The influence of remifentanil on the dynamic relationship between sevoflurane and surrogate anesthetic effect measures derived from the EEG

Abstract

Background: The 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). Methods: Thirty-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 1/2K e0, E MAX, E MIN, C 50, γ, CUP weight factors) were estimated using the population data analysis program NONMEM. Significant remifentanil model parameter dependencies (P < 0.01) were determined. Results: Determined from SEF, remifentanil had no effect on t 1/2K 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 1/2k 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 1/2k 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. Conclusions: Remifentanil 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.