We read with great interest the recent follow-up by Schuller et al.  to the well-known study from 2015 demonstrating a decrease in modified encephalography values in unsedated volunteers given neuromuscular blocking agents.  In this update, the unsettling accounts experienced by study participants was described. Details from this perspective serve well to enhance our understanding of and ability to empathize with patients having suffered this condition.

In addition, these supplemental descriptions hint that another factor might have been at play that was unaccounted for: the degree of hypercarbia. Subjects suffered an overwhelming sensation of “suffocation and panic,” felt that they were “going to die,” and literally felt like they were “bursting out of the water” once they were given sugammadex and were finally able to take large recovery breaths of 12 to 15 ml/kg. This experience mirrors the expected physiologic response to hypercarbia in people who are drowning.  It would then seem that, despite best efforts to target normocapnia in terms of 7 to 10 ml/kg tidal volumes and an end-tidal CO2 of 35 mmHg, mask ventilation might not have been sufficient. Actual achieved tidal volumes, end-tidal carbon dioxide, and, most importantly, arterial carbon dioxide partial pressures were not reported. Mask ventilation and measurement of end-tidal carbon dioxide alone are not sufficient to avoid relative hypercapnia, as arterial blood gas analysis of such patients demonstrates that a larger gradient exists between end-tidal carbon dioxide and the partial pressure of arterial carbon dioxide in mask ventilated patients compared to those with supraglottic or other adjunct airway devices.  Neither oral nor nasal airway use was mentioned, and subjects described their tongues as feeling large in their throats, leaving very little room for air to pass through.

These clues suggest that subjects might have been at least mildly hypercapnic, a variable previously implicated in impacting level of arousal and encephalographic signals.  Arterial carbon dioxide content has been shown to affect encephalography in dogs anesthetized with halothane  and in humans anesthetized with alfentanil and nitrous oxide.  Although the impact of mild hypercapnia on modified encephalography values in awake subjects has not been assessed, encephalographic changes have been observed in a population of awake subjects exposed to higher levels of inhaled carbon dioxide.  Conversely, one study of patients under general anesthesia using a propofol infusion and end-tidal carbon dioxide as a surrogate of arterial carbon dioxide level did not demonstrate an association between carbon dioxide levels on modified encephalographic readings.  Therefore, it is possible that this relationship is complex and changes in different pharmacologic contexts and levels of arousal. Given the importance of modified encephalography in the monitoring of anesthetic depth and the doubt in its reliability cast by the work by Schuller et al., the impact of hypercapnia is an area worthy of further investigation.