This study investigates the interactions between milrinone, a phosphodiesterase inhibitor used in critically ill patients, and extracorporeal life support (ECLS) systems, specifically extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Ex vivo experiments demonstrated that milrinone exhibits negligible interaction with ECMO circuits but is rapidly cleared (99% within two hours) by CRRT circuits. These findings suggest that while ECMO dosing adjustments are unnecessary, CRRT requires tailored dosing. Future studies incorporating patient physiology are recommended to refine dosing strategies.