Temporal linear mode complexity as a surrogate measure of the effect of remifentanil on the central nervous system in healthy volunteers

Abstract

AIMS: Previously, electroencephalographic approximate entropy (ApEn) effectively described both depression of central nervous system (CNS) activity and rebound during and after remifentanil infusion. ApEn is heavily dependent on the record length. Linear mode complexity, which is algorithmatically independent of the record length, was investigated to characterize the effect of remifentanil on the CNS using the combined effect and tolerance, feedback and sigmoid E max models. METHODS: The remifentanil blood concentrations and electroencephalographic data obtained in our previous study were used. With the recording of the electroencephalogram, remifentanil was infused at a rate of 1, 2, 3, 4, 5, 6, 7 or 8μgkg -1min -1 for 15-20min. The areas below (AUC effect) or above (AAC rebound) the effect vs. time curve of temporal linear mode complexity (TLMC) and ApEn were calculated to quantitate the decrease of the CNS activity and rebound. The coefficients of variation (CV) of median baseline (E 0), maximal (E max), and individual median E 0 minus E maxvalues of TLMC were compared with those of ApEn. The concentration-TLMC relationship was characterized by population analysis using non-linear mixed effects modelling. RESULTS: Median AUC effectand AAC reboundwere 1016 and 5.3 (TLMC), 787 and 4.5 (ApEn). The CVs of individual median E 0 minus E max were 35.6, 32.5% (TLMC, ApEn). The combined effect and tolerance model demonstrated the lowest Akaike information criteria value and the highest positive predictive value of rebound in tolerance. CONCLUSIONS: The combined effect and tolerance model effectively characterized the time course of TLMC as a surrogate measure of the effect of remifentanil on the CNS. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.