Opioid-free anesthesia (OFA) is an innovative approach to anesthesia management aimed at enhancing both the safety and the quality of perioperative outcomes. The efficacy and safety of these approaches are uncertain. The aim of our work was to compare the effectiveness and safety of different OFA regimens to opioid-based anesthesia (OBA). We conducted a systematic review and frequentist random-effects network meta-analysis of randomized controlled trials (RCTs). The primary outcome measure was the intensity of postoperative pain at 24 h, expressed in terms of numerical rating scale (NRS), visual analogue scale (VAS), or verbal rating scale (VRS) scores. The SUCRA was used to determine the likelihood that an intervention was ranked as the best. The certainty of the evidence was assessed according to the GRADE methodology for Network Meta-analysis (NMA). A total of 42 RCTs were included, for a total of 4666 patients. We have addressed the variety of available interventions. The random-effects network meta-analysis comparing OBA and different OFA regimens showed no difference in the pain intensity at 24 h. We performed the GRADE assessment for each comparison between each OFA regimen and OBA as a comparator. The certainty of evidence for the primary outcome ranges from moderate to very low among the different comparisons. We have identified a significant heterogeneity in OFA regimens evaluated and a moderate to high risk of bias in over 70% of studies reporting the primary outcome. No OFA regimens showed a statistically significant effect over OBA in reducing postoperative pain within the first 24 h following surgery. Current evidence does not support the superiority of the analgesic efficacy of OFA in the immediate postoperative period compared to the use of opioids. This study is registered in PROSPERO with the registration number CRD42024529236 (May 3, 2024).
Tripodi et al. (2025) studied this question.