Opioid-free anaesthesia and postoperative quality of recovery: a systematic review and meta-analysis with trial sequential analysis

There is still debate over whether opioid-free anaesthesia (OFA) can improve the patient-reported quality of recovery (QoR). A search was conducted across Pubmed, Cochrane Library, and EMBASE until June 2024 for randomized controlled trials comparing the impact of OFA and opioid-based anaesthesia (OBA) on QoR in adult patients undergoing general anaesthesia. The primary outcome was the quality of recovery measured with the QoR scale. The secondary outcomes were the five dimensions of the QoR scale. The analysis included 15 studies, and showed that compared with OBA, OFA improved the global QoR score at postoperative 24 h (SMD 0.87; 95% CI, 0.48 to 1.27; I2: 92%; low-level evidence). Among them, 10 studies revealed a greater QoR-40 score at postoperative 24 h in the OFA than in the OBA (MD 6.59; 95% CI, 2.84 to 10.34; I2: 93%; moderate-level evidence), which exceeded the minimal clinically important difference of 6.3. Conversely, the synthetic data of 4 studies did not reveal an improvement in the global QoR-15 score at postoperative 24 h (MD 9.94; 95% CI, -0.15 to 12.35; I2: 97%; low-level evidence). Regarding different domains of scale, OFA had positive effects on physical comfort (SMD 0.75; 95% CI, 0.25 to 1.25; I2: 93%; moderate-level evidence) and pain (SMD 0.59; 95% CI, 0.15 to 1.03; I2: 91%; moderate-level evidence). The meta-analysis indicate OFA can improve the quality of recovery at postoperative 24 h, particularly in terms of enhancing physical comfort and reducing pain. However, due to significant heterogeneity and moderate-to-low level of evidence, the external validity of OFA for improving postoperative recovery remains to be further validated. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database on December 07, 2023 (CRD42023486235).