Are estimates of MAC reliable?

Background: Potency of inhaled anesthetics (minimum alveolar concentration [MAC]) is typically studied in humans using an "up-down" approach in which the (quantal) response to skin Incision is assessed only once for each indi vidual, so that each Individual's MAC is never determined. The authors exam ined the Influence of interindividual variability and study design issues ( e.g., the number of patients enrolled in a study) on the accuracy of MAC es timates. Methods: The typical sequence of a MAC study was simulated. The authors var ied and tested the impact of several factors: anesthetic concentration used to start a study; number of "crossovers" (successive patients having diffe rent responses to skin incision) to terminate a study; concentration increm ent between consecutive patients; interindividual variability; and "measure ment error." For each factor, simulations were replicated 500 times, and th e resulting estimates were summarized. Results: Starting an experiment below or above the "true" value led to slig htly biased MAC estimates; in contrast, variability was underestimated with starting concentrations close to the true value. More than six crossovers improved MAC estimates minimally but increased variability estimates toward true values. A larger increment size affected MAC minimally and increased variability estimates toward true values. A larger Interindividual variabil ity led to more "outlier" estimates for MAC. Under many conditions, several of 500 replicates yielded MAC estimates that deviated more than 10% or eve n more than 25% from the "true" value. Conclusion: Individual experiments may yield inaccurate MAC estimates. This inaccuracy is minimized as the number of crossovers increases; however, im provement diminishes as the number of crossovers exceeds six.