Venous Admixture in COPD: Pathophysiology and Therapeutic Approaches

Abstract

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 ventilationperfusion mismatch withV /Q 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 highV /Q. However, in patients with lowV /Q 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.

Percutaneous Femoral Arteriovenous Shunt Creation for Advanced Chronic Obstructive Pulmonary Disease

“…6,7 Likewise, exerciseinduced arterial desaturation has been shown to be less pronounced after creation of an AVS. 9 Provided the functional limitation seen in patients with severe COPD is at least partially related to DO 2 , the conclusion that creation of an AVS may enhance functional capacity appears reasonable. In fact, initial experience with AVS in patients with endstage COPD has been encouraging.…”

The ROX coupler: Creation of a fixed iliac arteriovenous anastomosis for the treatment of uncontrolled systemic arterial hypertension, exploiting the physical properties of the arterial vasculature

“…The creation of a small, fixed, centrally located arteriovenous anastomosis using the ROX coupler results in an immediate reduction in systemic arterial pressure , as predicted by the addition of low‐resistance and high‐compliance venous attachment . The direct observation of an immediate BP‐lowering effect by way of invasive arterial monitoring refutes alternative explanations, such as a sham or placebo effect or the Hawthorne effect.…”

“…The development of a low‐volume, fixed‐diameter, percutaneously delivered, central arteriovenous anastomosis was initially considered for patients with chronic obstructive pulmonary disease and hypoxia to exploit the resulting increase in systemic oxygenation . The initial trials identified modest improvements in exercise tolerance, no significant procedure‐related or hemodynamic complications, and a significant reduction in arterial BP .…”

“…A novel device technology (ROX arteriovenous coupler, ROX Medical, Inc., San Clemente, CA) has been developed that causes an immediate and significant reduction of BP by exploiting the mechanical effects of the creation of a low‐resistance, high‐compliance venous segment to the central arterial tree . A prospective, randomized, blinded endpoint clinical trial, the ROX Control Hypertension Study (http://clinicaltrials.gov identifier NCT01642498), has completed enrollment, and the results are anticipated in the Autumn of 2014.…”

Arteriovenous Anastomosis

“…6 In retrospective analysis of these ill patients, investigators identified significant reductions in arterial BP. The observation led to a brief safety trial in patients with resistant hypertension, and now a prospective, multicenter, randomized trial, anticipating completion later in 2014.…”