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Spontaneous Breathing in Early Acute Respiratory Distress Syndrome

Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

van Haren, Frank, MD, PhD1,2,3; Pham, Tài, MD4,5,6; Brochard, Laurent, MD, HDR7,8; Bellani, Giacomo, MD, PhD9,10; Laffey, John, MD11,12; Dres, Martin, MD, PhD13,14; Fan, Eddy, MD, PhD15,16; Goligher, Ewan C., MD, PhD17,18; Heunks, Leo, MD, PhD19; Lynch, Joan, MPS20,21; Wrigge, Hermann, MD, PhD22,23; McAuley, Danny, MD, PhD24,25 and the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) and the European Society of Intensive Care Medicine (ESICM) Trials Group

doi: 10.1097/CCM.0000000000003519
Clinical Investigation: PDF Only

Objectives: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity.

Design: Planned secondary analysis of a prospective, observational, multicentre cohort study.

Setting: International sample of 459 ICUs from 50 countries.

Patients: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days.

Interventions: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation.

Measurements and Main Results: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92–1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93–1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0–22] vs 8 [0–20]; p = 0.014) and shorter duration of ICU stay (11 [6–20] vs 12 [7–22]; p = 0.04).

Conclusions: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

1Intensive Care Unit, Canberra Hospital, Woden, ACT, Australia.

2Australian National University, Medical School, Canberra, ACT, Australia.

3University of Canberra, Faculty of Health, Canberra, ACT, Australia.

4AP-HP, Hôpital Tenon, Unité de Réanimation médico-chirurgicale, Pôle Thorax Voies aériennes, Groupe hospitalier des Hôpitaux Universitaires de l’Est Parisien, Paris, France.

5UMR 1153, Inserm, Sorbonne Paris Cité, ECSTRA Team, Université Paris Diderot, Paris, France.

6UMR 915, Inserm, Université Paris Est Créteil, Créteil, France.

7Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, ON, Canada.

8Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.

9School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.

10Department of Emergency and Intensive Care, San Gerardo Hospital, Monza, Italy.

11Departments of Anesthesia and Critical Care Medicine, Keenan Research Centre for Biomedical Science, St Michael’s Hospital, Toronto, ON, Canada.

12Departments of Anesthesia, Physiology, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.

13Keenan Centre for Biomedical Research, St. Michael’s Hospital, Toronto, ON, Canada.

14Respiratory and Critical Care Department, Pitié Salpetriere Hospital, APHP, Paris, France.

15Department of Medicine, University Health Network, Mount Sinai Hospital, Toronto, ON, Canada.

16Interdepartmental Division of Critical Care Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.

17Division of Respirology, Department of Medicine, University Health Network, Toronto, ON, Canada.

18Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.

19Department of Intensive Care Medicine, VU University Medical Centre Amsterdam, The Netherlands.

20ICU, Liverpool Hospital, Sydney, NSW, Australia.

21Critical Care Research in Collaboration and Evidence Translation (CCRICET), Western Sydney University and Liverpool Hospital, Sydney, NSW, Australia.

22Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany.

23Department of Anaesthesiology, Intensive Care and Emergency Medicine, Bergmannstrost Hospital, Halle, Germany.

24Centre for Experimental Medicine, Queen’s University Belfast, 97 Lisburn Road, Belfast, Northern Ireland.

25Regional Intensive Care Unit, Royal Victoria Hospital, 274 Grosvenor Road, Belfast, Northern Ireland.

European Society of Intensive Care Medicine, 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 article; or decision to submit the article for publication.

Drs. van Haren and Pham are co-first authors.

Drs. van Haren, Pham, Brochard, Bellani, Laffey, Wrigge, McAuley conceptualized and designed the article. All authors analyzed and interpreted the article; drafted and revised the article for important intellectual content; and approved the final article.

Members of the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) steering committee, national coordinators and site investigators are listed in the supplemental data (Supplemental Digital Content 1, http://links.lww.com/CCM/E146).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, 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. The ESICM provided support in data collection and study coordination.

Dr. Brochard received funding from Medtronic Covodien, Air Liquide, and Fisher Paykel, and he received equipment from Philips. Dr. Heunks’ institution received funding from European Respiratory Society and Ventfree, and he received funding from Maquet (speaker’s fee). Dr. Wrigge received funding from Dräger Medical, Merck Sharp & Dohme, and InfectoPharm. Dr. McAuley’s institution received funding from National Institute for Health Research, Wellcome Trust and other grant funders; and he received funding from Bayer/GlaxoSmithKline, and Boehringer Ingelheim/Peptinnovate. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: fvanharen@me.com

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