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

doi:10.1007/s00134-016-4571-5

Observational Study

. 2016 Dec;42(12):1865-1876.

doi: 10.1007/s00134-016-4571-5. Epub 2016 Oct 18.

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

John G Laffey^{1

2}, Giacomo Bellani^{3

4}, Tài Pham^{5

6

7}, Eddy Fan^{8

9}, Fabiana Madotto¹⁰, Ednan K Bajwa¹¹, Laurent Brochard^{12

13}, Kevin Clarkson¹⁴, Andres Esteban¹⁵, Luciano Gattinoni¹⁶, Frank van Haren¹⁷, Leo M Heunks¹⁸, Kiyoyasu Kurahashi¹⁹, Jon Henrik Laake²⁰, Anders Larsson²¹, Daniel F McAuley²², Lia McNamee²², Nicolas Nin¹⁵, Haibo Qiu²³, Marco Ranieri²⁴, Gordon D Rubenfeld²⁵, B Taylor Thompson¹¹, Hermann Wrigge²⁶, Arthur S Slutsky^{12

13

27}, Antonio Pesenti^{28

29}; LUNG SAFE Investigators and the ESICM Trials Group

Affiliations

¹ Departments of Anesthesia and Critical Care Medicine, Keenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, Canada. laffeyj@smh.ca.
² Departments of Anesthesia, Physiology, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada. laffeyj@smh.ca.
³ School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.
⁴ Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.
⁵ AP-HP, Hôpital Tenon, Unité de Réanimation médico-chirurgicale, Pôle Thorax Voies aériennes, Groupe hospitalier des Hôpitaux Universitaires de l'Est Parisien, Paris, France.
⁶ UMR 1153, Inserm, Sorbonne Paris Cité, ECSTRA Team, Université Paris Diderot, Paris, France.
⁷ UMR 915, Inserm, Université Paris Est Créteil, Créteil, France.
⁸ Department of Medicine, University Health Network, Mount Sinai Hospital, Toronto, Canada.
⁹ Interdepartmental Division of Critical Care Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
¹⁰ Research Center on Public Health, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
¹¹ Division of Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹² Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Canada.
¹³ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
¹⁴ Department of Anaesthesia, National University of Ireland, Galway University Hospitals, Galway, Ireland.
¹⁵ Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain.
¹⁶ Department of Anesthesiology, Emergency and Intensive Care Medicine Universitätsmedizin Göttingen, Robert Koch Strasse 40, 37073, Göttingen, Germany.
¹⁷ Intensive Care Unit, The Canberra Hospital, Australian National University, Canberra, Australia.
¹⁸ Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
¹⁹ Department of Anesthesiology, Yokohama City University Medical Center, Kanagawa, Japan.
²⁰ Division of Critical Care, Department of Anaesthesiology, Rikshospitalet Medical Centre, Oslo University Hospital, Oslo, Norway.
²¹ Section of Anesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
²² 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.
²³ Department of Critical Care Medicine, Nanjing Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People's Republic of China.
²⁴ SAPIENZA Università di ROMA, Dipartimento di Anestesia e Rianimazione, Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy.
²⁵ Interdepartmental Division of Critical Care Medicine, University of Toronto and Program in Trauma, Emergency and Critical Care, Sunnybrook Health Sciences Center, Toronto, Canada.
²⁶ Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, 04103, Leipzig, Germany.
²⁷ Department of Medicine, University of Toronto, Toronto, Canada.
²⁸ Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Toronto, Canada.
²⁹ Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.

PMID: 27757516
DOI: 10.1007/s00134-016-4571-5

Observational Study

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

John G Laffey et al. Intensive Care Med. 2016 Dec.

. 2016 Dec;42(12):1865-1876.

doi: 10.1007/s00134-016-4571-5. Epub 2016 Oct 18.

Authors

Affiliations

¹ Departments of Anesthesia and Critical Care Medicine, Keenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, Canada. laffeyj@smh.ca.
² Departments of Anesthesia, Physiology, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada. laffeyj@smh.ca.
³ School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.
⁴ Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.
⁵ AP-HP, Hôpital Tenon, Unité de Réanimation médico-chirurgicale, Pôle Thorax Voies aériennes, Groupe hospitalier des Hôpitaux Universitaires de l'Est Parisien, Paris, France.
⁶ UMR 1153, Inserm, Sorbonne Paris Cité, ECSTRA Team, Université Paris Diderot, Paris, France.
⁷ UMR 915, Inserm, Université Paris Est Créteil, Créteil, France.
⁸ Department of Medicine, University Health Network, Mount Sinai Hospital, Toronto, Canada.
⁹ Interdepartmental Division of Critical Care Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
¹⁰ Research Center on Public Health, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
¹¹ Division of Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹² Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Canada.
¹³ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
¹⁴ Department of Anaesthesia, National University of Ireland, Galway University Hospitals, Galway, Ireland.
¹⁵ Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain.
¹⁶ Department of Anesthesiology, Emergency and Intensive Care Medicine Universitätsmedizin Göttingen, Robert Koch Strasse 40, 37073, Göttingen, Germany.
¹⁷ Intensive Care Unit, The Canberra Hospital, Australian National University, Canberra, Australia.
¹⁸ Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
¹⁹ Department of Anesthesiology, Yokohama City University Medical Center, Kanagawa, Japan.
²⁰ Division of Critical Care, Department of Anaesthesiology, Rikshospitalet Medical Centre, Oslo University Hospital, Oslo, Norway.
²¹ Section of Anesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
²² 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.
²³ Department of Critical Care Medicine, Nanjing Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People's Republic of China.
²⁴ SAPIENZA Università di ROMA, Dipartimento di Anestesia e Rianimazione, Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy.
²⁵ Interdepartmental Division of Critical Care Medicine, University of Toronto and Program in Trauma, Emergency and Critical Care, Sunnybrook Health Sciences Center, Toronto, Canada.
²⁶ Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, 04103, Leipzig, Germany.
²⁷ Department of Medicine, University of Toronto, Toronto, Canada.
²⁸ Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Toronto, Canada.
²⁹ Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.

PMID: 27757516
DOI: 10.1007/s00134-016-4571-5

Erratum in

Correction to: Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study.
Laffey JG, Bellani G, Pham T, Fan E, Madotto F, Bajwa EK, Brochard L, Clarkson K, Esteban A, Gattinoni L, van Haren F, Heunks LM, Kurahashi K, Laake JH, Larsson A, McAuley DF, McNamee L, Nin N, Qiu H, Ranieri M, Rubenfeld GD, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Laffey JG, et al. Intensive Care Med. 2018 Jan;44(1):157-165. doi: 10.1007/s00134-017-4981-z. Intensive Care Med. 2018. PMID: 29138899

Abstract

Purpose: 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/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.

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

Trial registration: ClinicalTrials.gov NCT02010073.

Keywords: Acute respiratory distress syndrome; Driving pressure; Patient outcome; Peak inspiratory pressure; Positive end-expiratory pressure.

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Comment in

Some remaining important questions after LUNG SAFE : Discussion of "Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study".
Dreyfuss D, Gaudry S, Madotto F, Laffey JG. Dreyfuss D, et al. Intensive Care Med. 2017 Apr;43(4):598-599. doi: 10.1007/s00134-017-4706-3. Epub 2017 Feb 17. Intensive Care Med. 2017. PMID: 28213623 No abstract available.
Respiratory rate and peak inspiratory pressure, new targets from the LUNG SAFE study analysis or physiopathological artifacts?
Guervilly C, Forel JM, Papazian L. Guervilly C, et al. J Thorac Dis. 2017 Feb;9(2):225-227. doi: 10.21037/jtd.2017.02.45. J Thorac Dis. 2017. PMID: 28275464 Free PMC article. No abstract available.
Modifiable risk factors and the role of driving pressure in acute respiratory distress syndrome.
Keeley JA, Kim DY. Keeley JA, et al. J Thorac Dis. 2017 May;9(5):E487-E488. doi: 10.21037/jtd.2017.03.140. J Thorac Dis. 2017. PMID: 28616317 Free PMC article. No abstract available.

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References

1. N Engl J Med. 1998 Feb 5;338(6):347-54 - PubMed
1. N Engl J Med. 2013 Jun 6;368(23):2159-68 - PubMed
1. Anaesthesia. 1997 Jan;52(1):9-14 - PubMed
1. Intensive Care Med. 2004 Oct;30(10):1960-3 - PubMed
1. JAMA. 2016 Feb 23;315(8):788-800 - PubMed

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[1] N Engl J Med. 1998 Feb 5;338(6):347-54 - PubMed

[2] N Engl J Med. 1998 Feb 5;338(6):347-54 - PubMed

[3] N Engl J Med. 2013 Jun 6;368(23):2159-68 - PubMed

[4] N Engl J Med. 2013 Jun 6;368(23):2159-68 - PubMed

[5] Anaesthesia. 1997 Jan;52(1):9-14 - PubMed

[6] Anaesthesia. 1997 Jan;52(1):9-14 - PubMed

[7] Intensive Care Med. 2004 Oct;30(10):1960-3 - PubMed

[8] Intensive Care Med. 2004 Oct;30(10):1960-3 - PubMed

[9] JAMA. 2016 Feb 23;315(8):788-800 - PubMed

[10] JAMA. 2016 Feb 23;315(8):788-800 - PubMed

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

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