Effect of Titrating Positive End-Expiratory Pressure (PEEP) with an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-F io ₂ Strategy on Death and Days Free from Mechanical Ventilation among Patients with Acute Respiratory Distress Syndrome: A Randomized Clinical Trial

Importance: Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS). Objective: To determine whether PEEP titration guided by esophageal pressure (P _ES ), an estimate of pleural pressure, was more effective than empirical high PEEP-fraction of inspired oxygen (Fio ₂ ) in moderate to severe ARDS. Design, Setting, and Participants: Phase 2 randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged 16 years and older with moderate to severe ARDS (Pao ₂ :Fio ₂ ≤200 mm Hg) were enrolled between October 31, 2012, and September 14, 2017; long-term follow-up was completed July 30, 2018. Interventions: Participants were randomized to P _ES -guided PEEP (n = 102) or empirical high PEEP-Fio ₂ (n = 98). All participants received low tidal volumes. Main Outcomes and Measures: The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Prespecified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy. Results: Two hundred patients were enrolled (mean [SD] age, 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite end point was not significantly different between treatment groups (probability of more favorable outcome with P _ES -guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P =.92). At 28 days, 33 of 102 patients (32.4%) assigned to P _ES -guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio ₂ died (risk difference, 1.7% [95% CI, -11.1% to 14.6%]; P =.88). Days free from mechanical ventilation among survivors was not significantly different (median [interquartile range]: 22 [15-24] vs 21 [16.5-24] days; median difference, 0 [95% CI, -1 to 2] days; P =.85). Patients assigned to P _ES -guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs 12/98 [12.2%]; risk difference, -8.3% [95% CI, -15.8% to -0.8%]; P =.04). None of the 7 other prespecified secondary clinical end points were significantly different. Adverse events included gross barotrauma, which occurred in 6 patients with P _ES -guided PEEP and 5 patients with empirical PEEP-Fio ₂ . Conclusions and Relevance: Among patients with moderate to severe ARDS, P _ES -guided PEEP, compared with empirical high PEEP-Fio ₂ , resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support P _ES -guided PEEP titration in ARDS. Trial Registration: ClinicalTrials.gov Identifier NCT01681225.