Magruder, J. Trent

OBJECTIVES: To investigate whether severe hyperoxia predisposes to end-organ complications and whether these complications contribute to in-hospital mortality among cardiogenic shock (CS) patients supported in venoarterial extracorporeal membrane oxygenation (VA-ECMO). DESIGN: Adult patients with CS from the Extracorporeal Life Support Organization Registry between 2010 and 2023 were categorized into normoxia (Pao 2 60–150 mm Hg), mild hyperoxia (Pao 2 151–300 mm Hg), and severe hyperoxia (Pao 2 > 300 mm Hg) based on their Pao 2 at 24 hours. The primary outcome was in-hospital mortality. End-organ complications were analyzed using multivariate logistic regression models, and causal mediation analysis was performed to estimate the direct and indirect effects of hyperoxia on mortality. SETTING: Multicenter, multinational prospective cohort study. PATIENTS: Adults with CS supported on VA-ECMO. INTERVENTIONS: Partial pressure of oxygen at 24 hours after VA-ECMO cannulation. MEASUREMENTS/MAIN RESULTS: A total of 10,541 patients were included (normoxia: 48.4%, mild hyperoxia: 30.0%, severe hyperoxia: 21.5%). There was higher in-hospital mortality in patients with severe hyperoxia (71.7%, adjusted OR [aOR]: 2.17; 95% CI, 1.19–2.50) and mild hyperoxia (63.8%, aOR: 1.34; 95% CI, 1.19–1.50) compared normoxia (52.7%; referent group). Severe hyperoxia was associated with more end-organ complications, which incrementally predicted higher mortality (aOR: 1.42; 95% CI, 1.25–1.61). Mediation analysis demonstrated that hyperoxia primary exerted a direct effect on mortality (86%), with contributions from neurologic (3.1%), hepatic (3.9%), renal (3.5%), and bleeding (2.3%) complications. CONCLUSIONS: Severe hyperoxia in patients with CS receiving VA-ECMO is associated with increased mortality and more end-organ complications. However, most of the effect of severe hyperoxia on mortality occurs via direct effects, independent of end-organ complications. These findings highlight the potential direct toxicity of hyperoxia and underscore the need for strategies to optimize oxygen delivery in this critically ill population.