Effect of driving pressure on mortality in ARDS patients during lung protective mechanical ventilationin two randomized controlled trials

Abstract

Background: Driving pressure (∆Prs) across the respiratory system is suggested as the strongest predictor of hospital mortality in patients with acute respiratory distress syndrome (ARDS). We wonder whether this result is related to the range of tidal volume (VT). Therefore, we investigated ∆Prs in two trials in which strict lung-protective mechanical ventilation was applied in ARDS. Our working hypothesis was that ∆Prs is a risk factor for mortality just like compliance (Crs) or plateau pressure (Pplat,rs) of the respiratory system. Methods: We performed secondary analysis of data from 787 ARDS patients enrolled in two independent randomized controlled trials evaluating distinct adjunctive techniques while they were ventilated as in the low VT arm of the ARDSnet trial. For this study, we used VT, positive end-expiratory pressure (PEEP), Pplat,rs, Crs, ∆Prs, and respiratory rate recorded 24hours after randomization, and compared them between survivors and nonsurvivors at day 90. Patients were followed for 90days after inclusion. Cox proportional hazard modeling was used for mortality at day 90. If colinearity between ∆Prs, Crs, and Pplat,rs was verified, specific Cox models were used for each of them. Results: Both trials enrolled 805 patients of whom 787 had day-1 data available, and 533 of these survived. In the univariate analysis, ∆Prs averaged 13.7±3.7 and 12.8±3.7 cmH2O (P=0.002) in nonsurvivors and survivors, respectively. Colinearity between ∆Prs, Crs and Pplat,rs, which was expected as these variables are mathematically coupled, was statistically significant. Hazard ratios from the Cox models for day-90 mortality were 1.05 (1.02-1.08) (P=0.005), 1.05 (1.01-1.08) (P=0.008) and 0.985 (0.972-0.985) (P=0.029) for ∆Prs, Pplat,rs and Crs, respectively. PEEP and VT were not associated with death in any model. Conclusions: When ventilating patients with low VT, ∆Prs is a risk factor for death in ARDS patients, as is Pplat,rs or Crs. As our data originated from trials from which most ARDS patients were excluded due to strict inclusion and exclusion criteria, these findings must be validated in independent observational studies in patients ventilated with a lung protective strategy. Trial registration: Clinicaltrials.gov NCT00299650. Registered 6 March 2006 for the Acurasys trial. Clinicaltrials.gov NCT00527813. Registered 10 September 2007 for the Proseva trial.