Influence of nitrous oxide added to general anaesthesia on postoperative mortality and morbidity: a systematic review and meta-analysis

Background: Nitrous oxide (N2O) is a common adjuvant to general anaesthesia. It is also a potent greenhouse gas and causes ozone depletion. We sought to quantify the influence of N2O as an adjuvant to general anaesthesia on postoperative patient outcomes. Methods: We searched Medline, EMBASE, and Cochrane Central for works published from inception to July 6, 2023. RCTs comparing general anaesthesia with or without N2O were included. Risk ratios (RRs) and standardised mean differences (SMDs) were calculated, along with 95% confidence intervals (CIs), using a random-effects model. Outcomes were derived from the Standardised Endpoints for Perioperative Medicine (StEP) outcome set. Primary outcomes were mortality and organ-related morbidity, and secondary outcomes were anaesthetic and surgical morbidity. Results: Of 3305 records, 179 full-text articles were assessed, and 71 RCTs, totalling 22 147 patients, were included in the meta-analysis. Addition of N2O to general anaesthesia did not influence postoperative mortality or most morbidity outcomes. N2O increased the incidence of atelectasis (RR 1.62, 95% CI 1.24 to 2.12) and postoperative nausea and vomiting (RR 1.27, 95% CI 1.15 to 1.40), and decreased intraoperative opioid consumption (SMD –0.19, 95% CI –0.35 to –0.04) and time to extubation (MD –2.17 min, 95% CI –3.32 to –1.03 min). Conclusions: N2O did not influence postoperative mortality or most morbidity outcomes. Considering the environmental effects of N2O, these findings confirm that current policy recommendations to limit its use do not affect patient safety. Systematic review protocol: PROSPERO CRD42023443287.