Shunt: pathophysiological mechanisms and clinical implications of ineffective circulating volume.

The classical concept of shunt confines the phenomenon to the pulmonary circulation, leaving microcirculatory flow maldistribution in distributive shock outside existing terminology. Tissue hypoxia can persist despite normal cardiac output; current hemodynamic stability criteria incorporate no microcirculatory dimension. This review addresses both gaps by proposing a unifying framework. We propose ineffective circulating volume (ICV) as blood flow that fails to achieve effective gas exchange, whether at the alveolar-blood interface (pulmonary shunt) or the blood-cell interface (systemic shunt). Pulmonary shunt and septic microcirculatory heterogeneity are established phenomena, whereas their unification as ICV-particularly the term systemic "functional shunt"-is a hypothesis requiring clinical validation. Anatomical shunt involves fixed structural bypasses correctable surgically; functional abnormalities reflect failure of active distribution mechanisms-hypoxic pulmonary vasoconstriction suppressed by inflammatory mediators, and conducted responses disrupted by endothelial injury. Supportive interventions may improve their physiological consequences, whereas durable reversal depends on resolution or treatment of the underlying disease. The ICV framework subdivides circulatory hypoxia into a macrocirculatory sublayer (global oxygen delivery insufficiency) and a microcirculatory sublayer (flow maldistribution), the latter potentially persisting even when macrocirculatory parameters are normalised. Acute respiratory distress syndrome and distributive shock may share three upstream molecular mechanisms-glycocalyx degradation, spatially heterogeneous inducible nitric oxide synthase overexpression, and neutrophil extracellular traps-that could impair regulatory systems at both interfaces. Changes in sepsis resuscitation targets are compatible with, but do not validate, the ICV framework's emphasis on macro-microcirculatory uncoupling. No study has simultaneously quantified shunt at both interfaces in the same patient cohort, and no randomised trial targeting the shared upstream mechanisms has used dual-interface ICV as a combined primary endpoint. Translating the ICV framework into prospectively defined clinical endpoints remains an open methodological challenge.