Oxygenation response to positive end-expiratory pressure predicts mortality in acute respiratory distress syndrome. A secondary analysis of the LOVS and ExPress trials.

RATIONALE Previous trials of higher positive end-expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) failed to demonstrate mortality benefit, possibly because of differences in lung recruitability among patients with ARDS. OBJECTIVES To determine whether the physiological response to increased PEEP is associated with mortality. METHODS In a secondary analysis of the Lung Open Ventilation Study (LOVS, n = 983), we examined the relationship between the initial response to changes in PEEP after randomization and mortality. We sought to corroborate our findings using data from a different trial of higher PEEP (ExPress, n = 749). MEASUREMENTS AND MAIN RESULTS The oxygenation response (change in ratio of arterial partial pressure of oxygen to fraction of inspired oxygen: P/F) after the initial change in PEEP after randomization varied widely (median, 9.5 mm Hg; interquartile range, -16 to 47) and was only weakly related to baseline P/F or the magnitude of PEEP change. Among patients in whom PEEP was increased after randomization, an increase in P/F was associated with reduced mortality (multivariable logistic regression; adjusted odds ratio, 0.80 [95% confidence interval, 0.72-0.89] per 25-mm Hg increase in P/F), particularly in patients with severe disease (baseline P/F [less-than-or-equal-to] 150 mm Hg). Changes in compliance and dead space were not associated with mortality. These findings were confirmed by a similar analysis of data from the ExPress trial. CONCLUSIONS Patients with ARDS who respond to increased PEEP by improved oxygenation have a lower risk of death. The oxygenation response to PEEP might be used to predict whether patients will benefit from higher versus lower PEEP.