Benefit and harm of pregabalin in acute pain treatment: a systematic review with meta-analyses and trial sequential analyses

Abstract

Pregabalin has demonstrated anti-hyperalgesic properties and was introduced into acute pain treatment in 2001. Our aim was to evaluate the beneficial and harmful effects of pregabalin in postoperative pain management. We included randomized clinical trials investigating perioperative pregabalin treatment in adult surgical patients. The review followed Cochrane methodology, including Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and used trial sequential analyses (TSAs). The primary outcomes were 24 h morphine i.v. consumption and the incidence of serious adverse events (SAEs) defined by International Conference of Harmonisation Good Clinical Practice guidelines. Conclusions were based primarily on trials with low risk of bias. Ninety-seven randomized clinical trials with 7201 patients were included. The 24 h morphine i.v. consumption was reported in 11 trials with overall low risk of bias, finding a reduction of 5.8 mg (3.2, 8.5; TSA adjusted confidence interval: 3.2, 8.5). Incidence of SAEs was reported in 21 trials, with 55 SAEs reported in 12 of these trials, and 22 SAEs reported in 10 trials with overall low risk of bias. In trials with overall low risk of bias, Peto's odds ratio was 2.9 (1.2, 6.8; TSA adjusted confidence interval: 0.1, 97.1). Based on trials with low risk of bias, pregabalin may have a minimal opioid-sparing effect, but the risk of SAEs seems increased. However, the GRADE-rated evaluations showed only moderate to very low quality of evidence. Consequently, a routine use of pregabalin for postoperative pain treatment cannot be recommended.

Gabapentin for post‐operative pain management – a systematic review with meta‐analyses and trial sequential analyses

“…The included trials were assessed for risk of bias according to the Cochrane Handbook and we decided a priori to report and conclude based on primarily results from trials classified as low risk of bias . The following domains were assessed: random sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other bias, including funding and confirmation bias .…”

The influence of pre- and perioperative administration of gabapentin on pain 3–4 years after total knee arthroplasty

“…Several old reviews and meta-analyses have highlighted a pain-relieving effect of preoperative administration of gabapentin on pain in the first postoperative days [18][19][20][21][22]. In contrast, more recent reviews have highlighted that gabapentinoids might have minimal opioid sparring effect in the acute postoperative phase, but the severe adverse events are increased [24], and the evidence is based on low quality studies [23]. A recent review on the effect of preoperative administration of gabapentin and pregabalin prior to breast cancer surgery found no associations between the administration of either drug on the development of chronic postoperative pain [39].…”

“…Several older reviews and meta-analyses [18][19][20][21][22], concludes that gabapentinoids reduce pain in the first postoperative days. However, recent meta-analyses have shed critical light on most of the perioperative gabapentinoid literature and concluded that the quality of evidence is low, firm evidence for the use in postoperative pain management is lacking, the clinically relevant beneficial effect seems absent, and there may be a risk of harm [23,24].…”

Coadyuvantes farmacológicos con efecto ahorrador de opioides en el periodo perioperatorio

“…Sin embargo, las evaluaciones GRADE mostraron evidencia de calidad moderada a muy baja. En consecuencia, según los autores, no se puede recomendar el uso habitual de pregabalina para el tratamiento del dolor postoperatorio debido a su baja eficacia como ahorrador de opioides (25).…”