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.


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.


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).


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
  • Myocardial injury after noncardiac surgery is associated with significantly increased morbidity and mortality.
  • Post hoc analyses of several previous trials suggest that intraoperative hyperoxia may associate with increased postoperative acute coronary syndrome and mortality in noncardiac surgical patients.
What This Article Tells Us That Is New
  • This is a 2 × 2 factorial, randomized, clinical trial (VIXIE [VitamIn and oXygen Interventions and cardiovascular Events] trial) designed to determine whether perioperative administration of 0.80 Fio2versus 0.30 Fio2, as well as perioperative administration of antioxidants (vitamin C and N-acetylcysteine) versus placebo, significantly impacted degree of myocardial injury after noncardiac surgery. Myocardial injury was assessed by measurement of high-sensitivity troponin.
  • The VIXIE trial found no association between increased perioperative Fio2 or administration of antioxidants and degree of myocardial injury after noncardiac surgery.