Katarzyna Kotfis, Shawniqua Williams Roberson, Jo Ellen Wilson, Wojciech Dabrowski, Brenda T. Pun, and E. Wesley Ely
We appreciate the thoughts and questions posed by Dr. Andrews and Dr. Benken about pharmacological considerations related to our manuscript entitled, “COVID-19: ICU delirium management during SARS-CoV-2 pandemic.” We agree wholeheartedly that resource constraints and drug shortages posed by the pandemic mandate that we develop alternative means by which to keep patients safe and comfortable while they are suffering on life support from severe acute respiratory distress syndrome (ARDS), shock, and other types of organ dysfunction. The rise in benzodiazepine use was especially disheartening, as we know that this creates a very high likelihood of our patients spending more time being delirious. This, in turn, increased the risk of acquired dementia and other elements of post-intensive care syndrome (PICS) resulting from immobilization that commonly occurs when someone is profoundly delirious.
The authors suggest that ketamine, valproic acid, and clonidine are more appropriate options than antipsychotics. In some circumstances, that may very well be true, and we are not inclined to disagree outright other than to say that there is a paucity of data upon which to base such a decision. In fact, we know of not a single randomized controlled trial that would support such a decision. Anecdote and expert opinion do serve a place in difficult times, and the COVID-19 pandemic has most certainly in some hospitals and scenarios created desperation. We believe, however, that such deviations from data should be the exception rather than the rule. In this case given by Dr. Andrews and Dr. Benken, the double use of hydroxychloroquine and azithromycin itself must be questioned as unsupported by data, and thus, first why increase the likelihood of QTc prolongation by these two anecdotally chosen agents. Perhaps instead they should be removed from the patient’s regimen unless they are part of an ongoing clinical trial or some convincing evidence for their benefit becomes available. At the time of this writing, there is not enough data to support this decision. Though it is now known that antipsychotics do not treat delirium itself [6,7,8,9], it is the case that they did not increase the risk of torsades de pointes or have other notable safety issues in the clinical trials recently published.