Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature

Objective: To compare the design and results of randomized trials investigating prolonged glucocorticoid treatment (>= 7 days) in patients with acute lung injury-acute respiratory distress syndrome (ALI-ARDS), and review factors affecting response to therapy, including the role of secondary prevention. Design: Trials were retrieved from the Cochrane Central Register of Controlled Trials (CENTRAL). Two investigators collected data on study characteristics, treatment intervention, and outcomes. The methodological quality of trials was determined and data were analyzed with Review Manager 4.2.3. Measurements and results: Five selected trials (n = 518) consistently reported significant improvement in gas exchange, reduction in markers of inflammation, and decreased duration of mechanical ventilation and intensive care unit stay (all p < 0.05). Two early small clinical trials showed marked reductions in the relative risk (RR) of death with glucocorticoid therapy (RR = 0.14, 95% CI 0.04-0.53; p = 0.004, I-2 = 0%). Three subsequent larger trials, when combined, although nominally beneficial, did not reproduce the marked reductions observed in the earlier trials (RR = 0.84; 95% CI 0.68-1.03; p = 0.09, I-2 = 9.1%), but achieved a distinct reduction in the RR of death in the larger subgroup of patients (n = 400) treated before day 14 of ARDS [82/214 (38%) vs. 98/186 (52.5%), RR = 0.78; 95% CI 0.64-0.96; p = 0.02, I-2 = 0%]. Conclusions: Prolonged glucocorticoid treatment substantially and significantly improves meaningful patient-centered outcome variables, and has a distinct survival benefit when initiated before day 14 of ARDS.