In this episode, I’ll discuss the use of droperidol for acute agitation in the ED.
After more than a decade in exile due to FDA black box warnings and medication shortages, droperidol is re-emerging as an option for acute agitation in the emergency department.
A comprehensive review to help guide the re-integration of droperidol into emergency medicine practice was recently published in AJHP.
Droperidol is an antipsychotic similar to haloperidol and also has beneficial effects in treating headache, nausea, agitation, and acute and chronic pain. Droperidol is an antagonist of dopamine, histamine, α 2, and serotonin receptors.
A black box warning mandated by the FDA highlighted a risk of QT interval prolongation and fatal arrhythmia, which curtailed the use of droperidol. This warning was based in part on case reports, of which three-quarters were from outside the US and 99% of which used doses of droperidol far higher than the 0.625 mg to 10 mg that US-based clinicians typically use.
Since the black box warning was published, many studies have been done (prospective and retrospective) on doses of droperidol in the range of 0.625 mg to 13.75 mg. These studies consistently put the incidence of a QTc above 500 msec in the ~1% or lower range.
As the AJHP reviewers point out, ondansetron and other commonly used medications have similar rates of QTc prolongation yet are widely used in the ED and elsewhere.
In 2014, the American Academy of Emergency Medicine published a position statement titled: Safety of Droperidol Use in the Emergency Department. The position statement reviewed 35 articles and concluded:
Droperidol is an effective and safe medication in the treatment of nausea, headache, and agitation. The literature search did not support mandating an electrocardiogram or telemetry monitoring for doses < 2.5 mg given either intramuscularly or intravenously. Intramuscular doses of up to 10 mg of droperidol seem to be as safe and as effective as other medications used for sedation of agitated patients.
One potential problem with relying on these studies that demonstrate the apparent safety of droperidol at lower doses is that all the studies excluded patients at high risk of torsades. The real-world application of droperidol would need to be in a similarly selected set of patients in order for the safety outcomes to be the same.
Droperidol was found in a 2016 Cochrane review to have high-quality evidence supporting it’s use as a first line treatment option in acute psychosis.
The authors of the AJHP article also provide recommendations for patient selection and monitoring:
In patients concomitantly receiving QTc-prolonging medication, a screening ECG to determine a baseline QTc value is reasonable.
For patients from whom an ECG is not obtainable, such as agitated patients, evaluating individual clinical risk factors for QTc prolongation is important.
In most cases QTc prolongation induced by the drug peaks around 15 minutes after administration and is shortlived.
In the event your hospital returns droperidol to formulary, keep in mind that there is nearly a generation of physicians and nurses that don’t have experience selecting patients with which to use droperidol. Also, the black box warning from the FDA is likely to persist. Consider proactively providing clinicians with education on the efficacy, safety, and patient selection that is key to safe use of droperidol.
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Droperidol versus ketamine for acute agitation? Wondering if ambulance service had to choose between the two… what drug would you stock?