Does Ondansetron Modify Sympathectomy Due to Subarachnoid Anesthesia?: Meta-analysis, Meta-regression, and Trial Sequential Analysis
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Published on: January 10, 2019
Abdullah S Terkawi1, Dimitris Mavridis, Pamela Flood
1From the Department of Anesthesiology, University of Virginia, Charlottesville, Virginia (A.S.T., M.T.); Department of Anesthesiology, King Fahad Medical City, Riyadh, Saudi Arabia (A.S.T.); Outcomes Research Consortium, Cleveland Clinic, Cleveland, Ohio (A.S.T.); Departments of Primary School Education and Hygiene and Epidemiology, University of Ioannina, Epirus, Greece (D.M.); Department of Anesthesiology Perioperative and Pain Medicine, Stanford University, Stanford, California (P.F.); Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark (J.W.); Children Hospital, King Fahad Medical City, Riyadh, Saudi Arabia (R.S.T.); Department of Internal Medicine, Cardiovascular disease section, University of Iowa Hospitals and Clinics, Iowa City, Iowa (A.A.B.A.); and Claude Moore Health Sciences Library, University of Virginia, Charlottesville, Virginia (M.S.N.).
Background:
Disagreement among many underpowered studies has led to an equivocal understanding of the efficacy of the 5-HT3 antagonist ondansetron in preventing the consequences of sympathectomy after subarachnoid anesthesia. The authors assessed the efficacy of ondansetron with respect to the overall quality and statistical power of the meta-analyses.
Methods:
The authors used a standard and a newer method of meta-analysis, trial sequential analysis (TSA), to estimate adjusted CIs based on how much information has been accrued. They also used random-effects meta-analyses techniques, small trial bias assessment, selection models, sensitivity analyses, and the Grading of Recommendations on Assessment, Development, and Evaluation system. These results from the aforementioned techniques were compared, and importance of consideration of these factors was discussed.
Results:
Fourteen randomized placebo-controlled trials (1,045 subjects) were identified and analyzed. By using conventional meta-analyses, the authors determined that ondansetron was associated with reduction in the incidence of hypotension (relative risk = 0.62 [95% CI, 0.46 to 0.83], P = 0.001; TSA-adjusted CI, 0.34 to 1.12; I = 60%, P = 0.002) and bradycardia (relative risk = 0.44 [95% CI, 0.26 to 0.73], P = 0.001; TSA-adjusted CI, 0.05 to 3.85; I = 0%, P = 0.84). However, the authors found indications of bias among these trials. TSAs demonstrated that the meta-analysis lacked adequate information size and did not achieve statistical significance when adjusted for sparse data and repetitive testing. The Grading of Recommendations on Assessment, Development, and Evaluation system showed that the results had low to very low quality of evidence.
Conclusions:
The analyses fail to confirm evidence that ondansetron reduces the incidence of hypotension and bradycardia after subarachnoid anesthesia due to the risk of bias and information sizes less than the required. As results from meta-analysis are given significant weight, it is important to carefully evaluate the quality of the evidence that is input.
Insights
Ondansetron did not show significant efficacy in preventing hypotension and bradycardia after subarachnoid anesthesia. Further meta-analyses require careful evaluation of evidence quality due to bias risks.
Area of Science:
- Anesthesiology
- Pharmacology
- Evidence-Based Medicine
Background:
- Conflicting results from underpowered studies question ondansetron's efficacy post-subarachnoid anesthesia.
- Assessing ondansetron's effectiveness requires robust meta-analysis considering study quality and statistical power.
Purpose of the Study:
- To evaluate the efficacy of ondansetron in preventing hypotension and bradycardia after subarachnoid anesthesia.
- To critically assess meta-analyses using advanced statistical methods to account for bias and information size.
Main Methods:
- Employed standard and trial sequential analysis (TSA) meta-analysis techniques.
- Utilized random-effects models, bias assessments, sensitivity analyses, and GRADE for evidence quality evaluation.
- Compared results from various meta-analytic approaches to determine statistical significance and reliability.
Main Results:
- Conventional meta-analysis suggested ondansetron reduced hypotension and bradycardia.
- Trial sequential analysis revealed insufficient information size and lack of statistical significance after adjustments for bias.
- GRADE assessment indicated low to very low quality of evidence for the observed effects.
Conclusions:
- Evidence confirming ondansetron's benefit in reducing hypotension and bradycardia after subarachnoid anesthesia is not established.
- Risk of bias and inadequate information size undermine the reliability of current meta-analyses.
- Emphasizes the critical need for rigorous quality assessment of evidence in meta-analytic reviews.
