Opioid-free versus opioid-inclusive anesthesia: what recent meta-analyses say about postoperative pain

Opioid-free anesthesia (OFA) replaces intraoperative opioids with non-opioid adjuncts. A 2023 meta-analysis of 38 randomized trials by Feenstra and colleagues found moderate-quality evidence of no clinically relevant difference in pain after surgery, although the pooled mean difference of 0.39 points (95% CI 0.19 to 0.59) on a numeric rating scale excluded zero ^[1]. The same review reported less nausea and vomiting but more bradycardia with OFA ^[1]. The comparator was opioid-based or opioid-inclusive anesthesia in all but one of the reviews below; the Ao review of laparoscopic bariatric surgery used opioid-sparing anesthesia ^[2].

What did the 2025 and 2026 reviews find?

An August 2025 network meta-analysis by Tripodi and colleagues of 42 trials (4,666 patients) found no difference in pain at 24 hours between OFA regimens and opioid-based anesthesia ^[3]. Tripodi and colleagues rated over 70% of the trials behind that result at moderate to high risk of bias ^[3]. A network meta-analysis by de Carvalho and colleagues, published online in January 2026, pooled 885 randomized trials from 59 countries ^[4]. The de Carvalho analysis compared six strategies, so the effect of a regional block could be split from the effect of OFA ^[4].

Does OFA lower pain or later opioid use?

In the de Carvalho analysis, techniques that included regional anesthesia ranked highest for pain, although the rankings at 2, 12 and 48 hours carried low certainty ^[4]. When a block was in place, de Carvalho and colleagues found minimal differences between OFA and opioid-inclusive anesthesia, at moderate certainty ^[4]. Without a block, the de Carvalho authors found no consistent pain advantage for either strategy ^[4].

A 2026 meta-analysis of 29 trials by Ayazbekova and colleagues, in which 26 trials reported pain scores, found lower pain scores with OFA (standardized mean difference, Hedges' g, −0.34; 95% CI −0.55 to −0.13; I² 84%, indicating high heterogeneity) ^[5]. The Ayazbekova team judged that this heterogeneity limits the clinical meaning of the result ^[5]. Unlike the Tripodi network meta-analysis, which found no difference at 24 hours, this review found lower pain scores with OFA ^[3][5]. The Ayazbekova review also found a small reduction in opioid use after surgery across 11 trials (Hedges' g −0.55; 95% CI −1.10 to −0.005; I² 96%), so the interval only just excludes no difference and heterogeneity was very high ^[5].

What differs beyond pain scores?

• Nausea and vomiting: the 2026 de Carvalho analysis linked OFA, especially when combined with regional techniques, to lower rates of nausea and vomiting ^[4].
• Quality of recovery: a 2025 meta-analysis of 13 trials by Wang and colleagues reported higher Quality of Recovery (QoR-40) scores with OFA (standardized mean difference 0.47; 95% CI 0.18 to 0.77; I² 82%; 1,464 patients) ^[6].
• Blood pressure: the Wang meta-analysis found less hypotension with OFA and no difference in bradycardia or time to extubation ^[6].
• Bariatric surgery: a 2025 network meta-analysis of 15 trials (1,310 patients) by Ao and colleagues found less nausea and vomiting with OFA than with opioid-sparing anesthesia (relative risk 0.6; 95% CI 0.5 to 0.9) ^[2].
• Heart rate: the Ao analysis found a higher risk of bradycardia with OFA than with opioid-sparing anesthesia (relative risk 2.6; 95% CI 1.2 to 5.9) ^[2].

Bradycardia findings differ across reviews: Feenstra and Ao reported more with OFA, and Wang reported no difference ^[1][2][6].

Where is the evidence uncertain?

The Tripodi review reported significant heterogeneity among the OFA regimens evaluated ^[3]. The Feenstra review found only one small study on chronic pain after surgery, and that study reported no effect ^[1]. In the Wang meta-analysis, heterogeneity for the Quality of Recovery-15 (QoR-15) score reached an I² of 98% ^[6].

At the point of care: what to check

• Whether a regional block covers the surgical site, since techniques with regional anesthesia ranked highest for pain in the de Carvalho analysis ^[4].
• Baseline risk of nausea and vomiting, since the de Carvalho analysis linked OFA, especially when combined with regional techniques, to lower rates ^[4].
• Bradycardia risk, since the Ao analysis of laparoscopic bariatric surgery found more with OFA than with opioid-sparing anesthesia ^[2].
• Which adjuncts the local OFA regimen uses, since the regimens pooled in the Tripodi review varied significantly ^[3].