Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial
Open accessAbstract
Importance: The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. Objective: To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. Design, Setting, and Participants: Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. Interventions: An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. Main Outcomes and Measures: The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. Results: A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, -1.1; 95% CI, -2.1 to -0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. Conclusions and Relevance: In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. Trial Registration: clinicaltrials.gov Identifier: NCT01374022.
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Instead of the "traditional" recruitment maneuver which consists of the application of sustained continuous positive airway pressure (e.g., 30-40 cm H2O for 30-40 s), both trials conducted lung recruitment with incremental PEEP levels, followed by a decremental PEEP titration according to either best respiratory-system static compliance or oxygen saturation.
“Instead of the “traditional” recruitment maneuver which consists of the application of sustained continuous positive airway pressure (e.g., 30–40 cm H2O for 30–40 s), both trials conducted lung recruitment with incremental PEEP levels, followed by a decremental PEEP titration according to either best respiratory-system static compliance [452] or oxygen saturation [437].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [452]
Two RCTs were published since the 2016 Guidelines, but they were not included in the meta-analyses because both studies applied recruitment maneuvers to titrate PEEP levels.
“Two RCTs [437, 438] were published since the 2016 Guidelines [12, 13], but we did not include these trials in the meta-analyses because both studies applied recruitment maneuvers to titrate PEEP levels.”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [438]
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- Authors
- Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators, Cavalcanti, A. B., Suzumura, É. A., Laranjeira, L. N., Paisani, D. D. M., Damiani, L. P., Guimarães, H. P., Romano, E. R., Regenga, M. D. M., Taniguchi, L. N. T., Teixeira, C., Pinheiro de Oliveira, R., Machado, F. R., Diaz-Quijano, F. A., Filho, M. S. D. A., Maia, I. S., Caser, E. B., Filho, W. D. O., Borges, M. D. C., Martins, P. D. A., Matsui, M., Ospina-Tascón, G. A., Giancursi, T. S., Giraldo-Ramirez, N. D., Vieira, S. R. R., Assef, M. D. G. P. D. L., Hasan, M. S., Szczeklik, W., Rios, F., Amato, M. B. P., Berwanger, O., & Ribeiro de Carvalho, C. R.
- Affiliations
- HCor Research Institute, São Paulo, Brazil
- Hospital Moinhos de Vento (BR)
- Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
- Anesthesiology, Pain, and Intensive Care Department, Federal University of São Paulo–UNIFESP, São Paulo, Brazil
- Epidemiology Department, School of Public Health, University of São Paulo, São Paulo, Brazil
- Hospital Maternidade São Vicente de Paulo, Barbalha, Brazil
- Hospital Nereu Ramos, Florianópolis, Brazil
- Hospital Unimed Vitória, Vitória, Brazil
- Universidade de São Paulo (BR)
- Universidade Federal da Grande Dourados (BR)
- Universidade Estadual do Oeste do Paraná (BR)
- Hospital Pablo Tóbon Uribe, Medellín, Colombia
- Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- Hospital Regional Hans Dieter Schmidt, Joinville, Brazil
- Jagiellonian University (PL)
- Hospital Nacional Alejandro Posadas, Moron, Argentina
- Cardio-Pulmonary Department, Pulmonary Division, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil
- Corresponding author
- Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators
- ORCID
- Cavalcanti, Alexandre Biasi
- Suzumura, Érica Aranha
- Damiani, Lucas Petri
- Teixeira, Cassiano
- Filho, Meton Soares de Alencar
- Filho, Wilson de Oliveira
- Borges, Marcos de Carvalho
- Martins, Priscilla de Aquino
- Matsui, Mirna
- Ospina-Tascón, Gustavo Adolfo
- Hasan, Mohd Shahnaz
- Szczeklik, Wojciech
- Amato, Marcelo Britto Passos
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2017-10-10
- Volume
- 318
- Issue
- 14
- Pages
- 1335
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC5710484
- OpenAlex
- W2758688195
- Semantic Scholar
- e59e9552a28028b188ddec852bd260a85feab5fc
- Cited by
- 1,018
- References
- 30
- Citations by year
- 2026: 67 · 2025: 73 · 2024: 114 · 2023: 96 · 2022: 123 · 2021: 141 · 2020: 170 · 2019: 119 · 2018: 107 · 2017: 8
- FWCI
- 91.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- Funders
- Hospital de Clínicas de Porto Alegre
- Universidade de São Paulo
- Faculdade de Medicina da Universidade de São Paulo
- Universidade Federal de Goiás
- Universidade Estadual de Campinas
- Ministério da Saúde
- Universidade Federal de Minas Gerais
- Sociedade Beneficente Israelita Brasileira Albert Einstein
- 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, lung recruitment maneuver, positive end-expiratory pressure titration, 28-day mortality, respiratory compliance, mechanical ventilation, ventilator-free days, barotrauma, pneumothorax, ICU length of stay, 6-month mortality, ARDSNet, weaning from mechanical ventilation, lung-protective ventilation
- MeSH terms
- Adult, Aged, Female, Humans, Intensive Care Units, Male, Middle Aged, Pneumothorax, Positive-Pressure Respiration, Respiratory Distress Syndrome, Tidal Volume, Treatment Failure
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