Mitigating the Risk of QTc Prolongation When Using Haloperidol for Acute Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents and Young Adults

<b>Background/Objectives</b>: Cannabinoid Hyperemesis Syndrome (CHS), associated with long-term cannabinoid use, has been increasingly observed in emergency room visits as more states in the U.S. have legislatively permitted medical and recreational marijuana use. The acute management of CHS primarily focuses on antiemetic treatment and supportive care. However, both the condition itself and the antiemetic drugs, such as haloperidol, may cause QTc prolongation. <b>Methods</b>: We reported two adolescent cases admitted to the emergency department for acute antiemesis management of CHS who received haloperidol treatment. A literature review was performed through October 2024 for previously published cases of QTc prolongation and/or Torsades de Pointes (TdP) in adolescents and young adults. <b>Results</b>: A 15-year-old female presented with hypokalemia and hypomagnesemia upon admission. She complained of chest pain and tachycardia, and the electrocardiogram (EKG) showed prolonged QTc (528 msec). The haloperidol infusion was discontinued. She recovered well post-discharge without complaints. A 17-year-old female had a borderline prolonged QT interval (476 msec). Her nausea and vomiting improved with a three-dose course of intravenous fosaprepitant before discharge. Our literature search identified five severe cases with life-threatening episodes of QTc prolongation and/or TdP in adolescents and young adults. <b>Conclusions</b>: Patients with CHS are at higher risk of QTc prolongation due to cannabis use, electrolyte imbalance, and antiemetic medications. We recommend vigilant EKG monitoring, particularly before initiating and throughout haloperidol treatment. If the patient presents with an increased risk of QTc prolongation, consider using topical capsaicin, lorazepam, aprepitant/fosaprepitant, and olanzapine as alternatives.