Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a supportive modality in patients with refractory cardiopulmonary failure.¹ VA-ECMO serves as a bridge to recovery, transplantation, or durable ventricular assist device (VAD). Peripheral VA-ECMO utilizing retrograde blood flow from the femoral cannulation creates dual circulation involving the interaction of native antegrade cardiac output and retrograde ECMO flow creating the prospect of differential gas exchange. Native cardiac output reflects pulmonary gas exchange, and ECMO flow reflects the membrane lung gas exchange. The aggregate of native cardiac output and retrograde ECMO flow will result in a mixing cloud at the point where the opposing circulations meet Roumy et al.^2,3

When the mixing cloud rests at a point distal to the brachiocephalic artery but proximal to the left common carotid artery, the potential for clinically relevant differential gas exchange exists. Differential hypercapnia, or RIDDLER syndrome, is characterized by an increase in carbon dioxide delivered to the brain from the extracorporeal circuit, which leads to respiratory acidosis in the cerebral circulation, creating the response by chemoreceptors to elevate the respiratory rate. This discordance in gas exchange can be furthered iatrogenically by the ECMO clinician basing sweep titrations on right upper extremity arterial blood gases, which are appreciated as global hypocapnia, further potentiating the presence of differential hypercapnia. This phenomenon, first identified in literature by Rosenberg and Thakuria,⁴ while growing in recognition, has sparse peer-reviewed literature addressing its recognition, neurophysiologic implications, clinical consequences, or approach to monitoring and management Asija et al.^1,2 Our case report details a patient who, through plausible inference, developed differential hypercapnia that was identified and managed successfully. The patient was subsequently bridged to a durable VAD and successfully discharged from the hospital.