| Summary: | Abstract Background Opioids are commonly used for the management of postoperative pain, but their use is limited by important adverse events, such as respiratory depression and the potential for addiction. Multimodal opioid-sparing analgesia regimens can be effectively employed to manage postoperative pain and reduce exposure to opioids. Gabapentinoids (pregabalin and gabapentin) represent an attractive class of drugs for use in multimodal regimens. The American Pain Society recommends the use of gabapentinoids during the perioperative period; however, evidence to inform such a recommendation is unclear. Methods We will conduct a systematic review and meta-analysis of randomized clinical trials evaluating the use of systemic gabapentinoids, in comparison to other analgesic regimens or placebo in adult patients undergoing surgery. We will search MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Web of Science, and ClinicalTrials.gov databases for relevant citations. Our primary outcome will be intensity of postoperative acute pain (12 h). Our secondary outcomes will be postoperative pain intensity at 6, 24, 48 h, and 72 h, cumulative dose of opioids administered within 24, 48, and 72 h following surgery, the length of stay, chronic pain, and adverse events. Two investigators will independently select trials and extract data. We will evaluate the risk of bias of included trials using the Cochrane risk of bias tools. We will represent pooled continuous data as weighted mean differences and pooled dichotomous data as risk ratios with a 95% confidence interval. We will use random effect models and assess statistical heterogeneity with the I 2 index. Discussion Our study will provide the best level of evidence to inform the effect of gabapentinoids in the management of postoperative acute pain. Systematic review registration PROSPERO CRD42017067029
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