Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study

H Beloeil (1) , A Albaladejo (2) , A. Sion (1) , M. Durand (3) , V. Martinez (4) , S. Lasocki (5) , E. Futier (6) , D. Verzili , V. Minville , C. Fessenmeyer , A. Belbachir , F. Aubrun (7) , A. Renault (8) , E. Bellissant (8) , D. Bedague , A. Blanié , M. Casez , Gerald Chanques (9, 10) , C. Chaize , G. Dessertaine , F. Ferré , L. Gaide Chevronnay , A. Hébrard , A. Hespel , Samir Jaber (9, 10) , Audrey de Jong (9, 10) , A. Lahjaouzi , M. Marino , H. Moury , A. Neau , D. Protar , D. Rhem , E. Rineau , S. Robin (11) , E. Rossignol (8) , M. Soucemarianadin , S. Veaceslav

1 UR - Université de Rennes
2 UGA UFRM - Université Grenoble Alpes - UFR Médecine
3 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
4 ENS de Lyon - École normale supérieure de Lyon
5 UA - Université d'Angers
6 CHU Estaing [Clermont-Ferrand]
7 Hôpital de la Croix-Rousse [CHU - HCL]
8 CIC - Centre d'Investigation Clinique [Rennes]
9 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
10 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
11 I4S - Intervention, innovation, imagerie, ingénierie en santé - UFC

Background: Head-to-head comparisons of combinations of more than one non-opioid analgesic (NOA) with morphine alone, for postoperative analgesia, are lacking. The objective of this multicentre, randomised, double-blind controlled trial was to compare the morphine-sparing effects of different combinations of three NOAs-paracetamol (P), nefopam (N), and ketoprofen (K)-for postoperative analgesia. Methods: Patients from 10 hospitals were randomised to one of eight groups: control (C) received saline as placebo, P, N, K, PN, PK, NK, and PNK. Treatments were given intravenously four times a day during the first 48 h after surgery, and morphine patient-controlled analgesia was used as rescue analgesia. The outcome measures were morphine consumption, pain scores, and morphine-related side-effects evaluated 24 and 48 h after surgery. Results: Two hundred and thirty-seven patients undergoing a major surgical procedure were included between July 2013 and November 2016. Despite a failure to reach a calculated sample size, 24 h morphine consumption [median (interquartile range)] was significantly reduced in the PNK group [5 (1-11) mg] compared with either the C group [27 (11-42) mg; P<0.05] or the N group [21 (12-29) mg; P<0.05]. Results were similar 48 h after surgery. Patients experienced less pain in the PNK group compared with the C, N, and P groups. No difference was observed in the incidence of morphine-related side-effects. Conclusions: Combining three NOAs with morphine allows a significant morphine sparing for 48 h after surgery associated with superior analgesia the first 24 h when compared with morphine alone.

Mots clés: opioid sparing; ketoprofen; postoperative analgesia; morphine; non-opioid analgesics; nefopam; paracetamol

Domaines: Sciences du Vivant [q-bio]

H Beloeil, A Albaladejo, A. Sion, M. Durand, V. Martinez, et al.. Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study. British Journal of Anaesthesia, 2019, 122 (6), pp.e98-e106. ⟨10.1016/j.bja.2018.10.058⟩. ⟨hal-02082182⟩