Abstract: We included 28 randomized clinical trials (9330 participants); in the 21 trials reporting relevant outcomes for this review, 7597 participants were randomly assigned to a high fraction of inspired oxygen versus a routine fraction of inspired oxygen. In trials with an overall low risk of bias, a high fraction of inspired oxygen compared with a routine fraction of inspired oxygen was not associated with all-cause mortality (random-effects model: RR 1.12, 95% confidence interval (CI) 0.93 to 1.36; GRADE: low quality) within the longest follow-up and within 30 days of follow-up (Peto odds ratio (OR) 0.99, 95% CI 0.61 to 1.60; GRADE: low quality). In a trial sequential analysis, the required information size was not reached and the analysis could not refute a 20% increase in mortality. Similarly, when all trials were included, a high fraction of inspired oxygen was not associated with all-cause mortality to the longest follow-up (RR 1.07, 95% CI 0.87 to 1.33) or within 30 days of follow-up (Peto OR 0.83, 95% CI 0.54 to 1.29), both of very low quality according to GRADE. Neither was a high fraction of inspired oxygen associated with the risk of surgical site infection in trials with low risk of bias (RR 0.86, 95% CI 0.63 to 1.17; GRADE: low quality) or in all trials (RR 0.87, 95% CI 0.71 to 1.07; GRADE: low quality). A high fraction of inspired oxygen was not associated with respiratory insufficiency (RR 1.25, 95% CI 0.79 to 1.99), serious adverse events (RR 0.96, 95% CI 0.65 to 1.43) or length of stay (mean difference -0.06 days, 95% CI -0.44 to 0.32 days). In subgroup analyses of nine trials using preoperative antibiotics, a high fraction of inspired oxygen was associated with a decrease in surgical site infections (RR 0.76, 95% CI 0.60 to 0.97; GRADE: very low quality); a similar effect was noted in the five trials adequately blinded for the outcome assessment (RR 0.79, 95% CI 0.66 to 0.96; GRADE: very low quality). We did not observe an effect of a high fraction of inspired oxygen on surgical site infections in any other subgroup analyses. As the risk of adverse events, including mortality, may be increased by a fraction of inspired oxygen of 60% or higher, and as robust evidence is lacking for a beneficial effect of a fraction of inspired oxygen of 60% or higher on surgical site infection, our overall results suggest that evidence is insufficient to support the routine use of a high fraction of inspired oxygen during anaesthesia and surgery. Given the risk of attrition and outcome reporting bias, as well as other weaknesses in the available evidence, further randomized clinical trials with low risk of bias in all bias domains, including a large sample size and long-term follow-up, are warranted.

Plain-language summary: We identified 28 randomized clinical trials. Eight trials with 4918 participants reported on risk of death, and 15 trials with 7219 participants reported on surgical site infections within 14 to 30 days of surgery. Four trials reported serious adverse events, three trials respiratory insufficiency, nine trials length of stay during the associated hospital admission and one trial quality of life. All trials were conducted without direct industry funding. The number of participants in each trial ranged from 38 to 2012. The mean age of participants was 50 years (range 15 to 92 years) and 63% were women. Types of surgery included abdominal surgery (eight trials), caesarean section (four trials), breast surgery (one trial), orthopaedic surgery (two trials) and various other surgical procedures (four trials). A high percentage of inspired oxygen was not statistically associated with increased risk of death, or with a decrease in surgical site infections, in all trials that measured these outcomes, in trials of highest quality and in those with longest follow-up. An increased risk of adverse events could not be proved right or wrong for a high percentage of inspired oxygen during anaesthesia and surgery. Only five of the included trials had low risk of bias. The trials randomly assigned 9330 participants, of whom only 7537 participants provided data for this review. The number of participants required to detect or reject a 20% relative risk reduction in deaths was not reached; therefore the observed results were uncertain.