Driving Pressure and Survival in the Acute Respiratory Distress Syndrome

BACKGROUND Mechanical-ventilation strategies that use lower end-inspiratory (plateau) airway pressures, lower tidal volumes (V-T), and higher positive end-expiratory pressures (PEEPs) can improve survival in patients with the acute respiratory distress syndrome (ARDS), but the relative importance of each of these components is uncertain. Because respiratory-system compliance (C-RS) is strongly related to the volume of aerated remaining functional lung during disease (termed functional lung size), we hypothesized that driving pressure (Delta P=V-T/C-RS), in which V-T is intrinsically normalized to functional lung size (instead of predicted lung size in healthy persons), would be an index more strongly associated with survival than V-T or PEEP in patients who are not actively breathing. METHODS Using a statistical tool known as multilevel mediation analysis to analyze individual data from 3562 patients with ARDS enrolled in nine previously reported randomized trials, we examined Delta P as an independent variable associated with survival. In the mediation analysis, we estimated the isolated effects of changes in Delta P resulting from randomized ventilator settings while minimizing confounding due to the baseline severity of lung disease. RESULTS Among ventilation variables, Delta P was most strongly associated with survival. A 1-SD increment in Delta P (approximately 7 cm of water) was associated with increased mortality (relative risk, 1.41; 95% confidence interval [CI], 1.31 to 1.51; P<0.001), even in patients receiving "protective" plateau pressures and V-T (relative risk, 1.36; 95% CI, 1.17 to 1.58; P<0.001). Individual changes in V-T or PEEP after randomization were not independently associated with survival; they were associated only if they were among the changes that led to reductions in Delta P (mediation effects of Delta P, P=0.004 and P=0.001, respectively). CONCLUSIONS We found that Delta P was the ventilation variable that best stratified risk. Decreases in Delta P owing to changes in ventilator settings were strongly associated with increased survival. (Funded by Fundacao de Amparo e Pesquisa do Estado de Sao Paulo and others.)