Abstract
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.
Originalsprog | Engelsk |
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Tidsskrift | Anesthesiology |
Vol/bind | 136 |
Udgave nummer | 3 |
Sider (fra-til) | 408-419 |
Antal sider | 12 |
ISSN | 0003-3022 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:Dr. Holse received departmental funding and grants from The Danish Society of Anaesthesiology and Intensive Care Medicine (Copenhagen, Denmark) and the Bispebjerg and Frederiksberg Hospital Research Foundation (Copenhagen, Denmark). Dr. Christensen is funded by a core grant to his institution from the Oak Foundation Denmark (Copenhagen, Denmark). Dr. Meyhoff received a grant from The Scandinavian Society of Anesthesiology and Intensive Care Medicine (Copenhagen, Denmark). Other support was provided solely from institutional sources.
Funding Information:
All authors have completed the Unified Competing Interest form (available on request from the corresponding author). Dr. Christensen reports grants from public and private foundations, companies, and private individuals to his institution, which is also supported by a core grant from the Oak Foundation Denmark (Copenhagen, Denmark). Dr. Christensen is a founding member of the Technical Advisory Group of OMERACT (Outcome Measures in Rheumatology; Toronto, Canada), an organization that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. Drs. Meyhoff and Aasvang are cofounders of the WARD (Wireless Assessment of Respiratory and circulatory Distress; Copenhagen, Denmark) project and a start-up company, WARD247 ApS (Copenhagen, Denmark), aiming to pursue regulatory and commercial activities of the WARD-project. WARD247 ApS has finalized terms for license agreement for any WARD project software and patents and have one patent filed (WARD – Clinical Support System [CSS], which is an automated clinical support system to improve patient safety and outcomes). Dr. Meyhoff also reports direct and indirect research funding from Merck, Sharp and Dohme Corp. (Copenhagen, Denmark), and Boehringer Ingelheim (Ingelheim, Germany), as well as lecture fees from Radiometer (Copenhagen, Denmark). None of the aforementioned entities have influence on the study design, conduct, analysis or reporting. All other authors report no conflicts.
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