Extracorporeal membrane oxygenation (ECMO) supports patients with severe refractory cardiac or respiratory failure but managing residual circuit blood after weaning lacks consensus. After decannulation, the oxygenator and circuit retain approximately 500–700 mL of blood, depending on tubing length, cannula size, and circuit configuration. Clinicians usually choose among direct reinfusion, cell-salvage processing, or disposal. Direct reinfusion maintains circulating red cell mass and may help avert allogeneic transfusion, especially in borderline cases, but carries the risk of reintroducing free hemoglobin, inflammatory mediators, microthrombi, and air emboli. Cell salvage offers an intermediary strategy by removing harmful elements through washing and centrifugation, but introduces delays in volume return, mechanical red cell damage, loss of platelets and clotting factors, and added cost. Discarding the blood eliminates reinfusion risks but increases reliance on banked blood, which poses risks such as immunomodulation, transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), and resource depletion. Modified CPD blood bags have shown promise for temporarily storing blood from ECMO or RRT circuits, particularly in neonatal and pediatric patients.

Additionally, residual blood salvage during ECMO circuit changes, an often-overlooked opportunity for autologous transfusion, deserves greater emphasis. In the absence of standardized guidelines, current practice remains heterogeneous. We advocate prospective, multicenter trials comparing these strategies with endpoints including transfusion requirements, hemolysis and inflammation biomarkers, fluid balance, organ dysfunction scores, cost implications, and survival. Evidence-based protocols will enhance patient safety, reduce costs, and standardize ECMO care.