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Contains fulltext : 81731.pdf (publisher's version ) (Closed access), 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.

Contains fulltext : 70268.pdf (publisher's version ) (Closed access), OBJECTIVE: We compared two PK/PD models, one with and one without a plateau effect. Bispectral (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend (NCT, MonitorTechnik, Bad Bramstedt, Germany, Version 4.0) indices were used as an electroencephalographic measure of desflurane drug effect. METHODS: With IRB approval and informed consent we investigated 20 adult patients scheduled for radical prostatectomy. At least 45 minutes after induction of general anaesthesia, end-tidal concentrations of desflurane was varied between 3 and 10 vol%. To evaluate the relationship between concentrations and EEG indices, two different pharmacodynamic models were applied: A conventional model based on a single sigmoidal curve, and a novel model based on two sigmoidal curves for BIS and NCT values with and without burst suppression. The parameters of the models were estimated by NONMEM V (GloboMax, Hanover, USA) by minimizing log likelihood. Statistical significance between the two models was calculated by the likelihood ratio test. RESULTS: The maximum end-tidal desflurane concentration during the two concentrations ramps was 10.0 +/- 1.4 vol%. The mean BIS and NCT values decreased significantly but slightly with increasing end-tidal desflurane concentrations between 4 and 8 vol%. Therefore a two sigmoidal curves PK/PD model including a plateau describes the effects of desflurane on BIS and Narcotrend better than a single sigmoidal curve model. The difference between the log likelihood values of the new PK/PD model with two connected sigmoidal curves and the classical E (max )model with one sigmoidal curve is 634 (P < 0.001) for the BIS monitor and 4089 (P < 0.001) for the NCT. CONCLUSIONS: BIS and Narcotrend are not useful to differentiate pharmacodynamic changes in the EEG between 4 and 9 vol% desflurane.