Additive or synergistic analgesic effect of metamizole on standard pain treatment at home after arthroscopic shoulder surgery: A randomised controlled superiority trial.

BACKGROUND: There is growing evidence that the analgesic effect of metamizole is mediated at least partly by central mechanisms, including the endocannabinoid/endovanilloid system. Consequently, metamizole may have additive or even synergistic analgesic effects with paracetamol and nonsteroidal anti-inflammatory drugs (NSAID). OBJECTIVE: This study aimed to assess if triple therapy with metamizole, ibuprofen and paracetamol (MIP) is superior to double therapy with ibuprofen and paracetamol (i.p.) in treating pain at home after ambulatory arthroscopic shoulder surgery. DESIGN/SETTING/PATIENTS/INTERVENTION: In this double-blind, controlled, high-volume single centre, superiority trial, 110 patients undergoing elective ambulatory arthroscopic shoulder surgery were randomised to receive either MIP ( n  = 55) or i.p. ( n  = 55) orally for 4 days between December 2019 and November 2021. Pain intensity at movement and rest, using a numeric rating scale (NRS), perceived pain relief, use of rescue medication and adverse effects of study medication were recorded at the post-anaesthesia care unit (PACU) and on postoperative day (POD) 1 to 4 and 7. Quality of Recovery (QoR) and satisfaction with study medication were measured at POD 7 with telephone follow-up. MAIN OUTCOME MEASURE: The primary outcome measure was postoperative pain intensity on movement measured by an 11-point NRS (where 0 = no pain and 10 = worst pain imaginable) on POD 1. RESULTS: For the primary outcome, superiority of MIP in reducing postoperative pain at movement on POD 1 was not confirmed: mean difference NRS [95% confidence interval (CI), -0.08 (-1.00 to 0.84)]. For pain on movement and at rest, no significant differences were found between groups in the PACU nor on POD 1 to 4 or day 7. Nausea was reported significantly more frequently in the metamizole group (22.6 vs. 58.5; P  < 0.001). Other adverse effects of study medication, rescue opioid consumption, perceived pain relief, QoR at POD 7, and overall patient satisfaction were similar in both groups. CONCLUSION: Clinically, triple oral treatment with metamizole, paracetamol and ibuprofen is not superior to oral paracetamol and ibuprofen in multimodal pain treatment at home after ambulatory arthroscopic shoulder surgery. TRIAL REGISTRATION: European Union Clinical Trials Register 2019-002801-23 and Clinicaltrials.gov NCT04082728.