Palonosetron as prophylaxis for post-discharge nausea and vomiting: a prospective, randomised, double-blind, placebo-controlled trial in ambulatory surgery.

BACKGROUND: Approximately 25% of ambulatory surgery patients experience post-discharge nausea and vomiting (PDNV). We aimed to investigate whether palonosetron, a long-acting anti-emetic, decreases the incidence of PDNV in high-risk patients. METHODS: In this prospective, randomised, double-blind, placebo-controlled trial, 170 male and female patients undergoing ambulatory surgery under general anaesthesia, with a high predicted risk for PDNV, were randomised to receive either palonosetron 75 µg i.v. (n=84) or normal saline (n=86) before discharge. During the first 3 postoperative days (PODs), we measured outcomes using a patient questionnaire. The primary outcome was the incidence of a complete response (no nausea, vomiting, or use of rescue medication) until POD 2. Secondary outcomes included the incidence of PDNV each day until POD 3. RESULTS: The incidence of a complete response until POD 2 was 48% (n=32) in the palonosetron group and 36% (n=25) in the placebo group (odds ratio 1.69 [95% confidence interval: 0.85-3.37]; P=0.131). No significant difference in the incidence of PDNV was observed between the two groups on the day of surgery (47% vs 56%; P=0.31). Significant differences in the incidence of PDNV were found on POD 1 (18% vs 34%; P=0.033) and POD 2 (9% vs 27%; P=0.007). No differences were observed on POD 3 (15% vs 13%; P=0.700). CONCLUSIONS: Compared with placebo, palonosetron did not reduce the overall incidence of post-discharge nausea and vomiting up to postoperative day 2. The lower incidence of post-discharge nausea and vomiting on poatoperative days 1 and 2 in the palonosetron group requires further investigation. CLINICAL TRIAL REGISTRATION: EudraCT 2015-003956-32.

What is the ideal combination antiemetic regimen?

Postoperative nausea and vomiting (PONV) and post-discharge nausea and vomiting (PDNV) are frequent unpleasant complaints that patients and clinicians report after surgery. PONV and PDNV have been associated with postoperative complications and hospital discharge delays. Despite the extensive evidence describing the use of several regimens in different surgical populations, the ideal regimen has not been established. Several antiemetic drugs have been evaluated in more than 1000 clinical controlled trials for management of this complex emetogenic pathway, including the 5-hydroxytryptamine (5-HT3) receptor antagonists, dopamine receptor antagonists, neurokinin-type receptor antagonists, antihistaminics, anticholinergics, and corticosteroids, with the 5-HT3 receptor antagonists being the most commonly used for PONV prophylaxis. Because of the complex emetogenic pathway and multifactorial etiology of PONV, a multimodal approach using two or more drugs that act at different neuro-receptor sites is suggested in patients with one or more risk factors to successfully address PONV and reduce its incidence. Nevertheless, the most studied regimens in randomized clinical trials (RCTs) are the combination of serotonin 5-HT3 receptor antagonists with dexamethasone or dopamine receptor antagonists (droperidol). Therefore, the safest and more effective combination regimen appears to be the use of serotonin 5-HT3 receptor antagonist antiemetic drugs with dexamethasone.