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

*This research was funded by the Drug Safety and Effectiveness Network (DSEN) and conducted by the following investigators: Andrea C. Tricco, Charlene Soobiah, Wing Hui, Jesmin Antony, Vladi Struchkov, Brian Hutton, Brenda Hemmelgarn, David Moher, Sharon E. Straus. The statements made herein are those of the stated authors, who are independent researchers.

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Summary

We conducted a systematic review to examine the comparative safety and effectiveness of 5-HT3 antagonists in patients undergoing surgical procedures. Using network meta-analysis we found that significantly more patients receiving granisetron and dexamethasone experienced arrhythmia. No other significant safety signals were identified. All agents were significantly more effective in reducing post-operative nausea and vomiting compared to placebo.

Implications

Overall, granisetron was found to carry the highest risk of arrhythmia of any of the 5-HT3 antagonists assessed. Though no significant safety effects were found for other outcomes, a lack of consistent harm reporting among the included studies was noted. Further research in the use of 5HT-3 antagonists for surgical patients should focus on harm reporting as well as effectiveness.

For more information, please contact Dr. Andrea Tricco: triccoa@smh.ca

What is the current practice in treating nausea and vomiting in patients undergoing surgery?

  • Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for patients undergoing surgery
  • Some evidence exists, which shows that 5-HT3 receptor antagonists may also cause harm such as arrhythmia
  • The aim of this review was to conduct a systematic review and network meta-analysis (NMA) to determine the effectiveness and safety of 5-HT3 receptor antagonists

How was the study conducted?

  • Eligible study designs included randomized clinical trials (RCTs) and non- randomized studies examining 5-HT3 antagonists (granisetron, ondansetron, dolasetron, tropisetron) vs. placebo in patients of all ages undergoing surgery
  • The outcomes of interest included arrhythmia, QT prolongation, PR prolongation, mortality, nausea, vomiting, and post-operative nausea and vomiting
  • Screening of literature search results, data abstraction, and risk-of-bias assessment were conducted independently by two reviewers
  • The protocol (or plan) for the review was registered and published
  • Network meta-analysis was conducted

What did the study find?

  • 452 relevant studies were included
  • A NMA (31 RCTs) was conducted to examine arrhythmia outcomes and 2 meta-analyses were conducted to examine mortality (3 RCTs) and QT prolongation (2 RCTs)
  • 3 NMAs were conducted to examine nausea (195 RCTs), vomiting (238 RCTs), and post-operative vomiting and nausea (125 RCTs)
  • Significantly more patients receiving granisetron plus dexamethasone experienced arrhythmia compared to all other interventions and placebo
  • No statistically significant differences were observed regarding mortality and QT prolongation in meta-analysis; no studies reported on PR prolongation or sudden cardiac death
  • Significantly fewer patients experienced nausea and vomiting when administered any drug versus placebo except for ondansetron plus metoclopramide (nausea) and palonosetron plus dexamethasone (vomiting)
  • Significantly fewer patients experienced post-operative nausea and vomiting when administered any drug versus placebo
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