Opioid-free vs. opioid-inclusive anaesthesia with or without regional anaesthesia for postoperative pain: a systematic review with network meta-analysis of randomised controlled trials

Citation: de Carvalho, El-Boghdadly, Guedes, Dantas, Tome, Ramos, Gomes, Alves, Bezerra, Santos Neto, Pandit, Braz. Opioid-free vs. opioid-inclusive anaesthesia with or without regional anaesthesia for postoperative pain: a systematic review with network meta-analysis of randomised controlled trials. Anaesthesia. 2026; doi:10.1111/anae.70121.

Study at a glance:

- Design and setting: Prospectively registered systematic review and Bayesian network meta-analysis (PRISMA-NMA; PROSPERO CRD42022318894) of 885 RCTs including 74,880 adults (mainly elective surgery). Six intra-operative strategies were compared, grouped by opioid use (opioid-free, remifentanil-only, other opioids) and presence/absence of regional anaesthesia. Last search: 15 January 2025.

- Interventions: (1) Opioid-inclusive anaesthesia with regional techniques (reference); (2) opioid-free with regional; (3) remifentanil as sole opioid with regional; (4) opioid-inclusive without regional; (5) opioid-free without regional; (6) remifentanil as sole opioid without regional.

- Primary outcome – pain (0–10) at 2–48 h: Versus opioid-inclusive with regional anaesthesia, opioid-free with regional produced very similar pain scores at all time-points (e.g. 2 h MD −0.14, 95%CrI −0.69 to 0.38; 48 h MD −0.01, −0.43 to 0.41; low-certainty evidence). All three non-regional strategies had clearly higher pain (e.g. at 2 h MD +1.45 to +2.18 points vs reference), suggesting that adding regional anaesthesia is far more important for analgesia than removing intra-operative opioids.

- Opioid consumption and recovery: Across 2–48 h, opioid-free with regional anaesthesia consistently ranked best for minimising postoperative opioid use, whereas remifentanil-only without regional ranked worst. At 24 h, differences between techniques often had wide credible intervals and should not be interpreted as proof of equivalence. Techniques without regional anaesthesia were associated with longer PACU stays, and opioid-inclusive anaesthesia without regional prolonged hospital stay compared with opioid-inclusive with regional (MD ~15.7 h longer).

- Adverse effects: Opioid-free with regional anaesthesia substantially reduced postoperative nausea and vomiting relative to opioid-inclusive with regional (OR ~0.54, 95%CrI 0.41–0.71) and had the best overall ranking (SUCRA 99%), whereas opioid-inclusive and remifentanil-only techniques without regional roughly doubled PONV odds. Both opioid-free strategies (with and without regional) ranked highest for minimising pruritus, and remifentanil-heavy regimens (especially without regional) markedly increased dizziness. At 24 h, urinary retention was less frequent with opioid-free and remifentanil-based techniques than with opioid-inclusive plus regional (moderate-certainty evidence).

- Risk of bias and certainty: Outcome-level RoB 2 showed mostly “some concerns” (60%) and relatively few high-risk judgements (4.6%), but the review itself was rated critically low by AMSTAR 2 and high risk of bias by ROBIS due to lack of a full excluded-studies list and no formal assessment of small-study effects, publication bias, or network inconsistency. The authors’ GRADE ratings indicate Low certainty for all pain outcomes and Moderate certainty for urinary retention, so while regional anaesthesia combined with more opioid-sparing strategies likely improves pain and side-effect profiles compared with opioid-heavy, non-regional techniques, the exact effect sizes and rankings should be interpreted with caution.