Permutation Entropy Does Not Track the Electroencephalogram-Related Manifestations of Paradoxical Excitation During Propofol-Induced Loss of Responsiveness: Results From a Prospective Observational Cohort Study

BACKGROUND: During the anesthetic-induced loss of responsiveness (LOR), a “paradoxical excitation” with activation of β-frequencies in the electroencephalogram (EEG) can be observed. Thus, spectral parameters—as widely used in commercial anesthesia monitoring devices—may mistakenly indicate that patients are awake when they are actually losing responsiveness. Nonlinear time-domain parameters such as permutation entropy (PeEn) may analyze additional EEG information and appropriately reflect the change in cognitive state during the transition. Determining which parameters correctly track the level of anesthesia is essential for designing monitoring algorithms but may also give valuable insight regarding the signal characteristics during state transitions. METHODS: EEG data from 60 patients who underwent general anesthesia were extracted and analyzed around LOR. We derived the following information from the power spectrum: (i) spectral band power, (ii) the spectral edge frequency as well as 2 parameters known to be incorporated in monitoring systems, (iii) beta ratio, and (iv) spectral entropy. We also calculated (v) PeEn as a time-domain parameter. We used Friedman’s test and Bonferroni correction to track how the parameters change over time and the area under the receiver operating curve to separate the power spectra between time points. RESULTS: Within our patient collective, we observed a “paradoxical excitation” around the time of LOR as indicated by increasing beta-band power. Spectral edge frequency and spectral entropy values increased from 19.78 [10.25–34.18] Hz to 25.39 [22.46–30.27] Hz ( P = .0122) and from 0.61 [0.54–0.75] to 0.77 [0.64–0.81] ( P < .0001), respectively, before LOR, indicating a (paradoxically) higher level of high-frequency activity. PeEn and beta ratio values decrease from 0.78 [0.77–0.82] to 0.76 [0.73–0.81] ( P < .0001) and from −0.74 [−1.14 to −0.09] to −2.58 [−2.83 to −1.77] ( P < .0001), respectively, better reflecting the state transition into anesthesia. CONCLUSIONS: PeEn and beta ratio seem suitable parameters to monitor the state transition during anesthesia induction. The decreasing PeEn values suggest a reduction of signal complexity and information content, which may very well describe the clinical situation at LOR. The beta ratio mainly focuses on the loss of power in the gamma-band. PeEn, in particular, may present a single parameter capable of tracking the LOR transition without being affected by paradoxical excitation.