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

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Remifentanil, an intravenous ultra short-acting opioid, depresses central nervous system activity with an increase in the delta band power, and causes beta activation after discontinuation, resulting in a rebound of the processed electroencephalographic parameters, including 95% spectral edge frequency, the canonical univariate parameter and electroencephalographic approximate entropy.• A sigmoid Emax model, in which the highest predicted values of processed electroencephalographic parameters are restricted to the baseline value, cannot describe a rebound of these parameters.• Electroencephalographic approximate entropy correlated well with the remifentanil blood concentration and demonstrated high baseline stability. WHAT THIS STUDY ADDS• A combined effect and tolerance model effectively characterized the time course of the remifentanil effect on the central nervous system, including the rebound which occurred during recovery from the remifentanil effect.• Temporal linear mode complexity was comparable with approximate entropy as a univariate electroencephalographic descriptor of the effect of remifentanil on the central nervous system. AIMSPreviously, 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 Emax models. METHODSThe 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 8 mg kg -1 min -1 for 15-20 min. The areas below (AUCeffect) or above (AACrebound) 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 (E0), maximal (Emax), and individual median E0 minus Emax values of TLMC were compared with those of ApEn. The concentration-TLMC relationship was characterized by population analysis using non-linear mixed effects modelling. RESULTSMedian AUCeffect and AACrebound were 1016 and 5.3 (TLMC), 787 and 4.5 (ApEn). The CVs of individual median E0 minus Emax 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. CONCLUSIONSThe combined effect and tolerance model effectively characterized the time course of TLMC as a surrogate measure of the effect of remifentanil on the CNS.

Response surface modelling of the pharmacodynamic interaction between propofol and remifentanil in patients undergoing anaesthesia

“…The remifentanil concentrations used in this study were up to 8 ng/mL, and the observed additive behaviours in relation to LOC may have been due to the lower maximum concentrations of propofol applied . The TLMC and ApEn values were observed within a relatively narrow range in this study compared with the values from previous studies, and these limited data may be insufficient to develop an adequate surface model. However, the additive interactions demonstrated by the processed electroencephalographic parameters were consistent with the results of an earlier study .…”

“…However, the BIS is insensitive to clinically relevant opioid concentrations, and ApEn is heavily dependent on the length of the recording . Temporal linear mode complexity (TLMC) measures the complexity of the temporal linear mode in a single‐channel electroencephalogram (EEG) irrespective of the length of the recording . The appropriateness of TLMC as a surrogate measure of the effects of remifentanil and sevoflurane on the central nervous system was evaluated in our preliminary studies .…”

Temporal linear mode complexity as a surrogate measure of the anesthetic drug effects during sevoflurane anesthesia

“…However, it was well known that BIS did not show the good correlation with effect-site concentration of opioid [18,19], indicating that BIS was not a sensitive surrogate measure of opioid effect. On the other hand, ApEn and TLMC showed the good performance for the assessment of the remifentanil effect on the electroencephalogram in previous studies [3,10]. Hence, TLMC can be used to quantify the effect of anesthetic agents, including hypnotics and opioids, on central nervous system.…”

Novel Methods for Measuring Depth of Anesthesia by Quantifying Dominant Information Flow in Multichannel EEGs

“…The selection criteria for each EEG index used in this study were as follows: (1) every 30 s during the first 10 min, every 1 min during the second 60 min, after the beginning of the propofol infusion; (2) every 30 s during the first 20 min, every 1 min during the second 20 min, and every 2 min during the third 20 min, after the termination of the propofol infusion [33]. …”