Paradox of bispectral index and entropy during burst suppression (2021)

Editor, Georgii and co-workers have made a great contribution in their article State entropy and burst suppression ratio can show contradictory information. A retrospective study.1 In their work, Georgii et al. present how state entropy values are sometimes on the recommended range of surgical anaesthesia (40 to 60), while at the same time burst suppression ratio (BSR) indicates suppressed EEG periods. The results of Georgii et al. are of considerable interest. However, their finding is not novel, and several works have demonstrated how bispectral index (BIS) has the same characteristic and, according to Georgii et al., contradictory property. Georgii et al. hypothesise that BSR and state entropy and response entropy variables are not interconnected, and that this may cause contradictory entropy values. It is true that BSR is an independent variable, that is BSR value is not affected by response entropy or state entropy. However, response entropy and state entropy are interconnected with BSR. The principle is explained in the Entropy algorithm description2: ‘The part of the signal that contains suppressed EEG is treated as a perfectly regular signal with zero entropy, whereas the entropy associated with the bursts is computed as described previously’. The equation following the principle is3:burst compensated entropy=entropy1−BSR(%)100%, which is analogous to what has been presented earlier with spectral edge frequency.4 Note, that if BSR is 0, burst compensated entropy and entropy are equal. Therefore, burst compensated entropy can be replaced by response entropy or state entropy and, as a consequence, response entropy and state entropy are derived by the same formula in the whole continuum of anaesthetic depth. This is in contrast to BIS, which alternates between different subparameters.5 The use of the above equation explains why response entropy and state entropy do not follow a straight line as a function of BSR. This is different from BIS, which is defined by its suppression ratio solely in the range of suppression ratio 40 to 100.6–9 The concept of burst compensated entropy relies on experimental studies, which have demonstrated the relationship of intracell activity within the neocortex and thalamus to the frequency content of individual bursts.10 In other words, more spikes on intracellular level lead to more irregular burst pattern, thus higher entropy. Interestingly, also, the results of Georgii et al. demonstrate how the entropy term of the above equation decreases with increasing BSR (absolute value of BSR coefficient and bias decreases from 0.46 and 38.7 to 0.33 and 30.6 from BSR ≥5 to BSR ≥40), indicating that entropy of the nonsuppressed EEG periods decrease with deepening suppressions. Thus, it seems plausible to incorporate the information of the nonsuppressed EEG periods in terms of entropy when estimating the level of neuronal activity in the burst suppression range. Behaviour of Entropy parameters and BIS during burst suppression have been studied before. The results in propofol anaesthesia demonstrate that entropy declines monotonically in range BSR 20 to 100, whereas BIS has plateau in suppression ratio range 20 to 40.7,8 Similar behaviour can also be noticed in sevoflurane anesthesia.9 BIS may also display notably high BIS values when suppression ratio is below 30. Retrospective analysis of the previously published data11 reveals multiple BIS values in range 60 to 100 when suppression ratio is below 30 (Fig. 1). In this case, high BIS values are most likely caused by epileptiform activity. A recent article with modern BIS Vista demonstrates multiple BIS values in the range 60 to 80 at low suppression ratio.6 BIS and state entropy values in the range 40 to 60 have also been reported in sevoflurane anesthesia,9 also when burst suppression was verified from EEG waveform.12Fig. 1: Bispectral index and suppression ratio value pairs obtained from the previously published data.11 When SR is in the range 1 to 30, BIS may display values in the range 10 to 100.Contrary to common belief, also presented by Georgii et al., BIS may also display values below 30 without suppression, similarly to Entropy. For example, BIS values around 20 during slow wave sleep13,14 and isoflurane anaesthesia15 have been presented. During slow wave EEG (delta/theta) activity in sevoflurane anaesthesia, BIS is typically, but not always, higher than state entropy.12 Thus, there exists a certain entropy/BIS range wherein significant amount of suppression may be present or not: this range starts from around 20 and in some cases may continue above 40. Georgii et al. have highlighted this paradox and contradictory behaviour. Current evidence indicates that this paradox is common to both BIS and entropy. With entropy, simultaneous monitoring of response entropy, state entropy and BSR parameters and further information from EEG waveform help to recognise this situation.