The Dose-Response Relationship of Ondansetron in Preventing Postoperative Emesis in Pediatric Patients Undergoing Ambulatory Surgery

Background Postoperative nausea and vomiting is a distressing anesthetic complication that may delay discharge after ambulatory surgery. Effective prophylaxis for postoperative nausea and vomiting can be achieved in adults with lower doses of ondansetron, a 5-hydroxytryptamine subtype 3 receptor antagonist, compared with chemotherapy-induced emesis. However, the doses of ondansetron used in preventing postoperative nausea and vomiting in children are based on data from chemotherapy-induced emesis. The dose-related efficacy of intravenous ondansetron in the prophylaxis of postoperative emesis in the pediatric outpatient population was determined. Methods In a double-blind, randomized placebo-controlled study, 130 patients (mean age 5.7 +/- 3.4 yr) received placebo, 10, 50, or 100 micrograms/kg ondansetron during a standardized anesthetic. Episodes of postoperative vomiting or retching were recorded. Results Intravenous ondansetron in a dose of 50 micrograms/kg was more effective than placebo or a dose of 10 micrograms/kg in controlling the incidence and frequency of emesis in the hospital and during the first 24 postoperative hours. Increasing the dose of ondansetron to 100 micrograms/kg intravenously did not significantly reduce the incidence or frequency of emesis compared to 50 micrograms/kg intravenously. Conclusions Intravenous ondansetron in a dose of 50 micrograms/kg is as effective as larger doses for the prophylaxis of emesis in children undergoing surgical procedures known to be associated with an increased risk for postoperative nausea and vomiting.

A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy.

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.