Background: Hyperoxia induces oxidative stress and can exacerbate inflammatory response to Veno-Arterial Extracorporeal Life Support (VA–ECLS). This study aimed to evaluate the association between hyperoxia during VA–ECLS and morbidity, complications, and in-hospital mortality. 

Methods: This study included pediatric patients who received VA–ECLS between 2014 and 2019. Hyperoxia severity was categorized as mild (PaO₂: 101–200 mmHg), moderate (PaO₂: 201–300 mmHg), and severe (PaO₂ > 300 mmHg. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included a composite measure of cardiovascular or renal complications, AKI, and change in Functional Status. 

Results: Among 229 patients supported on VA–ECLS runs, 73.4% involved neonates. Median age and weight of the entire cohort were 2.5 months (IQR 0.3, 19.0), and 4.4 kg (IQR 3.2, 10.7), respectively. Cardiac indications accounted for 48.9% of cases. Hyperoxia occurred in 79% of patients and was more common in those requiring ECLS for cardiac indications. The overall in-hospital mortality rate was 45%, increasing to 64% in the severe hyperoxia cohort (p = 0.23). Severe hyperoxia was significantly associated with the composite outcome of cardiovascular or renal complications but not in-hospital mortality in multivariable analysis. No association was found between hyperoxia, AKI, and adverse functional outcomes.

Conclusions: Standardized PaO₂ targets to minimize hyperoxia may improve outcomes for patients supported on VA–ECLS.