Pooled analysis of three large clinical trials to determine the optimal dose of dolasetron mesylate needed to prevent postoperative nausea and vomiting. The Dolasetron Prophylaxis Study Group

Abstract

Study objective: To identify the maximally effective dolasetron dose (i.e., maximum efficacy with minimum adverse events) for prevention of postoperative nausea and vomiting (PONV) using the statistical power generated in a pooled patient sample from three large, nearly identical clinical trials.

Design: Three randomized, multicenter, placebo-controlled, double-blinded trials.

Setting: Trials 1, 2, and 3 enrolled patients at 10, 25, and 17 hospitals and/or surgical centers, respectively.

Patients: A total of 1,946 ASA physical status, I, II, and III patients. Trials 1 and 2 enrolled only female patients (n = 916) undergoing gynecologic surgery. Trial three enrolled 722 females (approximately 70% gynecologic surgeries) and 308 males (approximately 46% orthopedic surgeries) undergoing a variety of surgical procedures.

Interventions: All surgical procedures used balanced general anesthesia. Patients received 12.5, 25, 50, or 100 mg of the antiemetic, dolasetron, near the end of anesthesia.

Measurements and main results: Efficacy endpoints were identical and measured for 24 hours: complete response (no vomiting or rescue medication) and maximum nausea, reported using a 100-mm visual analog scale (VAS). Safety was assessed using adverse event reports, laboratory and electrocardiographic data, and vital signs. All four dolasetron doses produced significant increases in complete response and decreases in maximum VAS nausea compared with placebo (p < 0.01). No increased efficacy was observed with dolasetron doses higher than 12.5 mg. Safety was similar between each dolasetron dose and placebo.

Conclusion: Dolasetron 12.5 mg, given near the end of anesthesia, is the maximally effective dose studied for preventing postoperative nausea and vomiting.