Background Hyperoxia and oxidative stress may be associated with increased risk of myocardial injury. The authors hypothesized that a perioperative inspiratory oxygen fraction of 0.80 versus 0.30 would increase the degree of myocardial injury within the first 3 days of surgery, and that an antioxidant intervention would reduce degree of myocardial injury versus placebo. Methods A 2 × 2 factorial, randomized, blinded, multicenter trial enrolled patients older than 45 yr who had cardiovascular risk factors undergoing major noncardiac surgery. Factorial randomization allocated patients to one of two oxygen interventions from intubation and at 2 h after surgery, as well as antioxidant intervention or matching placebo. Antioxidants were 3 g IV vitamin C and 100 mg/kg N-acetylcysteine. The primary outcome was the degree of myocardial injury assessed by the area under the curve for high-sensitive troponin within the first 3 postoperative days. Results The authors randomized 600 participants from April 2018 to January 2020 and analyzed 576 patients for the primary outcome. Baseline and intraoperative characteristics did not differ between groups. The primary outcome was 35 ng · day/l (19 to 58) in the 80% oxygen group; 35 ng · day/l (17 to 56) in the 30% oxygen group; 35 ng · day/l (19 to 54) in the antioxidants group; and 33 ng · day/l (18 to 57) in the placebo group. The median difference between oxygen groups was 1.5 ng · day/l (95% CI, −2.5 to 5.3; P = 0.202) and −0.5 ng · day/l (95% CI, −4.5 to 3.0; P = 0.228) between antioxidant groups. Mortality at 30 days occurred in 9 of 576 patients (1.6%; odds ratio, 2.01 [95% CI, 0.50 to 8.1]; P = 0.329 for the 80% vs. 30% oxygen groups; and odds ratio, 0.79 [95% CI, 0.214 to 2.99]; P = 0.732 for the antioxidants vs. placebo groups). Conclusions Perioperative interventions with high inspiratory oxygen fraction and antioxidants did not change the degree of myocardial injury within the first 3 days of surgery. This implies safety with 80% oxygen and no cardiovascular benefits of vitamin C and N-acetylcysteine in major noncardiac surgery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

BackgroundThe external validity of randomized controlled trials (RCTs) is critical for the relevance of trial results in a clinical setting. We aimed to assess the external validity of RCTs investigating postoperative pain treatment after total hip and knee arthroplasty (THA and TKA) by comparing patient characteristics in these trials with a clinical cohort. Further, we assessed the use of exclusion criteria of the included RCTs.MethodsWe searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant RCTs up to June 2019. Data on patient characteristics from this research population were compared with an unselected clinical cohort from the Danish Hip and Knee Arthroplasty Registries in the period 2005–2019. Trends in patient characteristics and the use of exclusion criteria were assessed with control charts.ResultsIn total, 550 RCTs with 48 962 participants were included in the research cohort. The clinical cohort included 101 439 THA patients and 90 505 TKA patients. Patient characteristics (age, body mass index (BMI), American Society of Anesthesiologists (ASA) score and sex distribution) in the research cohort resembled those of the clinical cohort. Age, BMI and ASA scores did not change over time in the research cohort. In the clinical cohort, age increased among both THA and TKA patients, and BMI and ASA scores increased among TKA patients. Most commonly used exclusion criteria in the RCTs were high ASA score (62%), older age (45%), obesity (32%) and chronic opioid use (41%). Exclusion of chronic opioid users and individuals with obesity increased over time.ConclusionPatient characteristics in research trials investigating postoperative pain management after THA and TKA currently resemble those of a clinical cohort. However, individuals in the clinical cohort are getting older, and TKA patients more obese with increasing ASA scores. Concomitantly, RCTs increase the tendency to exclude patients with older age, obesity, chronic pain and/or opioid use. This trending discrepancy can hinder the generalizability of future research results, and therefore increased focus on pragmatic trials resembling real-world conditions are needed.PROSPERO registration numberCRD42019125691

Background: Several studies in surgery and initial management of critical illness have indicated harmful effects of short-term exposure to hyperoxia. Exposure to and consequences of excessive oxygen administration in hospital wards are sparsely investigated.The aim of this study was to investigate the association between excessive oxygen administration in patients admitted to surgical or medical wards and 30-day mortality. Methods:We included patients in the Capital Region of Denmark who were admitted to hospital in 2014 for either myocardial infarction, acute exacerbation of chronic obstructive pulmonary disease (COPD), hip fracture or open abdominal surgery. We defined groups of inadequate, adequate or excessive oxygen administration based on peripheral oxygen saturation and oxygen administration values in the first 48 hours after admission. The primary outcome was mortality within 30 days, and data were analysed with multivariable logistic regression for age, gender and comorbidities. Results:We retrieved data from 11 196 patients, of which 81% had adequate, 18% had excessive and 1.8% inadequate oxygen administration. Mortality at 30 days was 4.2%, 7.6% and 27%, respectively, OR 1.46 (95%CI 1.16-1.84), P = .001 for patients with excessive compared to adequate oxygen administration. The association was significant in subgroups of patients admitted for acute exacerbation of COPD (OR 1.67, 95%CI 1.19-2.34) and myocardial infarction (OR 3.50, 95%CI 1.55-7.89). Conclusion:Patients who received excessive oxygen administration in surgical and medical wards during the first 48 hours of admission had a higher mortality risk within 30 days compared to patients with adequate oxygen administration. However, inadequate oxygen therapy still renders highest mortality and should be avoided. Editorial CommentDelivering the optimal amount of oxygen to patients on general hospital wards is desirable but can be a challenge. This study described who had at some time too much or too little oxygen delivered to them based on pulse oximetry measures. Increased mortality risk was associated with both extremes.