Explaining heterogeneity and efficacy of analgesics for postoperative pain: a systematic review and meta-regression analysis adjusted for baseline risk

Doleman, Brett and Sutton, Alex J. and Sherwin, Matthew and Lund, Jonathan N. and Williams, John P. (2017) Explaining heterogeneity and efficacy of analgesics for postoperative pain: a systematic review and meta-regression analysis adjusted for baseline risk. Anesthesia & Analgesia . ISSN 1526-7598 (In Press)

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Introduction: Statistical heterogeneity can increase the uncertainty of results and reduce the quality of evidence derived from systematic reviews. At present, it is uncertain what are the major factors that account for heterogeneity in meta-analyses of analgesic adjuncts. Therefore, the aim of this review was to identify whether various covariates could explain statistical heterogeneity and use this to improve accuracy when reporting the efficacy of analgesics.

Methods: We searched for reviews using MEDLINE, EMBASE, CINAHL, AMED and Cochrane Database of Systematic Reviews. Firstly, we identified the existence of considerable statistical heterogeneity. Secondly, we conducted meta-regression analysis for the outcome of 24-hour morphine consumption using baseline risk and other covariates. Finally, we constructed a league table of analgesic adjuncts assuming a fixed consumption of postoperative morphine.

Results: We included 344 randomized controlled trials with 28,130 participants. 91% of analyses showed considerable statistical heterogeneity. Baseline risk was a significant cause of between-study heterogeneity for acetaminophen, NSAIDS/COX- 2 inhibitors, tramadol, ketamine, alpha-2 agonists, gabapentin, pregabalin, lidocaine, magnesium and dexamethasone (R2 15-100%; p<0.05). There was some evidence that methodological limitations of the trials explained some of the residual heterogeneity. Type of surgery was not independently associated with analgesic efficacy. Assuming fixed baseline risk, gabapentin, acetaminophen, alpha-2 agonists and NSAIDS/COX-2 inhibitors were the most effective analgesics.

Discussion: This is the first review to identify a major source of between-study heterogeneity in reviews of analgesic adjuncts. Moreover, we have utilized these findings to present a novel method of reporting effect estimates, which both reduces confounding from variable baseline risk in included trials and is able to adjust for other clinical and methodological confounding variables. We recommend use of these methods in future reviews of analgesics for postoperative pain. Other implications for clinical practice, primary and secondary research studies are discussed.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Medical Sciences and Graduate Entry Medicine
Depositing User: Eprints, Support
Date Deposited: 13 Nov 2017 13:33
Last Modified: 13 Nov 2017 13:37
URI: http://eprints.nottingham.ac.uk/id/eprint/48095

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