Physiological mechanism and spatial distribution of increased alveolar dead-space in early ARDS: An experimental study.

Abstract

We aimed to investigate the physiological mechanism and spatial distribution of increased physiological dead-space, an early marker of ARDS mortality, in the initial stages of ARDS. We hypothesized that: increased dead-space results from the spatial redistribution of pulmonary perfusion, not ventilation; such redistribution is not related to thromboembolism (ie, areas with perfusion=0 and infinite ventilation-perfusion ratio, ), but rather to moderate shifts of perfusion increasing in non-dependent regions. Five healthy anesthetized sheep received protective ventilation for 20hours, while endotoxin was continuously infused. Maps of voxel-level lung ventilation, perfusion, , CO2 partial pressures, and alveolar dead-space fraction were estimated from positron emission tomography at baseline and 20hours. Alveolar dead-space fraction increased during the 20hours (+0.05, P=.031), mainly in non-dependent regions (+0.03, P=.031). This was mediated by perfusion redistribution away from non-dependent regions (-5.9%, P=.031), while the spatial distribution of ventilation did not change, resulting in increased in non-dependent regions. The increased alveolar dead-space derived mostly from areas with intermediate (0.5≤ ≤10), not areas of nearly "complete" dead-space ( >10). In this early ARDS model, increases in alveolar dead-space occur within 20hours due to the regional redistribution of perfusion and not ventilation. This moderate redistribution suggests changes in the interplay between active and passive perfusion redistribution mechanisms (including hypoxic vasoconstriction and gravitational effects), not the appearance of thromboembolism. Hence, the association between mortality and increased dead-space possibly arises from the former, reflecting gas-exchange inefficiency due to perfusion heterogeneity. Such heterogeneity results from the injury and exhaustion of compensatory mechanisms for perfusion redistribution.