Droperidol is associated with reduced length of stay in the treatment of cannabinoid hyperemesis syndrome

Droperidol is a butyrophenone-class drug with potent antiemetic properties that may be useful for treating the acute symptoms of cannabinoid hyperemesis syndrome. We evaluated the effectiveness of droperidol in emergency department patients with cannabinoid hyperemesis syndrome. This was a retrospective study of encounters that occurred between March 1, 2024 and August 31, 2024 at two tertiary academic emergency departments in Atlanta, Georgia. We identified cases of cannabinoid hyperemesis syndrome via diagnosis codes and manual review of relevant non-specific diagnoses codes. We stratified patients by use of droperidol in the emergency department. The primary outcome was length of stay and secondary outcomes were total medication use, use of opioids, disposition, and key safety outcomes (medication adverse events, dysrhythmias). There were 211 encounters among 158 unique patients included in the study. Droperidol was used in 77 (36.5%) of encounters at a median dose of 1.25 mg. The length of stay was significantly reduced in the droperidol group (409 min versus 641 min). After adjustments, droperidol use was associated with a reduced length of stay (mean ratio 0.76; 95% CI: 0.62 0.94; <i>P</i> = 0.01), decreased total medication administration (OR 0.34; 95% CI: 0.20–0.58; <i>P &lt;</i>0.001) and decreased usage of opioids (OR 0.16; 95% CI: 0.07–0.39; <i>P &lt;</i>0.001). Discharge dispositions were non-significant (OR 1.19; 95% CI: 0.57–2.48; <i>P</i> = 0.64). There were two mild adverse drug reactions in the droperidol group. Several drug classes with plausible mechanisms are used to treat the symptoms of cannabinoid hyperemesis syndrome. Droperidol use was associated with several favorable outcomes including decreased length of stay, total medication use, and opioid use. We believe that droperidol may be considered as a first line treatment in patients with cannabinoid hyperemesis syndrome. Future studies should identify optimal dosing regimens using a randomized controlled trial design.