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A Model for Evaluating Droperidol’s Effect on the Median QTc Interval

Controversy surrounds the use of the antiemetic droperidol, because of the Food and Drug Administration-imposed “black box” warning alleging that even small doses of the drug can lead to serious (even fatal) arrhythmias when it is used for antiemetic prophylaxis during the perioperative period. We used mathematical modeling of electrocardiographic QT interval data published in a peer-reviewed manuscript to evaluate the relationship between the dose of droperidol (0.1–0.25 mg/kg IV) and QTc prolongation. In comparing the calculated QTc values based on the logarithm model (27–63 ms), the linear model (27–67 ms) and the square-root model (36–57 ms) to the actual measured QTc values (37–59 ms), the square-root model provided the best simulation of the experimental findings. Other models that we evaluated included the polynomial model and various exponent models (e.g., quartic-root model, cubic-root model, square model, and cubic model). The estimated median prolongation of the median QTc interval produced by droperidol 0.625–1.25 mg IV would vary from 9 ± 3 to 18 ± 3 ms. Therefore, this regression analysis suggests that small “antiemetic” doses of droperidol (≤1.25 mg) would be unlikely to produce proarrhythmogenic effects in the perioperative period.