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Intensive Care Medicine
Published in: Intensive Care Medicine 5/2016

01-05-2016 | Systematic Review

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

Authors: G. Umberto Meduri, Lisa Bridges, Mei-Chiung Shih, Paul E. Marik, Reed A. C. Siemieniuk, Mehmet Kocak

Published in: Intensive Care Medicine | Issue 5/2016

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Abstract

Purpose

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

Methods

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.

Results

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).

Conclusions

Prolonged methylprednisolone treatment accelerates the resolution of ARDS, improving a broad spectrum of interrelated clinical outcomes and decreasing hospital mortality and healthcare utilization.
Appendix
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Metadata
Title
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
Authors
G. Umberto Meduri
Lisa Bridges
Mei-Chiung Shih
Paul E. Marik
Reed A. C. Siemieniuk
Mehmet Kocak
Publication date
01-05-2016
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 5/2016
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-015-4095-4

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