Comparative safety of serotonin (5-HT3) receptor antagonists in patients undergoing surgery: a systematic review and network meta-analysis

BMC Med. 2015 Jun 18;13:142. doi: 10.1186/s12916-015-0379-3.


Background: Serotonin (5-HT3) 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-HT3 receptor antagonists.

Methods: Searches were done in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify studies comparing 5-HT3 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antiemetics / therapeutic use*
  • Humans
  • Postoperative Nausea and Vomiting / prevention & control*
  • Registries
  • Serotonin 5-HT3 Receptor Antagonists / therapeutic use*
  • Vomiting / prevention & control*


  • Antiemetics
  • Serotonin 5-HT3 Receptor Antagonists