Randomized, double-blind, placebo-controlled, dosed-finding study of the antiemetic effects and tolerability of ramosetron in adults undergoing middle ear surgery.

BACKGROUND

Ramosetron is a selective serotonin receptor antagonist (SSRA) that is approved for the treatment of emetic symptoms induced by cytotoxic drugs in Japan. We have reported that ramosetron 0.3 mg had comparable efficacy to granisetron 3 mg, another SSRA, in preventing emetic symptoms in adults in the first 48 hours after the start of anesthesia for middle ear surgery. Although it has been shown that a high dose of ramosetron can cause adverse effects (AEs), such as severe headache, the minimal effective dose of ramosetron is unknown.

OBJECTIVE

The aim of this study was to determine the minimum effective and tolerable dose of ramosetron needed to prevent postoperative emetic symptoms in adult patients undergoing middle ear surgery.

METHODS

This randomized, double-blind, placebo-controlled, dose-finding study was conducted at the Department of Anesthesiology, Toride Kyodo General Hospital (Toride, Japan). Patients aged > or =20 years scheduled for middle ear surgery were randomized to receive either placebo or ramosetron at 1 of 3 doses (0.15, 0.3, or 0.6 mg), regardless of body weight, i.v. immediately before anesthesia induction. Emetic symptoms (nausea, retching, or vomiting) occurring from 0 to <24 and 24 to 48 hours after the start of anesthesia were recorded. Other AEs also were assessed.

RESULTS

A total of 100 patients (55 women, 45 men; mean [SD] age, 44 [12] years; mean [SD] body weight, 56 [8] kg; mean [SD] height, 159 [8] cm) were enrolled. Each treatment group comprised 25 patients. The treatment groups were comparable with regard to demographic characteristics and type of surgery After the second 24 hour postanesthesia period, significantly more patients in the ramosetron 0.3-mg and 0.6-mg groups were emesis free than in the placebo group (both P<0.001). The number of emesis-free patients in the ramosetron 0.15-mg group and the placebo group were similar after both study periods. No significant difference in antiemetic efficacy was found between the ramosetron 0.3-mg and 0.6-mg groups. No relationship between body weight and the efficacy of ramosetron was observed. The incidence of AEs was similar in all 4 groups.

CONCLUSIONS

Ramosetron 0.3 mg, regardless of body weight, was more effective than either ramosetron 0.15 mg or placebo and as effective as ramosetron 0.6 mg for the prevention of emetic symptoms in the first 48 hours after the start of anesthesia in this selected population of adult patients who underwent middle ear surgery.