Decompensated differential carbon dioxide (CO2) removal can occur during spontaneous breathing on peripheral venoarterial extracorporeal membrane oxygenation (V-A ECMO) when a low right radial arterial partial pressure of carbon dioxide (PaCO2) prompts sweep gas flow (SGF) reduction, decreasing extracorporeal CO2 removal and shifting the compensatory burden to the native lung. When cardiac output (CO) remains low, this shift may require disproportionately higher alveolar ventilation, manifesting as tachypnea and increased work of breathing. We therefore frame this phenotype as a CO-dependent CO2 “budget” imbalance that is modulated by the aortic mixing point, rather than solely cerebral exposure to CO2-rich retrograde ECMO blood. We outline a pragmatic, non-protocol bedside heuristic anchored to post-membrane pH/PaCO2 targets, using multi-site blood gases to contextualize the mixing point and guide physiologic optimization of preload, ECMO blood flow, and SGF. Treating the loop, rather than isolated right-radial values, may reduce iatrogenic escalation and provide a testable foundation for future mechanistic studies.
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