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Original Investigation
Caring for the Critically Ill Patient
February 18, 2019

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

Author Affiliations
  • 1Center for Acute Respiratory Failure and Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians & Surgeons, New York, New York
  • 2Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
  • 3Division of Critical Care Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
  • 4Department of Medicine, St Joseph’s Hospital and McMaster University, Hamilton, Ontario, Canada
  • 5Soroka Clinical Research Center, Soroka University Medical Center, Beer-Sheva, Israel
JAMA. 2019;321(9):846-857. doi:10.1001/jama.2019.0555
Visual Abstract. Effect of Titrating PEEP With an Esophageal Pressure–Guided Strategy vs an Empirical High PEEP-Fio2 Strategy in ARDS
Effect of Titrating PEEP With an Esophageal Pressure–Guided Strategy vs an Empirical High PEEP-Fio2 Strategy in ARDS
Key Points

Question  What is the clinical benefit of titrating positive end-expiratory pressure (PEEP) according to lung mechanics, delineated using esophageal pressure (PES), compared with an empirical high PEEP–fraction of inspired oxygen (Fio2) strategy in the supine patient with moderate to severe acute respiratory distress syndrome (ARDS)?

Finding  In this randomized clinical trial that included 200 patients, PEEP titration guided by PES measurement, compared with empirical high PEEP-Fio2 titration, resulted in no significant difference in a composite outcome that incorporated death and days free from mechanical ventilation through day 28 (estimated probability of a more favorable outcome with PES-guided PEEP, 49.6%).

Meaning  These findings do not support the use of PES measurements, instead of an empirical high PEEP-Fio2 strategy, to guide PEEP titration in patients with moderate to severe ARDS.

Abstract

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 (PES), 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 PES-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 PES-guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P = .92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-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 PES-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 PES-guided PEEP and 5 patients with empirical PEEP-Fio2.

Conclusions and Relevance  Among patients with moderate to severe ARDS, PES-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 PES-guided PEEP titration in ARDS.

Trial Registration  ClinicalTrials.gov Identifier NCT01681225

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