Differential carbon dioxide in awake peripheral veno-arterial extracorporeal membrane oxygenation: a neglected clinical challenge

Awake veno-arterial extracorporeal membrane oxygenation (VA ECMO) is increasingly used to provide circulatory support while avoiding sedation and mechanical ventilation. While differential hypoxemia is well recognized, differential carbon dioxide (CO₂) remains poorly explored, especially in awake patients with preserved respiratory drive. We describe a 38-year-old patient with severe dilated cardiomyopathy, severe mitral regurgitation and cardiogenic shock supported with awake femoro-femoral VA ECMO as a bridge to heart transplant. Initial settings included 2.6 L/min of blood flow and 1 L/min of sweep gas. On day three, bilateral arterial sampling demonstrated marked differential carbon dioxide: right arm PaCO₂ 17 mmHg (pH 7.58) versus left arm PaCO₂ 40 mmHg (pH 7.35). Increasing the sweep gas flow to 2 L/min substantially reduced this gradient, yielding similar PaCO₂ values (30 vs. 29 mmHg) without hemodynamic instability. The mixing point was likely located between the innominate and left subclavian arteries; potentially, creating asymmetric perfusion and exposing the brain to heterogeneous CO₂ tensions. Differential CO₂ exchange may occur despite preserved pulmonary function. Resulting regional hypocapnia can induce cerebral vasoconstriction, potentially compromising cerebral blood flow in vulnerable awake VA ECMO patients. Detection requires bilateral arterial blood gases and careful sweep gas titration together with serial neurologic assessment. Neuromonitoring tools such as near-infrared spectroscopy, electroencephalography, and transcranial doppler may assist in evaluating cerebrovascular effects. Differential carbon dioxide is an underrecognized but clinically relevant phenomenon in awake VA-ECMO. Systematic detection and individualized CO₂ management are essential to reduce neurological risk.