Relationship between dynamic respiratory mechanics and disease heterogeneity in sheep lavage injury

Objective: Acute respiratory distress syndrome and acute lung injury are characterized by heterogeneous flooding/collapse of lung tissue. An emerging concept for managing these diseases is to set mechanical ventilation so as to minimize the impact of disease heterogeneity on lung mechanical stress and ventilation distribution. The goal of this study was to determine whether changes in lung mechanical heterogeneity with increasing positive end-expiratory pressure in an animal model of acute lung injury could be detected from the frequency responses of resistance and elastance. Design: Prospective, experimental study. Setting: Research laboratory at a veterinary hospital. Subjects, Female sheep weighing 48 2 kg. Interventions. In five saline-lavaged sheep, we acquired whole-lung computed tomography scans, oxygenation, static elastance, and dynamic respiratory resistance and elastance at end-expiratory pressure levels of 7.5-20 cm H2O. Measurements and Main Results. As end-expiratory pressure increased, computed tomography-determined alveolar recruitment significantly increased but was accompanied by significant alveolar overdistension at 20 cm H2O. An optimal range of end-expiratory pressures (15-17.5 cm H2O) was identified where alveolar recruitment was significantly increased without significant overdistension. This range corresponded to the end-expiratory pressure levels that maximized oxygenation, minimized peak-to-peak ventilation pressures, and minimized indexes reflective of the mechanical heterogeneity (e.g., frequency dependence of respiratory resistance and low-frequency elastance). Static elastance did not demonstrate any significant pressure dependence or reveal an optimal end-expiratory pressure level. Conclusions., We conclude that dynamic mechanics are more sensitive than static mechanics in the assessment of the functional trade-off of recruitment relative to overdistension in a sheep model of lung injury. We anticipate that monitoring of dynamic respiratory resistance and elastance ventilator settings can be used to optimize ventilator management in acute lung injury.