Effect of Esophageal Pressure-Guided Positive End-Expiratory Pressure on Survival from Acute Respiratory Distress Syndrome: A Risk-Based and Mechanistic Reanalysis of the EPVent-2 Trial.

Abstract

RATIONALE\nIn acute respiratory distress syndrome (ARDS), the effect of positive end-expiratory pressure (PEEP) may depend on the extent to which multiorgan dysfunction contributes to risk of death, and the precision with which PEEP is titrated to attenuate atelectrauma without exacerbating overdistension.\n\n\nOBJECTIVE\nTo evaluate whether multiorgan dysfunction and lung mechanics modified treatment effect in EPVent-2, a multicenter trial of esophageal pressure (PES)-guided PEEP versus empirical high PEEP in moderate-to-severe ARDS.\n\n\nMETHODS\nThis post-hoc reanalysis of EPVent-2 evaluated for heterogeneity of treatment effect on mortality by baseline multiorgan dysfunction, determined via Acute Physiology and Chronic Health Evaluation-II (APACHE-II). It also evaluated whether PEEP titrated to end-expiratory transpulmonary pressure near 0 cmH2O was associated with survival.\n\n\nMEASUREMENTS AND MAIN RESULTS\nAll 200 trial participants were included. Treatment effect on 60-day mortality differed by multiorgan dysfunction severity (p=0.03 for interaction). PES-guided PEEP was associated with lower mortality among patients with lower APACHE-II (HR 0.43, 95% CI 0.20-0.92 for APACHE-II less than median) and may have had the opposite effect in patients with higher APACHE-II (HR 1.69; 95% CI 0.93-3.05). Independent of treatment group or multiorgan dysfunction severity, mortality was lowest when PEEP titration achieved end-expiratory transpulmonary pressure near 0 cmH2O.\n\n\nCONCLUSIONS\nThe effect on survival of PES-guided PEEP, compared to empirical high PEEP, differed by multiorgan dysfunction severity. Independent of multiorgan dysfunction, PEEP titrated to end-expiratory transpulmonary pressure closer to 0 cmH2O was associated with greater survival than more positive or negative values. These findings warrant prospective testing in a future trial.