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

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 _max values 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 _effect and AAC _rebound were 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.