Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients

Objective: A single-center retrospective study initial recently identified ventilator settings as a major risk factor for the development of acute respiratory distress syndrome (ARDS) in mechanically ventilated patients who do not have ARDS from the outset. We tested this hypothesis in a larger sample of patients prospectively enrolled in a multicenter study on mechanical ventilation. Design and setting: From a large international mechanical ventilation study database we identified patients who required mechanical ventilation for 48 h or more but did not have ARDS at the onset of mechanical ventilation. We extracted information on demographics, initial severity of illness, ventilator settings and major underlying ARDS risk factors. Primary outcome was development of ARDS after the onset of mechanical ventilation. Measurements and results: Of 3,261 mechanically ventilated patients who did not have ARDS at the outset 205 (6.2%) developed ARDS 48 h or more after the onset of mechanical ventilation. Multivariate logistic regression analysis adjusted for baseline patient characteristics (age, gender, Simplified Acute Physiology Score, hypoxemia) and underlying ARDS risk factors (sepsis, trauma, pneumonia) found the development of ARDS to be associated with the initial ventilator settings: high tidal volume (odds ratio 2.6 for tidal volume > 700 ml), high peak airway pressure (odds ratio 1.6 for peak airway pressure > 30 cmH(2)O), and high positive end-expiratory pressure (odds ratio 1.7 for end-expiratory pressure > 5 cmH(2)O). Conclusions: The association with the potentially injurious initial ventilator settings, in particular large tidal volumes, suggests that ARDS in mechanically ventilated patients is in part a preventable complication. This hypothesis needs to be tested in a prospective study.