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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
Open accessAbstract
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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“Esophageal pressure guided PEEP titration has been evaluated in two trials [447, 448].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [447]
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Metadata
- Authors
- Beitler, J. R., Sarge, T., Banner-Goodspeed, V. M., Gong, M. N., Cook, D., Novack, V., Loring, S. H., Talmor, D., & for the EPVent-2 Study Group
- Affiliations
- Columbia University (US)
- Beth Israel Deaconess Medical Center (US)
- Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
- Albert Einstein College of Medicine (US)
- McMaster University (CA)
- Soroka Medical Center (IL)
- Corresponding author
- Talmor, Daniel
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2019-03-05
- Volume
- 321
- Issue
- 9
- Pages
- 846
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC6439595
- OpenAlex
- W2912354430
- Cited by
- 469
- References
- 43
- Citations by year
- 2026: 49 · 2025: 53 · 2024: 64 · 2023: 61 · 2022: 65 · 2021: 80 · 2020: 52 · 2019: 45
- FWCI
- 44.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (UM1HL108724, K23HL133489, L30 HL129438)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Nosocomial Infections in ICU
- Keywords
- acute respiratory distress syndrome, positive end-expiratory pressure, PEEP titration, esophageal pressure, pleural pressure, mechanical ventilation, low tidal volume, fraction of inspired oxygen, 28-day mortality, weaning from mechanical ventilation, salvage therapy, lung injury, ARDSNet
- MeSH terms
- Adult, Aged, Esophagus, Female, Humans, Male, Middle Aged, Positive-Pressure Respiration, Pressure, Respiratory Distress Syndrome, Respiratory Physiological Phenomena
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