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

Tricco AC, Soobiah C, Blondal E, Veroniki AA, Khan PA, Vafaei A, Ivory J, Strifler L, Ashoor H, MacDonald H, Reynen E, Robson R, Ho J, Ng C, Antony J, Mrklas K, Hutton B, Hemmelgarn BR, Moher D, Straus SE - BMC Med (2015)

Bottom Line: We conducted a systematic review on the comparative safety of 5-HT3 receptor antagonists.PROSPERO registry number: CRD42013003564.Overall, 120 studies and 27,787 patients were included after screening of 7,608 citations and 1,014 full-text articles.

View Article: PubMed Central - PubMed

Affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, ON, M5B 1W8, Canada. TriccoA@smh.ca.

ABSTRACT

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.

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Related in: MedlinePlus

Network meta-analysis results for arrhythmia. All treatments are compared to placebo. The black horizontal lines represent the 95 % confidence intervals (CI) of the summary treatment effects and red horizontal lines the 95 % predictive intervals (PrI). Results are presented on the odds ratio (OR) scale. Among patients of all ages receiving granisetron plus dexamethasone, significantly more experienced arrhythmia compared with placebo (OR 2.96, 95 % 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). Note: Reference treatment is placebo. CI: Confidence interval; OR: Odds ratio; PrI: Predictive interval
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Fig3: Network meta-analysis results for arrhythmia. All treatments are compared to placebo. The black horizontal lines represent the 95 % confidence intervals (CI) of the summary treatment effects and red horizontal lines the 95 % predictive intervals (PrI). Results are presented on the odds ratio (OR) scale. Among patients of all ages receiving granisetron plus dexamethasone, significantly more experienced arrhythmia compared with placebo (OR 2.96, 95 % 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). Note: Reference treatment is placebo. CI: Confidence interval; OR: Odds ratio; PrI: Predictive interval

Mentions: The network meta-analysis for arrhythmia included 31 RCTs with 6,623 patients [40, 43, 45, 53, 59, 74, 78, 79, 83, 86–89, 97, 102, 108, 112–115, 117, 119, 123, 125, 128, 130, 132, 138, 141, 142, 150]. The network geometry and included drugs can be found in Fig. 2a. Twenty-one studies were excluded from the analysis because they reported zero events in all arms [39, 43, 57, 60, 61, 71, 73, 81, 82, 86, 90, 92–94, 98, 110, 121, 127, 145, 155, 156]. Although the definitions of arrhythmia varied across the studies (Additional file 1: Appendix 10), there was no evidence of network inconsistency (χ2 = 3.49, degrees of freedom = 10, P = 0.968, heterogeneity variance = 0.01), and the within-network heterogeneity variance was estimated to be 0.00. Among patients of all ages receiving granisetron plus dexamethasone, significantly more experienced arrhythmia compared with placebo (OR 2.96, 95 % 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) (Fig. 3, Table 3, Additional file 1: Appendix 11). According to the SUCRA curves (Additional file 1: Appendix 12), the safest agents for arrhythmia were ondansetron plus dexamethasone (83 % probability) and dolasetron (82 % probability).Fig. 2


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

Tricco AC, Soobiah C, Blondal E, Veroniki AA, Khan PA, Vafaei A, Ivory J, Strifler L, Ashoor H, MacDonald H, Reynen E, Robson R, Ho J, Ng C, Antony J, Mrklas K, Hutton B, Hemmelgarn BR, Moher D, Straus SE - BMC Med (2015)

Network meta-analysis results for arrhythmia. All treatments are compared to placebo. The black horizontal lines represent the 95 % confidence intervals (CI) of the summary treatment effects and red horizontal lines the 95 % predictive intervals (PrI). Results are presented on the odds ratio (OR) scale. Among patients of all ages receiving granisetron plus dexamethasone, significantly more experienced arrhythmia compared with placebo (OR 2.96, 95 % 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). Note: Reference treatment is placebo. CI: Confidence interval; OR: Odds ratio; PrI: Predictive interval
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4472408&req=5

Fig3: Network meta-analysis results for arrhythmia. All treatments are compared to placebo. The black horizontal lines represent the 95 % confidence intervals (CI) of the summary treatment effects and red horizontal lines the 95 % predictive intervals (PrI). Results are presented on the odds ratio (OR) scale. Among patients of all ages receiving granisetron plus dexamethasone, significantly more experienced arrhythmia compared with placebo (OR 2.96, 95 % 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). Note: Reference treatment is placebo. CI: Confidence interval; OR: Odds ratio; PrI: Predictive interval
Mentions: The network meta-analysis for arrhythmia included 31 RCTs with 6,623 patients [40, 43, 45, 53, 59, 74, 78, 79, 83, 86–89, 97, 102, 108, 112–115, 117, 119, 123, 125, 128, 130, 132, 138, 141, 142, 150]. The network geometry and included drugs can be found in Fig. 2a. Twenty-one studies were excluded from the analysis because they reported zero events in all arms [39, 43, 57, 60, 61, 71, 73, 81, 82, 86, 90, 92–94, 98, 110, 121, 127, 145, 155, 156]. Although the definitions of arrhythmia varied across the studies (Additional file 1: Appendix 10), there was no evidence of network inconsistency (χ2 = 3.49, degrees of freedom = 10, P = 0.968, heterogeneity variance = 0.01), and the within-network heterogeneity variance was estimated to be 0.00. Among patients of all ages receiving granisetron plus dexamethasone, significantly more experienced arrhythmia compared with placebo (OR 2.96, 95 % 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) (Fig. 3, Table 3, Additional file 1: Appendix 11). According to the SUCRA curves (Additional file 1: Appendix 12), the safest agents for arrhythmia were ondansetron plus dexamethasone (83 % probability) and dolasetron (82 % probability).Fig. 2

Bottom Line: We conducted a systematic review on the comparative safety of 5-HT3 receptor antagonists.PROSPERO registry number: CRD42013003564.Overall, 120 studies and 27,787 patients were included after screening of 7,608 citations and 1,014 full-text articles.

View Article: PubMed Central - PubMed

Affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, ON, M5B 1W8, Canada. TriccoA@smh.ca.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus