NMS Clinical Manual of Anesthesia -------------------------------------------------------------------------------------------------------------------------------------------- General Procedures: NEJM Videos In Clinical Medicine: http://content.nejm.org/misc/videos.dtl 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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Transcript of 38642877 Anesthesiology Notes

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Study Notes – Anesthesiology James Lamberg 25May2010

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Textbooks: Miller Anesthesia, Anesthesia Secrets, NMS Clinical Manual of Anesthesia -------------------------------------------------------------------------------------------------------------------------------------------- General Procedures: NEJM Videos In Clinical Medicine: http://content.nejm.org/misc/videos.dtl 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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* 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 (<1 minute) and short duration (5-8 minutes). IV Anesthetics, Thiopental: * Pro: Excellent brain protection, stops seizures, cheap. * Con: Myocardial depression, vasodilation, histamine release, can precipitate porphyria in susceptible patients. IV Anesthetics, Propofol: * Pro: Prevents nausea/vomiting, quick recovery if used as solo anesthetic agent. * Con: Pain on injection, expensive, supports bacterial growth, myocardial depression (the most of the four), vasodilation. IV Anesthetics, Etomidate: * Pro: Least myocardial effect of IV anesthetics. * Con: Pain on injection, adrenal suppression (?significance if used only for induction), myoclonus, nausea/vomiting. IV Anesthetics, Ketamine: • Pro: Works IV, PO, PR, IM – good choice in uncooperative patient without IV, stimulation of SNS - good for hypovolemic trauma patients, often preserves airway reflexes. • Con: Dissociative anesthesia with postop dysphoria and hallucinations, increases ICP/IOP and CMRO2, stimulation of SNS - bad for patients with compromised cardiac function, increases airway secretions. Local Anesthetics, Esters: * Metabolized by plasma esterases – one metabolite is PABA, which can cause allergic reactions. * Patients with “allergy to novacaine” usually do well with amides for this reason. * All have only one “i” in their name, eg. Procaine, Tetracaine. Local Anesthetics, Amides: * Metabolized by hepatic enzymes. All have at least two “i”s in their name, eg. Lidocaine, Bupivacaine. Opioids, Morphine: * Long acting, histamine release, renally excreted active metabolite with opiate properties - beware in renal failure. Opioids, Dilaudid: * Long acting, no active metabolites or histamine release, same onset/duration as morphine. Opioids, Demerol: * Euphoria, stimulates catecholamine release, so beware in patients using MAOI’s, renally excreted active metabolite associated with seizure activity, renally excreted metabolite with seizure potential therefore beware in renal failure. Opioids, Fentanyl/Alfentanil/Sufentanil: * Low doses produce brief effect, but larger doses are long acting, increased incidence of chest wall rigidity vs. other opiates, no active metabolites. Opioids, Remifentanil: * Almost instantaneous onset/offset of action due to metabolism by plasma esterases, must be given as continuous infusion, significant incidence of chest wall rigidity and nausea/vomiting muscle relaxants. Muscle Relaxants, Muscle Relaxants, Depolarizing:

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* Succinylcholine inhibits the post-junctional receptor and passively diffuses off the membrane, while circulating drug is metabolized by plasma esterases. * Associated with increased ICP/IOP, muscle fasciculations and postop muscle aches, triggers MH, increases serum potassium especially in patients with burns, crush injury, spinal cord injury, muscular dystrophy or disuse syndromes. * Rapid and short acting. Muscle Relaxants, Nondepolarizing: * Many different kinds, all ending in “onium” or “urium”. * Each has different site of metabolism, onset, and duration making choice depend on specific patient and case. * Some examples: Pancuronium - Slow onset, long duration, tachycardia due to vagolytic effect. * Cisatracurium - Slow onset, intermediate duration, Hoffman (nonenzymatic) elimination so attractive choice in liver/renal disease. * Rocuronium - Fastest onset making it useful for rapid sequence induction, intermediate duration. Reversal Agents: * All are acetylcholinesterase inhibitors, thereby allowing more acetylcholine to be available to overcome the neuromuscular blocker effect at the nicotinic receptor, but also causing muscarinic stimulation. * Neostigmine – shares duration of action with glycopyrrolate. * Edrophonium – shares duration of action with atropine. * Physostigmine – crosses the BBB, therefore useful for atropine overdose. Anticholinergics: * Given with reversal agents to block the muscarinic effects of cholinergic stimulation, also excellent for treating bradycardia and excess secretions. * Atropine – used in conjunction with edrophonium, crosses the BBB causing drowsiness, so maybe bad at end of surgery for reversal, some use as premed for all children since they tend to become bradycardic with intubation and produce copious drool. * Glycopyrrolate – used in conjunction with neostigmine, does not cross the BBB. -------------------------------------------------------------------------------------------------------------------------------------------- Pre-Operative Cardiac Assessment for Non-Cardiac Surgery Step 1: Emergency Surgery * Decision: Proceed to surgery with medical risk reduction and perioperative surveillance. Step 2: Active Cardiac Conditions * Unstable coronary syndromes (unstable or severe angina, recent MI). * Decompensate HF (new onset, NYHA class IV). * Significant arrhythmias (Mobitz II or 3rd degree heart block, SVT or AF with rapid ventricular rate, symptomatic ventricular arrhythmia or bradycardia, new VT). * Severe valvular disease (severe AS or MS). * Decision: Postpone surgery until stabilized or corrected. Step 3: Low-Risk Surgery (risk < 1%) * Superficial or endoscopic, cataract or breast, ambulatory. * Decision: Proceed to surgery. Step 4: Functional Capacity * Good if > 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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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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* 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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* 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 “performance-shaping 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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* 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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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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* 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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* 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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* 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. Re-expression 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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--------------------------------------------------------------------------------------------------------------------------------------------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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* 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, stress-induced 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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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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* 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, low-dose 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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adenosine monophosphate, which is frequently a target of G protein stimulation or inhibition; inositol 1,4,5-triphosphate 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 knock-out/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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* 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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* 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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* 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 negative-pressure 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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* 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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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 (<24 hours) postoperative sedation, although it is finding increasing use in the perioperative period as an adjunct sedative. Its primary action is as an agonist on α2 receptors in the locus caeruleus. It has minimal effect on respiration. Dexmedetomidine produces a biphasic effect on blood pressure; at low concentrations, mean blood pressure is decreased, and at higher concentrations, blood pressure is increased. Heart rate and cardiac output show a concentration-dependent decrease. Dosing for sedation is a loading dose of 0.25 to 1 mg/kg over a 10-minute period, followed by an infusion of 0.1 to 1 µg/kg/hr. * Droperidol, a butyrophenone and major tranquilizer, was initially used to produce a state of neuroleptanesthesia. More recent concern regarding its effect on prolonging the QT interval has resulted in its withdrawal in several countries and its limitation to the treatment of postoperative nausea and vomiting (PONV) with a black box warning in the United States. Because the use of low-dose droperidol (<1.25 mg) for PONV has not been approved by the U.S. Food and Drug Administration (FDA), the black box warning does not relate to this use. Clinically significant prolongation of the QT interval by doses used for PONV (0.625 to 1.25 mg) has been challenged by several editorials, and this effect has not been substantiated by review of the cases reported or any literature. Low-dose droperidol remains an effective antiemetic therapy. --------------------------------------------------------------------------------------------------------------------------------------------Opioids * An increased understanding of the molecular pharmacology of opioid receptors and opioid-induced cellular responses allows the use of innovative techniques for analgesia. * Opioids suppress pain by their action in the brain, spinal cord, and peripheral nervous system. * Opioids affect many organ systems, including the respiratory and cardiovascular systems, and can cause a variety of adverse effects. Proper dosing and monitoring allow the adverse effects to be minimized. * New pharmacokinetic principles have allowed more intelligent use of opioids along with more predictable durations of action. * The pharmacokinetic and pharmacodynamic properties of opioids are affected by a variety of factors, such as age, body weight, organ failure, and shock. To appropriately use opioids, these factors should be taken into consideration. * During total intravenous anesthesia, the use of opioids is a vital part of providing the analgesic component of anesthesia. Short-acting drugs, such as remifentanil, allow dissipation of total intravenous anesthesia even more rapidly than with inhaled anesthetics. * New opioid delivery systems, such as transdermal fentanyl patches, are continually being developed. Such systems allow more flexibility in providing analgesia, both inside and outside the operating room. * Opioids can pharmacokinetically or pharmacodynamically interact with drugs used perioperatively. Drug interaction should be understood for proper patient management. --------------------------------------------------------------------------------------------------------------------------------------------Intravenous Drug Delivery Systems * Anesthetic drugs are described by multicompartmental models. Accurate intravenous drug delivery requires adjusting the dose for accumulation of drug in peripheral tissues. * The biophase is the site of action of anesthetic drugs. Initiation, maintenance, and titration of intravenous anesthetics must account for the delay in equilibration between plasma and the site of drug effect. * Some drug effects directly reflect the concentration of drug in the biophase (direct-effect models). Other drug effects reflect the alteration of feedback systems by anesthetics (indirect-effect models). The influence of opioids on ventilation reflects the dynamic influence of opioids on the feedback between ventilation and carbon dioxide and is thus an example of an indirect drug effect. * The target concentration in the effect site is the same as the target concentration in plasma at steady state. The target concentration is influenced by patient physiology, surgical stimulation, and concurrent drug administration. Typically, one must set a target concentration for the hypnotic (volatile anesthetic or propofol) and the analgesic (opioid) that properly accounts for the synergy between them. * To achieve an effective target concentration, the conventional teaching of administering a loading dose calculated as target concentration times volume of distribution, followed by a maintenance rate calculated as target concentration times clearance, is inaccurate. The initial loading dose may be calculated as the target concentration

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times the volume of distribution at peak effect. Maintenance rates must initially account for distribution of drug in peripheral tissues and are turned down to the target concentration times clearance only after equilibration with peripheral tissues. * The terminal half-life does not reflect the clinical time course of drug concentration. The context-sensitive decrement time is the time for a given decrement in drug concentration as a function of the duration of infusion for an infusion that maintains a steady plasma concentration. Context-sensitive decrement times properly incorporate the multicompartmental behavior of intravenous anesthetics. The context-sensitive half-time is the time for a 50% decrement in concentration. * Alfentanil, fentanyl, sufentanil, remifentanil, propofol, thiopental, methohexital, etomidate, ketamine, and midazolam can all be given by intravenous infusion. Specific caveats, infusion rates, and titration guidelines are presented in the text. * Target-controlled infusions use pharmacokinetic models to titrate intravenous anesthetics to specified plasma or effect-site drug concentrations. The Diprifusor is a propofol target-controlled infusion system that is available worldwide except in North America. * Closed-loop drug delivery systems have used the median electroencephalographic frequency, bispectral index, and auditory evoked potentials to control intravenous anesthetic delivery. These systems have generally performed well clinically but remain investigational. --------------------------------------------------------------------------------------------------------------------------------------------Pharmacology of Muscle Relaxants and Their Antagonists * Two different populations of nicotinic acetylcholine receptors exist at the mammalian neuromuscular junction. In adults, the nicotinic acetylcholine receptor at the postsynaptic (muscular) membrane is composed of α2βδε-subunits. Each of the two α-subunits has an acetylcholine binding site. The presynaptic (neuronal) nicotinic receptor is also a pentameric complex composed of α3β2-subunits. * Nondepolarizing muscle relaxants produce neuromuscular blockade by competing with acetylcholine for postsynaptic α-subunits. In contrast, succinylcholine produces prolonged depolarization that results in decreased sensitivity of the postsynaptic nicotinic acetylcholine receptor and inactivation of sodium channels so that propagation of the action potential across the muscle membrane is inhibited. * Different forms of neuromuscular stimulation test for neuromuscular blockade at different areas of the motor end plate. Depression of the response to single-twitch stimulation is probably due to blockade of postsynaptic nicotinic acetylcholine receptors, whereas fade in the response to tetanic and train-of-four stimuli results from blockade of presynaptic nicotinic receptors. * Succinylcholine is the only available depolarizing neuromuscular blocker. It is characterized by rapid onset of effect and ultrashort duration of action because of its rapid hydrolysis by butyrylcholinesterase. * The nondepolarizing neuromuscular blockers available can be classified according to chemical class (steroidal, benzylisoquinolinium, or other compounds) or, alternatively, according to onset or duration of action (long-, intermediate-, and short-acting drugs) of equipotent doses. * The speed of onset is inversely proportional to the potency of nondepolarizing neuromuscular blocking agents. With the exception of atracurium, molar potency is highly predictive of a drug's rate of onset of effect. Rocuronium has a molar potency (ED95 ≈ 0.54 µM/kg) that is about 13% that of vecuronium and 9% that of cisatracurium. Its onset of effect is more rapid than that of either of these agents. * Neuromuscular blockade develops faster, lasts a shorter time, and is recovered from more quickly in the more centrally located neuromuscular units (e.g., laryngeal adductors, diaphragm, and masseter muscle) than in the more peripherally located adductor pollicis. * The long-acting neuromuscular blockers undergo minimal or no metabolism, and they are eliminated, largely unchanged, primarily by renal excretion. Neuromuscular blockers with an intermediate duration of action have more rapid clearance than the long-acting agents do because of multiple pathways of degradation, metabolism, and elimination. Mivacurium, a short-acting neuromuscular blocker, is cleared rapidly and almost exclusively via metabolism by butyrylcholinesterase. * After the administration of nondepolarizing neuromuscular blocking agents, it is essential to ensure adequate return of normal neuromuscular function. Residual paralysis decreases upper esophageal tone, coordination of the esophageal musculature during swallowing, and the hypoxic ventilatory drive. --------------------------------------------------------------------------------------------------------------------------------------------Local Anesthetics * Local anesthetics block voltage-gated sodium channels and thereby interrupt initiation and propagation of impulses in axons, but they have a wide variety of other biologic actions, desirable and undesirable. * Currently available local anesthetics are of two chemical classes: aminoesters and aminoamides.

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* The low potency and lack of specificity of available local anesthetics are due in part to the very weak structural constraints at their binding site on the sodium channel. Most of their features derive from the requirement for high solubility and rapid diffusion in both aqueous environments and the lipid phases of biologic membranes. * Reversible protonation of the tertiary amine group tends to make local anesthetics less charged at more basic pH and more charged at neutral or acidic pH; the neutral base forms are more soluble in lipid environments, whereas the charged acid forms are more soluble in aqueous environments. * Aminoesters are metabolized primarily by plasma esterases, and aminoamides are metabolized primarily by hepatic cytochrome P450–linked enzymes. * The principal systemic toxicities of local anesthetics involve the heart (including atrioventricular conduction block, arrhythmias, myocardial depression, and cardiac arrest) and the brain (including agitation, lethargy, seizures, and generalized central nervous system depression). Hypoxemia and acidosis exacerbate these toxicities. Resuscitation after bupivacaine overdose is particularly difficult. Therefore, prevention of intravascular injection or overdose is crucial, and major nerve blockade should involve incremental, fractionated dosing. * Local anesthetics are directly toxic to nerve at the concentrations supplied in commercial solutions. Intraneural concentrations during regional anesthesia are generally (but not always) below a threshold for toxicity because of spread of solutions through tissues and diffusion gradients from injection sites into nerve. Injection into a constrained tissue space increases the risk for local toxicity. * Optimal use of local anesthetics in regional anesthesia requires an understanding of (1) the individual patient's clinical situation; (2) the location, intensity, and duration of regional anesthesia and analgesia required; (3) anatomic factors affecting deposition of drug near nerves; (4) proper drug selection and dosing; and (5) ongoing assessment of clinical effects after administration of a local anesthetic. * Recent efforts have led to the development of several new formulations for topical anesthesia. Single-stereoisomer (as opposed to a racemic mixture) formulations have been developed in an effort to reduce systemic toxicity and improve sensory selectivity. * Local anesthetics are increasingly being used for postoperative infusions and via both local and systemic administration for the management of chronic pain. Further research and development may lead to safe, more selective agents that will facilitate more prolonged administration in the setting of acute or chronic pain. --------------------------------------------------------------------------------------------------------------------------------------------Nitric Oxide and Inhaled Pulmonary Vasodilators * Endogenous nitric oxide (NO) is produced from oxygen and l-arginine by a group of enzymes called nitric oxide synthases with l-citrulline as a by-product. * Most of the effects of NO on the cardiovascular system are mediated by activation of the enzyme soluble guanylate cyclase, which catalyzes formation of the second messenger cyclic guanosine monophosphate (cGMP) from guanosine 5′-triphosphate. NO stimulates soluble guanylate cyclase to synthesize cGMP, which in turn activates cGMP-dependent protein kinase and thereby leads to vascular relaxation. * Because NO binds rapidly to hemoglobin with high affinity, the vasodilatory effect of inhaled NO is limited to the lung. * NO can be safely inhaled when delivered by facemask, nasal cannula, or an endotracheal tube. * According to a survey in 2000, 94% of pediatric cardiologists consider inhaled NO to be a clinically proven agent to test pulmonary vasoreactivity in the cardiac catheterization laboratory. * Several clinical trials of inhaled NO in patients with acute lung injury demonstrated no effect on mortality or the duration of mechanical ventilation; however, the frequency of progression to severe respiratory failure from milder respiratory failure was decreased by inhaled NO in one study. * Inhaled NO has been reported to ameliorate the postoperative pulmonary hypertension of congenital heart disease and decrease the need for postoperative extracorporeal membrane oxygenation. * The vasodilatory response to inhaled NO is variable in patients with valvular heart disease. The variability in dilator response is likely to be related to the balance between pulmonary vascular remodeling and active vasoconstriction. * In contrast to therapy with intravenous vasodilators, which often cause systemic hypotension, inhaled NO has been shown in a small group of patients to selectively reduce peripheral vascular resistance and enhance right ventricular stroke work after cardiac transplantation. * A trial of inhaled NO is recommended before consideration of implantation of a right ventricular assist device because this invasive procedure may be avoided if there is a salutary response to inhaled NO. * Inhaled NO can combine with hemoglobin to form nitrosylhemoglobin, which is rapidly oxidized to methemoglobin. The enzyme methemoglobin reductase rapidly converts methemoglobin to hemoglobin in the red

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blood cell. Because neonates have reduced activity of this enzyme, they are at greater risk than adults for the development of significant methemoglobinemia after the inhalation of high levels of NO for a prolonged period. --------------------------------------------------------------------------------------------------------------------------------------------Complementary and Alternative Therapies * Despite lack of federal oversight, herbal medication use has increased dramatically in the overall population and particularly in preoperative patients. * Patients may not volunteer information unless they are specifically queried about herbal medication use. * Many commonly used herbs have side effects that affect drug metabolism, bleeding, and neuronal function. * Although stopping the use of herbal medication up to 2 weeks preoperatively can eliminate many of these problems, patients often arrive for surgery without a preoperative visit 2 weeks before surgery. Knowledge of specific interactions and metabolism of these herbs can provide practical guidelines to facilitate care. * Other complementary therapies, including acupuncture and music therapy, have become increasingly popular, although less is known about their effectiveness. --------------------------------------------------------------------------------------------------------------------------------------------Risk of Anesthesia * Perioperative risk is multifactorial and depends on the interaction of anesthesia-, surgery-, and patient-specific factors. * Anesthesia-related (and surgery-related) risk includes morbidity and mortality within 30 days, although shorter periods may be relevant, depending on the extent of surgery. * Anesthesia and the actions of anesthesiologists may completely or partially cause perioperative morbidity and mortality, but the actions of the anesthesiologist may also decrease or modify risk related to patient disease. * In the literature on anesthesia-related risk, rates of morbidity and mortality depend on the wide variety of definitions found. * Studies of anesthesia-related risk have found that postanesthesia respiratory depression is the major cause of death and coma totally attributable to anesthesia; this finding prompted the development of postanesthesia care units. * Research into anesthesia-related cardiac arrest has found it to be attributable to medication administration, airway management, and technical problems of central venous access. * Multivariate modeling using logistic regression equations can be used to determine factors associated with increased risk in the cohort and in individuals and has been used to develop risk indices such as the Cardiac Risk Index. * Surveys of maternal mortality suggest that the absolute rate of complications by anesthesia type has not decreased but that the increased use of regional anesthesia has led to improvements in outcome. * Medication-related and cardiovascular causes of cardiac arrest were the most common causes in the Pediatric Perioperative Cardiac Arrest Registry. * With increases in outpatient surgery, increased surveillance is required to ensure that appropriate procedures are performed in appropriate locations. --------------------------------------------------------------------------------------------------------------------------------------------Preoperative Evaluation * The anesthesia preoperative evaluation is the clinical foundation and framework of perioperative patient management and can potentially reduce operative morbidity and enhance patient outcomes. * The fundamental purpose of preoperative evaluation is to obtain pertinent information regarding the patient's current and past medical history and to formulate an assessment of the patient's intraoperative risk and requisite clinical optimization. * Basic and complex medical diseases and syndromes that can potentially affect anesthesia perioperative management require the anesthesiologist to be clinically knowledgeable and current in many aspects of internal medicine. * Patients require preoperative diagnostic and laboratory studies that are consistent with their medical history, the proposed surgical procedure, and the potential for intraoperative blood loss. Routine preoperative testing cannot be justified and is costly and clinically inappropriate. * Preoperative patient education and individual discussion can significantly reduce patient anxiety and fears of the perioperative anesthesia process. * Under the clinical directorship of an anesthesiologist, the anesthesia preoperative evaluation clinic can enhance operating room efficiency, decrease day-of-surgery cancellations and delays, reduce hospital costs, and enhance the quality of patient care. * New and updated preoperative evaluation consensus and evidence-based guidelines published by multiple medical specialties have led to evaluation protocols for preparing patients for anesthesia and surgery.

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* Increasing regulatory and reporting requirements involving preoperative issues by agencies such as the Joint Commission on Accreditation of Healthcare Organizations require awareness and compliance by anesthesiologists. * Information technology and decision support systems in preoperative evaluation can enhance the quality of patient care and clinical management through electronic integration and standardization of patient data. * The anesthesiologist is the perioperative medical specialist and the only preoperative evaluation physician who can truly evaluate the risks associated with anesthesia, discuss these risks with the patient, and manage them intraoperatively. --------------------------------------------------------------------------------------------------------------------------------------------Anesthetic Implications of Concurrent Diseases * The history and physical examination most accurately predict the risks and the likelihood of changes in monitoring or therapy. * For diabetic patients, end-organ dysfunction and the degree of glucose control in the perioperative and periprocedural periods are the critical issues with regard to risk. * The key to managing blood glucose levels in diabetic patients perioperatively is to set clear goals and then monitor blood glucose levels frequently enough to adjust therapy to achieve these goals. * Obesity is associated with multiple comorbid conditions, including diabetes, hyperlipidemia, and chololithiasis, but the primary concern is derangements of the cardiopulmonary system. * Obstructive sleep apnea is important to recognize because of the increased sensitivity to and the consequence of depressing the effects of hypnotics and opioids on airway muscle tone and respiration, as well as the difficulty with laryngoscopy and mask ventilation. * Although no controlled, randomized prospective clinical studies have been performed to evaluate the use of adrenergic receptor blocking drugs in patients undergoing resection of pheochromocytoma, the preoperative use of such drugs is generally recommended. * For patients with hypertension, we recommend the routine administration of all drugs preoperatively except angiotensin-converting enzyme inhibitors and angiotensin II antagonists. * Evaluation of a patient with cardiovascular disease depends on clinical risk factors, the extent of surgery, and exercise tolerance. * In patients with pulmonary disease, the following should be assessed: dyspnea, coughing and the production of sputum, recent respiratory infection, hemoptysis, wheezing, previous pulmonary complications, smoking history, and physical findings. * In patients with pulmonary disease, several strategies have been suggested, including cessation of smoking 8 weeks or more before surgery. * Risk factors for perioperative renal dysfunction include advanced age, congestive heart failure, previous myocardial revascularization, diabetes, and elevated baseline creatinine. * The main concern for a patient with renal disease is making it worse and thereby increasing the chance for renal failure, coma, and death. * Mild perioperative anemia may be significant only in patients with ischemic heart disease. * Careful management of chronic drug administration can include questions about the effects and side effects of alternative as well as prescription drugs. --------------------------------------------------------------------------------------------------------------------------------------------Patient Positioning and Anesthesia * Patient positioning is a major responsibility that is shared by the entire operating room team. A balance between optimal surgical positioning and patient well-being is sometimes required. * Many patient positions that are used for surgery result in undesirable physiologic consequences, including significant cardiovascular and respiratory compromise. Anesthetics blunt natural compensatory mechanisms, rendering surgical patients vulnerable to positional changes. * Peripheral nerve injury, although rare, accounted for 18% of cases in the 1990-1994 American Society of Anesthesiologists (ASA) Closed Claims Database, second only to death. Peripheral nerve injury is often a result of patient positioning. The mechanisms of injury are stretching, compression, and ischemia. * Ulnar neuropathy is the most common postoperative nerve injury, followed by injury to the brachial plexus, lumbosacral nerve roots, and spinal cord. * Not all postoperative neuropathies, including ulnar neuropathy, are currently explainable and may not be entirely preventable. Many postoperative ulnar nerve deficits do not seem to be related to intraoperative patient position because they appear days after surgery.

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* The ASA issued a Practice Advisory in 2000 for the prevention of perioperative peripheral neuropathies. Only 6 of 509 studies reviewed met the standard, however, for a scientifically proven relationship between intervention and outcome. * Postoperative visual loss is a rare but devastating complication that is associated with the prone position. The causes are multifactorial and incompletely understood. * Anesthetics administered outside classic operating rooms present special challenges with regard to patient positioning because of equipment limitations and differences in the work environment and culture. --------------------------------------------------------------------------------------------------------------------------------------------Neuromuscular Disorders and Malignant Hyperthermia * Dystrophin, along with dystrophin-associated glycoproteins, is involved in sarcolemmal stability. Its defects are responsible for Duchenne's muscular dystrophy (DMD) and Becker's muscular dystrophy (BMD). * Whereas the risk for a malignant hyperthermia (MH) mutation in DMD/BMD patients is similar to that in the general population, the incidence of MH-like anesthetic events has been reported to be 0.002 with DMD and 0.00036 with BMD. * Succinylcholine is contraindicated in DMD/BMD patients because of the risk of rhabdomyolysis and hyperkalemia as a result of their unstable sarcolemmal membrane. * The majority of complications in patients with myotonic dystrophy (MD) were found to be pulmonary related. Pulmonary complications of MD are the result of hypotonia, chronic aspiration, and central and peripheral hypoventilation. * Although patients with sodium channel pathology have often been considered to be susceptible to MH, there is no increased risk for MH in these patients. * MH is an anesthetic-related disorder of increased skeletal muscle metabolism. It is an inherited condition and it occurs in swine and humans. * Skeletal muscle accounts for approximately 40% of body weight; its increased metabolism therefore has a profound effect on whole-body metabolism. * Signs of MH, including tachycardia, increased expired CO2, muscle rigidity, and increased temperature, are related to the increased metabolism. * The abnormal function of the ryanodine receptor of skeletal muscle in MH causes barely controlled concentration of calcium within the cell when it is not exposed to triggering agents. * The added loss of control of intracellular calcium on exposure to triggering agents or heat stress leads to marked metabolic stimulation within the cell to provide extra adenosine triphosphate to drive the calcium pumps that restore calcium to its reservoirs (e.g., sarcoplasmic reticulum, mitochondria, extracellular fluid). * Dantrolene markedly attenuates myoplasmic Ca2+ concentrations and thereby restores metabolism to normal, with reversal of the signs of metabolic stimulation. * MH is inherited; one mutation accounts for all porcine MH, whereas more than 130 mutations account for human MH. * Evaluation of persons susceptible to MH includes contracture of a skeletal muscle biopsy specimen with halothane and caffeine and evaluation of DNA to identify mutations. Only DNA testing is needed to evaluate swine MH. * Future MH goals include advancement of genetic evaluations in North American and European medical programs and stronger finances to support genetic studies, identification of the mode of action of dantrolene, determination of the immediate cause of triggering of MH, and the development of effective, nondestructive tests for MH susceptibility. --------------------------------------------------------------------------------------------------------------------------------------------Fundamental Principles of Monitoring Instrumentation * Accuracy and precision are different. Accuracy is how close a value is to the true value. Precision is how repeatable the measurements are. An inaccurate, but precise monitor can be recalibrated to be accurate, but an imprecise monitor cannot be improved. * Filtering can improve the signal display, but it also can result in smoothing and loss of information. * A signal can be extracted from noise by repeated measurements because the noise is random over time, but the signal is not. * Electrical signals can be converted from analog to digital. Conversion can introduce some artifacts, but can allow for greater storage and analysis capabilities. * Invasive pressure monitors are affected by damping and resonance. Damping leads to distortion, signal loss, and reduction of peak values. Resonance can lead to amplification and overestimation of the peak value. * Pulse oximetry combines analysis of optical plethysmography and absorption analysis with empirical data to produce an estimate of Sao2.

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* Wavelength and frequency are related to the speed of the wave by the following formula: speed = wavelength × frequency. Shorter wavelengths improve the resolution of light and ultrasound measurements. * Flow measurements are among the most difficult to obtain and usually involve indirect measures. (For example, a temperature change or pressure decrease is measured, and a flow value is derived. A small error in the initial measurement leads to a much larger error in the derived flow value.) --------------------------------------------------------------------------------------------------------------------------------------------Monitoring the Depth of Anesthesia * The definition of “depth of anesthesia” has constantly evolved since the first demonstration of clinical anesthesia in the 1840s. The changing definitions have revolved around the available drugs used to provide anesthesia and the body of knowledge on their effects in humans. * Anesthesia is not a single pharmacologic process. It is a complex interaction of multiple stimuli, diverse responses, and the drug-induced probability of nonresponsiveness to the stimuli. * Anesthesia can be defined by hypnotic (unconsciousness) and analgesic (pain relief) components. The hypnotic component can be created by intravenous and inhaled anesthetics, whereas the analgesic component can be created by opioids and local anesthetics. Some drugs, such as ether, nitrous oxide, and ketamine, provide both hypnotic and analgesic components to some degree. * Hypnotics, when given alone, allow significant hemodynamic response to intense noxious stimuli. Opioids, when given alone, do not guarantee consistent unconsciousness or lack of movement response to intense noxious stimuli. The combination of the two can result in predictable unconsciousness and lack of hemodynamic response to intense noxious stimuli. * The interaction of the hypnotic and analgesic components can be characterized by a three-dimensional surface with hypnotic concentration on the y axis, analgesic concentration on the x axis, and the probability of nonresponse on the z axis. * Characterization of the three-dimensional surface requires precise stimuli to be applied and specific responses to be measured at defined effect-site concentrations of the hypnotic and analgesic. * The specific stimuli-response pairs used to define anesthetic depth range from easily suppressed responses to mild stimulation, such as the verbal response to a verbal command, to difficult-to-suppress responses to intense stimuli, such as the hemodynamic response to intubation. * The interaction of hypnotics and analgesics is generally synergistic. * Current clinical anesthesia involves the physician carefully observing the clinical response to defined stimuli and then adjusting the hypnotic or analgesic dosage (or both) by using the synergistic interaction to achieve the clinical goals of hemodynamic control, lack of awareness, and rapid, safe induction and emergence. * The hypnotic effects of the intravenous and inhaled anesthetics can be measured with empirically derived indices calculated from the electroencephalogram (EEG). * EEG-based indices of hypnotic drug effect correlate with hypnotic-induced sedation, amnesia, loss of consciousness, and reduced cerebral metabolic rate. * A consequence of inadequate anesthetic depth is intraoperative awareness. The incidence of awareness in healthy patients is approximately 0.1% and can increase to 1.0% to 1.5% in higher-risk patient populations. * There is emerging evidence that intraoperative monitoring of the hypnotic component of an anesthetic regimen may significantly decrease the risk of awareness associated with anesthesia. However, it does not totally eliminate the risk. * Maintenance of a high steady-state concentration of a volatile anesthetic may reduce the risk of awareness if the consequences of a high concentration can be tolerated by the patient. --------------------------------------------------------------------------------------------------------------------------------------------Cardiovascular Monitoring * Although a stethoscope should be present in every anesthetizing location, continuous stethoscopy is an insensitive method for early detection of untoward hemodynamic events. * Most automated noninvasive blood pressure measuring devices use an oscillometric measurement technique and rarely cause complications. Caution should be exercised in patients who cannot complain of arm pain, those with irregular rhythms that force repeated cuff inflation, and individuals receiving anticoagulant therapy. * Direct arterial pressure monitoring should be widely used in operative patients with severe cardiovascular diseases or those undergoing major surgical procedures that involve significant blood loss or fluid shifts. * The Allen test for palmar arch collateral arterial flow is not a reliable method to predict complications from radial artery cannulation. Despite the absence of anatomic collateral flow at the elbow, brachial artery catheterization for perioperative blood pressure monitoring is a safe alternative to radial or femoral arterial catheterization.

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* The accuracy of a directly recorded arterial pressure waveform is determined by the natural frequency and damping coefficient of the pressure monitoring system. Optimal dynamic response of the system will be achieved when the natural frequency is high, thereby allowing accurate pressure recording across a wide range of damping coefficients. * Rather than the common placement at the midaxillary line, the preferred position for alignment (or “leveling”) of external pressure transducers is approximately 5 cm posterior to the sternomanubrial junction. When using external transducers and fluid-filled monitoring systems, this transducer location will eliminate confounding hydrostatic pressure measurement artifacts. * Because of wave reflection and other physical phenomena, arterial blood pressure recorded from peripheral sites has a wider pulse pressure than central aortic pressure does. * Dynamic measures of cardiac preload, such as systolic pressure variation and pulse pressure variation, are better predictors of volume responsiveness than static indicators such as central venous pressure (CVP) or pulmonary capillary wedge pressure. * Selecting the best site, catheter, and method for safe and effective central venous cannulation requires that the physician consider the purpose of the catheterization, the patient's underlying medical condition, the intended operation, and the skill and experience of the physician performing the procedure. Right internal jugular vein cannulation is favored by most anesthesiologists because of its consistent, predictable anatomic location and its relative ease of access intraoperatively. * Methods to reduce mechanical complications from central venous catheters include the use of ultrasound vessel localization, venous pressure measurement before insertion of large catheters, and radiographic confirmation that the catheter tip rests outside the pericardium and parallel to the walls of the superior vena cava. * When using CVP as a measure of intravascular volume, the influences of ventricular compliance and intrathoracic pressure must be taken into consideration. In general, a trend in CVP values or its change with therapeutic maneuvers is more reliable than a single measurement. Important pathophysiologic information can be obtained by careful assessment of the CVP waveform morphology. * Of the many complications of central venous and pulmonary artery catheters, catheter misuse and data misinterpretation are among the most common. * Pulmonary artery wedge pressure is a delayed and damped reflection of left atrial pressure. The wedge pressure provides a close estimate of pulmonary capillary pressure in many cases but may underestimate capillary pressure when postcapillary pulmonary vascular resistance is increased, as in patients with sepsis. * Use of central venous, pulmonary artery diastolic, or pulmonary artery wedge pressure as an estimate of left ventricular preload is subject to many confounding factors, including changes in diastolic ventricular compliance and juxtacardiac pressure. * Most randomized prospective clinical trials have failed to show that pulmonary artery catheter monitoring results in improved patient outcome. Reasons cited for these results include misinterpretation of catheter-derived data and failure of hemodynamic therapies that are guided by specific hemodynamic indices. * Thermodilution cardiac output monitoring, the most widely used clinical technique, is subject to measurement errors introduced by rapid intravenous fluid administration, intracardiac shunts, and tricuspid valve regurgitation. * Mixed venous hemoglobin oxygen saturation is a measure of the adequacy of cardiac output relative to body oxygen requirements. It is also dependent on arterial hemoglobin oxygen saturation and hemoglobin concentration. * Newer methods of cardiac output monitoring, including esophageal Doppler and pulse contour analysis, allow beat-to-beat estimation of left ventricular stroke volume and measurement of other cardiovascular variables. --------------------------------------------------------------------------------------------------------------------------------------------Transesophageal Echocardiography * One of the category I indications for transesophageal echocardiography (TEE) is evaluation of intubated, hemodynamically unstable patients. * Guidelines expected in 2009 will probably recommend the use of TEE during all cardiac and other major surgical procedures in which severe hemodynamic instability is anticipated. * The speed of sound in the heart is assumed to be constant at 1540 m/sec. * The higher the transducer frequency, the better the image quality, but the more limited the depth of penetration. * Doppler echocardiography is used to measure the velocity of blood in the cardiac chambers and across the valves. * The modified Bernoulli equation transforms velocities into pressure gradients. Pressure gradient = 4V2, where V = velocity in m/sec. * Continuous wave Doppler measures high velocities but does not precisely identify their location. * Pulsed wave Doppler permits measurement of velocities at an exact location but is limited in its ability to measure high velocities.

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* Color Doppler codes for flow: blue away from the probe, red toward the probe (BART). * The abbreviated TEE examination will be adequate for the practice of basic TEE as defined by the 1996 SCA/ASA TEE guidelines. * TEE has been shown to be more sensitive than electrocardiography for the intraoperative detection of myocardial ischemia. --------------------------------------------------------------------------------------------------------------------------------------------Electrocardiography * Electrocardiographic monitoring is mandatory and a standard of care. * Electrocardiography permits detection of electrical disturbances that may influence the mechanical function of the heart. * With carefully selected lead combinations, most arrhythmias and myocardial ischemic events can be detected in the perioperative setting. * Appropriate diagnosis of arrhythmias and ischemia will allow proper and effective treatment. --------------------------------------------------------------------------------------------------------------------------------------------Implantable Cardiac Pulse Generators: Pacemakers and Cardioverter-Defibrillators * Identify the generator manufacturer and whether the generator is a pacemaker or defibrillator. * Have the pacemaker or defibrillator interrogated by a competent authority shortly before administration of the anesthetic. * Obtain a copy of this interrogation. Ensure that the device will pace the heart. * Consider replacing any device near its elective replacement period in a patient scheduled to undergo either major surgery or surgery within 25 cm of the generator. * Determine the patient's underlying rate and rhythm, which then determines the need for backup (external) pacing support. * Identify the magnet rate and rhythm, if any. * Program minute ventilation rate responsiveness off, if present. * Program all rate enhancements off. * Consider increasing the lower rate limit to optimize oxygen delivery to tissues for major cases. * Disable antitachycardia therapy if a defibrillator is present. --------------------------------------------------------------------------------------------------------------------------------------------Respiratory Monitoring * Hypoxemia is caused by reduced Pio2, hypoventilation, increased ventilation-perfusion (V/Q) heterogeneity, increased shunt, and diffusion nonequilibrium. Hypercapnia is almost always due to hypoventilation. * During mechanical ventilation in the operative and intensive care settings, hypoxemia is most often due to increased V/Q heterogeneity and shunt. * A clinically useful approximation to the alveolar gas equation for O2 is given by Pao2 = (Pb − 47) × Fio2 − 1.2 × Pco2. Exchange of O2 and CO2 takes place independently in the lung. * The alveolar-arterial (a-a) gradient increases with age and supplemental O2. The Pao2/Fio2 and a/a ratios typically do not change with increased age or inspired O2. * When derangements in gas tensions are noted on arterial blood gas analysis, it is important to verify that the sample was obtained and analyzed in an appropriate and timely manner. * Refinements and further studies on continuous intravascular blood gas monitors may one day lead to widespread routine use of these devices. * Pulse oximetry is a rapid, reliable indicator of oxygenation status in surgical and critically ill patients. Newer oximeters feature reduced capability for errors attributable to motion artifact and hypoperfusion. * Multiwavelength pulse oximeters are commercially available and allow measurement of carboxyhemoglobin and methemoglobin. Pulse oximetry may one day prove to be a reliable noninvasive monitor of volume status and fluid responsiveness. * A sudden decrease in Petco2 usually results from a circuit disconnection, airway obstruction, abrupt decrease in cardiac output, or pulmonary embolism. Petco2 is not always a reliable approximation of Paco2, particularly during general anesthesia or in the critically ill. * Mapping of pressure-volume curves in patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) can provide valuable information about lung mechanics and help guide positive end-expiratory pressure (PEEP) and tidal volume settings. Sustained high airway pressure is needed to open collapsed alveoli, and PEEP stabilizes the recruited lung units.

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* Computed tomography has greatly increased our understanding of the complicated interaction between PEEP and lung recruitment in ARDS. Electrical impedance tomography may in the future emerge as a useful bedside monitor of lung recruitment, pulmonary edema, and respiratory mechanics. * Recruitment strategies and low–tidal volume ventilation have been shown to improve outcomes in ARDS and ALI. High-frequency ventilators are safe and effective in refractory ARDS and may some day prove to be the ideal mode of lung protective ventilation. --------------------------------------------------------------------------------------------------------------------------------------------Renal Function Monitoring * Perioperative acute renal failure (ARF), although uncommon, is associated with extremely high morbidity and mortality rates. * The mechanism for perioperative ARF is complex and most commonly involves multiple factors such as ischemia/reperfusion, inflammation, and toxins. * Repeated direct perioperative assessment of renal hemodynamics, tubular function, or pathogenesis of perioperative renal dysfunction is impractical; therefore, indirect assessments, such as serum creatinine trends, are the best practical currently available perioperative tool to assess renal function. * Intraoperative urine formation depends on a number of factors and is an insensitive and unreliable method for assessing postoperative risk of renal dysfunction. * Serum chemistries and urine indices such as blood urea nitrogen, creatinine, fractional excretion of sodium, and free water clearance are generally late indicators of renal function deterioration and do not enable the clinician to clearly delineate the cause of renal failure. * Creatinine clearance is the most sensitive and specific clinical method for determining renal function, but it is limited by time and measurement restrictions. * Early biochemical markers for renal function hold promise and are a current focus for research that may soon lead to new tests able to provide prompt clinical information. --------------------------------------------------------------------------------------------------------------------------------------------Neurologic Monitoring * There are four key principles of intraoperative neurologic monitoring. * The pathway at risk during the surgical procedure must be amenable to monitoring. * If evidence of injury to the pathway is detected, there must be some intervention possible. * If changes in the neurologic monitor are detected, and no intervention is possible, although the monitor may be of prognostic value, it does not have the potential to provide direct benefit to the patient from early detection of impending neurologic injury. * The monitor must provide reliable and reproducible data. * There are few randomized prospective studies evaluating the efficacy of neurologic monitoring modalities. * Based on clinical experience and nonrandomized studies, practice patterns for use of neurologic monitoring have emerged. * There are procedures for which monitoring is recommended and used by most centers * There are procedures for which monitoring is used frequently in some centers, but not in others. * There are procedures for which there is no clear clinical experience or evidence indicating that monitoring is useful at all (experimental use). * There are procedures in which monitoring is used selectively for patients believed to be at higher-than-usual risk for intraoperative neurologic injury. --------------------------------------------------------------------------------------------------------------------------------------------Neuromuscular Monitoring * Residual postoperative neuromuscular blockade causes decreased chemoreceptor sensitivity to hypoxia, functional impairment of the pharyngeal and upper esophageal muscles, impaired ability to maintain the airway, and an increased risk for the development of postoperative pulmonary complications. * It is difficult and often impossible to exclude with certainty clinically significant residual curarization by clinical evaluation of recovery of neuromuscular function. * Absence of tactile fade in the response to train-of-four (TOF) stimulation, tetanic stimulation, and double-burst stimulation does not exclude significant residual blockade. * Adequate recovery of postoperative neuromuscular function cannot be guaranteed without objective neuromuscular monitoring. * Good evidence-based practice dictates that clinicians should always quantitate the extent of neuromuscular blockade by objective monitoring.

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* To exclude clinically significant residual neuromuscular blockade, the TOF ratio, when measured mechanically or by electromyography, must exceed 0.9. * Total twitch depression during surgery should be avoided. Whenever possible, one or two TOF responses should be maintained. * Antagonism of the neuromuscular block with a cholinesterase inhibitor should not be initiated before at least two or preferably three or four responses to TOF stimulation are observed. * If sufficient recovery (TOF ≥ 0.9) has not been documented objectively at the end of the surgical procedure, the neuromuscular block should be antagonized. --------------------------------------------------------------------------------------------------------------------------------------------Temperature Regulation and Monitoring * General anesthetics decrease the thresholds (triggering core temps) for vasoconstriction and shivering by 2-3°C. * Anesthetic-induced impairment of thermoregulatory control, combined with a cool operating room environment, makes most patients hypothermic. * The major initial cause of hypothermia in most patients is core-to-peripheral redistribution of body heat. * Neuraxial anesthesia impairs both central and peripheral thermoregulatory control and is associated with substantial hypothermia. * Large randomized trials have proved that even mild hypothermia (i.e., 1.5°C to 2.0°C) causes adverse outcomes, including a threefold increase in morbid myocardial outcomes, a threefold increase in risk for wound infection, coagulopathy and need for allogeneic transfusion, prolonged recovery, and prolonged hospitalization. * Body temperature should be monitored in patients undergoing surgery lasting longer than 30 minutes, and core temperature should be maintained at 36°C or higher whenever possible. Forced-air warming currently offers the best combination of high efficacy, low cost, and remarkable safety. --------------------------------------------------------------------------------------------------------------------------------------------Perioperative Acid-Base Balance * The presence of a significant acid-base abnormality often signals a serious underlying problem. * All acid-base abnormalities result from alterations in the dissociation of water. * Only three factors independently affect acid-base balance—the Paco2, the strong ion difference (SID), and the total concentration of weak acids (ATOT). * Respiratory acidosis is caused by hypercarbia, and respiratory alkalosis is caused by hypocarbia. * Metabolic acidosis is caused by decreased SID or increased ATOT. Decreased SID results from accumulation of metabolic anions (shock, ketoacidosis, and renal failure), hyperchloremia, and free water excess. Increased ATOT results from hyperphosphatemia. * Metabolic alkalosis is caused by increased SID or decreased ATOT. SID increases as a result of sodium gain, chloride loss, or free water deficit. ATOT decreases in hypoalbuminemia and hypophosphatemia. This is particularly common in critical illness. * Most acid-base disorders are treated by reversal of the cause. --------------------------------------------------------------------------------------------------------------------------------------------Airway Management in the Adult * Three basic decisions needed before induction of anesthesia in every patient are whether to use awake intubation, use a percutaneous technique, or maintain spontaneous ventilation. * Conditions requiring particular caution include lesions at the base of the tongue, recent onset of hoarseness, upper airway obstruction, and obstructive sleep apnea. * The combination of mouth opening, jaw protrusion, and head extension is the core of airway assessment. The examination described by El-Ganzouri (mouth opening, prognathic ability, head extension, thyromental distance, and the Mallampati test) has been used with minor modification by others. It can be performed rapidly and is the most quantifiable (recording of actual values is recommended) of the tests included in the guidelines of the American Society of Anesthesiologists (ASA). * Radiology studies have shown that head extension is the most important single maneuver in maintaining space between the pharyngeal soft tissues. Head extension stretches the anterior neck structures and moves the hyoid bone and attached structures anteriorly. * Four principles are central to prevention of complications during tracheal intubation: a. Maintenance of oxygenation must take priority over all other issues. Preoxygenation should be performed before induction of anesthesia. Mask ventilation should be used between attempts at tracheal intubation. b. Trauma must be prevented. The first attempt at tracheal intubation should be performed under optimal conditions, including patient position, preoxygenation, and equipment preparation. The number of attempts with blind techniques should ideally be zero and certainly not more than four.

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c. Anesthesiologists should have a sequence of backup plans in place before starting the primary technique. They should have the skills and the equipment needed to execute these plans. When unanticipated difficulty occurs in non-lifesaving surgery, the safest plan is to terminate attempts at tracheal intubation, awaken the patient, and postpone surgery. d. Anesthesiologist should seek the best help available (“call for help”) as soon as difficulty with tracheal intubation is experienced. * Immediate confirmation of correct tracheal tube placement is an essential and integral part of tracheal intubation. Several tests should be used because no single test is completely reliable. The most important safeguard is clinical suspicion. Visual confirmation of passage of the tracheal tube between the vocal cords is reliable, but not always possible, and experienced anesthesiologists are occasionally misled. * All anesthesiologists should be skilled in at least one alternative technique of tracheal intubation under vision. Strategies that include algorithms for the management of unanticipated difficult intubation have been devised by several organizations, including the ASA and the Difficult Airway Society, a U.K. organization. The ASA algorithm is the standard guide. * If noninvasive techniques do not restore oxygenation, cricothyrotomy is the percutaneous airway of choice because tracheotomy may take too long. It is not possible to define the Spo2 at which cricothyrotomy should be performed—it depends on the degree of hypoxemia and how rapidly it is deteriorating. --------------------------------------------------------------------------------------------------------------------------------------------Spinal, Epidural, and Caudal Anesthesia * Low neuraxial anesthesia (i.e., T10 or lower sensory level) carries a physiologic impact different from that of a block performed to produce high (T5) neuraxial anesthesia. * Neuraxial anesthesia carries more risk with the perioperative introduction of low-molecular-weight heparin and potent (glycoprotein) platelet inhibitors. * Many spinal and epidural anesthetics fail because of inadequate intravenous sedation and anxiolysis rather than technically flawed blocks. * Bupivacaine, levobupivacaine, and ropivacaine provide excellent quality of anesthesia for neuraxial techniques. * It is estimated that cerebrospinal fluid volume accounts for 80% of the variability in peak block height and regression of sensory and motor block. Except for body weight, the volume of cerebrospinal fluid does not correlate with other anthropomorphic measurements available clinically. * The epidural space is more segmented and less uniform than previously believed, and the ligamentum flavum is not uniform from skull to sacrum or even within an intervertebral space. * During neuraxial anesthesia, venous and arterial vasodilation occurs, but because of the large amount of blood in the venous system (approximately 75% of the total blood volume), the venodilation effect predominates. * It has long been taught that the decrease in blood pressure after a neuraxial block can be minimized by the administration of crystalloids intravenously before the block; however, this logic needs rethinking. * Nausea and vomiting may be associated with neuraxial block in up to 20% of patients, and atropine is almost universally effective in treating the nausea associated with high (T5) neuraxial anesthesia. * As facility with spinal anesthesia increases, the use of smaller, similarly tipped needles will decrease the incidence of headache if the number of spinal punctures does not increase. * Transient neurologic symptoms after spinal anesthesia develop most frequently after ambulatory procedures, especially in patients placed in the lithotomy or knee arthroscopy positions. * The lower frequency of headache with cone-shaped needle tips may be the result of exposure of more inflammatory mediators around the opening rather than the often-quoted more gentle spreading of the meninges at the site of puncture. * Epidural blood patches are more than 90% effective in relieving post–spinal puncture headache. * One method of increasing the likelihood of correct caudal needle placement is to inject 5 mL of saline rapidly through the caudal needle while palpating the skin overlying the sacrum. If no midline bulge is detected, the needle is probably positioned correctly. If a midline bulge is detected during saline injection, the needle is positioned incorrectly. * Local anesthetic–induced systemic toxicity occurs primarily through unintentional administration of the drug into an epidural vein. --------------------------------------------------------------------------------------------------------------------------------------------Nerve Blocks * In performing peripheral nerve blocks, elicitation of a paresthesia is equivalent to electrical stimulation. The success rate and time of onset are further improved if multiple stimulations are performed.

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* Direct visualization of spread of local anesthetic by ultrasound produces similar success as a multistimulation technique. * Diaphragmatic paresis occurs in 100% of patients undergoing an interscalene block, even with dilute local anesthetic solutions. * A complete lumbar plexus block may be accomplished through a proximal (psoas compartment) approach, but rarely with the femoral 3-in-1 or fascia iliaca techniques. * Continuous peripheral blockade improves outcome and rehabilitation after major orthopedic surgery, including knee, hip, and shoulder replacement surgery. * The sciatic nerve divides into its tibial and peroneal components 7 to 10 cm above the knee; a popliteal fossa block should be performed at this level. * Regardless of the level of blockade, a tibial motor response elicited by neurostimulation techniques is more efficacious than a peroneal response during performance of a sciatic nerve block. * The total local anesthetic dosage should be determined and kept within acceptable limits. Accumulation with time may occur with continuous techniques. * The frequency of neurologic complications after peripheral blockade is less than that associated with neuraxial techniques. Neurotoxicity and direct needle trauma are the major causes of neurologic complications. --------------------------------------------------------------------------------------------------------------------------------------------Ultrasound Guidance for Regional Anesthesia * Ultrasound imaging elucidates the structure of peripheral nerves and adjacent anatomy for regional block. * Ultrasound also provides real-time imaging for needle tip placement and drug injection. * Peripheral nerves have a characteristic “honeycomb” echotexture formed by their connective tissue and nerve fibers. Sliding the ultrasound transducer along the known course of a nerve with it viewed in short axis is often the best way of visualizing fascicles to confirm nerve identity. With training, operators will learn to naturally tilt the transducer to enhance the received echoes from a nerve. * Successful local anesthetic injections clarify the border of the nerve and track along the nerve path and its branches. Anatomic variation in nerve location, which is a potential source of block failure, can be directly visualized. * Ultrasound imaging can prevent and detect critical events such as intravascular or intraneural injection, which may improve safety during regional anesthesia procedures. * The use of ultrasound imaging has become a common adjunct for regional block anesthetics techniques. --------------------------------------------------------------------------------------------------------------------------------------------Intravascular Fluid and Electrolyte Physiology * Water is the major component of all fluid compartments within the body and represents approximately 60% of body weight. * Sodium is the most abundant positive ion of the extracellular fluid (ECF) compartment and is crucial in determining the extracellular and intracellular osmolality. * Potassium is the most abundant positive ion in the intracellular fluid and plays an important role in the membrane potential of cells. * Calcium is the key component that mediates muscle contraction; exocrine, endocrine, and neurocrine secretion; cell growth; and the transport and secretion of fluids and electrolytes. * Magnesium is essential for many biochemical reactions; its pharmacologic properties have only more recently been appreciated. * Phosphate stores and releases energy through high-energy phosphate bonds and is integral to the structure of proteins, lipids, and bone. * Chloride is the predominant anion in the ECF. * Glucose is a crucial fuel source, and insulin facilitates glucose movement into cells in a process that also requires potassium and phosphate. * Diabetes affects multiple organ systems, and the perioperative effect of diabetes can be profound. * The most common causes of metabolic alkalosis are antacid therapy, incidental administration of citrate with blood products, sodium bicarbonate administration, gastric drainage, and renal bicarbonate retention. * Metabolic acidosis is commonly caused by low cardiac output and end-stage liver disease. * Transfusion of blood products improves tissue oxygenation and decreases bleeding, but it also increases the risk of transmission of infectious diseases, transfusion reactions, immunosuppression, and alloimmunization. * Anesthetics may blunt the normal physiologic responses to hypovolemia and the stress response. * Shock is dysfunction of intracellular processes caused by the lack of energy.

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--------------------------------------------------------------------------------------------------------------------------------------------Transfusion Therapy * The most common causes of transfusion-induced death are bacterial contamination transfusion-related acute lung injury, transfusion reactions (i.e., ABO mismatch), and bacterial contamination. * Although the overall condition of the patient is of prime importance, a transfusion trigger of a hemoglobin level of 8 g/dL or less can be tolerated by relatively healthy, younger patients. Those who are not critically ill or have severe cardiorespiratory disease may require a transfusion trigger of 9 to 11 g/dL. * Because of storage at room temperature, platelets are the blood component most frequently contaminated with bacteria, which is the cause of platelet-induced sepsis. * Transfusion-transmitted hepatitis and human immunodeficiency virus (HIV) infection are rare. West Nile virus infection was a rapidly emerging problem but now can be tested for and is now rare. * Like in many countries in Europe and also Canada, leukoreduction of blood products is becoming universal in the United States. * Human and bovine modified hemoglobin products are undergoing clinical trials as synthetic blood or oxygen carriers, similar to allogeneic blood. Whether they will ever be used routinely is very questionable. --------------------------------------------------------------------------------------------------------------------------------------------Coagulation * Under normal physiologic conditions, clot formation requires participation of vascular endothelium, platelets, and plasma-mediated hemostasis. * Tissue factor (extrinsic pathway) initiates plasma-mediated hemostasis, whereas factor XI (intrinsic pathway) amplifies the response. * Thrombin generation proves the key regulatory enzymatic step in hemostasis. * Platelets participate in clot formation as (1) anchoring sites for coagulation factor activation complexes; (2) delivery “vehicles” releasing hemostatically active proteins; and (3) major structural components of the clot. * A carefully performed history of bleeding remains the most effective means for identifying bleeding and thrombotic tendencies. * Thrombosis is potentiated by stasis, vascular endothelial injury, and underlying hypercoagulable conditions. * Heparin-induced thrombocytopenia (HIT) comprises a heparin-mediated autoimmune response potentiating platelet activation as well as venous and arterial thromboses. --------------------------------------------------------------------------------------------------------------------------------------------Autologous Transfusion, Recombinant Factor VIIa, and Bloodless Medicine * Reinfusion of shed blood was employed as early as 1818. Preoperative donation of autologous blood was advocated in the 1930s when the first blood banks were established. Autologous transfusion has grown in popularity in response to the increase in complex operative procedures and new technologic advances that allow its safe use. * The two primary reasons for employing autologous transfusion are avoidance of complications associated with allogeneic transfusion and conservation of blood resources. * The three types of autologous blood transfusion are preoperative autologous donation (PAD), acute normovolemic hemodilution (ANH), and intraoperative and postoperative blood recovery (salvage). * PAD became accepted as a standard practice in certain elective surgical settings such as total joint replacement surgery, so that by 1992 more than 6% of the blood transfused in the United States was autologous. Subsequently, substantial improvements in blood safety have been accompanied by a decline in PAD as well as an interest in ANH as an alternative, lower cost strategy. * The criteria for autologous donors are not as stringent as those for allogeneic donors. Transfusion service policies, implemented under the auspices of hospital transfusion committees, differ regarding collection and use of autologous blood with positive viral markers. It is common practice to preclude the blood reactive for hepatitis B surface antigen and human immunodeficiency virus because of concerns for the safety of both patients and personnel. Contraindications include evidence of infection and risk of bacteremia, scheduled surgery for correction of aortic stenosis, and unstable angina. * Although autologous blood collections have become popular, the costs associated with their collection are higher than those associated with the collection of allogeneic blood. * ANH is the removal of whole blood from a patient while restoring the circulating blood volume with an acellular fluid shortly before an anticipated significant surgical blood loss. The chief benefit of ANH is the reduction of red blood cell losses when whole blood is shed perioperatively at lower hematocrit levels after ANH is completed. * Because there is no good evidence that either PAD or ANH is effective at eliminating allogeneic blood transfusions, these autologous blood collection techniques cannot be considered cost-effective alternatives to allogeneic blood.

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* The term intraoperative blood collection or recovery describes the technique of collecting and reinfusing blood lost by a patient during surgery. The oxygen-transport properties of recovered red blood cells are equivalent to stored allogeneic red blood cells. The survival of recovered blood cells appears to be at least comparable to that of transfused allogeneic red blood cells. * Postoperative blood collection denotes the recovery of blood from surgical drains followed by reinfusion, with or without processing. Postoperative autologous blood transfusion is practiced widely but not uniformly. * Fibrin glue is derived from a source of fibrinogen and factor XIII (fibrin-stabilizing factor), in which a solution of fibrinogen is mixed with a solution of thrombin and applied to a surgical field. These preparations represent additional allogeneic blood donor exposure. Patients should be made aware of the potential complications as well as the potential benefits. * Recombinant factor VIIa (rfVIIa) has been approved for treatment of bleeding in hemophilia patients with inhibitors. It has also been successful in patients without hemophilia with acquired antibodies against factor VIII (acquired hemophilia). Pharmacologic doses of rfVIIa enhance the thrombin generation on already activated platelets and, therefore, may also be of benefit in providing hemostasis in other situations, such as those characterized by profuse bleeding and impaired thrombin generation. * Bloodless medicine and surgery is defined using a team approach that reduces blood loss and employs the best available alternatives to allogeneic transfusion therapy while focusing on the provision of the best possible medical care to all patients. Some patients, however, object to receiving blood or blood products as part of their medical treatment on religious grounds or because of concern about the safety of blood transfusions, regardless of their religious background. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia and Treatment of Chronic Pain * The normal physiology of neuronal function, receptors, ion channels, and plasticity is altered by persistent pain. * Because of the large number of sources and manifestation of chronic pain, classification needs to include cancer-related, non–cancer-related, neuropathic, inflammatory, arthritis, and musculoskeletal pain. * Interdisciplinary management of chronic pain must include specialists in psychology, physical therapy, occupational therapy, and anesthesiology. * Drugs used for chronic pain are multiple and include opioids, nonsteroidal anti-inflammatory drugs and antipyretic analgesics, serotonin receptor ligands, antiepileptics, antidepressants, topical analgesics (e.g., nonsteroidal anti-inflammatory drugs, capsaicin, local anesthetics, opioids), other analgesics, and adjuvants such as local anesthetics, α2-agonists, baclofen, botulinum toxin, antiemetics, laxatives, novel drugs such as cannabinoids, and ion channel blockers. * Interventional management of chronic pain includes the use of diagnostic blocks, therapeutic blocks, continuous catheter techniques, and stimulation techniques such as acupuncture, transcutaneous electrical nerve stimulation, and spinal cord stimulation. * Perioperative management of patients with chronic pain involves the use of opioid and nonopioid analgesics; evaluation for dependence, addiction, and pseudo-addiction; and practical considerations. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Thoracic Surgery * Patients undergoing pulmonary resection should have a preoperative assessment of their respiratory function in three areas: lung mechanical function, pulmonary parenchymal function, and cardiopulmonary reserve (the “three-legged stool” of respiratory assessment). * After lung resection surgery, it is usually possible to wean and extubate patients with adequate predicted postoperative respiratory function in the operating room provided they are “AWaC” (alert, warm, and comfortable). * Interventions that have been shown to decrease the incidence of respiratory complications in high-risk patients undergoing thoracic surgery include cessation of smoking, physiotherapy, and thoracic epidural analgesia. * Geriatric patients are at a high risk for cardiac complications, particularly arrhythmias, after large pulmonary resections. Preoperative exercise capacity is the best predictor of post-thoracotomy outcome in the elderly. * The ability to perform fiberoptic bronchoscopy and a detailed knowledge of bronchial anatomy are necessary for anesthesiologists to provide reliable lung isolation. * Use of double-lumen endobronchial tubes (DLTs) is the standard method of providing lung isolation in adults. Bronchial blockers are a reasonable alternative for lung isolation in patients with abnormal upper or lower airways. * With the use of intravenous anesthetic techniques or volatile anesthetics at less than or equal to 1-MAC doses, hypoxemia during one-lung ventilation (OLV) occurs infrequently. The use of continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) as treatment for hypoxemia during OLV should be guided by the individual patient's lung mechanics.

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* The use of large tidal volumes during OLV (e.g., 10 mL/kg) can contribute to acute lung injury, particularly in patients at increased respiratory risk, such as after pneumonectomies. * Anesthetic management of a patient with an anterior or superior mediastinal mass should be guided by the patient's symptoms and the preoperative CT scan and echocardiography. The fundamental principle of anesthetic management for these patients is noli ponti ignii consumere (“don't burn your bridges”). * Continuous paravertebral local anesthetic blockade combined with multimodal analgesia is a reasonable alternative to epidural analgesia for thoracic surgery with fewer side effects. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Cardiac Surgical Procedures * The most common causes of central nervous system injury or dysfunction in cardiac surgical patients are thought to be microemboli and macroemboli. * After coronary revascularization, mortality was far lower in patients with normal renal function (0.9%) than in patients with acute renal failure (63%). * In addition to activating the extrinsic and intrinsic hemostatic pathways, cardiopulmonary bypass (CPB) directly affects platelet function through the effects of hemodilution, hypothermia, and contact activation by bypass circuit materials. * When choosing anesthetic agents and doses during induction and maintenance, one should consider any pharmacodynamic properties that might affect blood pressure, heart rate, or cardiac output, as well as the desirability of “early” extubation (i.e., within a few hours after the operation is completed). * Patients undergoing “redo” cardiac surgery (i.e., those who have had a previous median sternotomy) warrant special concern about the possibility of sudden massive hemorrhage. * Right ventricular dysfunction or failure may also occur after CPB because of inadequate myocardial protection, inadequate revascularization with resultant right ventricular ischemia or infarction, preexisting pulmonary hypertension, intracoronary or pulmonary air embolism, chronic mitral valve disease, or tricuspid regurgitation. * Numerous clinical approaches have been shown to measurably reduce the inflammatory response in cardiac surgical patients: modification of surgical and perfusion techniques, modification of circuit components, and pharmacologic strategies. * No single anesthetic “recipe” is suitable for all patients undergoing coronary artery bypass graft (CABG) procedures. * Randomized trials comparing off-pump CABG with on-pump CABG have not found convincing or consistent evidence to support one approach over another. * Types of procedures that are performed in the cardiac catheterization laboratory include (1) electrophysiologic assessment of rhythm disorders and management by ablation or by implantation of devices, (2) biventricular pacing for heart failure, (3) stenting of abdominal or thoracic aortic aneurysms, (4) balloon dilation and stenting for valvular and subvalvular lesions, and (5) the use of occlusion or umbrella devices to close an atrial or ventricular septal defect or a patent ductus arteriosus. Sedation or anesthesia improves the efficacy and safety of many procedures. * Even after uncomplicated cardiac surgery, a midline sternotomy (or thoracotomy) causes a significant reduction in total lung capacity, vital capacity, forced expiratory volume in 1 second, and functional residual capacity. * In 2007, the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists published a joint statement on practice guidelines for transfusion and blood conservation in cardiac surgery. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Correction of Cardiac Arrhythmias * Cardiac arrhythmias are caused by disorders of impulse formation or disorders of impulse conduction, or both. Cardiac arrhythmia may be life-threatening because of a reduction in cardiac output, reduction in myocardial blood flow, or precipitation of a more serious arrhythmia. * Radiofrequency ablation is the therapy of choice for many types of cardiac arrhythmias. * Electrophysiologic studies are used to map out normal and abnormal intracardiac structures. In this process, the mechanism of arrhythmia is delineated, and ablation can be performed at the same time. * Pacing technologies have been developed to treat heart failure resulting in increases in pulse pressure, left ventricular stroke volume, cardiac index, and wedge pressure. * Implantable pacemakers are placed for treatment of symptomatic bradycardia with the ability to respond to changing hemodynamic demands. * The development of implantable cardioverter-defibrillators (ICDs) to terminate ventricular tachyarrhythmias by delivering high-voltage shocks to the ventricle has revolutionized therapy for cardiac arrhythmias. * The main purpose of ICD placement is to prevent sudden cardiac death resulting from hemodynamically unstable ventricular arrhythmias.

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* An ICD also can be placed for cardiac resynchronization. Cardiac resynchronization therapy has been shown to improve heart failure symptoms, quality of life, exercise capacity, and electrocardiographic variables. * Anesthetic management of patients for correction of cardiac arrhythmias depends on associated comorbid illness and the procedure that is planned. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Vascular Surgery * Recent advances in our understanding of the biology of atherogenesis suggest that endothelial dysfunction is a critical element in the pathogenesis of atherosclerotic cardiovascular disease and its complications. Inflammation in the artery wall probably plays a fundamental role as well. * Major vascular surgery is particularly challenging to the anesthesiologist because these are high-risk operations in a patient population with a high prevalence of either overt or occult coronary artery disease, which is the leading cause of perioperative and long-term mortality after vascular surgery. * Accurate clinical assessment of the pretest probability of significant coronary artery disease is necessary for prudent use and rational interpretation of preoperative cardiac testing. * Guidelines on perioperative cardiovascular evaluation and care suggest that coronary intervention is rarely necessary to simply lower the risk of surgery unless such intervention is indicated irrespective of the preoperative context. Current evidence does not support the role of prophylactic coronary revascularization as a means to reduce perioperative or long-term morbidity after major vascular surgery. * Perioperative management of patients undergoing vascular surgery requires an understanding of the underlying pathophysiology of the specific vascular lesion. * Patients should be maintained on their usual cardiovascular medications throughout the perioperative period. Antiplatelet therapy requires special consideration and must be individualized to each patient. * Prevention and treatment of perioperative myocardial ischemia require careful control of the determinants of myocardial oxygen supply and demand. ST-segment monitoring, particularly with computerized ST-segment analysis, should be used to detect myocardial ischemia during the perioperative period. * Clinical trial data suggest that initiation of perioperative β-blocker therapy has potential benefits and risks. * The clinical usefulness of any intraoperative monitoring technique ultimately depends on patient selection, accurate interpretation of data, and appropriate therapeutic intervention. * Evidence suggests that maintenance of vital organ perfusion and function by the provision of stable perioperative hemodynamics is more important to overall outcome after aortic surgery than is the choice of anesthetic agent or technique. * The pathophysiology of aortic cross-clamping and unclamping is complex and depends on many factors, including the level of the cross-clamp, the extent of coronary artery disease and myocardial dysfunction, blood volume and distribution, activation of the sympathetic nervous system, and the anesthetic agents and techniques. * The degree of preoperative renal insufficiency is the strongest predictor of postoperative renal dysfunction. * Endovascular aortic surgery has recently emerged as a less invasive alternative to conventional open aortic repair. Endoleak, or the inability to obtain or maintain complete exclusion of the aneurysm sac from arterial blood flow, is a complication specific to endovascular aortic repair. * The primary clinical utility of cerebral monitoring during carotid endarterectomy is to identify patients in need of carotid artery shunting; secondarily, such monitoring is used to identify patients who may benefit from blood pressure augmentation or change in surgical technique. * Postoperative hypothermia is associated with many undesirable physiologic effects and may contribute to adverse cardiac outcome. --------------------------------------------------------------------------------------------------------------------------------------------Neurosurgical Anesthesia * For the purposes of planning a control strategy for intracranial pressure (ICP), the clinician should consider the four subcompartments of the intracranial space: cells, interstitial and intracellular fluid, cerebrospinal fluid, and blood. * The venous side of the cerebral circulation is a largely passive compartment that is often the cause of increased ICP or “tightness” of the surgical field, but that is commonly overlooked by clinicians. * Cerebral perfusion pressure (CPP) should be supported at or near waking normal levels in patients with recent cerebral injuries (e.g., traumatic brain injury [TBI], subarachnoid hemorrhage [SAH]) because of low resting cerebral blood flow and impaired autoregulation. * When patients are managed in the sitting position, blood pressure should be corrected to the level of the external auditory meatus, and mean arterial pressure (MAP) should be maintained at 60 mm Hg in normotensive adults.

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* The minimal standard of care for monitoring to detect venous air embolism in at-risk situations includes the precordial Doppler and end-tidal carbon dioxide analysis. * Despite encouraging preclinical data, therapeutic mild hypothermia cannot currently be advocated in the care of head-injured patients in the intensive care unit or during the operative management of patients with intracranial aneurysms because of negative human trials in those patient groups. * The most important consideration in the anesthetic management of patients undergoing clipping or coiling after acute SAH is the prevention of paroxysmal hypertension with its attendant risk of aneurysm rerupture. Nonetheless, adequate perfusion pressure is needed if temporary clips are used or during management of cerebral vasospasm. * Although induced hypotension is very rarely employed electively in aneurysm surgery, the clinician must be ready to reduce blood pressure immediately and accurately in the event of aneurysm rupture. * Tracheal intubation of a head-injured patient with an undefined cervical spine injury can be accomplished using a rapid-sequence induction with manual in-line stabilization (occiput held rigidly to the backboard) with only a very small risk of injury to the spinal cord. * CPP (CPP = MAP − ICP) should be supported at 60 mm Hg in the first 48 hours after TBI in adults. * Hypocapnia has the potential to cause cerebral ischemia, particularly in recently injured brain and in brain beneath retractors; it should be used only when absolutely necessary for the control of critically increased or uncertain ICP. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Bariatric Surgery * In the United States, 200 million people are overweight or obese. Across the globe, more people are obese than malnourished. Obesity may become the largest single preventable cause of death, and it results in major morbidity and mortality. * Metabolic syndrome includes abdominal obesity, decreased high-density lipoprotein, increased insulin, glucose tolerance, and hypertension and is present in nearly 50 million people in the United States alone. * The biggest single risk factor for sleep apnea is obesity; a majority of patients affected have increased oral and pharyngeal tissue, which makes ventilation, intubation, and extubation more challenging. * Choices for medical management of obesity are limited, and success with just medical management is uncommon. Changes in behavior are important for success. * Surgery for obesity is recommended at a body mass index (BMI) of 40 kg/m2 or at a BMI greater than 30 kg/m2 with comorbid conditions expected to respond to weight loss secondary to surgical therapy, such as hypertension, diabetes, and hypercholesterolemia. In clinical trials, long- term survival is better in the surgically treated group than in those managed medically. * Preoperative evaluation should focus on cardiopulmonary issues and securing an airway, along with the problems of diabetes, hypertension, sleep apnea, and other conditions. * Anesthetic drugs should be tailored according to their lipid solubility and knowledge of their lingering depressive effects on respiration. * Preparation and positioning are key to successful airway management. Preoperative pressure-support ventilation should be used adjunctively if possible. * Intraoperative ventilation is assisted by complete paralysis, moderate positive end-expiratory pressure, tidal volumes based on ideal body weight, and recruitment maneuvers as needed. * Common serious postoperative complications are deep venous thrombosis and staple line issues. * Obese patients undergoing non–weight loss surgery would benefit from an approach similar to that for bariatric surgery. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia and the Renal and Genitourinary Systems * Innervation of the intra-abdominal components of the genitourinary system—the kidney and the ureter—is primarily thoracolumbar (T8-L2). The nerve supply of the pelvic organs—the bladder, the prostate, the seminal vesicles, and the urethra—is primarily lumbosacral with some lower thoracic input. * The spinal level of pain conduction for the external genitourinary organs is S2-4 except for the testes (T10-L1). * The kidneys receive 15% to 25% of the total cardiac output, with most of this blood directed to the renal cortex. Renal medullary papillae are more vulnerable to ischemic insults. Kidneys successfully autoregulate their blood flow between 60 mm Hg and 160 mm Hg mean arterial pressures. * The glomerular filtration rate (GFR) is the best measure of glomerular function. Creatinine clearance is a good measure of the GFR; urine output is not. * Hypervolemia, acidemia, hyperkalemia, cardiorespiratory dysfunction, anemia, and bleeding disturbances are manifestations of chronic renal failure.

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* Although renal transplantation reverses most of the abnormalities in end-stage renal disease, dialysis improves only some, and introduces additional complications of its own. * Newer techniques, such as laser prostatectomy, are making transurethral resection of the prostate (TURP) syndrome a rare event. TURP syndrome is a constellation of symptoms caused by the absorption of hypotonic bladder irrigants. Cardiovascular and neurologic changes are due to hypo-osmolality, hyponatremia, hyperglycinemia, hyperammonemia, and hypervolemia. * Regional anesthesia offers several advantages over general anesthesia for standard, but not laser, TURP, although 30-day mortality rates remain unchanged at 0.2% to 0.8%. * Laparoscopic surgery in urology frequently requires insufflation of carbon dioxide into the retroperitoneal space. In lengthy procedures, pneumomediastinum and subcutaneous emphysema of the head and neck may occur. * Extracorporeal shock wave lithotripsy (ESWL) is associated with significant physiologic changes related to immersion if a water bath is used. Shock waves can cause arrhythmias and injury to the lungs. Pregnancy and untreated bleeding disorders are contraindications to ESWL. * Of renal tumors, 5% to 10% extend into the renal vein, inferior vena cava, and right atrium. Complications ranging from circulatory failure to embolization of tumor during surgery may occur. Cardiopulmonary bypass may be necessary for surgery. * Radical prostatectomy is accompanied by significant blood loss. Intraoperative venous air embolism has been reported. Regional anesthesia with spontaneous ventilation is associated with less blood loss than general anesthesia and intermittent positive-pressure ventilation. Other advantages of epidural anesthesia include decreased deep vein thrombosis and preemptive analgesia. Although some studies report better outcomes with epidural anesthesia, others do not. * Robotic radical prostatectomy is associated with reduced blood loss and postoperative pain compared with open radical prostatectomy. Anesthetic concerns are related to steep head-down tilt and pneumoperitoneum and include hypercarbia, hypoxemia, increased intraocular and intracranial pressures, decreased perfusion pressure to lower extremity, and positional injuries. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia and the Hepatobiliary System * All volatile anesthetics decrease hepatic blood flow, but desflurane and sevoflurane have the least significant effect on total hepatic blood flow and hepatic oxygen delivery, whereas halothane induces the most profound reductions in hepatic blood flow. * Advanced liver disease may impair the elimination, prolong the half-life, and potentiate the clinical effects of several drugs, including morphine, meperidine, alfentanil, vecuronium, rocuronium, mivacurium, benzodiazepines, and dexmedetomidine. These drugs should be used cautiously in patients with cirrhosis or end-stage liver disease from any cause and their dosage and administration should be adjusted accordingly. * Abnormal liver enzyme test results may be seen in up to 4% of normal individuals and up to 36% of psychiatric patients, although the prevalence of clinically significant hepatic dysfunction in these individuals is less than 1%, thus suggesting that further costly preoperative testing is unnecessary in asymptomatic patients. * Patients with asymptomatic elevations in serum transaminase levels (less than two times normal values) may undergo surgery with minimal impact on perioperative outcome. * Retrospective data suggest that patients with acute hepatitis from any cause are at increased risk for hepatic failure and death after elective surgery. Thus, elective surgery should be delayed in these individuals until resolution of acute hepatocellular dysfunction can be confirmed. * Asymptomatic patients with any form of chronic hepatitis should be carefully assessed before elective surgery and meticulous care should be taken to maintain hepatic perfusion in the perioperative period and to avoid any hepatotoxic drugs or significant hypotension that might precipitate liver failure or hepatic encephalopathy. * Based on large retrospective studies, patients with cirrhosis who are undergoing abdominal surgery, especially those in CPT class C, appear to have an increased risk of perioperative death. Elective surgery in these individuals should be avoided, if possible, in favor of less invasive procedures. * Postoperative jaundice may occur as a result of intraoperative hepatobiliary injury, anesthetic-induced hepatotoxicity, severe hepatic hypoperfusion (e.g., cardiogenic or hypovolemic shock), and a variety of medications. * Patients with the most advanced forms of liver disease (e.g., CPT class B or C cirrhosis) should receive management designed to maximize hepatic perfusion and hepatic oxygen delivery and to prevent and treat the complications of hepatic encephalopathy, cerebral edema, coagulopathy, hemorrhage, and portal hypertension. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Abdominal Organ Transplantation Solid Organ Transplantation

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* Solid organ transplantation is an accepted treatment of end-stage organ disease. * The discrepancy between the number of organ donors and organ recipients is increasing. * To increase the donor pool, living organ donors and extended criteria donors are being used. * Preoperative evaluation of organ systems should consider interval changes. Kidney Transplantation * Patients with end-stage renal disease are subject to accelerated atherosclerosis and should be considered to have a significant perioperative cardiac risk. * Maintenance of adequate perfusion pressure to the newly transplanted kidney is crucial for initial graft function. * Anesthetic drugs that are dependent on renal excretion, especially muscle relaxants or their metabolites, should be used with caution. Pancreas Transplantation * Patients may undergo pancreas transplantation alone, in combination with kidney transplantation, or after kidney transplantation. * Close glucose monitoring is required throughout the procedure. * Administration of colloids is preferred intraoperatively. * The immunosuppressive drug OKT3 can cause significant hemodynamic instability and noncardiogenic pulmonary edema. Liver Transplantation * The model of end-stage liver disease calculates the severity of liver disease. * Preparation for massive transfusion and significant hemodynamic instability is essential. * Extubation in the operating room can be safely performed in selected patients. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Laparoscopic Surgery * CO2 pneumoperitoneum results in ventilatory and respiratory changes. Pneumoperitoneum decreases thoracopulmonary compliance. Paco2 increases (15% to 25%) due to CO2 absorption from the peritoneal cavity. Capnography reliably reflects this increase, which plateaus after 20 to 30 minutes. * In compromised patients, cardiorespiratory disturbances aggravate the increase in Paco2 and enlarge the gradient between Paco2 and Petco2. * Any increase in Petco2 larger than 25% or occurring later than 30 minutes after the beginning of peritoneal CO2 insufflation should suggest CO2 subcutaneous emphysema, the most frequent respiratory complication during laparoscopy. * Peritoneal insufflation induces alterations of hemodynamics, characterized by decreases of cardiac output, elevations of arterial pressure, and increases of systemic and pulmonary vascular resistances. Hemodynamic changes are accentuated in high-risk cardiac patients. * The pathophysiologic hemodynamic changes can be attenuated or prevented by optimizing preload before pneumoperitoneum and by vasodilating agents, α2-adrenergic receptors agonists, high doses of opioids, and β-blocking agents. * Similar pathophysiologic changes occur during pregnancy and in children. Laparoscopy can be safely managed in pregnant women before the 23rd week of pregnancy provided that hypercarbia is prevented. The open laparoscopy approach should be considered to avoid damaging the uterus. * Gasless laparoscopy may be helpful to reduce pathophysiologic changes induced by CO2 pneumoperitoneum but unfortunately increases technical difficulty. * Laparoscopy results in multiple postoperative benefits, allowing for quicker recovery and shorter hospital stay. These advantages explain the increasing success of laparoscopy, which is proposed for many surgical procedures. * Although no anesthetic technique has proved to be clinically superior to any other, general anesthesia with controlled ventilation seems to be the safest technique for operative laparoscopy. * Improved knowledge of the intraoperative repercussions of laparoscopy permits safe management of patients with more and more severe cardiorespiratory disease, who may subsequently benefit from the multiple postoperative advantages offered by this technique. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Obstetrics * Functional residual capacity (FRC) begins to decrease in the second trimester of pregnancy and is decreased to 80% of the nonpregnant value at full term. This decrease in FRC causes maternal hypoxemia to develop very quickly after apnea associated with the induction of general anesthesia. Although general anesthesia is no longer routinely used for elective cesarean deliveries, it continues to have a place in current practice.

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* The presence of fetal heart rate (FHR) variability is predictive of fetal well-being and early neonatal health. FHR accelerations signal fetal well-being, whereas late decelerations are suggestive of fetal hypoxia. * Animal studies have suggested that vasopressors with predominantly α-adrenergic activity cause a reduction in uterine blood flow that can adversely affect the fetus. Studies in women undergoing elective cesarean section have not confirmed these animal data and have suggested that small doses of phenylephrine may improve the mother's hemodynamics without adversely affecting the fetus. * No epidural test dose will exclude all instances of intravenous or intrathecal placement of catheters; however, aspiration of a multiorificed catheter will detect many of them. The combination of aspiration, test dose, and fractionation of doses increases the safety of epidural anesthesia. * If an accidental dural puncture occurs during placement of an epidural block, threading the epidural catheter into the spinal space to provide continuous spinal anesthesia offers many advantages. If the epidural block is relocated to another interspace, however, the loss of resistance to air technique should not be used because of the risk of pneumocephalus and severe headache. * Many cases of failed intubation occur when a “difficult airway” is not recognized before induction of general anesthesia. Airways change during pregnancy and may worsen during labor, especially in a preeclamptic patient. Careful airway evaluation, although imperfect, must be performed before initiation of general anesthesia. * Uterine rupture is a rare event that can cause maternal and fetal mortality. Its incidence during vaginal birth after cesarean section is greater than previously thought. A sudden increase in baseline uterine tone or the sudden absence of uterine pressure coupled with evidence of acute fetal bradycardia may indicate uterine rupture. * Magnesium sulfate is the agent of choice for seizure control in preeclamptic patients and is a first-line tocolytic therapy for preterm labor. Treatment with magnesium can produce hypotension and may later potentiate the maternal hemodynamic response to pressors. Magnesium also potentiates the action of both depolarizing and nondepolarizing muscle relaxants. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Orthopedic Surgery * Older age is a significant risk factor for poor outcome after orthopedic surgery. Elderly patients presenting for orthopedic surgery often have multiple comorbid conditions that must be considered in the perioperative anesthetic plan. * Patients with arthritis (osteoarthritis, rheumatoid arthritis, ankylosing spondylitis) have special problems that must be addressed in an anesthetic plan. * For many orthopedic procedures, regional anesthesia may reduce perioperative complications compared with general anesthesia, and may provide superior analgesia. * Fat embolism syndrome is a well-recognized complication of orthopedic trauma and major joint replacement. Early intervention and stabilization of these patients may avoid significant morbidity. * Corrective surgery for spinal deformities (scoliosis, kyphosis, kyphoscoliosis) presents a significant challenge to the anesthesiologist. These patients are at risk for large blood loss, pulmonary complications, neurologic deficits, and postoperative loss of vision. Changes in anesthetic management may reduce the incidence of some of these complications. --------------------------------------------------------------------------------------------------------------------------------------------Geriatric Anesthesia * Two important principles must be kept in mind when discussing the physiology of aging. First, aging is associated with a progressive loss of functional reserve in all organ systems. Second, the extent and onset of these changes vary from individual to individual. * Generally, elderly patients are more sensitive to anesthetic agents. Less medication is usually required to achieve a desired clinical effect, and drug effect is often prolonged. * The greatest concern of the elderly patient is to maintain independence. The most important outcome and overall objective of perioperative care of geriatric patients is to speed recovery and avoid functional decline. * Surgical risk and outcome in patients 65 years old and older depend primarily on four factors: age, the patient's physiologic status and coexisting disease (American Society of Anesthesiologists class), whether the surgery is elective or urgent, and the type of procedure. * When performing preoperative evaluation of a geriatric patient, one should have a high index of suspicion for disease processes commonly associated with aging, and one should assess the degree of functional reserve of specific, pertinent organ systems, and the patient as a whole, before surgery. * Important issues of special concern in caring for elderly patients are cognitive dysfunction and perioperative delirium.

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* Current data suggest that routine testing on the basis of age alone is not indicated. Instead, selective testing should be done on the basis of the history and physical examination and the specific surgical procedure. * Preoperative comorbid disease is a greater determinant of postoperative complications than anesthetic management. Perioperative care should be tailored to comorbid disease and requirements of the surgical procedure. * Preoperative and postoperative management of pulmonary problems in elderly patients is of particular importance in the prevention of morbidity and mortality. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Trauma * Trauma anesthesiology is a unique subspecialty of our profession. Optimal anesthetic care of trauma patients depends on an understanding of trauma system design and surgical priorities. * Successful emergency airway management is based on having a clear plan, such as the American Society of Anesthesiologists algorithm for difficult airways. In general, rapid-sequence induction of anesthesia accompanied by cricoid pressure and in-line cervical stabilization, followed by direct laryngoscopy, is the safest and most effective approach. * Recognition of hemorrhagic shock is at the center of advanced trauma life support. Hemorrhagic shock indicates the need for rapid operative treatment, with the possibility of a “damage control” approach. * Resuscitation during acute hemorrhagic shock is controversial, but current recommendations are to maintain deliberate hypotension during active bleeding by limitation of crystalloid infusion and to emphasize maintenance of blood composition by early transfusion of red blood cells, plasma, and platelets. * Management of patients with severe traumatic brain injury poses unique challenges for the anesthesiologist. Monitoring and maintenance of cerebral perfusion are the keys to operative and intensive care of these patients. * Trauma anesthesiology includes a substantial component of critical care practice. Operating room use of advanced ventilator strategies, including permissive hypercapnia and facilitated spontaneous ventilation (bilevel or airway pressure release ventilation), may improve outcomes. * Prehospital, interhospital, and intrahospital transport of critically injured patients is the province of the trauma anesthesiology team and requires planning and attention to detail. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia and Prehospital Emergency and Trauma Care * Anesthesiology was instrumental in creating critical care and emergency medicine. In many countries, worldwide anesthesiology departments are responsible for prehospital emergency and trauma care. Physician-based emergency medical services (EMS) systems exist in many European countries, whereas paramedics are the mainstay of EMS in the United States. * The basics of prehospital care follow the general form of basic life support (BLS) and advanced life support (ALS), depending on the nature of the EMS system in place for a given region or country. * In major trauma, prehospital care must aim at limiting the time spent on the scene, controlling hemorrhage, and expediting transport to a trauma center, often ideally via rescue helicopter. Prehospital fluid resuscitation for major trauma is controversial and patients with penetrating torso injuries and hemorrhagic shock might benefit from limited fluid resuscitation, in particular in urban settings. Prevention of the lethal triad in trauma of hypothermia, acidosis, and coagulopathy is paramount. * In acute coronary syndrome (ACS), achieving rapid reperfusion of the ischemic myocardium is the main goal. Opioids (morphine), oxygen, nitrates, and aspirin (MONA) are the main components of prehospital therapy. Fibrinolysis for ACS has been used with much success in the prehospital setting but requires very close supervision by EMS physicians. * Prehospital endotracheal intubation and rapid-sequence induction (RSI) have been shown in more than 15 studies to be associated with increased mortality and poorer neurologic outcomes, in particular after traumatic brain injury. It appears that what anesthesiologists consider the standard of care in the operating room may not be the ideal approach for less experienced EMS providers. Perhaps reappraising intubation and RSI in favor of alternate airways such as the laryngeal mask airway or laryngeal tube can improve outcomes. * Medical simulation is rapidly becoming the future standard for teaching and training prehospital EMS personnel in the management of complex emergency scenarios. --------------------------------------------------------------------------------------------------------------------------------------------Chemical and Biological Warfare Agents: The Role of the Anesthesiologist * The management of injury from chemical and biological warfare (CBW) is a continuing process from the site of release of noxious agents to the hospital. The anesthesiologist may be involved at all stages in the provision of essential early life support through intensive care unit care.

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* CBW management requires advanced life support and other specialized skills that are part of the anesthesiologist's sphere of operation. * CBW injury should not be approached in isolation from the many clinical lessons that already exist from accidental hazardous materials (HAZMAT) releases and natural epidemic infections. CBW release poses a risk to the medical responder, and he or she should be trained and equipped to operate safely in a contaminated or infected zone. * Chemical and biological hazards form part of a continuous hazard spectrum. Agents from different parts of the spectrum may have common effects on susceptible somatic systems. Because detection of a released agent may not be immediate, response should be based on presenting signs and symptoms and may require the provision of life support. * Each hazard in the spectrum has four key properties: toxicity, latency, persistency, and transmissibility. The first two determine the management of the patient, and the second two determine the management of the incident. * A wide range of potential hazards (often loosely described as threats) have been suggested in a climate of apprehension because of the possibility of terrorist attack. On the basis of preexisting military and intelligence information, these potential hazards can be refined down to provide a framework of genuine hazards and management protocols that can be applied across the hazard spectrum. * CBW agents should not be regarded medically as weapons of mass destruction (WMD); rather, they are agents that may cause mass injury. Early life support and specific therapy can break the link between mass injury and mass loss of life. * Most of the toxic hazards likely in civil life are part of the United Nations HAZMAT classification. Planning for accidental industrial releases is relevant to the management of deliberated CBW release. * Toxic agents have been used in military and civil releases over the past 30 years and currently should be regarded as a potential terrorist threat. * Management of exposed patients depends on the protection of medical responders, early provision of life support, and specific antidote and antimicrobial therapy. Decontamination of patients may cause delays in starting treatment and is not always necessary. Essential life support (TOXALS) should be given during decontamination if required. Mass ventilation capability in the hospital is important in the management of accidental and deliberate respiratory failure from chemical and biological causes. * Military chemical warfare agents, such as nerve agents, vesicants, pulmonary edemagens, cyanides, and certain toxins, pose the greatest hazard in civil releases. Many industrial chemicals are equally hazardous. * Classic biological warfare agents, such as anthrax and plague, are used in deliberately induced epidemics with far longer latencies than chemical warfare attacks. Anesthetic involvement is usually at the intensive care stage. * Lessons learned from the current fears of deliberate toxic release will have value for the management of the increasing number of accidental individual and mass toxic exposures that form the greater risk for human life in the 21st century. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Eye, Ear, Nose, and Throat Surgery Ear, Nose, and Throat * Patients can present with an acute onset of stridor from various conditions, including epiglottitis, laryngotracheobronchitis, inhaled foreign bodies, angioneurotic edema, tracheitis, burns, and bilateral vocal cord palsies after surgery. * Facial injuries can produce severe bleeding with the aspiration of blood, bone, loose teeth, and soft tissue fragments, so the priority is to clear and secure the airway. * For ear surgery, several anesthesia and airway management devices are available, all of which offer different advantages and disadvantages. * Bleeding from a tonsil after surgery usually occurs within the first 6 hours. * The optimal anesthetic technique for endoscopy procedures depends on the patient's general condition; the size, mobility, and location of the laryngeal lesion; the use of a laser; and surgical requirements. Eye * Understanding ocular anatomy and physiology and the systemic effects of ophthalmic medications is essential to prepare an appropriate anesthesia plan. * Pressure on the globe or any orbital contents can result in a trigeminovagal or oculocardiac reflex with bradycardia, atrioventricular block, or asystole. * The blood supply to the retina is driven by the ocular perfusion pressure, which is determined by the arterial blood pressure and the intraocular pressure (IOP). * Deep inhaled anesthesia reduces IOP, whereas ketamine and succinylcholine can increase IOP.

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* Sudden increases in IOP in the setting of open globe injury can lead to vitreous loss and blindness. * Complications of retrobulbar block include retrobulbar hemorrhage, increased IOP, intra-arterial injection with convulsions, and subarachnoid injection via the optic nerve sheath with respiratory arrest. * Nitrous oxide should be avoided for 15 minutes before the use of intraocular gas. Nitrous oxide must be avoided for 7 to 45 days after use, or until the gas bubble is resorbed. * True ophthalmic emergencies, such as chemical burns and central retinal artery occlusions, must be treated within minutes to avoid permanent vision loss. Open globe injuries and other urgent procedures can be scheduled after appropriate NPO status. * Eye compression from a facemask or positioning can lead to central retinal artery occlusion. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Robotic Surgery * Robotic surgery is accomplished by an autonomous, reprogrammable manipulator designed to move and articulate specialized instruments through programmed motions that achieve a specific task. A robot can be given three-dimensional coordinates from any imaging device (e.g., computed tomography) that allows it to recognize surfaces on which it will do a specific, programmed task. * Robotically assisted surgery involves mechanical devices that move by a motorized system under partially programmed control, and that can be instantly controlled or modified by a surgeon's intervention. * Computer-assisted surgery involves systems that are manually controlled by the surgeon, and that include a tracking system, sensors, and end-effector instruments. This system provides direct and continuous control of movements. * Telesurgery refers to the ability to perform surgery using computer-assisted instruments from a remote location. * Telemanipulation refers to the ability to produce electronically precise instrument movements at a distance from a remote location. * Telepresence refers to virtual projection of images from remote sites. This virtual projection allows the surgeon to visualize intended robotic movements at distant locations. It also enables telementoring, which is supervision and instruction from a distant location. * Initially, robotically assisted surgical thoracic procedures increased the duration of required general anesthesia. Concomitantly, the duration of one-lung ventilation has been taken to new time extremes, which has given us insight into the respiratory physiology of prolonged one-lung ventilation. As surgeons gain expertise with robotically assisted surgery, operative times are expected to shorten dramatically to approach those for traditional open surgery. * Because of the proximity of the side cart to the patient, the patient must be guarded against inadvertent contact from the motions of the robotic arms. Even more important, after the instruments are engaged to the arms of the robot and are inside the patient, the patient's body position cannot be modified unless the instruments are disengaged entirely and removed from the body cavity. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Laser Surgery * The energy of a photon depends on its frequency. Higher-frequency photons (toward ultraviolet) have more energy than lower-frequency photons (toward infrared). * Stimulated emission is the basis for laser phenomena. Stimulated emission creates a chain reaction leading to the creation of many photons of the same energy. * The biomedical application of laser light involves its ability to focus intense energy in a small area. Focus is determined by monochromicity, collimation, and phase synchrony, all of which are superior in laser light than in ordinary light. * Carbon dioxide (CO2) lasers pose a high risk of remote fires. CO2 laser light is invisible infrared and usually is transmitted to the surgical site in a beam through free air. * Potassium titanyl phosphate (KTP)–type lasers are not usually transmitted through air. These lasers are conducted by fiberoptics to a direct contact tip that creates heat from light, coagulating adjacent tissue. * Infrared laser light at 10.6 µm is strongly absorbed by water molecules. This frequency of laser light, generated by CO2 lasers, explosively converts water to steam. * Different laser sources require different eye protection. Any glass or plastic lens can block CO2 laser light, but other lasers require type-specific protection. * All nonmetal endotracheal tubes have the potential to burn in the airway. * Nitrous oxide should not be used to dilute the fraction of inspired oxygen (Fio2) during airway surgery. Nitrous oxide supports combustion similar to oxygen. * If possible, the Fio2 should be held at less than 40% during airway surgery.

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--------------------------------------------------------------------------------------------------------------------------------------------Ambulatory (Outpatient) Anesthesia * The continued growth in ambulatory surgery is related to expansion in minimally invasive surgical techniques and office-based procedures. * Pre-existing medical conditions are rarely an exclusionary criterion for ambulatory surgery. * Routine laboratory testing is not recommended before ambulatory surgery. * The choice of anesthetic technique has a significant effect on postoperative side effects and discharge time. The use of local anesthesia with sedation, so-called monitored anesthesia care, is associated with the fewest side effects and the shortest time to discharge home. * The use of propofol for induction or maintenance of anesthesia (or both) is associated with a reduced incidence of postoperative nausea and vomiting (PONV). * The use of desflurane or nitrous oxide (or both) in conjunction with antiemetic prophylaxis will facilitate the “fast-track” recovery process. * The use of potent opioid analgesics (e.g., fentanyl, sufentanil) in combination with local anesthetics will decrease the time to discharge home after spinal anesthesia. * Multimodal (“balanced”) analgesic and antiemetic regimens will allow most outpatients to be fast-tracked after ambulatory surgery under general anesthesia. * Fast-tracking after ambulatory surgery is accomplished by taking the patient directly from the operating room to the day-surgery step-down unit (“bypassing the PACU”) or simply discharging the patient home from the PACU (“PACU bypassing”). * Outcomes after ambulatory (and office-based) surgery are no different than after inpatient (hospital-based) surgery procedures. Recent data suggest that for elderly patients the surgical outcome may be improved --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia at Remote Locations * Standards of anesthesia care and patient monitoring do not vary with the anesthetizing location. * Open communication between anesthesiologists and physicians working in non–operating room anesthetizing locations is key to efficient and timely provision of anesthetic care to patients in these areas. * Anesthesiologists working in areas where radiology equipment is in use need to be knowledgeable regarding radiation safety and take adequate precautions to ensure their own safety. * The iodinated contrast media used in the radiology and neuroradiology suites, as well as the cardiac catheterization laboratory, may cause significant adverse reactions, and patients receiving contrast media require close monitoring. * The unique nature of the magnetic resonance imaging suite with its powerful magnetic fields mandates special care and training to avoid disastrous adverse events. * Provision of quality anesthetic management in the cardiac catheterization laboratory requires an understanding of the patient's underlying condition and the procedure to be performed. * Electroconvulsive therapy has profound physiologic effects that must be understood and dealt with by anesthesiologists providing care to patients undergoing such therapy. * Provision of anesthesia services in areas where therapeutic radiation is used requires further understanding of radiation safety and is facilitated by the installation of devices to allow remote monitoring of patients under general anesthesia. --------------------------------------------------------------------------------------------------------------------------------------------Clinical Care in Extreme Environments: At High and Low Pressure and in Space * Hyperbaric oxygen (HBO) exposure (breathing oxygen at increased ambient pressure, typically 2-3 atmospheres absolute [ATA]) causes an increase in arterial and tissue Po2 and no significant change in arterial pH or Pco2. * During HBO therapy, cardiac output is reduced, systemic vascular resistance is increased, and pulmonary vascular resistance is decreased. * Acute illnesses for which HBO is indicated include carbon monoxide (CO) poisoning (based on randomized, controlled studies), gas bubble disease (gas embolism and decompression sickness), and soft tissue necrotizing infections (the latter two based on clinical experience and meta-analysis). * The decision to use HBO to treat a patient with arterial gas embolism or decompression sickness should be based on clinical criteria, including the presence of symptoms, abnormal physical examination, or a history of arterial gas embolism within a few hours even in the absence of symptoms. Neither neurophysiologic testing nor radiographic imaging is useful except, rarely, to exclude other pathologic processes. * The decision to use HBO to treat a patient with CO poisoning should be based on clinical criteria, including a history of impaired consciousness or other neurologic manifestation, pregnancy, or severe exposure (e.g., peak

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carboxyhemoglobin [HbCO] > 25%). The HbCO level correlates poorly with the severity of the illness and is generally useful only to make the diagnosis. * Oxygen-induced seizures are rare and self-limited. Appropriate management includes discontinuation of inhaled oxygen. Chamber pressure should not be altered during the seizure. Decompression can result in pulmonary barotrauma. * The principles of treatment of acute altitude illness include descent and supplemental oxygen. If these options are not available, for acute mountain sickness (AMS) or high-altitude cerebral edema (HACE), dexamethasone and acetazolamide are recommended; for high-altitude pulmonary edema (HAPE), drugs that lower pulmonary artery pressure, such as nifedipine, are recommended. * When providing anesthesia for otherwise healthy acclimatized patients at altitude, supplemental oxygen should be used only to maintain arterial oxygen saturation at baseline (not normal levels). Liberal administration of oxygen may reverse acclimatization. * As ambient pressure is altered, anesthetic vaporizers deliver a variable concentration but fixed partial pressure. Therefore, there is no need to adjust vaporizer settings when delivering anesthesia in a hyperbaric chamber or at altitude. * Unexpected complications have been observed after anesthetics for minor procedures in primates after spaceflight. Physiologic and pharmacologic effects of neuraxial or general anesthesia during or after spaceflight are largely unknown but could include hypotension, resistance to nondepolarizing muscle relaxants, and exaggerated hyperkalemia due to succinylcholine. --------------------------------------------------------------------------------------------------------------------------------------------Regional Anesthesia in Children * Over the past 30 years, regional anesthesia has progressively become a major technique of pain management in surgical and nonsurgical pediatric patients. It was made easier and safer by the development of needles and catheters specifically designed for pediatric patients. Over the years, many pediatric studies involving large series of patients from the neonatal period to the end of adolescence have evaluated virtually all techniques of nerve blockade, thus allowing precise delimitation of their indications, contraindications, and adverse effects. With the use of nerve stimulators, peripheral blocks can now be safely achieved in anesthetized patients provided that no muscle relaxants had been previously administered. * Ultrasound imaging techniques represent the second revolution of regional anesthesia. The advantage of ultrasonography over neurostimulation is to make visible the spread of the local anesthetic, thus allowing both adjustment of needle positioning in case of inappropriate spread and dose reduction when complete circumferential spread of the local anesthetics is clearly obtained. --------------------------------------------------------------------------------------------------------------------------------------------Pediatric Anesthesia * During the first few weeks of life, neonates are vulnerable to the so-called flip-flop circulation, that is, going from an adult-type to a fetal-type circulation. Factors such as hypoxia, hypercapnia, acidosis, infection, hypothermia, and prematurity increase the potential for sudden increases in pulmonary artery pressure and subsequent shunting of blood past the lungs through a patent foramen ovale or the ductus arteriosus, which may reopen, particularly during the first 10 days of life. * The reduced cellular mass of the neonatal heart devoted to contractility results in less compliant ventricles. This leads to sensitivity to volume loading, poor tolerance of afterload (i.e., the development of biventricular failure), and rate-dependent cardiac output. In addition, the reduced cardiac calcium stores produces increased susceptibility to myocardial depression by potent anesthetic agents. This also makes neonates dependent on exogenous calcium (blood ionized calcium) values and vulnerable to the negative inotropic effects of ionized hypocalcemia, particularly that caused by infusion of citrated blood products such as fresh frozen plasma. * The neonatal airway differs from the adult airway in five ways: the tongue is larger, the larynx is located higher in the neck, the glottis is shaped differently and angled over the laryngeal inlet, the vocal cords are angled, and the narrowest portion is the subglottic region at the level of the cricoid cartilage. Accordingly, straight blades are more useful than curved blades in neonates, and uncuffed endotracheal tubes are commonly used. * Glomerular filtration and tubular function are immature but develop rapidly in the newborn period; adult levels are achieved at approximately the age of 2 years. The frequency with which medications excreted by the kidneys (e.g., antibiotics) can be administered during the first month of life changes rapidly. Particular attention is required in this period to avoid drug-induced toxicity (e.g., ototoxicity) caused by excessive plasma drug levels. * Hepatic metabolic capacity is immature at birth. Some cytochrome P450 enzymes (phase I reactions) are fully developed, whereas others are approximately 50% of adult values. Phase II reactions, that is, reactions that make a drug more water soluble, are usually impaired in neonates. Some of these reactions do not achieve maturity until the

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age 1 year. This hepatic immaturity can have important clinical implications regarding a neonate's ability to excrete some medications, such as benzodiazepines. * Cardiac dysfunction from anesthetic overdose is a particular danger for neonates and infants because of a combination of factors, including immaturity of the myocardium, decreased calcium stores of the neonatal myocardium, and the “systems issue” of the vaporizers for halothane and sevoflurane having different maximum minimum alveolar concentration (MAC) delivery capability; that is, nearly 6 MAC multiples of halothane may be delivered to a newborn, whereas only 2.5 MAC multiples can be delivered with sevoflurane. Thus, anesthetic agent–induced cardiac arrest is a function of vaporizer design and vulnerability of the neonatal myocardium to anesthetic-induced cardiac depression, especially on changing from spontaneous to controlled respirations. * Remifentanil is a unique potent opioid in neonates. Unlike virtually every other medication used in newborns, its half-life is shorter rather than longer as in older children. This, then, makes the ability to rapidly induce or stop an intense opioid effect even easier to achieve in neonates than in older children. Careful attention to opioid-induced bradycardia and chest wall rigidity is obviously very important. * Former preterm infants younger than 60 weeks’ postconceptual age are potentially at risk for postoperative apnea, and those who are anemic are at particular risk (i.e., hemoglobin <10 gm/dL). Both gestational age and postconceptual age at the time of surgery are independent risk factors. The use of regional anesthesia in these children may reduce but does not eliminate the incidence of postanesthesia apnea. Postoperative apnea has been associated with all of the inhaled agents, including desflurane and sevoflurane. * Preoperative laboratory testing is minimal for most pediatric patients. The only groups of children who require routine hemoglobin measurement are infants younger than 6 months to assess the severity of the physiologic hemoglobin nadir (especially former preterm infants with a potential risk for apnea) and older children expected to experience significant blood loss. Preoperative chest radiographs are not generally indicated. Children who have undergone chemotherapy with anthracyclines, children with congenital heart disease, and neonates at risk for associated cardiac anomalies may require a preoperative echocardiogram. Children undergoing chemotherapy should usually have a complete recent hematology profile, including platelet counts. Children taking antiseizure medications will generally benefit from preoperative assessment to ensure therapeutic levels. * Temperature regulation is a particular issue for neonates and infants. Because of the large body surface–to–weight ratio, they are especially vulnerable to intraoperative hypothermia. Efforts to maintain a warm operating room, use of warming devices such as hot air mattresses, warm surgical skin preparation solutions, and transport in an appropriate transport device, as well as keeping the patient covered during transport, all help prevent dangerous hypothermia. --------------------------------------------------------------------------------------------------------------------------------------------Anesthesia for Pediatric Cardiac Surgery * Organ system maturation, from birth through adolescence (e.g., cardiovascular, central nervous system [CNS], pulmonary, renal, hematologic), affects physiologic function and therefore anesthetic and surgical management and outcome. * Physiologic understanding of congenital heart disease and consequent anesthetic management are based on the pathophysiologic determinants of four categories of defects: shunts, mixing lesions, stenotic lesions, and regurgitant lesions. * The chronic sequelae of congenital heart disease—repaired, palliated, or unrepaired—affect anesthetic management: ventricular failure, residual hemodynamic effects (e.g., valve stenosis), arrhythmias, and pulmonary blood flow changes (e.g., pulmonary artery hypertension). * Preoperative assessment of cardiac status (e.g., review of history and physical examination, echocardiography, and catheterization data and consulting with the patient's cardiologist) and planning are the keys to a successful anesthetic outcome. * Intraoperative transesophageal echocardiography and CNS monitoring enhance surgical outcome and reduce morbidity. * Selecting an induction technique is dependent on the degree of cardiac dysfunction, the cardiac defect, the degree of sedation provided by the premedication, and the presence or absence of an indwelling venous catheter. The maintenance of anesthesia depends on the age and condition of the patient, the nature of the surgical procedure, the duration of cardiopulmonary bypass (CPB), and the need for postoperative ventilation. * The physiologic effects of CPB on neonates, infants, and children are significantly different from the effects on adults. During CPB, pediatric patients are exposed to biologic extremes not seen in adults, including deep hypothermia (18°C), hemodilution (threefold to fivefold greater dilution of circulating blood volume), low perfusion pressures (20 to 30 mm Hg), and wide variation in pump flow rates (ranging from 200 mL/kg/min to total circulatory arrest).

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* After the repair of complex congenital heart defects, the anesthesiologist and surgeon may have difficulty separating patients from CPB. Under these circumstances, the underlying cause must be determined, which may be (a) an inadequate surgical result with a residual defect requiring repair, (b) pulmonary artery hypertension, or (c) right or left ventricular dysfunction. * The use of modified ultrafiltration (MUF) reverses the deleterious effects of hemodilution and the inflammatory response associated with CPB in children. Perioperative blood loss and blood use are significantly reduced when MUF is used. MUF also improves left ventricular function and systolic blood pressure and increases oxygen delivery. Pulmonary compliance and brain function after CPB are also improved. * Neonates, infants, and children undergoing cardiac surgery with CPB have a higher rate of postoperative bleeding than that seen in older patients. This is due to several factors: (a) There is disproportionate exposure to the nonendothelialized extracorporeal circuit, which produces an inflammatory-like response. This inflammatory response to CPB is inversely related to patient age; the younger the patient, the more pronounced the response. (b) The type of surgery performed in neonates and infants usually involves more extensive reconstruction and suture lines, creating more opportunities for surgical bleeding than in adult cardiac patients. (c) Operations are frequently performed using deep hypothermia or circulatory arrest, which may further impair hemostasis. (d) The immature coagulation system in neonates may also contribute to impaired hemostasis. (e) Patients with cyanotic heart disease demonstrate an increased bleeding tendency before and after CPB. * The guiding principle in the management of the postoperative patient is an understanding of both normal and abnormal convalescence after anesthesia and cardiac surgery. The immediate postoperative period, even that of normal convalescence, is one of continuous physiologic change because of the pharmacologic effects of residual anesthetic agents and the ongoing physiologic changes secondary to abrupt alteration in hemodynamic loading conditions, surgical trauma, and extracorporeal circulation. * There are additional anesthetic considerations in patients with congenital heart disease who undergo transplantation, closed heart operations without CPB, cardiac interventional procedures, and noncardiac surgery. --------------------------------------------------------------------------------------------------------------------------------------------Pediatric and Neonatal Intensive Care * Critically ill children cared for in pediatric intensive care units have improved outcomes when compared with children treated in intensive care units that do not specialize in the treatment of children. * The autonomic nervous system has predominantly a parasympathetic vagal tone at birth and gradually shifts to a sympathetic tone in older children. * Because the Frank-Starling mechanism is less effective in the newborn, a greater but not exclusive dependence on heart rate is necessary for maintenance of cardiac output. * Improvements in ventilation strategies for children with acute lung injury have led to decreased mortality. * Microprocessor technology in ventilators has made volume-preset modes of ventilation possible in babies and small children. * A multidisciplinary task force has developed a set of guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. * The leading causes of death in children 1 to 14 years of age are accidents and trauma. * Pediatric critical care transport systems not only provide a means of transferring a sick patient to a more appropriate facility but also initiate appropriate intensive care monitoring and treatment of the patient before leaving the referring hospital. * Mortality from sudden infant death syndrome dropped threefold with institution of the “Back to Sleep” campaign. * Pediatric cardiopulmonary arrest is usually manifested initially as respiratory compromise or arrest, followed by secondary cardiac arrest. --------------------------------------------------------------------------------------------------------------------------------------------The Postanesthesia Care Unit * Emergence from general anesthesia and surgery may be accompanied by a number of physiologic disturbances that affect multiple organ systems. Most common are PONV, hypoxia, hypothermia and shivering, and cardiovascular instability. * In a prospective study of more than 18,000 consecutive admissions to the PACU, the complication rate was found to be as high as 24%. Nausea and vomiting (9.8%), the need for upper airway support (6.8%), and hypotension (2.7%) were the most common problems. * The most frequent cause of airway obstruction in the immediate postoperative period is the loss of pharyngeal muscle tone in a sedated or obtunded patient. The persistent effects of inhaled and intravenous anesthetics, neuromuscular blocking drugs, and opioids all contribute to the loss of pharyngeal tone in the PACU patient. * Pharyngeal function is not normalized until an adductor pollicis train-of-four ratio is greater than 0.90.

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* The ability to strongly oppose the incisor teeth against a tongue depressor is a reliable indicator of pharyngeal muscle tone. This maneuver correlates with an average train-of-four ratio of 0.85 as opposed to 0.60 for the sustained head lift. * An estimated 8% to 10% of patients who undergo abdominal surgery subsequently require intubation and mechanical ventilation in the PACU. Respiratory failure in the immediate postoperative period is often due to transient and rapidly reversible conditions such as splinting from pain, diaphragmatic dysfunction, muscular weakness, and pharmacologically depressed respiratory drive. * Although a combination of leads II and V5 will reflect 80% of the ischemic events detected on a 12-lead ECG, visual interpretation of the cardiac monitor is often inaccurate. Because of human error, the American College of Cardiology guidelines recommend that computerized ST-segment analysis be used (if available) to monitor high-risk patients in the immediate postoperative period. * In one study, urinary retention was defined as bladder volume greater than 600 mL in conjunction with inability to void within 30 minutes and the incidence of postoperative urinary retention in the PACU was 16%. The most significant predictive factors were age older than 50 years, intraoperative fluid greater than 750 mL, and bladder volume on entry to PACU greater than 270 mL. * Perioperative attention to adequate hydration is indicated in any patient who has received an intravenous contrast agent. Aggressive hydration with normal saline provides the single most effective protection against contrast nephropathy. * Rhabdomyolysis has been reported to occur in 22.7% of 66 consecutive patients undergoing laparoscopic bariatric surgery. Risk factors include increased body mass index and duration of operation. * The incidence of postoperative shivering may be as high as 65% (range, 5% to 65%) after general anesthesia and 33% after epidural anesthesia. Identified risk factors include male gender and the choice of induction agent; propofol is more commonly associated with shivering than pentothal is. * Approximately 10% of adult patients older than age 50 who undergo elective surgery will experience some degree of postoperative delirium within the first 5 postoperative days. The incidence is much higher for certain procedures, such as repair of hip fracture (>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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* 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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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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* 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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* 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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--------------------------------------------------------------------------------------------------------------------------------------------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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* 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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* 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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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 pacemaker-dependent 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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* 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 true-negative 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. --------------------------------------------------------------------------------------------------------------------------------------------