Droperidol and Cardiac Risks: A Practical Review for CL Psychiatrists

Abstract: Background/Significance:
Droperidol is a butyrophenone derivative that has been used clinically over many decades for management of acute agitation, psychosis, pain control, postoperative nausea, headaches, and sedation during anesthesia. A black box warning issued by the Food and Drug Administration (FDA) in 2001 noted significant risk of QTc prolongation and arrhythmias and consequently led to an abrupt decline in the use of droperidol. Recently, the agent has re-gained popularity in emergency medicine settings, particularly for management of acute agitation (Calver, 2013; Gaw, 2020). The purpose of this narrative review is to summarize the cardiac risks associated with droperidol and provide consultation-liaison (CL) psychiatrists with a practical guide for its appropriate use.

Methods:
A PubMed search was conducted using the following search terms: “droperidol AND (QT OR arrhythmia OR sudden cardiac death OR torsades).” Two reviewers identified relevant studies from the 224 search results. Animal studies, studies with exclusively pediatric patients, and studies that were not available in English and were not easily translated were excluded, for a final total of 56 included studies. Data extraction and analysis is ongoing.

Results:
Thirteen randomized control trials, 21 non-randomized prospective studies, 13 non-randomized retrospective studies, 7 case reports, 1 systematic review, and 1 meta-analysis were included. Data extraction will include article characteristics, study design and aim, study population (including pre-morbid history), droperidol dosing and indication, and cardiac outcomes (including QTc changes, arrythmias and sudden cardiac death).

Discussion:
This narrative review aims to synthesize findings from selected studies to provide readers a better understanding of the cardiovascular side effects associated with droperidol. We will also discuss the potential advantages and disadvantages of droperidol in CL and emergency psychiatry settings, how droperidol and haloperidol differ clinically, and considerations for dosing and monitoring when using droperidol, especially with regards to adverse cardiac outcomes.

Conclusion/Implications:
The FDA black box warning for droperidol generated notable contention and controversary (Horowitz 2002; Dershwitz 2002). Two decades later, droperidol has experienced a resurgence in clinical use. We hope this narrative review will help CL psychiatrists feel more comfortable utilizing droperidol appropriately.