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Randomized Controlled Trial
. 2025 Nov;69(10):e70118.
doi: 10.1111/aas.70118.

Effects of Hyperoxia and Antioxidants on Mortality, Hospital Admissions, and Myocardial Infarction After Noncardiac Surgery: 1-Year Follow-Up of a Randomized Controlled Trial

Frederik C Loft  1 , Cecilie Holse  2 , Eske K Aasvang  3   4 , Morten Vester-Andersen  4   5 , Lars S Rasmussen  6 , Lars N Jørgensen  4   7 , Christian S Meyhoff  1   4
Affiliations
Randomized Controlled Trial

Effects of Hyperoxia and Antioxidants on Mortality, Hospital Admissions, and Myocardial Infarction After Noncardiac Surgery: 1-Year Follow-Up of a Randomized Controlled Trial

Frederik C Loft et al. Acta Anaesthesiol Scand. 2025 Nov.

Abstract

Background: Perioperative hyperoxia may be associated with increased long-term mortality, whereas perioperative antioxidants may be associated with reduced long-term mortality. This study aimed to determine if high perioperative inspiratory oxygen fraction (FiO2) (0.80) compared with normal FiO2 (0.30) would increase mortality, hospital admissions, and myocardial infarction (MI) within 1 year after surgery, and whether antioxidants compared with placebo would reduce this.

Methods: This was the preplanned 1-year follow-up of 600 patients with cardiovascular risk factors, scheduled for noncardiac surgery. They were randomized in a 2 × 2 factorial design to perioperative FiO2 of 0.80 or 0.30 and to receive antioxidants (vitamin C and N-acetylcysteine) or matching placebo. The primary 1-year outcome was all-cause mortality, and secondary 1-year outcomes were one or more hospital admissions and MIs, respectively. All outcomes were assessed using medical records and analyzed with the Cox proportional hazards model.

Results: Follow-up was completed for 594 patients (99%). Twenty-five of 298 patients (8.4%) allocated to FiO2 of 0.80 died within 1 year as compared with 17 out of 296 (5.7%) allocated to FiO2 of 0.30, HR 1.46 (95% CI, 0.79-2.70), p = 0.23. A total of 260 patients had one or more hospital admissions (44%), and seven patients had MI (1.2%) with no significant difference when comparing FiO2 of 0.80 with 0.30. Antioxidants had a HR of 0.98 (95% CI, 0.54-1.80), p = 0.96 for all-cause mortality vs. placebo. The interaction between the FiO2 and antioxidant administration was statistically significant (p = 0.04) with fatalities overrepresented in patients given 80% oxygen and placebo.

Conclusions: Differences in all-cause mortality, hospital admission, or MI were not statistically significant at 1-year follow-up for either oxygen fractions or antioxidant administration in patients undergoing major noncardiac surgery.

Editorial comment: In this preplanned long-term study of the VIXIE trial, no differences in total mortality, hospitalization, or myocardial infarction were found for oxygen fractions of 0.80 compared to 0.30 or antioxidant administration compared to placebo. Interestingly, the study showed a higher rate of fatalities with 80% oxygen which appeared only to be present in patients not given the antioxidant intervention, but this is hypothesis-generating and needs to be further investigated in new clinical trials.

Trial registration: Clinicaltrials.gov identifier: NCT03494387.

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Conflict of interest statement

C.H. is an employee of Novo Nordisk A/S. C.S.M. and E.K.A. are founders of a start‐up company, WARD24/7 ApS, with the aim of pursuing the regulatory and commercial activities of the WARD‐project (Wireless Assessment of Respiratory and circulatory Distress, a project developing a clinical support system for continuous wireless monitoring of vital signs). WARD24/7 ApS has obtained license agreement for any WARD‐project software and patents. One patent has been filed: ‘Wireless Assessment of Respiratory and circulatory Distress (WARD), EP 21184712.4 and EP 21205557.8’. F.C.L., M.V.A., L.S.R., L.N.J. declare no conflicts of interest. None of the mentioned entities affected the study design, conduct, analysis, or reporting.

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier plots for all‐cause mortality of patients randomized to perioperative 0.80 or 0.30 FiO2.
FIGURE 2
FIGURE 2
Kaplan–Meier plots for all‐cause mortality of patients randomized to perioperative antioxidants or placebo.
See this image and copyright information in PMC

References

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