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Br J Anaesth. 2017 Jan;118(1):22-31. doi: 10.1093/bja/aew391.

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

Author information

1
Service d'Anesthésie Réanimation Chirurgicale, Hôpital Raymond Poincaré, Assistance Publique Hôpitaux de Paris, 104 boulevard Raymond Poincaré F-92380 Garches, France valeria.martinez@rpc.aphp.fr.
2
INSERM, U-987, Hôpital Ambroise Paré, Centre d'Evaluation et de Traitement de la Douleur, F-92100 France, Université Versailles Saint-Quentin, F-78035, France.
3
INSERM, UMR 1153, Centre of Research in Epidemiology and Statistics, Sorbonne Paris Cité-(CRESS), METHODS team, Paris, France.
4
American hospital of Paris, 92 200 Neuilly-sur-Seine, Paris, France.
5
Service d'Anesthésie Réanimation Chirurgicale, Hôpital Raymond Poincaré, Assistance Publique Hôpitaux de Paris, 104 boulevard Raymond Poincaré F-92380 Garches, France.
6
CHU de Rennes, université Rennes 1, pôle anesthésie-réanimation-urgences-SAMU, Inserm UMR 991, 2, avenue H.-Le-Guillou, 35033 Rennes, France.
7
Assistance Publique-Hôpitaux de Paris, Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, 1 place du Parvis Notre-Dame, 75004 Paris.
8
Université Paris Descartes-Sorbonne Paris Cité, 12 Rue de l'École de Médecine, 75006 Paris, France.
9
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, USA.

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.

KEYWORDS:

analgesics; balanced analgesia; postoperative pain; surgery; systematic review

PMID:
28039239
DOI:
10.1093/bja/aew391
[Indexed for MEDLINE]
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