Intensive Care Medicine

, Volume 42, Issue 12, pp 1865–1876 | Cite as

Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study

  • John G. LaffeyEmail author
  • Giacomo Bellani
  • Tài Pham
  • Eddy Fan
  • Fabiana Madotto
  • Ednan K. Bajwa
  • Laurent Brochard
  • Kevin Clarkson
  • Andres Esteban
  • Luciano Gattinoni
  • Frank van Haren
  • Leo M. Heunks
  • Kiyoyasu Kurahashi
  • Jon Henrik Laake
  • Anders Larsson
  • Daniel F. McAuley
  • Lia McNamee
  • Nicolas Nin
  • Haibo Qiu
  • Marco Ranieri
  • Gordon D. Rubenfeld
  • B. Taylor Thompson
  • Hermann Wrigge
  • Arthur S. Slutsky
  • Antonio Pesenti
  • The LUNG SAFE Investigators and the ESICM Trials Group
Seven-Day Profile Publication



To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality.


The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1–2 who received invasive mechanical ventilation.


2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO2/FiO2 ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores.


Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS.

Trial Registration: NCT02010073.


Acute respiratory distress syndrome Positive end-expiratory pressure Patient outcome Driving pressure Peak inspiratory pressure 



Funding/support: This work was funded and supported by the European Society of Intensive Care Medicine (ESICM), Brussels, Belgium, by St Michael’s Hospital, Toronto, Canada, and by the University of Milan-Bicocca, Monza, Italy.

Role of the funders: The ESICM provided support in data collection and study coordination. ESICM, St Michael’s Hospital, and University of Milan-Bicocca had no role in the design and conduct of the study; management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Compliance with ethical standards

Conflicts of interest

The authors attest that they have no conflicts of interest in regard to the subject of this manuscript.

Supplementary material

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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2016

Authors and Affiliations

  • John G. Laffey
    • 1
    • 2
    Email author
  • Giacomo Bellani
    • 3
    • 4
  • Tài Pham
    • 5
    • 6
    • 7
  • Eddy Fan
    • 8
    • 9
  • Fabiana Madotto
    • 10
  • Ednan K. Bajwa
    • 11
  • Laurent Brochard
    • 12
    • 13
  • Kevin Clarkson
    • 14
  • Andres Esteban
    • 15
  • Luciano Gattinoni
    • 16
  • Frank van Haren
    • 17
  • Leo M. Heunks
    • 18
  • Kiyoyasu Kurahashi
    • 19
  • Jon Henrik Laake
    • 20
  • Anders Larsson
    • 21
  • Daniel F. McAuley
    • 22
  • Lia McNamee
    • 22
  • Nicolas Nin
    • 15
  • Haibo Qiu
    • 23
  • Marco Ranieri
    • 24
  • Gordon D. Rubenfeld
    • 25
  • B. Taylor Thompson
    • 11
  • Hermann Wrigge
    • 26
  • Arthur S. Slutsky
    • 12
    • 13
    • 27
  • Antonio Pesenti
    • 28
    • 29
  • The LUNG SAFE Investigators and the ESICM Trials Group
  1. 1.Departments of Anesthesia and Critical Care Medicine, Keenan Research Centre for Biomedical ScienceSt Michael’s HospitalTorontoCanada
  2. 2.Departments of Anesthesia, Physiology, Interdepartmental Division of Critical Care MedicineUniversity of TorontoTorontoCanada
  3. 3.School of Medicine and SurgeryUniversity of Milan-BicoccaMonzaItaly
  4. 4.Department of Emergency and Intensive CareSan Gerardo HospitalMonzaItaly
  5. 5.AP-HP, Hôpital Tenon, Unité de Réanimation médico-chirurgicale, Pôle Thorax Voies aériennesGroupe hospitalier des Hôpitaux Universitaires de l’Est ParisienParisFrance
  6. 6.UMR 1153, Inserm, Sorbonne Paris Cité, ECSTRA TeamUniversité Paris DiderotParisFrance
  7. 7.UMR 915, InsermUniversité Paris Est CréteilCréteilFrance
  8. 8.Department of MedicineUniversity Health Network, Mount Sinai HospitalTorontoCanada
  9. 9.Interdepartmental Division of Critical Care Medicine and Institute of Health Policy, Management and EvaluationUniversity of TorontoTorontoCanada
  10. 10.Research Center on Public Health, School of Medicine and SurgeryUniversity of Milano-BicoccaMonzaItaly
  11. 11.Division of Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  12. 12.Keenan Research Centre, Li Ka Shing Knowledge InstituteSt Michael’s HospitalTorontoCanada
  13. 13.Interdepartmental Division of Critical Care MedicineUniversity of TorontoTorontoCanada
  14. 14.Department of Anaesthesia, National University of IrelandGalway University HospitalsGalwayIreland
  15. 15.Hospital Universitario de GetafeCIBER de Enfermedades RespiratoriasMadridSpain
  16. 16.Department of AnesthesiologyEmergency and Intensive Care Medicine Universitätsmedizin GöttingenGöttingenGermany
  17. 17.Intensive Care Unit, The Canberra HospitalAustralian National UniversityCanberraAustralia
  18. 18.Department of Intensive Care MedicineRadboud University Medical CenterNijmegenThe Netherlands
  19. 19.Department of AnesthesiologyYokohama City University Medical CenterKanagawaJapan
  20. 20.Division of Critical Care, Department of Anaesthesiology, Rikshospitalet Medical CentreOslo University HospitalOsloNorway
  21. 21.Section of Anesthesiology and Intensive Care, Department of Surgical SciencesUppsala UniversityUppsalaSweden
  22. 22.Centre for Experimental Medicine, Queen’s University of Belfast, Wellcome-Wolfson Institute for Experimental Medicine, Belfast and Regional Intensive Care UnitRoyal Victoria HospitalBelfastNorthern Ireland, UK
  23. 23.Department of Critical Care Medicine, Nanjing Zhongda Hospital, School of MedicineSoutheast UniversityNanjingPeople’s Republic of China
  24. 24.SAPIENZA Università di ROMA, Dipartimento di Anestesia e RianimazionePoliclinico Umberto IRomeItaly
  25. 25.Interdepartmental Division of Critical Care Medicine, University of Toronto and Program in Trauma, Emergency and Critical CareSunnybrook Health Sciences CenterTorontoCanada
  26. 26.Department of Anesthesiology and Intensive Care MedicineUniversity of LeipzigLeipzigGermany
  27. 27.Department of MedicineUniversity of TorontoTorontoCanada
  28. 28.Dipartimento di Anestesia, Rianimazione ed Emergenza UrgenzaFondazione IRCCS Cà Granda-Ospedale Maggiore PoliclinicoTorontoCanada
  29. 29.Dipartimento di Fisiopatologia Medico-Chirurgica e dei TrapiantiUniversità degli Studi di MilanoMilanItaly

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