We appreciate the interest of Liu et al. in our article.1  This offers the opportunity to put more emphasis on the role of sedation level, displayed by the parameter bispectral index, on analgesic monitoring. As Liu et al. pointed out, the patients’ Bispectral Index (BIS) values in the study were lower than recommended values during surgical procedures. As they assumed in their letter, these low values are caused by the initial bolus of propofol for induction of general anesthesia and successful placement of the laryngeal mask. Persistence of low BIS values with a standard dosage of propofol of 4 to 5 mg · kg–1 · h–1 is not unusual when considering that patients were in a stimulus-reduced dark and silent room. The aim of our study was to compare the detection of nociceptive stimuli on different analgesic levels but on the same level of sedation, and accordingly the BIS values were low throughout the whole intervention period. We agree that tetanic stimulation obviously was not sufficient to provoke electrocortical activation in the sense of “arousal” from deep sedation. This is exactly our point: The nociceptive stimulus provoked a significant change in analgesic indices and pupil dilation, but not in BIS values. Furthermore, the extent of the change in analgesic indices and pupil dilation was diminished by an increase of opioid administration (fig. 2).1  Thus, the Analgesia Nociception Index and Surgical Pleth Index as well as the pupil diameter are proven to reflect the analgesic level. BIS in contrast did not correlate at all with the application of a nociceptive stimulus. Consequently, BIS does not display the analgesic level. Other authors’ findings support our conclusion that BIS monitoring is unable to detect and predict stimulation response.2,3 

Yet some studies demonstrate a synergy between sedatives and analgesics that causes a significant interaction for the response to tetanic stimulation. In a study published in 2018 by Sabourdin et al.,4  pupillary reflex dilation was more sensitive in detecting a noxious stimulation at BIS levels around 55 than at 25. Sabourdin et al. conclude that BIS is displaying the level of cortical inhibition and not nociceptive status. But to a certain extent, BIS monitoring can be able to detect somatic responsiveness.5  In these situations, BIS reveals secondary information from the noxious stimulus when reaching the cerebral cortex via ascending pathways. Thus, it is rather a marker of arousability than measuring the balance between nociception and antinociception. In that regard, the literature that Liu et al. reference is not contradictory to our results.

The underlying study was an investigator-initiated trial and was supported by departmental funds only. The three monitoring devices used were loaned by the companies mentioned throughout the publication.

The authors declare no competing interests.

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