Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study

John G. Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fabiana Madotto, Ednan K. Bajwa, Laurent Brochard, Kevin Clarkson, Andres Esteban, Luciano Gattinoni, Frank van Haren, Leo M. Heunks, Kiyoyasu Kurahashi, Jon Henrik Laake, Anders Larsson, Daniel F. McAuley, Lia McNamee, Nicolas Nin, Haibo Qiu, Marco Ranieri, Gordon D. Rubenfeld, B. Taylor Thompson, Hermann Wrigge, Arthur S. Slutsky, Antonio Pesenti

To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality. The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1-2 who received invasive mechanical ventilation. 2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO2/FiO2 ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores. Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS. ClinicalTrials.gov NCT02010073.