Comparative pharmacodynamic modeling of desflurane, sevoflurane and isoflurane.
BACKGROUND
We compared dose-response curves of the hypnotic effects of desflurane, sevoflurane and isoflurane. In addition, we analyzed the k(e0) values of the different anesthetics. The EEG parameters Bispectral index (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend index (MonitorTechnik, Bad Bramstedt, Germany, version 4.0) were used as measures of the pharmacodynamic effect.


METHODS
With IRB approval and informed consent we analyzed the data of three studies including 61 adult patients scheduled for radical prostatectomies. At least 45 min after induction of general anesthesia, end-tidal concentrations of desflurane, sevoflurane or isoflurane were varied between 0.5 and 2 MAC. We transferred the end-tidal concentrations into age-related MAC values. The relationship between MAC effect compartment concentrations and EEG was modeled with a variation of the classical fractional sigmoid E(max) model with two linked sigmoidal curves. All parameters were calculated as a population fit by NONMEM V (GloboMax, Hanover, USA) by minimizing log likelihood.


RESULTS
The k(e0) values of the population fit derived from BIS data were 0.54 min(-1) for desflurane, 0.24 min(-1) for sevoflurane and 0.16 min(-1) for isoflurane, from the Narcotrend index 0.43 min(-1) for desflurane, 0.26 min(-1) for sevoflurane and 0.18 min(-1) for isoflurane. The change between the first and the second sigmoidal curve was positioned at nearly the same Narcotrend- and BIS index values between 41 and 44.


CONCLUSIONS
The first order rate constant (k(e0) value) determining the equilibration between age-related MAC values and MAC effect site concentration is substantially higher for desflurane than for sevoflurane or isoflurane.
Kreuer
Sascha
S
Department of Anaesthesiology and Intensive Care Medicine, University of Saarland, Homburg/Saar, Saarland, Germany. sascha.kreuer@uniklinik-saarland.de
Bruhn
Jörgen
J
Wilhelm
Wolfram
W
Grundmann
Ulrich
U
Rensing
Hauke
H
Ziegeler
Stefan
S
D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D003198:Computer Simulation; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D004569:Electroencephalography / Q000187:drug effects*; D006801:Humans; D007530:Isoflurane / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000493:pharmacokinetics; D008875:Middle Aged; D008954:Models, Biological; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane