UMEM Educational Pearls

Bottom Line: With the increasing acceptance and legalization of marijuana and its derivatives, emergency departments have seen an increase in patients with cannabis hyperemesis syndrome (CHS). In this patient population, when other pathologies have been excluded, consider droperidol (0.625 mg – 2.5 mg) or haloperidol (0.05 mg/kg or 0.1 mg/kg) for management of symptoms.

 

 

Two separate articles were reviewed for this pearl. One is a systematic review of existing literature, and the other is a randomized controlled trial.

The systematic review examined 17 existing studies, including case reports, RCTs, retrospective studies, and other systematic reviews. This included adults aged 18-85 who were using recreational or medicinal cannabinoids. There was a consensus that cessation of cannabinoid use is the best way to alleviate symptoms of CHS. Other options discussed include: 

1. Hot water hydrotherapy (ie hot baths or showers), which redirects blood flow to the skin and activates a vanilloid receptor which releases substance P, a neuropeptide associated with inflammation and pain. While this provides temporary relief of symptoms, the receptor can become unresponsive with chronic THC exposure. Only qualitative evidence was available for this therapy.
2. Topical capsaicin cream, which is theorized to have a similar mechanism as hot water hydrotherapy. 0.025-0.1% creams were discussed, with studies agreeing on shorter length of stay and improvement in nausea and vomiting; however all studies used small cohorts (of 4 or less).
3. Droperidol is a short-acting dopamine antagonist. In a systematic review, use of 0.625-2.5 mg of IV droperidol was the only treatment showed a statistically significant difference in visual analog scale when compared to placebo. Use of droperidol also results in shorter length of stay and decreased need for other anti-emetics.
4. Benzodiazepines have limited evidence, but one case study of four patients showed 2 doses of 0.5 mg clonazepam lead to rapid relief of symptoms and discharge within 24 hours.
5. Haloperidol is another dopamine antagonist with good eppicacy in cessation of nausea vomiting. Various studies have been performed, with most being case studies, with varying doses recommended. One study was a randomized controlled trial, more on this below.
6. Propranolol was discussed in a single case study, with two doses 1 mg IV given one hour apart leading to complete resolution of symptoms. This was the only such case study in the body of literature.
7. Aprepitant is a neurokinin1 receptor agonist and acts similar to capsaicin with regards to substance P. A case report discussed a patient that was refractory to all other treatments; however, a dose was not described.

As mentioned above, the HaVOC study examined various doses of haloperidol versus odansetron. This randomized controlled trial was triple blinded and had three groups: haloperidol 0.05 mg/kg or 0.1 mg/kg or odansetron 8 mg IV. The outcome of interest was reduction in abdominal pain and nausea at two hours after treatment. Either dose of haloperidol was found to be superior to odansetron, with improvements in pain and nausea (54% versus 29%; 95% CI -16% to 59%), and less use of rescue antiemetics (31% versus 59%, with 95% CI -61% to 13%). Haloperidol also resulted in shorter ED length of stay (3.1 h vs 5.6 h, 95% CI 0.1-5.0 h, p=0.03). However, 2 patients in the high dose haloperidol group had dystonic reactions precipitating return visits. The study does not specifically discuss differences in outcomes between the high and lower dose haloperidol groups.

 

Neither paper discussed the best alternatives when QTc prolongation is of concern. Clinicians should use their best judgment and the available information when deciding on a treatment option.

 

Additional Information

References

Senderovich H, Patel P, Jimenez Lopez B, Waicus S. A Systematic Review on Cannabis Hyperemesis Syndrome and Its Management Options. Med Princ Pract. 2022;31(1):29-38. doi:10.1159/000520417

Ruberto AJ, Sivilotti MLA, Forrester S, Hall AK, Crawford FM, Day AG. Intravenous Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized, Controlled Trial. Ann Emerg Med. 2021;77(6):613-619. doi:10.1016/j.annemergmed.2020.08.021