Plasma protein levels are markers of pulmonary vascular permeability and degree of lung injury in critically ill patients with or at risk for acute lung injury/acute respiratory distress syndrome

Objectives: To evaluate the diagnostic value of plasma protein levels for pulmonary vascular permeability and acute respiratory distress syndrome. During acute lung injury and acute respiratory distress syndrome, increased vascular permeability induces protein-rich fluid extravasation. We hypothesized that plasma protein levels predict increased vascular permeability and acute respiratory distress syndrome. Design: A prospective, observational study. Patients: Eighty-three consecutive, mechanically ventilated patients with or at risk for acute lung injury/acute respiratory distress syndrome, of whom 18 had sepsis. Patients with increased pulmonary capillary wedge pressures or central venous pressures were excluded. Interventions: Patients were subjected to pulmonary capillary wedge pressure/central venous pressure-guided fluid loading with saline or colloid fluids. Measurements and Main Results: We measured plasma albumin and transferrin levels and determined the (67)Gallium-transferrin pulmonary leak index, the American European Consensus Conference criteria, and the lung injury score. Measurements were performed before and after fluid loading to evaluate effects of fluid loading. Plasma albumin and transferrin levels were approximately 30% lower in acute respiratory distress syndrome than patients with acute lung injury (p < .01) and patients without lung injury (p < .05). Protein levels inversely related to the pulmonary leak index (standardized regression coefficient -0.28, p < .001 for albumin; standardized regression coefficient -0.30, p = .003 for transferrin) and the lung injury score (standardized regression coefficient -0.19, p = .01 for albumin), independently of presence of sepsis, severity of disease, and fluid loading. Albumin and transferrin levels had a high sensitivity (77-93%) and negative predictive value (80-98%) for elevated pulmonary vascular permeability and acute respiratory distress syndrome (American European Consensus Conference criteria and lung injury score). The addition of hypoalbuminemia (<17.5 g/L) and hypotransferrinemia (<0.98 g/L) as criteria to the American European Consensus Conference criteria or the lung injury score increased their predictive values for elevated pulmonary vascular permeability. Conclusions: In critically ill patients, decreased plasma albumin and transferrin levels parallel increased pulmonary vascular permeability irrespective of underlying disease and fluid status. While normal levels help to exclude acute respiratory distress syndrome, hypoalbuminemia and hypotransferrinemia increase the diagnostic accuracy of the American European Consensus Conference criteria and lung injury score for elevated pulmonary vascular permeability. (Crit Care Med 2011; 39:89-97)