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A Randomized Controlled Trial

G. Umberto Meduri, MD; A. Stacey Headley, MD; Emmel Golden, MD; Stephanie J. Carson, RN; Reba A. Umberger, RN; Tiffany Kelso, PharmD; Elizabeth A. Tolley, PhD

JAMA. 1998;280:159-165.

Context.— No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome (ARDS) and mortality remains greater than 50%.

Objective.— To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS.

Design.— Randomized, double-blind, placebo-controlled trial.

Setting.— Medical intensive care units of 4 medical centers.

Participants.— Twenty-four patients with severe ARDS who had failed to improve lung injury score (LIS) by the seventh day of respiratory failure.

Interventions.— Sixteen patients received methylprednisolone and 8 received placebo. Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment.

Main Outcome Measures.— Primary outcome measures were improvement in lung function and mortality. Secondary outcome measures were improvement in multiple organ dysfunction syndrome (MODS) and development of nosocomial infections.

Results.— Physiological characteristics at the onset of ARDS were similar in both groups. At study entry (day 9 [SD, 3] of ARDS), the 2 groups had similar LIS, ratios of PaO₂ to fraction of inspired oxygen (FIO₂), and MODS scores. Changes observed by study day 10 for methylprednisolone vs placebo were as follows: reduced LIS (mean [SEM], 1.7 [0.1] vs 3.0 [0.2]; P<.001); improved ratio of PaO₂ to FIO₂ (mean [SEM], 262 [19] vs 148 [35]; P<.001); decreased MODS score (mean [SEM], 0.7 [0.2] vs 1.8 [0.3]; P<.001); and successful extubation (7 vs 0; P=.05). For the treatment group vs the placebo group, mortality associated with the intensive care unit was 0 (0%) of 16 vs 5 (62%) of 8 (P=.002) and hospital-associated mortality was 2 (12%) of 16 vs 5 (62%) of 8 (P=.03). The rate of infections per day of treatment was similar in both groups, and pneumonia was frequently detected in the absence of fever.

Conclusions.— In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.

From the University of Tennessee Lung Research Program, the Baptist Memorial Hospitals (Drs Meduri, Headley, and Golden and Mss Carson and Umberger), the Veterans Affairs Medical Center (Dr Meduri), and the Departments of Medicine (Drs Meduri, Headley, and Golden and Mss Carson and Umberger) and Preventive Medicine (Dr Tolley), College of Medicine, and the College of Pharmacy (Dr Kelso), University of Tennessee, Memphis.

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