Background:
Refractory cardiogenic shock remains associated with high mortality despite macrocirculatory stabilization with V-A ECMO. We investigated the association between initial ECMO flow-index, organ dysfunction, inflammatory activation, hemolysis, and clinical outcome.

Methods:
In this retrospective single-center study, 553 patients receiving V-A ECMO between 2014 and 2024 were divided into low-flow (< 1.63 L/min/m2, n = 269) and high-flow (≥ 1.63 L/min/m2, n = 284) groups. Patients were additionally stratified according to eCPR status. Multivariable logistic regression was used to assess factors associated with multi-organ failure (MOF), and exploratory mediation analyses evaluated day-1 free hemoglobin and IL-6 as potential mediators.

Results:
High-flow patients were more hemodynamically compromised, with higher lactate, vasoactive-inotropic support, inflammatory markers, and early hemolysis. After exclusion of cerebral death, MOF occurred more frequently in the high-flow group (32.7% vs. 23.0%, p = 0.028). Initial flow-index remained independently associated with MOF in the overall cohort (OR 1.102 per 0.1 L/min/m2, 95% CI 1.001–1.214, p = 0.048) and in the eCPR subgroup (OR 1.117, 95% CI 1.028–1.214, p = 0.008). Day-1 free hemoglobin was independently associated with MOF, and mediation analysis demonstrated a significant indirect effect through early hemolysis. No significant indirect effect through IL-6 was observed. Higher flow index was also associated with worse neurological outcome and reduced survival.

Conclusions:
Higher initial V-A ECMO flow-index is associated with greater shock severity and multi-organ failure. Early hemolysis may partly contribute to this association, particularly in eCPR patients. These findings support individualized flow management with close monitoring of hemolysis and evolving organ dysfunction.