Non-opioid analgesics in adults after major surgery : systematic review with network meta-analysis of randomized trials Article - 2017

V. Martinez, H. Beloeil, E. Marret, D. Fletcher, P. Ravaud, L. Trinquart

V. Martinez, H. Beloeil, E. Marret, D. Fletcher, P. Ravaud, L. Trinquart, « Non-opioid analgesics in adults after major surgery : systematic review with network meta-analysis of randomized trials  », British Journal of Anaesthesia, 2017, pp. 22-31. ISSN 0007-0912

Abstract

BACKGROUND : Morphine, and analgesics other than morphine (AOM), are commonly used to treat postoperative pain after major surgery. However, which AOM provides the best efficacy-safety profile remains unclear. METHODS : Randomized trials of any AOM alone or any combination of AOM compared with placebo or another AOM in adults undergoing major surgery and receiving morphine patient-controlled analgesia were included in a network meta-analysis. The outcomes were morphine consumption, pain, incidence of nausea, vomiting at 24 h and severe adverse effects. RESULTS : 135 trials (13,287 patients) assessing 14 AOM alone or in combination were included. For all outcomes, comparisons with placebo were over-represented. Few trials assessed combinations of two AOM and none the combination of three or more. Network meta-analysis found morphine consumption reduction was greatest with the combination of two AOM (acetaminophen + nefopam, acetaminophen + NSAID, and tramadol + metamizol) : -23.9 (95% CI -40 ;-7.7), -22.8 (-31.5 ;-14) and -19.8 (35.4 ;-4.2) mg per 24 h, respectively. For AOM used alone, morphine consumption reduction was greatest with α-2 agonists, NSAIDs, and COX-2 inhibitors. When considering the risk of nausea, NSAIDs, corticosteroids and α-2 agonists used alone were the most efficacious (OR 0.7 [95% CI : 0.6-0.8], 0.36 [0.18-0.79], 0.41 [0.15-.64], respectively). The paucity of severe adverse effects data did not allow assessment of efficacy-safety balance. CONCLUSIONS : A combination of aetaminophen with either an NSAID or nefopam was superior to most AOM used alone, in reducing morphine consumption. Efficacy was best with three AOM used alone (α-2 agonists, NSAIDs and COX-2 inhibitors) and least with tramadol and acetaminophen. There is insufficient trial data reporting adverse events. CLINICAL TRIAL REGISTRATION : PROSPERO : CRD42013003912.

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