• Erik Olofsen, James W Sleigh, and Albert Dahan.
• Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands. e.olofsen@lumc.nl
• Anesthesiology. 2002 Mar 1;96(3):555-64.

BackgroundThe authors modeled the influence of remifentanil on the dynamics of sevoflurane using three parameters derived from the electroencephalogram: 95% spectral edge frequency (SEF), canonical univariate parameter (CUP), and Bispectral Index (BIS).MethodsThirty-six patients with American Society of Anesthesiologists physical status class I or II were recruited, of which 12 received a target remifentanil concentration of 0 ng/ml, eight 2 ng/ml, eight 4 ng/ml, and another eight 8 ng/ml. Next (before surgery), several step-wise changes in the end-tidal sevoflurane concentration (F(ET,sevo)) were performed. A data acquisition system simultaneously recorded F(ET,sevo), the raw electroencephalogram, BIS, and SEF. The authors used a combination of an effect compartment and an inhibitory sigmoid E(MAX) model to describe the relation between F(ET,sevo) and BIS, SEF, and CUP. Model parameters (t(1/2)k(e0), E(MAX), E(MIN), C(50), gamma, CUP weight factors) were estimated using the population data analysis program NONMEM. Significant remifentanil model parameter dependencies (P < 0.01) were determined.ResultsDetermined from SEF, remifentanil had no effect on t(1/2)k(e0) (1.91 +/- 0.26 min [mean +/- standard error]) but caused an increase in C(50) (baseline = 1.48 +/- 0.12%; 80% increase at 8 ng/ml) and decrease in E(MIN) (baseline = 10.8 +/- 0.6 Hz; 80% reduction at 8 ng/ml). Determined from CUP, remifentanil caused a dose-dependent decrease in t(1/2)k(e0) (baseline = 4.31 +/- 1.00 min; 60% decrease at 8 ng/ml), with no effect on C(50) (baseline = 0.88 +/- 0.13%). Determined from BIS, remifentanil caused a dose-dependent decrease in t(1/2)k(e0) (baseline value = 3.11 +/- 0.32 min; 40% decrease at 8 ng/ml), without affecting C(50) (baseline = 1.12 +/- 0.05%). Median R(2) values of the pooled data set were 0.815 for SEF, 0.933 for CUP (P < 0.01 vs. SEF), and 0.952 for BIS (P < 0.01 vs. SEF and CUP). Addition of remifentanil increased the R(2) values for CUP only.ConclusionsRemifentanil accelerates sevoflurane blood-brain equilibration without affecting its hypnotic potency as determined from BIS and CUP. In terms of R(2), the authors' pharmacodynamic model describes the anesthetic-BIS relation best.

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