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Review
. 2017 Nov 1:10:2547-2563.
doi: 10.2147/JPR.S138519. eCollection 2017.

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

Maria Louise Fabritius  1 , Jørn Wetterslev  2 , Ole Mathiesen  3 , Jørgen B Dahl  1
Affiliations
Review

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

Maria Louise Fabritius et al. J Pain Res. .

Abstract

Background: During 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 methods: Data 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.

Results: One 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.

Conclusion: Data 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.

Keywords: 1-(aminomethyl)cyclohexaneacetic acid; analgesic; dose effect; gabapentin; postoperative pain management.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Bias evaluation of the six bias domains. Note: The “other” bias domain consists of an evaluation of financial and confirmatory bias.
Figure 2
Figure 2
Forest plot of 24-hour morphine consumption from trials with overall low risk of bias. Abbreviations: df, degrees of freedom; CI, confidence interval; SD, standard deviation; IV, inverse variance.
Figure 3
Figure 3
Forest plot of 24-hour morphine consumption from all trials estimates regardless of bias evaluation. Abbreviations: df, degrees of freedom; CI, confidence interval; SD, standard deviation; IV, inverse variance.
Figure 4
Figure 4
Forest plot of the odds of serious adverse events from trials with overall low risk of bias. Abbreviations: df, degrees of freedom; CI, confidence interval.
Figure 5
Figure 5
Forest plot of the odds of serious adverse events from all trials estimates, regardless of bias evaluation. Abbreviation: df, degrees of freedom.
See this image and copyright information in PMC

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