Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is increasingly used to manage severe respiratory failure. Unfortunately, refractory hypoxemia often complicates VV-ECMO support. Both circuit- and patient-related etiologies can drive this, and a structured approach is necessary to diagnose and treat the condition. We present the case of a patient on VV-ECMO for acute respiratory distress syndrome who suffered from several distinct etiologies of refractory hypoxemia over a short timeframe. Frequent recalculation of cardiac output and oxygen delivery enabled early diagnosis and treatment of these conditions. We highlight the need for a structured and oft-repeated approach to this complex problem.
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