title: Determining minimum alveolar anesthetic concentration of halothane in rats: the effect of incremental change in halothane concentration and number of crossovers.
abstract: 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.
authors.affiliation: *Division of Anesthesiology, ‡Department of Surgery, and §Department of Neurosurgery, Soroka Medical Center, Beer Sheva, Israel; †Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva, Israel; ∥Department of Surgery, Barzilay Medical Center, Askelon, Israel; and ¶Department of Anesthesiology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Avner
authors.initials: A
authors.lastname: Leon
authors.forename: Olga
authors.initials: O
authors.lastname: Mayzler
authors.forename: Mony
authors.initials: M
authors.lastname: Benifla
authors.forename: Michael
authors.initials: M
authors.lastname: Semionov
authors.forename: Yulia
authors.initials: Y
authors.lastname: Fuxman
authors.forename: Israel
authors.initials: I
authors.lastname: Eilig
authors.forename: Vadim
authors.initials: V
authors.lastname: Passuga
authors.forename: Maryana K
authors.initials: MK
authors.lastname: Doitchinova
authors.forename: Boris
authors.initials: B
authors.lastname: Gurevich
authors.forename: Alan A
authors.initials: AA
authors.lastname: Artru
authors.forename: Yoram
authors.initials: Y
authors.lastname: Shapira
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015331:Cohort Studies; D003198:Computer Simulation; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D005260:Female; D006221:Halothane / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012107:Research Design
chemical_list: D018685:Anesthetics, Inhalation; D006221:Halothane