Comparative safety of serotonin (5-HT(3)) receptor antagonists in patients undergoing surgery: a systematic review and network meta-analysis

BACKGROUND: Serotonin (5-HT(3)) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients, but these agents may be harmful. We conducted a systematic review on the comparative safety of 5-HT(3) receptor antagonists. METHODS: Searches were done in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify studies comparing 5-HT(3) receptor antagonists with each other, placebo, and/or other antiemetic agents for patients undergoing surgical procedures. Screening search results, data abstraction, and risk of bias assessment were conducted by two reviewers independently. Random-effects pairwise meta-analysis and network meta-analysis (NMA) were conducted. PROSPERO registry number: CRD42013003564. RESULTS: Overall, 120 studies and 27,787 patients were included after screening of 7,608 citations and 1,014 full-text articles. Significantly more patients receiving granisetron plus dexamethasone experienced an arrhythmia relative to placebo (odds ratio (OR) 2.96, 95 % confidence interval (CI) 1.11–7.94), ondansetron (OR 3.23, 95 % CI 1.17–8.95), dolasetron (OR 4.37, 95 % CI 1.51–12.62), tropisetron (OR 3.27, 95 % CI 1.02–10.43), and ondansetron plus dexamethasone (OR 5.75, 95 % CI 1.71–19.34) in a NMA including 31 randomized clinical trials (RCTs) and 6,623 patients of all ages. No statistically significant differences in delirium frequency were observed across all treatment comparisons in a NMA including 18 RCTs and 3,652 patients. CONCLUSION: Granisetron plus dexamethasone increases the risk of arrhythmia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0379-3) contains supplementary material, which is available to authorized users.