Intravenous, Oral, and the Combination of Intravenous and Oral Ramosetron for the Prevention of Nausea and Vomiting After Laparoscopic Cholecystectomy: A Randomized, Double-Blind, Controlled Trial

Background: Patients undergoing general anesthesia for laparoscopic cholecystectomy have a high risk of postoperative nausea and vomiting (PONV) with incidences up to 75%. Ramosetron, a serotonin subtype 3 (5-HT(3)) antagonist, has been shown to be effective as an antiemetic after chemotherapy and surgery. Consensus guidelines recommend a combination of antiemetic therapies in high-risk groups. Until now, no published data have been available on the use of combination oral plus intravenous ramosetron. Objective: The goal of this prospective, randomized, double-blind study was to compare the efficacy and tolerability of intravenous, oral, and the combination of oral and intravenous ramosetron for PONV prophylaxis in patients undergoing laparoscopic cholecystectomy. Methods: Patients scheduled for laparoscopic cholecystectomy were double-randomly allocated to 1 of 3 groups. Patients were randomly allocated to receive either 0.3 mg of intravenous ramosetron (group A), 0.1 mg of oral ramosetron (group B), or the combination of 0.1 mg of oral ramosetron and 0.3 mg of intravenous ramosetron (group C). All patients received standardized balanced anesthesia with desflurane and remifentanil. Postoperative nausea, retching, vomiting, pain, and adverse effects were assessed at 0 to 2, 2 to 24, and 24 to 48 hours after surgery. Results: A total of 124 Korean patients (67 women, 57 men; age range, 25-65 years) were randomized to 1 of 3 study groups (42 in group A [mean age, 49.8 years], 41 in group B [mean age, 47.4 years], and 41 in group C [mean age, 48.9 years]). No statistical differences were observed among the 3 groups with regard to patient characteristics and information on surgery and anesthesia. During postoperative period 0 to 2 hours, complete response occurred in 31 (74%) patients in group A, 27 (66%) in group B, and 37 (90%) in group C. During the postoperative period of 2 to 24 hours, complete response was observed in 36 (86%), 33 (80%), and 40 (98%) patients in groups A, B, and C, respectively; there was a statistically significant difference in group C compared with group A or group B. During the postoperative period of 0 to 48 hours, incidences of rescue antiemetic use were 13 (31%), 14 (34%), and 3 (7%) in groups A, B and C, respectively. Common adverse effects (headache, dizziness, and drowsiness) were observed, but there was no significant difference in the incidences of adverse effects among the 3 groups (P > 0.05). Conclusions: The combination of 0.1-mg oral and 0.3-mg intravenous ramosetron was more effective than either 0.3-mg intravenous ramosetron or 0.1-mg oral ramosetron alone for the prophylaxis of nausea and vomiting after laparoscopic cholecystectomy during the first 24 hours after surgery. In addition, differences did not reach the level of statistical significance between 0.1 mg of oral ramosetron and 0.3 mg of intravenous ramosetron for the prevention of PONV in this patient population. Oral, intravenous, and combined oral and intravenous ramosetron appears well tolerated in the population studied. ClinicalTrials.gov identifier: NCT 01041183. (Clin Ther. 2011;33:1162-1172) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.