Single dose intravenous ondansetron induces QTc prolongation in adult emergency department patients: is it predictable and persistent? A prospective observational study

Background: Ondansetron is one of the most routinely used drugs in the emergency department (ED) for treating nausea and vomiting, particularly in intravenous (IV) form. Nevertheless, it has been shown to prolong QT interval and increase the risk of fatal ventricular dysrhythmias. The accurate prediction of QTc interval prolongation induced by just a single-dose IV ondansetron in the ED remains unclarified in the literature. This study further evaluated the associations between IV ondansetron dosage and subsequent QTc prolongation. Methods: In this prospective observational study, a total number of 106 patients presenting to the ED in a 3-month period with nausea and vomiting treated with IV ondansetron were enrolled. QTc intervals were measured at baseline (QTc0), 30 minutes (QTc30) and 60 minutes (QTc60) following a single-dose administration of ondansetron at 4 or 8 mg doses. Results: In the multivariable logistic regression, ondansetron IV dose and QTc0 were independently associated with QTc60 > 480msec. The area under curves (AUC) for prediction of prolonged QTc60 were 0.71 and 0.64 for dosage and QTc0, respectively. There was a 100% sensitivity for QTc0 = 400msec to predict QTC60  460msec predicted QTC60 > 480msec with 98% specificity. Each msec increment in QTc0 increased the likelihood of prolonged QTc60 by 3%, while increasing the single dose of 4mg to 8mg increased prolonged QTc60 odds by 33%. Conclusions: Based on our results, single doses of up to 8 mg ondansetron could be safely injected for patients with no risk factors for QTc prolongation and initial QTc of 400msec or less. Above this QTc cutoff, using the 4mg dose instead of 8mg as a precaution may be advisable if the baseline QTc is not prolonged and ondansetron administration is necessary.