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