Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-FIO2 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 lunginjury and improve patient outcomes inacute 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 (FIO2) 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 (PaO2: FIO2 <= 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-FIO2 (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-FIO2 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-FIO2. CONCLUSIONS AND RELEVANCE Amongpatients with moderate to severe ARDS, P-ES-guided PEEP, compared with empirical high PEEP-FIO2, 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.