Perioperative oxygen therapy, oxidative stress, and cardiac outcomes

BACKGROUND: The optimal perioperative oxygen regimen remains clinically debated. As preclinical studies implicate oxidative pathways in cardiovascular pathophysiology, an evaluation of the oxygen, oxidative stress and cardiac outcome triad is therefore crucial for perioperative oxygen treatment. METHODS: A meta-analysis based on RCTs was conducted to reveal the impact of hyperoxia on oxidative stress indicators and cardiac complications compared with normoxia. Two-sample mendelian randomization (MR) analysis was conducted to investigate the influence of oxidative stress on cardiac complications. Trial sequential analysis (TSA) was performed to ascertain the necessary sample size and evaluate the reliability for definitive conclusions. RESULTS: The meta-analysis revealed no significant differences in cardiac complications between hyperoxia and normoxia groups, including atrial fibrillation (AF; RR 1.06, 95% CI 0.89-1.27), myocardial infarction (MI; RR 0.73, 95% CI 0.45-1.20), myocardial injury (RR 1.02, 95% CI 0.81-1.28), arrhythmia (RR 0.92, 95% CI 0.72-1.26), and low cardiac output syndrome (LCOS; RR 0.84, 95% CI 0.49-1.44). Perioperative hyperoxia significantly increased intraoperative plasma total oxidant status (TOS; SMD 0.86, 95% CI 0.42-1.30) and F2-isoprostane levels (SMD 0.71, 95% CI 0.05-1.38). MR analysis demonstrated that uric acid (UA) was positively associated with MI (OR 1.0021, 95% CI 1.0009-1.0033), cardiovascular disease (CVD; OR 1.0012, 95% CI 1.0005-1.0020), and ischemic heart disease (IHD; OR 1.001, 95% CI 1.000-1.002), while CAT and GST showed negative associations with CVD (OR 0.97, 95% CI 0.95-0.99) and AF (OR 0.96, 95% CI 0.96-0.99), respectively. False discovery rate (FDR) adjustment confirmed causal links for UA with MI and CVD, and TSA validated adequate sample size for AF and MI conclusions. No significant differences were found on other complications. CONCLUSIONS: Based on the comprehensive evidence presented, including the equivalent safety profile of perioperative normoxia across organ systems, the significant increase in systemic oxidative stress associated with hyperoxia, and the MR-confirmed causal links between oxidative stress biomarkers and cardiovascular risks, is recommend as the preferred oxygenation strategy in perioperative care​due to the safety and potential cardiovascular benefits.