Analysis of pharmacodynamic interaction of sevoflurane and propofol on bispectral index during general anaesthesia using a response surface model

Propofol and sevoflurane act on the GABA(A) receptor, modulating the function of this receptor in an additive manner. The pharmacodynamic interaction of both drugs considering their effect on EEG activity analysed by the bispectral index (BIS) was identified as additive, but this has not been studied in a clinical setting. The objective of this study was to analyse the pharmacodynamic interaction of propofol and sevoflurane on BIS using a surface response model in patients undergoing general anaesthesia with i.v. induction and inhalation maintenance. We performed a prospective study in 24 patients undergoing general anaesthesia with propofol induction and sevoflurane maintenance. Anaesthetic depth was measured with a BIS VISTA Bilateral monitor. Propofol biophase concentration was determined using a three-compartment pharmacokinetic model, and sevoflurane end-tidal concentration was measured continuously. The response surface model described by Minto and colleagues was used to analyse the interaction. Statistical analysis was performed with Excel 2002 and SPSS v11.0. The mean value of U-50(theta) was 0.956 (sd 0.029) in the overall estimated data, and remained within the predefined range for all ratios theta of the drugs, fulfilling the criterion of additivity. The median of the weighted residuals between the actual BIS value and the BIS value predicted by the model was -5.926%. Under the study conditions, it was confirmed that sevoflurane and propofol have an additive effect on BIS, with no evidence suggesting the existence of a synergistic effect for the concentrations of both drugs typically used in clinical practice.