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

Anesthesiology. 1999 Aug;91(2):397-405. doi: 10.1097/00000542-199908000-00013.

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 lambda = 0.86+/-0.06. The Ke0 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anesthetics, Inhalation / pharmacology*
  • Desflurane
  • Dose-Response Relationship, Drug
  • Electroencephalography / drug effects*
  • Female
  • Humans
  • Isoflurane / analogs & derivatives*
  • Isoflurane / pharmacology*
  • Male
  • Methyl Ethers / pharmacology*
  • Middle Aged
  • Prospective Studies
  • Sevoflurane

Substances

  • Anesthetics, Inhalation
  • Methyl Ethers
  • Sevoflurane
  • Desflurane
  • Isoflurane