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.
OBJECTIVE
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.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Memphis Veterans Affairs Medical Center (111), 1030 Jefferson Avenue, Suite Room #CW444, Memphis, TN, 38104, USA. gmeduri@uthsc.edu.
G Umberto
GU
Meduri
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Memphis Veterans Affairs Medical Center (111), 1030 Jefferson Avenue, Suite Room #CW444, Memphis, TN, 38104, USA.
Lisa
L
Bridges
Department of Veterans Affairs, Cooperative Studies Program Coordinating Center, Palo Alto, CA, USA.|Department of Health Research and Policy, Stanford University, Stanford, CA, USA.
Mei-Chiung
MC
Shih
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Eastern Virginia Medical School, Norfolk, VA, USA.
Paul E
PE
Marik
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.|Department of Medicine, University of Toronto, Toronto, ON, Canada.
Reed A C
RAC
Siemieniuk
Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
Mehmet
M
Kocak
D005938:Glucocorticoids / Q000627:therapeutic use*; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008775:Methylprednisolone / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000401:mortality
D005938:Glucocorticoids; D008775:Methylprednisolone
Adult respiratory distress syndrome; Glucocorticoid treatment; Mechanical ventilation; Survival