Abstract

Rationale: Pressures and volumes needed to induce ventilator-induced lung injury in healthy lungs are far greater than those applied in diseased lungs. A possible explanation may be the presence of local inhomogeneities acting as pressure multipliers (stress raisers). Objectives: To quantify lung inhomogeneities in patients with acute respiratory distress syndrome (ARDS). Methods: Retrospective quantitative analysis of CT scan images of 148 patients with ARDS and 100 control subjects. An ideally homogeneous lung would have the same expansion in all regions; lung expansion was measured by CT scan as gas/tissue ratio and lung inhomogeneities were measured as lung regions with lower gas/tissue ratio than their neighboring lung regions. We defined as the extent of lung inhomogeneities the fraction of the lung showing an inflation ratio greater than 95th percentile of the control group (1.61). Measurements and Main Results: The extent of lung inhomogeneities increased with the severity of ARDS(14 +/- 5, 18 +/- 8, and 23 +/- 10% of lung volume in mild, moderate, and severe ARDS; P< 0.001) and correlated with the physiologic dead space (r(2) = 0.34; P< 0.0001). The application of positive end-expiratory pressure reduced the extent of lung inhomogeneities from 18 +/- 8 to 12 +/- 7% (P 0.0001) going from 5 to 45 cm H2O airway pressure. Lung inhomogeneities were greater in nonsurvivor patients than in survivor patients (20 +/- 9 vs. 17 +/- 7% of lung volume; P = 0.01) and were the only CT scan variable independently associated with mortality at backward logistic regression. Conclusions: Lung inhomogeneities are associated with overall disease severity and mortality. Increasing the airway pressures decreased but did not abolish the extent of lung inhomogeneities.