The Aortic Watershed Phenomenon and Differential Hypoxemia During Peripheral Venoarterial ECMO: A Scoping Review of Clinical and Experimental Evidence

Extracorporeal membrane oxygenation (ECMO) is a widely used technology in cardiac surgery practice. A clinically significant yet underexplored presentation that occurs during peripheral femoro-femoral venoarterial ECMO (VA-ECMO) is differential hypoxemia (DH) or Harlequin syndrome. This phenomenon may occur when the aortic mixing interface shifts distally, and the coronary and supra-aortic circulations receive predominantly hypoxemic native blood. DH may reduce cerebral and myocardial oxygen delivery and produce clinically meaningful arterial partial pressure of carbon dioxide (PaCO2) gradients.This scoping review aimed to synthesize clinical and experimental evidence on the mechanisms, detection, management, and outcomes of DH during peripheral VA-ECMO.A scoping review of the watershed phenomenon during peripheral VA-ECMO was conducted using MEDLINE and EMBASE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The initial search identified 245 records. After screening, 16 studies were included.DH frequency ranged from 1.5% to 13.3%, but estimates varied substantially across case definitions, diagnostic thresholds, and cohort compositions. Regarding management, configuration-targeted strategies improved surrogates of upper-body oxygenation and perfusion, which included shifting venous drainage toward the superior vena cava/upper right atrium, in turn converting to veno-arteriovenous ECMO with internal jugular return (with flow-splitting control) and relocating arterial return to more proximal/antegrade sites. Detection extended beyond paired upper- and lower-body oximetry/arterial blood gases; reported approaches included contrast-enhanced ultrasound, Doppler mapping, and positional computed tomography angiography (CTA). Experimental models described why DH may persist despite higher ECMO flow as native output increases, and they highlight anatomy- and cannulation-dependent cerebral and coronary vulnerability.DH appears to be a predictable, physiology-driven complication best mitigated by modifying drainage position and/or circuit configuration rather than increasing ECMO flow. To further explore this phenomenon, adopting standardized definitions, investigating bedside localization tools, and conducting prospective comparative studies could be considered.