Opioid-free anesthesia: A systematic review and meta-analysis

J Clin Anesth. 2023 Nov:90:111215. doi: 10.1016/j.jclinane.2023.111215. Epub 2023 Jul 27.


Study objective: To evaluate all available evidence thus far on opioid based versus opioid-free anesthesia and its effect on acute and chronic postoperative pain.

Design: Systematic review and meta-analysis of randomized clinical trials.

Setting: Operating room, postoperative recovery room and ward.

Patients: Patients undergoing general anesthesia.

Interventions: After consulting MEDLINE, EMBASE and Cochrane database, studies which compared opioid free anesthesia (OFA) with opioid based anesthesia (OBA) were included (last search April 15th 2022).

Measurements: Primary outcomes were acute and chronic pain scores in NRS or VAS. Secondary outcomes were quality of recovery and postoperative opioid consumption. Risk of bias was assessed using the RoB2 tool and a random effects model for the meta-analysis was conducted.

Main results: We identified 1245 citations, of which 38 studies met our inclusion criteria. There is moderate quality evidence showing no clinically relevant difference of Numeric Rating Scale (NRS) scores or opioid consumption in the postoperative period (pooled mean difference of 0.39 points with a CI of 0.19-0.59 and 4.02 MME with a CI of 1.73-6.30). We found only one small-sized study reporting no effect of opioid-free anesthesia on chronic pain. The quality of recovery was superior in patients with opioid-free anesthesia (mean difference of 8.26 points), however, this pooled analysis was comprised of only two studies. Postoperative nausea and vomiting (PONV) occurred less in opioid-free anesthesia, but bradycardia was more frequent.

Conclusions: We concluded that we cannot recommend one strategy over the other. Future studies could focus on quality of recovery as outcome measure and adequately powered studies on the effects of opioid-free anesthesia on chronic pain are eagerly awaited.

Keywords: Adverse effects; Opioid-free anesthesia; Pain; Postoperative.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Analgesics, Opioid* / adverse effects
  • Anesthesia, General / adverse effects
  • Chronic Pain* / drug therapy
  • Chronic Pain* / etiology
  • Humans
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / etiology
  • Pain, Postoperative / prevention & control
  • Postoperative Nausea and Vomiting / drug therapy
  • Postoperative Nausea and Vomiting / epidemiology
  • Postoperative Nausea and Vomiting / etiology


  • Analgesics, Opioid