Droperidol the psycho dropper or heart stopper?

Clinical Scenario:
You are working a typical EM-1 shift loaded full of psychiatric patients, EMS brings you another agitated male with a history of schizophrenia. He is shouting absurdities and threatening staff members.  The RN glances over at you, 5/2 doc? You're feeling a little different today and order 10mg of droperidol IM. The drug is administered and the patient calms down. With pride you present the patient to your attending. Your attending is alarmed and immediately requests an EKG and places the patient on a cardiac monitor and tells you the patient is in imminent danger of converting into torsades de pointes (TdP) secondary to prolonged QT.  You perform a rapid review of the literature.

Literature Review:

Droperidol is a butyrophenone that has been used since the mid 1970's primarily for acute agitation but it has also found a role in treating nausea, headaches, and abdominal pain. In 2001, droperidol received a black box warning by the FDA because of its association with QT prolongation and potential fatal arrhythmias.

FDA Black Box warning

There is no consensus as to what degree of QT prolongation is clinically significant, but several papers have cited QT longer than 500ms or delta QT of 60ms as at risk for TdP. (1) Mechanistically, in animal models Droperidol has been shown to both block efflux of myocardial potassium and induce early depolarization in cardiac fibers. Human studies have shown varied results, but lean towards droperidol causing some degree of prolonged QT without clinically significant arrhythmias. (2) 

 Lischke et al performed a randomized, double blind study on 40 patients undergoing cardiac surgery that were given either 7 mg,12.5 mg, or 17.5 mg of droperidol prior to surgery. Serial ECGs were obtained and QT prolongation ranged from 37 to 59ms in all groups in a dose dependent manner, however there were no recorded dysrhythmias or fatal events. (3) Again, Guy et al performed a prospective study in 55 patients who received 0.25mg/kg of droperidol prior to surgery, mean QT increased by 24ms, however no arrhythmias were noted. A 2014 prospective study by Calver involved continuous Holter monitoring for 24hrs in patients who had received 10-30mg IM of droperidol for acute agitation. Four out of 46 patients had abnormal QT greater than 480ms, but only one case was temporally associated with droperidol administration.  No arrhythmias were recorded. (4)  Kao et al reviewed decades of published literature including multiple systematic reviews and randomized controlled trials with outcome measures specifically observing for adverse effects of droperidol, and none cited any cases of fatal arrythmias. (1)

 Kao et al reviewed the FDA surveillance data cited by the FDA as cardiac events related to droperidol administrations, and found that the case reports were plagued by confounders and failed to show causation between droperidol administration and fatal arrhythmias.   Many of the European studies cited by FDA used doses of 50 -100mg IM, significantly higher than doses typically used in the US.  

Kao et al FDA surveillance data

Furthermore, similar case studies are described with haloperidol another commonly used antipsychotic.  

Take home points:

Bottom line is there are no randomized trials that demonstrate that droperidol causes fatal arrhythmias, there is data to show the droperidol prolongs QT in a likely clinically insignificant manner. There are rare case reports that suggest cardiac events might be associated with droperidol administration, but most cases involve confounders and cannot demonstrate causation.  Therefore it is likely reasonable to administer droperidol in most cases without any type of cardiac monitoring. However use of droperidol in this manner falls outside of FDA approval, therefore it is likely reasonable to take some precations (EKG or cardiac monitoring) in high risk groups (ESRD, severe cardiac disease) or consider alternative agents.  

Submitted by Louis Jamtgaard PGY-3 @Lgaard
Faculty reviewed by Evan Schwarz @TheSchwarziee

1. Kao LW Droperidol, QT prolongation, and sudden death: what is the evidence? Ann Emerg Med. 2003 Apr;41(4):546-58.

2. JM Guy, X Andre-Fouet, J Porte, et al. Torsades de pointes and prolongation of the duration of QT interval after injection of droperidol [in French] Ann Cardiol Angeiol (Paris), 40 (1991), pp. 541–545

3. V Lischke, M Behne, P Doelken, et al. Droperidol causes a dose-dependent prolongation of the QT interval Anesth Analg, 79 (1994), pp. 983–986

4. Calver L1 Br J Clin Pharmacol. 2014 May;77(5):880-6. doi: 10.1111/bcp.12272. High dose droperidol and QT prolongation: analysis of continuous 12-lead recordings.