title: Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study.
abstract: OBJECTIVE
  To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality.
  
  
  METHODS
  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.
  
  
  RESULTS
  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/FiO2ratio, 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.
  
  
  CONCLUSIONS
  Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02010073.
authors.affiliation: Departments of Anesthesia and Critical Care Medicine, Keenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, Canada. laffeyj@smh.ca.|Departments of Anesthesia, Physiology, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada. laffeyj@smh.ca.
authors.forename: John G
authors.identifier: http://orcid.org/0000-0002-1246-9573
authors.initials: JG
authors.lastname: Laffey
authors.affiliation: School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.|Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bellani
authors.affiliation: AP-HP, Hôpital Tenon, Unité de Réanimation médico-chirurgicale, Pôle Thorax Voies aériennes, Groupe hospitalier des Hôpitaux Universitaires de l'Est Parisien, Paris, France.|UMR 1153, Inserm, Sorbonne Paris Cité, ECSTRA Team, Université Paris Diderot, Paris, France.|UMR 915, Inserm, Université Paris Est Créteil, Créteil, France.
authors.forename: Tài
authors.initials: T
authors.lastname: Pham
authors.affiliation: Department of Medicine, University Health Network, Mount Sinai Hospital, Toronto, Canada.|Interdepartmental Division of Critical Care Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
authors.forename: Eddy
authors.initials: E
authors.lastname: Fan
authors.affiliation: Research Center on Public Health, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Madotto
authors.affiliation: Division of Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ednan K
authors.initials: EK
authors.lastname: Bajwa
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Canada.|Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Brochard
authors.affiliation: Department of Anaesthesia, National University of Ireland, Galway University Hospitals, Galway, Ireland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Clarkson
authors.affiliation: Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Andres
authors.initials: A
authors.lastname: Esteban
authors.affiliation: Department of Anesthesiology, Emergency and Intensive Care Medicine Universitätsmedizin Göttingen, Robert Koch Strasse 40, 37073, Göttingen, Germany.
authors.forename: Luciano
authors.initials: L
authors.lastname: Gattinoni
authors.affiliation: Intensive Care Unit, The Canberra Hospital, Australian National University, Canberra, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: van Haren
authors.affiliation: Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Leo M
authors.initials: LM
authors.lastname: Heunks
authors.affiliation: Department of Anesthesiology, Yokohama City University Medical Center, Kanagawa, Japan.
authors.forename: Kiyoyasu
authors.initials: K
authors.lastname: Kurahashi
authors.affiliation: Division of Critical Care, Department of Anaesthesiology, Rikshospitalet Medical Centre, Oslo University Hospital, Oslo, Norway.
authors.forename: Jon Henrik
authors.initials: JH
authors.lastname: Laake
authors.affiliation: Section of Anesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Wellcome-Wolfson Institute for Experimental Medicine, Belfast and Regional Intensive Care Unit, Royal Victoria Hospital, Grosvenor Road, Belfast, Northern Ireland, UK.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: McAuley
authors.affiliation: Centre for Experimental Medicine, Queen's University of Belfast, Wellcome-Wolfson Institute for Experimental Medicine, Belfast and Regional Intensive Care Unit, Royal Victoria Hospital, Grosvenor Road, Belfast, Northern Ireland, UK.
authors.forename: Lia
authors.initials: L
authors.lastname: McNamee
authors.affiliation: Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nin
authors.affiliation: Department of Critical Care Medicine, Nanjing Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People's Republic of China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Qiu
authors.affiliation: SAPIENZA Università di ROMA, Dipartimento di Anestesia e Rianimazione, Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ranieri
authors.affiliation: Interdepartmental Division of Critical Care Medicine, University of Toronto and Program in Trauma, Emergency and Critical Care, Sunnybrook Health Sciences Center, Toronto, Canada.
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Rubenfeld
authors.affiliation: Division of Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Wrigge
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Canada.|Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.affiliation: Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Toronto, Canada.|Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pesenti
mesh_terms: D000328:Adult; D000368:Aged; D015897:Comorbidity; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000706:statistics & numerical data*; D012128:Respiratory Distress Syndrome / Q000401:mortality* / Q000628:therapy; D012307:Risk Factors; D012720:Severity of Illness Index; D013990:Tidal Volume; D016896:Treatment Outcome
keywords: Acute respiratory distress syndrome; Driving pressure; Patient outcome; Peak inspiratory pressure; Positive end-expiratory pressure