Abstract
BackgroundOpioids 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.MethodsWe 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 I2 index.DiscussionOur study will provide the best level of evidence to inform the effect of gabapentinoids in the management of postoperative acute pain.Systematic review registrationPROSPERO CRD42017067029
Highlights
MethodsWe 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
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
Gabapentinoids are widely used as an off-label treatment for the relief of chronic pain condition and are increasingly used for the management of postoperative acute pain, while the level of evidence supporting such usage is unclear [4]
Summary
Aims Our primary objective is to evaluate the analgesic effect of gabapentinoids in perioperative care in adult surgical patients compared to placebo or any other analgesic regimen. We hypothesize that the following factors may explain heterogeneity: type of funding (pharmaceutical industry or not), type of surgery (overall type and surgery associated with a greater risk of chronic pain), type of follow-up (inpatient or ambulatory surgery), type of population (previous diagnostic of chronic pain condition, addiction to opioids or not, women or others, and geriatric patients or not), type of anesthesia (general, regional, or others), type of drug (gabapentin or pregabalin or both), the dosage regimen (high dose (pregabalin ≥ 300 mg/day and gabapentin ≥ 900 mg/day), low dose (pregabalin < 300 mg/day and gabapentin < 900 mg/day), or both and single or multiple intake), timing of the intervention (preoperative, postoperative, or both), context of pain assessment (rest, dynamic, or unknown), type of comparator (with an analgesic effect or not), type of co-analgesia (regional analgesia or not, opioids or not, and any co-analgesia or not), and the overall risk of bias (low, high, or unclear) [38, 39]. We will perform sensitivity analyses of this analysis with the thresholds of minimally important difference of 20, 30, and 50 points [33]
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