To the Editor:

In a recent article, Shirozu et al. [1] evaluated the level of sedation during general anesthesia with remimazolam using several different indicators. The authors found that the bispectral index (BIS) and patient state index (PSI) value were relatively high during anesthesia with remimazolam, which was similar to findings of other studies. They pointed out that an increment of β waves in electroencephalogram (EEG) was thought to be the cause of high BIS and PSI value. We congratulate the authors for their work and would like to provide two suggestions to their research.

In their study protocol, rocuronium (0.6 mg/kg) was administered during induction of anesthesia. The authors did not provide information regarding the maintenance and monitoring of perioperative neuromuscular blockade. In addition, they did not mention whether the neuromuscular blockade was reversed at the end of surgery. Studies have shown that increased electromyogram (EMG) activity increases BIS value [2]. As a result, the lack of standardization in neuromuscular blockade may cause data contamination to Shirozu et al.’s study results. Their study design could be improved if quantitative measurement of neuromuscular blockade is employed to rule out the interreference of EMG to BIS value.

BIS and PSI are processed EEG indices computed by commercially undisclosed algorithms. Studies have reported that ketamine, dexmedetomidine and xenon influences the manner in which these indices are calculated [3]. Similar principles probably apply to remimazolam. Nowadays, most anesthesia depth monitors provide density spectral array (DSA) monitoring, a two-dimensional plot of EEG activity over time, to facilitate the interpretation of the unprocessed EEG. Due to the difference in neuropharmacology and clinical electrophysiology, each anesthetic produces a signature of DSA spectrum [4]. In Shirozu et al.’s study, there were a few patients showing BIS > 60 and PSI > 50, but without awareness during anesthesia. Their discussion would be significantly strengthened if the DSA spectrum of these specific patients are included and compared to the rest of the study samples. To our knowledge, the literature is scanty regarding DSA monitoring in remimazolam anesthesia. Subgroup analyses of these patients may also be performed to examine whether specific characteristics were associated with their above-target BIS and PSI value.