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ANESTHETIC PHARMACOLOGY

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

Yongfeng Zhang, PhD^*, Ziping Luo, PhD^*, and Paul F. White, PhD MD, FANZCA

*New Drug Center at Amphastar Pharmaceuticals Inc., Rancho Cucamonga, California; and Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Address correspondence and reprint requests to Paul F. White, PhD, MD, Department of Anesthesiology and Pain Management, 5323 Harry Hines Blvd., Dallas, TX 75390–9068. Address e-mail to paul.white{at}utsouthwestern.edu

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 QT_c prolongation. In comparing the calculated QT_c 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 QT_c 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 QT_c 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.

IMPLICATIONS: Using a square-root curve fit model to evaluate the relationship between the dose of droperidol and QT_c prolongation, small-dose droperidol (0.625–1.25 mg IV) would be expected to produce <30-ms prolongation of the QT_c interval. Therefore, small "antiemetic" doses of droperidol would not be expected to produce proarrhythmogenic effects when used for prophylaxis in surgical patients.

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