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. 2025 Aug 13;5(1):53.
doi: 10.1186/s44158-025-00272-9.

Effectiveness and safety of opioid-free anesthesia compared to opioid-based anesthesia: a systematic review and network meta-analysis

Vincenzo Francesco Tripodi #  1 , Salvatore Sardo #  2 , Mariachiara Ippolito  3   4 , Andrea Cortegiani  5   6
Affiliations

Effectiveness and safety of opioid-free anesthesia compared to opioid-based anesthesia: a systematic review and network meta-analysis

Vincenzo Francesco Tripodi et al. J Anesth Analg Crit Care. .

Abstract

Background: 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).

Study design and methods: 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).

Results: 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.

Conclusions: 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.

Trial registration: This study is registered in PROSPERO with the registration number CRD42024529236 (May 3, 2024).

Keywords: Analgesia; OFA; Opioid; Opioid consumption; Opioid-free anesthesia; Postoperative nausea and vomiting (PONV); Postoperative pain; Recovery; Safety.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not obtained as this is a systematic review and meta-analysis of published studies. Consent for publication: Not applicable; all authors approved for the submission of the manuscript. Conflict of interest: The authors declare no conflict of interest.

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