Optimal oxygenation strategies during cardiopulmonary bypass (CPB) in children with cyanotic congenital heart disease remain controversial. Although hyperoxia has traditionally been used to compensate for chronic hypoxemia, concerns exist regarding reoxygenation injury and oxidative stress. This systematic review and meta-analysis aimed to compare perioperative normoxic versus hyperoxic strategies during CPB in this population.

We performed a literature search in MEDLINE, Embase, and the Cochrane Library from inception to November 2025. Random-effects models were used to pool risk ratios (RRs) for binary outcomes and mean differences for continuous outcomes. Heterogeneity was assessed using the I2 statistic, and risk of bias was evaluated using the RoB 2 tool.

Five randomized controlled trials comprising 241 children were included, with 121 patients allocated to normoxia and 120 to hyperoxia. There were no statistically significant differences between groups in all-cause mortality (RR 1.31; 95% confidence interval [CI] 0.37-4.67; P = .67; I² = 0%). Postoperative recovery outcomes, including intensive care unit (ICU) stay, ventilation time, length of hospital stay, and duration of inotropic support, were also comparable. Operative parameters (CPB time and aortic cross-clamp time) and safety outcomes, such as neurological complications, arrhythmias, and cardiac arrest, did not differ significantly between strategies.

In children with cyanotic congenital heart disease undergoing surgery with CPB, normoxic, and hyperoxic oxygenation strategies were associated with statistically similar mortality, recovery, operative, and safety outcomes. These findings suggest that carefully monitored normoxic strategies may represent a safe and physiologically sound alternative to routine hyperoxia during CPB.