Furyk and colleagues (7) conducted a Cochrane Review looking at the safety and efficacy of anti-emetic medications in the Emergency Department, including 8 randomized control trials with a total of 952 patients. The included trials examined a number of anti-emetic medications. In comparison to placebo, droperidol was the only medication to result in a significant change in a nausea visual analog scale (VAS) at 30 minutes. Comparing droperidol to active control (i.e. other anti-emetics), there was no evidence that droperidol was more effective than metoclopramideor prochlorperazine. It should be noted that the data for this part of the Cochrane Review came from a single study by Bruade and colleagues (8). The authors in this study did note a significantly higher incidence of self-reported akathisia at 24 hr follow-up for droperidol vs all other agents (71.4% vs 23.5%).

Migraine/Headache

A systematic review by Thomas and colleagues (9) looked at the efficacy of droperidol for the treatment of migraine and acute headache. Droperidol showed improved pain relief as measured by VAS when compared to placebo (1 study), prochlorperazine (2 studies), and meperidine (1 study). The 2 most interesting studies in this article were the studies comparing droperidol to prochlorperazine. Miner et al (10) enrolled a convenience sample of 168 patients, randomizing them to either receive droperidol (5 mg IM or 2.5 mg IV) or prochlorperazine (10 mg IM or IV). Baseline characteristics were similar between groups. Droperidol was more effective as judged by VAS at 30 and 60 min but rates of rescue medication use were similar in both groups. Incidence of akathisia was 6.1% in the droperidol group and 8.1% in the prochlorperazine group. There were no reports of adverse cardiac events. The second of these 2 studies of interest was by Weaver and colleagues (11). It was a prospective, randomized controlled trial comparing droperidol 2.5 mg IV to prochloperazine 10 mg IV for patients presenting with headache and a normal neurologic exam. The trial was stopped early because of the FDAs black box warning which was released mid-study. The investgators had initially sought to enroll 230 patients per group based on their power analysis, but only ended up enrolling 48 patients in each group. They did find that a higher proportion of patients in the droperidol group had a >50% reduction in pain scores at 30 min as compared to prochlorperazine (83.3% vs 72.3%) with similar rates of akathisia in each group.

Acute Agitation

Chan and colleagues (12) conducted a multi-center, randomized, double-blind, controlled trial evaluating a control (midazolam), droperidol (5 mg IV), and olanzapine (5 mg IV). Patients were included if they were determined to be acutely agitated requiring ‘sedative containment’ by the treating physician. The primary outcome of the study was time to achieve adequate sedation and proportion of patients sedated at 5 and 10 minutes. 336 patients were enrolled and randomized to the 3 groups. Baseline characteristics were well matched and protocol violations were similar across all three groups. Droperidol and olanzapine performed similarly well against the midazlolam only group. Median time to sedation was 6 min for droperidol and 5 min for olanzapine compared to 10 min for midazlolam. Need for additional sedating medications was lower in the droperidol group (12.5%) as compared to the olanzapine group (18.4%). There were no arrhythmias reported in the droperidol group. One patient in the olanzapine group had an arrhythmia.

Gottlieb and Schiebout (13) conducted a systematic review of the literature looking at the efficacy of droperidol for acute psychosis-induced agitation. They identified 6 trials which met their inclusion criteria, 3 of which were conducted in the ED setting. In the studies, a higher proportion of patients that received droperidol were sedated within 30 minutes as compared to placebo but no difference was found in time to sedation when compared with haloperidol, midazlolam, or olanzapine. There were no reports of increased cardiac or respiratory events in the droperidol groups of the included trials.