Multiscale permutation entropy analysis of EEG recordings during sevoflurane anesthesia

Electroencephalogram (EEG) monitoring of the effect of anesthetic drugs on the central nervous system has long been used in anesthesia research. Several methods based on nonlinear dynamics, such as permutation entropy (PE), have been proposed to analyze EEG series during anesthesia. However, these measures are still single-scale based and may not completely describe the dynamical characteristics of complex EEG series. In this paper, a novel measure combining multiscale PE information, called CMSPE (composite multi-scale permutation entropy), was proposed for quantifying the anesthetic drug effect on EEG recordings during sevoflurane anesthesia. Three sets of simulated EEG series during awake, light and deep anesthesia were used to select the parameters for the multiscale PE analysis: embedding dimension m, lag tau and scales to be integrated into the CMSPE index. Then, the CMSPE index and raw single-scale PE index were applied to EEG recordings from 18 patients who received sevoflurane anesthesia. Pharmacokinetic/pharmacodynamic (PKPD) modeling was used to relate the measured EEG indices and the anesthetic drug concentration. Prediction probability (P(k)) statistics and correlation analysis with the response entropy (RE) index, derived from the spectral entropy (M-entropy module; GE Healthcare, Helsinki, Finland), were investigated to evaluate the effectiveness of the new proposed measure. It was found that raw single-scale PE was blind to subtle transitions between light and deep anesthesia, while the CMSPE index tracked these changes accurately. Around the time of loss of consciousness, CMSPE responded significantly more rapidly than the raw PE, with the absolute slopes of linearly fitted response versus time plots of 0.12 (0.09-0.15) and 0.10 (0.06-0.13), respectively. The prediction probability P(k) of 0.86 (0.85-0.88) and 0.85 (0.80-0.86) for CMSPE and raw PE indicated that the CMSPE index correlated well with the underlying anesthetic effect. The correlation coefficient for the comparison between the CMSPE index and RE index of 0.84 (0.80-0.88) was significantly higher than the raw PE index of 0.75 (0.66-0.84). The results show that the CMSPE outperforms the raw single-scale PE in reflecting the sevoflurane drug effect on the central nervous system.