MAC revisited
Myron Yaster MD and Jeffrey Feldman MD
One of my favorite experiences at Hopkins was the orientation and “imprinting” of new anesthesia residents in the month of July. Rather than giving the new residents keys to the Ferrari/space shuttle, the new residents were assigned 1:1 or 1:2 with a single attending for 2 weeks and then again with another attending during the 2nd 2 weeks of the month (and I hope they are still doing this!). The goal was to “imprint” the resident with the style and thinking of a single attending and was much like the “imprinting” of baby ducklings and thereby help the new residents establish their identity, form a bond, and follow their mother duck (me) through their careers. I’ve got to admit that I loved this and my bonds with my many, many “ducklings” continue to this day. Why do I bring this up? During the first week of that 2-week period, I insisted on using only inhalational agents (nitrous oxide and sevoflurane) in as many of our cases as possible so my residents (ducklings) could learn about uptake and distribution of anesthetic agents, FA/Fi ratios, MAC, and how the anesthesia machine and the various monitors, particularly those that measure end-tidal carbon dioxide and vapor anesthetic levels could be used to guide anesthetic management.
How MAC is defined, and its importance to anesthetic management is the foundation of modern anesthesia and is the focus of today’s Pediatric Anesthesia Article of the Day. I would recommend these articles to all of you to read in their entirety, particularly those of you involved in education. They would be terrific in journal clubs and as primary sources in your anesthesia lecture rotations. I’ve asked Jeff Feldman from the Children’s Hospital of Philadelphia to join me. This is an area of his expertise and his insights are invaluable. Finally, Steve Shafer gave perhaps the BEST Rovenstine lecture EVER at the 2021 ASA annual meeting that discussed the life of Ted Eger, who along with Larry Saidman did the original work on MAC. If you haven’t seen/heard this lecture, PLEASE do so at your earliest convenience. I’m attaching the link to the video of this lecture…it starts at around the 25-minute mark. Myron Yaster MD
https://www.asahq.org/annualmeeting/education/videos?&ct=b3c251cea2f1b2fd76113ff5dfaa632a7bbf64710042317cdddd97c8cc45428c757c6b6faa3907a7ec319073cda2b7df2ef7e927e60e11e632444e1a34d3ce8b
Original Article
Jan F A Hendrickx , Andre M De Wolf . End-tidal Anesthetic Concentration: Monitoring, Interpretation, and Clinical Application. Anesthesiology. 2022 Jun 1;136(6):985-996 PMID: 35483048
Editorial
Evan D Kharasch. Anesthetic MAC: Origin, Utility, and Nomenclature Revisited. Anesthesiology. 2022 Jun 1;136(6):885-887. PMID: 35482957
MAC is a term commonly used in the operating room and often displayed on the anesthetic agent monitor as a calculated value based upon the end-tidal agent concentration. Hendrickx and De Wolf have provided an excellent review reminding us that the definition of MAC is quite nuanced. These nuances are important when using MAC to manage clinical effect, especially for the pediatric anesthetist given the significant influence of age on MAC.
Is the definition of MAC minimum alveolar concentration or median alveolar concentration (akin to the effective concentration 50)? The original experiments defined MAC as the minimum end-expired halothane concentration required to keep an experimental dog from responding with gross movement to a painful stimulus (tail clamp or electrical stimulus) or in human studies to surgical stimulation. The human studies did not determine the minimum effective concentration, but rather the median effective concentration (ED50) in the population studied.
These original studies presumed that measuring the response to a painful stimulus (movement) would equate to other desirable clinical effects like loss of consciousness or blunting of autonomic responses to surgical stimulus like blood pressure and heart rate. We have since learned that there are multiple definitions of MAC depending upon the clinical effect of interest. While the classic definition of MAC is defined by lack of movement to surgical stimulation (perhaps MAC-immobility), consciousness (MAC awake or MAC unconsciousness) is reliably lost at about 0.7 MAC. Blunting autonomic response (MAC BAR) occurs at higher MAC levels or not at all.
As a guide to the desired clinical effect, MAC provides an estimate of the probability of achieving that effect. Since the response of an individual patient can be difficult to predict, MAC values approaching 99-100% probability rather than just 50% are better dosing guides absent an independent measure of effect such as processed EEG to assess the potential for awareness.
MAC is primarily affected by AGE. In humans, MAC increases by 30% from birth until 1 to 6 months of age and then decreases by about 6 to 7% every decade after 20 years. Many of the pediatric studies were done with halothane by George Gregory, Jerry Lerman, and Robert Friesen in the 1980s.1-5
Finally, Hendrickx and De Wolf elegantly show that there is a delay between changes in FET and changes in the partial pressure of anesthetic drug in the CNS, the effect site. Thus, during initial delivery (wash-in) of volatile anesthetics, FET is higher than the CNS partial pressure, and during wash-out of anesthetic, FET is lower than the CNS partial pressure (“hysteresis”).
The calculated MAC value displayed on anesthesia workstations and agent monitors is derived from the measured end-tidal anesthetic concentration, is typically age-adjusted and intended to indicate the probability of movement in response to incision. How should this calculated MAC value be used? There are a variety of reasons why the displayed MAC value is not a useful indicator of inhaled anesthetic dosing but rather more like a spiritual guide.
First of all, the MAC calculation is not standardized and there can be significant variation in the calculated MAC value between devices for the same exhaled concentration. Second, the standard MAC definition used in these calculators is an ED50, not an ED99 which is a more reliable predictor of clinical effect. Third, the agent monitor is measuring the end-tidal agent concentration, not the alveolar concentration. Finally, unlike Myron’s experience with his “ducklings”, virtually no one is a “purist” and other drugs like opioids, neuromuscular blocking agents, or propofol are given at the induction of anesthesia, or concomitant infusions of dexemedetomidine are given to prevent emergence delirium at the conclusion of an anesthetic. As Hendrickx and De Wolf indicate in their review, all of these influences affect the actual MAC value required to achieve the desired clinical effect in an individual patient. Independent measures of desired clinical effect like EEG can be quite useful for individualizing anesthetic doses to the needs of the patient. The anesthetic state, rather than fixating on a MAC number, is always how we should provide anesthesia.
References
1. Lerman J, Robinson S, Willis MM, Gregory GA: Anesthetic requirements for halothane in young children 0-1 month and 1-6 months of age. Anesthesiology 1983; 59: 421-424
2. LeDez KM, Lerman J: The minimum alveolar concentration (MAC) of isoflurane in preterm neonates. Anesthesiology 1987; 67: 301-307
3. Gregory GA, Eger EI, 2d, Munson ES: The relationship between age and halothane requirement in man. Anesthesiology 1969; 30: 488-491
4. Gregory GA: The baroresponses of preterm infants during halothane anaesthesia. Can.Anaesth.Soc.J. 1982; 29: 105-107
5. Friesen RH, Lichtor JL: Cardiovascular depression during halothane anesthesia in infants: study of three induction techniques. Anesth.Analg. 1982; 61: 42-45