Intensive Care Medicine

, Volume 42, Issue 5, pp 829–840 | Cite as

Prolonged glucocorticoid treatment is associated with improved ARDS outcomes: analysis of individual patients’ data from four randomized trials and trial-level meta-analysis of the updated literature

  • G. Umberto MeduriEmail author
  • Lisa Bridges
  • Mei-Chiung Shih
  • Paul E. Marik
  • Reed A. C. Siemieniuk
  • Mehmet Kocak
Systematic Review



To investigate the effect of prolonged glucocorticoid treatment for patients with acute respiratory distress syndrome (ARDS).


We conducted two sets of intention-to-treat analyses: (1) a primary analysis of individual patients’ data (IPD) of four randomized controlled trials (RCTs) which investigated methylprednisolone treatment (n = 322) and (2) a trial-level meta-analysis incorporating four additional RCTs which investigated hydrocortisone treatment in early ARDS (n = 297). We standardized definitions to derive outcomes in all datasets. The primary outcome for the IPD analysis was time to achieving unassisted breathing (UAB) by study day 28. Secondary outcomes included mechanical ventilation (MV) and intensive care unit (ICU)-free days, hospital mortality, and time to hospital mortality by day 28.


By study day 28, compared to the placebo group, the methylprednisolone group had fewer patients who died before achieving UAB (12 vs. 29 %; p < 0.001) and more patients who achieved UAB (80 vs. 50 %; p < 0.001). In the methylprednisolone group, time to achieving UAB was shorter [hazard ratio 2.59, 95 % confidence interval (CI) 1.95–3.43; p < 0.001], and hospital mortality was decreased (20 vs. 33 %; p = 0.006), leading to increased MV (13.3 ± 11.8 vs. 7.6 ± 5.7; p < 0.001) and ICU-free days (10.8 ± 0.71 vs. 6.4 ± 0.85; p < 0.001). In those patients randomized before day 14 of ARDS onset, the trial-level meta-analysis indicated decreased hospital mortality (36 vs. 49 %; risk ratio 0.76, 95 % CI 0.59–0.98, I 2 = 17 %, p = 0.035; moderate certainty). Treatment was not associated with increased risk for infections (risk ratio 0.77, 95 % CI 0.56–1.08, I 2 = 26 %; p = 0.13; moderate certainty).


Prolonged methylprednisolone treatment accelerates the resolution of ARDS, improving a broad spectrum of interrelated clinical outcomes and decreasing hospital mortality and healthcare utilization.


Adult respiratory distress syndrome Glucocorticoid treatment Mechanical ventilation Survival 



The NHLBI ARDS network graciously provided and assisted with the ARDSnet02 Dataset on the “Efficacy of Corticosteroids as Rescue Therapy for the Late Phase of Acute Respiratory Distress Syndrome (LaSRS)”. Dr. Nasef Rezk (Mansoura University, Egypt) graciously provided unpublished data of his publication. Dr. Jeff Zuber (Memphis Veterans Affairs Medical Center) for assistance in organizing the IPD files.

Compliance with ethical standards

Conflicts of interest

The authors have no competing interests to declare or any real or perceived financial interest in any product or commodity mentioned in this paper.


This material is the result of work supported with the resources and use of facilities at the Memphis VA Medical Center. The contents of this commentary do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Funding for the respective trials was disclosed in the original publications. None of the sponsors had any role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, the preparation, review, or approval of the report, or the decision to submit the manuscript for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Supplementary material

134_2015_4095_MOESM1_ESM.doc (1.9 mb)
Supplementary material 1 (DOC 1993 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • G. Umberto Meduri
    • 1
    Email author
  • Lisa Bridges
    • 1
  • Mei-Chiung Shih
    • 2
    • 3
  • Paul E. Marik
    • 4
  • Reed A. C. Siemieniuk
    • 5
    • 6
  • Mehmet Kocak
    • 7
  1. 1.Division of Pulmonary, Critical Care and Sleep Medicine, Department of MedicineMemphis Veterans Affairs Medical Center (111)MemphisUSA
  2. 2.Department of Veterans AffairsCooperative Studies Program Coordinating CenterPalo AltoUSA
  3. 3.Department of Health Research and PolicyStanford UniversityStanfordUSA
  4. 4.Division of Pulmonary and Critical Care Medicine, Department of MedicineEastern Virginia Medical SchoolNorfolkUSA
  5. 5.Department of Clinical Epidemiology and BiostatisticsMcMaster UniversityHamiltonCanada
  6. 6.Department of MedicineUniversity of TorontoTorontoCanada
  7. 7.Department of Preventive MedicineUniversity of Tennessee Health Science CenterMemphisUSA

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