Dose-related beneficial and harmful effects of gabapentin in postoperative pain management – post hoc analyses from a systematic review with meta-analyses and trial sequential analyses

Abstract

BackgroundDuring the last 15 years, gabapentin has become an established component of postoperative pain treatment. Gabapentin has been employed in a wide range of doses, but little is known about the optimal dose, providing the best balance between benefit and harm. This systematic review with meta-analyses aimed to explore the beneficial and harmful effects of various doses of gabapentin administered to surgical patients.Materials and methodsData in this paper were derived from an original review, and the subgroup analyses were predefined in an International Prospective Register of Systematic Reviews published protocol: PROSPERO (ID: CRD42013006538). The methods followed Cochrane guidelines. The Cochrane Library’s CENTRAL, PubMed, EMBASE, Science Citation Index Expanded, Google Scholar, and FDA database were searched for relevant trials. Randomized clinical trials comparing gabapentin versus placebo were included. Four different dose intervals were investigated: 0–350, 351–700, 701–1050, and >1050 mg. Primary co-outcomes were 24-hour morphine consumption and serious adverse events (SAEs), with emphasis put on trials with low risk of bias.ResultsOne hundred and twenty-two randomized clinical trials, with 8466 patients, were included. Sixteen were overall low risk of bias. No consistent increase in morphine-sparing effect was observed with increasing doses of gabapentin from the trials with low risk of bias. Analyzing all trials, the smallest and the highest dose subgroups demonstrated numerically the most prominent reduction in morphine consumption. Twenty-seven trials reported 72 SAEs, of which 83% were reported in the >1050 mg subgroup. No systematic increase in SAEs was observed with increasing doses of gabapentin.ConclusionData were sparse, and the small number of trials with low risk of bias is a major limitation for firm conclusions. Taking these limitations into account, we were not able to demonstrate a clear relationship between the dosage of gabapentin and opioid-sparing or harmful effects. These subgroup analyses are exploratory and hypothesis-generating for future trialists.

Perioperative Gabapentinoids

“…The analysis was well executed, the number of patients robust, the quality of evidence properly evaluated, the results clearly presented, and the conclusions well supported and unambiguous. This article is entirely consistent with previous reports [2][3][4][5][6] but also brings forth additional information. The new analysis evaluated a broad surgical population, a long duration of outcomes, included additional trials, and, importantly, assessed minimally important clinical differences rather than just statistical differences.…”

“…6 Recent years have seen a reversal of fortune for perioperative gabapentinoids, brought about by improved clinical research and its synthesis into informative and actionable evidence. [1][2][3][4][5] Compared with placebo, patients receiving perioperative gabapentinoids sometimes have pain and/ or opioid consumption that is less, statistically, but small in magnitude (a few percentage points less pain and sparing only a few milligrams of opioid) and short-lived (often only a day) but not clinically meaningful and not preventing chronic postsurgical pain or opioid use.…”

Effects of a single dose of preoperative pregabalin and gabapentin for acute postoperative pain: a network meta-analysis of randomized controlled trials

“…Recently, the study performed by Fabritius et al 92 demonstrated that they could not confirm a distinct relationship between the dose of GBP and the consumption of opioids, dividing all treatments into subgroups despite single or multiple doses, preoperative or postoperative administrations. In the present study, we presented an NMA to validate the effect of analgesic and risk of adverse events by a series of doses of PGB or GBP administration.…”

Published Multimodal Anesthetic Protocols Using Gabapentin Risk Substantial Side Effects and Are Not Recommended

“…Additionally, the use in the postoperative period is associated with multiple described side effects. 3,4,5,6,7 A study on the use of gabapentin following total knees determined, "On the basis of this meta-analysis, we found no evidence to support the routine use of gabapentinoids in the management of acute pain following total knee arthroplasty." 8 And in a large meta-analysis of pain after surgery, it was determined, "No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed.…”