Meta‐analyses of gabapentinoids for pain management after knee arthroplasty: A caveat emptor? A narrative review

Abstract

The use of gabapentinoids for perioperative pain management after total knee arthroplasty has been the subject of nine systematic reviews and meta-analyses. A critical analysis of the clinical aspects of the methodology of these publications shows major flaws which limit the interpretation for the recommended use of perioperative gabapentinoids in pain management for unilateral primary total knee arthroplasty. Consequently, readers and authors of systematic reviews and metaanalyses should critically assess the clinical aspects of the included studies. EDITORIAL COMMENTIn this narrative review, the authors highlight and discuss some of the challenges and limitations of systematic reviews and meta-analyses.

Is clinical heterogeneity the foremost prominent threat to the validity of meta‐analyses?

“…In this issue of Acta Anaesthesiologica Scandinavica, Joshi and Kehlet raise concern on the pooling of heterogenous data in several meta-analyses assessing the efficacy of perioperative gabapentinoid in randomized clinical trials on total knee arthroplasty. 1 Joshi and Kehlet question the conclusions and recommendations of the published systematic reviews, not due to their methodological shortcomings or bias but merely due to a critical assessment of the clinical aspects (interventions, settings, comparators, etc.) of the included trials.…”

“…Interestingly, nine systematic reviews were detected during the authors' literature search and, according to Joshi and Kehlet, none managed to address the clinical heterogeneity of the included studies but all apparently reached flawed conclusions. 1 The authors argue for the use of gabapentinoids in multimodal analgesic regimen which may lead to further clinical heterogeneity due to various combinations. It is understandable that the authors present a call for a uniform and evidence-based set-up in design of RCTs.…”

“…The authors Joshi and Kehlet find positive conclusions based on negative results in some of the published systematic reviews and none of the published meta-analyses from systematic reviews on gabapentin had a conclusion aligned with the narrative review by Joshi and Kehlet. 1 Reporting bias is a well-known problem in RCTs 9 and there is little reason why this issue should not progress into the data and conclusions of systematic reviews. The validity of some of the RCTs in the gabapentinoid literature has previously been questioned and has been suspected to be biased by medical industry involvement (funding bias and conflicts of interest).…”

“…In this issue of Acta Anaesthesiologica Scandinavica, Joshi and Kehlet raise concern on the pooling of heterogenous data in several meta‐analyses assessing the efficacy of perioperative gabapentinoid in randomized clinical trials on total knee arthroplasty 1 …”

“…Furthermore, expert knowledge on the clinical topic and adequate peer review should ideally be able to handle clinical heterogeneity of the included studies. Interestingly, nine systematic reviews were detected during the authors’ literature search and, according to Joshi and Kehlet, none managed to address the clinical heterogeneity of the included studies but all apparently reached flawed conclusions 1 …”