Determining minimum alveolar anesthetic concentration of halothane in rats: The effect of incremental change in halothane concentration and number of crossovers

Computer simulations for the technique of estimating minimum alveolar anesthetic concentration (MAC) in patients (quantal design) suggest that incremental concentration changes and the number of crossovers affect MAC. We hypothesized that these variables may also apply to estimating MAC in rats (bracketing design). This study tested that hypothesis and also examined whether these variables might mask differences in MAC between groups in which MAC might be expected to differ (pregnant [P] versus nonpregnant [NP]). There were 2 cohorts (n = 27 and n = 30 rats). Each cohort included NP females, females in early P, and females in late P. MAC was tested by using an incremental concentration change of 0.20% and one within-subject crossover in the first cohort and by using an increment size of 0.10% and four crossovers in the second cohort. MAC was statistically significantly increased in the three groups in the second cohort (NP, 1.16 ± 0.12; early P, 1.14 ± 0.10; late P, 1.07 ± 0.10; mean ± SD) compared with values in the three comparable groups in the first cohort (NP, 0.95 ± 0.06; early P, 1.01 ± 0.09; late P, 0.93 ± 0.13). Values did not differ among groups within each cohort. Post hoc simulations indicated that up to 36% of the difference between cohorts was due to increment size, with the balance due to experimental factors. Our findings confirmed the hypothesis that increment size affects estimates of MAC when a bracketing design is used.