RESPIRATORY MECHANICS AND SURFACTANT IN THE ACUTE RESPIRATORY-DISTRESS SYNDROME

1. Although abnormalities in pulmonary surfactant were initially impli cated in the pathogenesis of the acute respiratory distress syndrome ( ARDS) 30 years ago, most subsequent research has focused on mediators of the parenchymal acute lung injury (ALI) and the associated increase in alveolocapillary permeability, 2. Surfactant is essential for norm al breathing and the severity of ALI correlates with surfactant dysfun ction and abnormalities in surfactant composition; however, no relatio nship has been shown with respiratory system compliance. In neonates a nd most animal models, respiratory system compliance will directly ref lect the elastic properties of the lung. However, the greater vertical height of the chest wall in adults, in combination with the increase in lung density due to ALI, results in dependent collapse of alveoli. Because simple, global measurement of compliance Is strongly influence d by the volume of aerated lung, alternative measures of respiratory m echanics may reflect surfactant dysfunction, 3. Using a dynamic, volum e-dependent model of respiratory mechanics to indirectly reflect this heterogeneous inflation, we have found direct relationships with surfa ctant composition in patients with ARDS, A failure of surfactant to in crease surface tension in large alveoli may also explain why lung over distension occurs at relatively low pressures. Furthermore, surfactant dysfunction will exaggerate heterogeneous lung inflation, augmenting regional overinflation, and is essential for ALI secondary to repetiti ve opening and closing of alveoli during tidal ventilation, 4. Ventila tion-induced ALI has also been shown to result in massive increases in pro-inflammatory cytokines within the lung. Because ALI itself fails to compartmentalize cytokines, with spillover into the systemic circul ation resulting in distant organ dysfunction, surfactant dysfunction m ay have widespread implications.