Comparative pharmacodynamic modeling of the electroencephalography- slowing effect of isoflurane, sevoflurane, and desflurane

Abstract

Background: The most common measure to compare potencies of volatile anesthetics is minimum alveolar concentration (MAC), although this value describes only a single point on a quantal concentration-response curve and most likely reflects more the effects on the spinal cord rather than on the brain. To obtain more complete concentration-response curves for the cerebral effects of isoflurane, sevoflurane, and desflurane, the authors used the spectral edge frequency at the 95th percentile of the power spectrum (SEF95) as a measure of cerebral effect. Methods: Thirty-nine patients were randomized to isoflurane, sevoflurane, or desflurane groups. After induction with propofol, intubation, and a waiting period, end-tidal anesthetic concentrations were randomly varied between 0.6 and 1.3 MAC, and the EEG was recorded continuously. Population pharmacodynamic modeling was performed using the software package NONMEM. Results: The population mean EC50 values of the final model for SEF95 suppression were 0.66 ± 0.08 (±SE of estimate) vol% for isoflurane, 1.18 ± 0.10 vol% for sevoflurane, and 3.48 ± 0.66 vol% for desflurane. The slopes of the concentration-response curves were not significantly different; the common value was λ = 0.86 ± 0.06. The K(e0) value was significantly higher for desflurane (0.61 ± 0.11 min-1), whereas separate values for isoflurane and sevoflurane yielded no better fit than the common value of 0.29 ± 0.04 min-1. When concentration data were converted into fractions of the respective MAC values, no significant difference of the C50 values for the three anesthetic agents was found. Conclusions: This study demonstrated that (1) the concentration-response curves for spectral edge frequency slowing have the same slope, and (2) the ratio C50(SEF95)/MAC is the same for all three anesthetic agents. The authors conclude that MAC and MAC multiples, for the three volatile anesthetics studied, are valid representations of the concentration-response curve for anesthetic suppression of SEF95.