Results of a prospective, randomized, double-blind, placebo-controlled, dose-ranging trial to determine the effective dose of ramosetron for the prevention of vomiting after tonsillectomy in children

Abstract

Background: Postoperative vomiting (POV) is an important adverse effect of anesthesia and surgery, and children undergoing tonsillectomy may be particularly at risk.

Objective: The aim of this study was to determine the effective dose of ramosetron, a 5-hydroxytryptamine type 3 receptor antagonist, for prophylaxis of severe POV (> or =2 episodes) in children undergoing general anesthesia for tonsillectomy.

Methods: Standard general anesthetic technique and postoperative analgesia were used in this prospective, randomized, double-blind, placebo-controlled, dose-ranging trial of pediatric patients. Patients who had experienced POV, had taken an antiemetic medication within 24 hours before surgery of had a history of motion sickness were excluded. Only patients aged 4 to 10 years were included, because of their ability to answer questions. Patients received a single administration of either i.v. placebo or i.v. ramosetron at 3, 6, or 12 microg/kg immediately after the end of surgery. During the first 48 hours after anesthesia, episodes of retching, vomiting, and adverse events were recorded by nursing staff blinded to treatment assignment.

Results: Eighty children (20 in each group)--42 girls and 38 boys--were enrolled. There were no differences in patient demographic characteristics among the treatment groups. The rates of complete response (no vomiting, retching, or need for another antiemetic medication) from 0 to 24 hours after anesthesia were 35% (7/20) with ramosetron 3 microg/kg, 90% (18/20) with ramosetron 6 micro/kg, and 90% (18/20) with ramosetron 12 microg/kg compared with placebo (30% [620], P=NS, P=0.001, and P=0.001 vs placebo, respectively); the corresponding rates from 24 to 48 hours after anesthesia were 35% (7/20), 90% (18/20), and 95% (19/20) compared with placebo (35% [7/20]; P=NS, P=0.001, and P=0.001 vs placebo, respectively). No difference in antiemetic efficacy was observed between ramosetron 6 and 12 microg/kg. No clinically serious adverse events attributable to the study drug were observed in any group.

Conclusions: In the pediatric population studied, ramosetron 6 microg/kg was effective for the prevention of vomiting after tonsillectomy from 0 to 48 hours after anesthesia. Increasing the dose to 12 microg/kg did not appear to provide further benefit.