Venous Admixture in COPD: Pathophysiology and Therapeutic Approaches

Chronic obstructive and interstitial lung diseases impair pulmonary gas exchange leading to wasted ventilation (alveolar dead space) and wasted perfusion (venous admixture). These two fundamental types of abnormality represent opposite ends of the spectrum of ventilation-perfusion mismatch with V(over dot)/Q(over dot) ratios of infinity and zero. Treatment approaches that improve airway function, reduce air trapping and hyperinflation have received much attention and might be successful at ameliorating the problems associated with high V(over dot)/Q(over dot). However, in patients with low V(over dot)/Q(over dot) abnormality in whom venous admixture leads to hypoxemia, there are few therapeutic options. Indeed, some patients are refractory to treatment with supplemental oxygen particularly during exercise. Theoretically these patients could benefit from an intervention that increased mixed venous oxygen content thereby ameliorating the deleterious effects of venous admixture. In this perspective article we discuss the mechanisms whereby venous admixture contributes to hypoxemia and reduced oxygen delivery to tissues. We explore methods which could potentially increase mixed venous oxygen content thus ameliorating the deleterious effects of venous admixture. One such intervention that warrants further investigation is the therapeutic creation of an arterio-venous fistula. Such an approach would be novel, simple and minimally invasive. There is reason to believe that complications would be minor leading to a favorable risk-benefit analysis. This approach to treatment could have significant impact for patients with COPD but should also benefit any patient with chronic hypoxemia that impairs exercise performance.