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Am Fam Physician. 1998;58(8):1872-1874

Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure and is associated with a mortality rate higher than 50 percent. Previous studies have not shown a benefit from a short course of treatment with high-dose methylprednisolone in patients with ARDS. However, long-term therapy with this agent may improve lung function and general outcome if treatment is started before end-stage fibrosis develops. Meduri and associates conducted a randomized, double-blind, placebo-controlled trial to evaluate the safety and effectiveness of long-term therapy with methylprednisolone in improving lung function and decreasing mortality in patients with unresolving ARDS.

Patients in an adult intensive care unit were included in the study if they had been diagnosed with ARDS, had no evidence of untreated infection and had been on mechanical ventilation for at least seven days with a lung injury score (LIS) of at least 2.5 and less than one point of improvement since the original diagnosis of ARDS. Patients were excluded if they had ARDS for three weeks or more, had extensive burns or a history of recent major gastrointestinal bleeding, were pregnant or terminally ill, or required methylprednisolone therapy for another medical condition. Patients were randomized to receive either a placebo or methylprednisolone in a loading dose of 2 mg per kg by intravenous push every six hours, then a single oral daily dose once oral intake was restored. For the next two weeks, patients received 2 mg per kg of methylprednisolone daily. The daily doses were reduced by one half every seven days until patients were taking only 0.125 mg per kg on the last two days of the study. Patients whose LIS failed to improve after 10 days were crossed over to the other intervention. Patients were also monitored for the development of infections or gastrointestinal bleeding. Improvements in lung function and mortality were the main outcome measures.

Twenty-four patients were included in the study. Sixteen patients were randomized to the methylprednisolone group and eight to the placebo group. All patients in the treatment group showed significant improvement in lung function after 10 days, including ratio of PaO2 (partial pressure of arterial oxygen) to FiO2 (percentage of inspired oxygen), LIS, static lung compliance and mean pulmonary artery pressure. None of these variables improved in the placebo group during the first 10 days of treatment; four of the control subjects crossed over to the treatment group because of failure to improve. Two patients in the placebo group improved by day 10, and two patients died. Those who crossed over from placebo to methylprednisolone had a significantly higher mortality rate than those who had received methylprednisolone from the beginning of the study. Eighty-seven percent of the patients in the methylprednisolone group survived to discharge from the intensive care unit, compared with 37 percent of patients in the placebo group.

The authors conclude that lung injury scores and mortality rates can be improved in patients with ARDS through the prolonged use of methylprednisolone therapy.

In a related editorial, Brun-Buisson and Brochard note that the sample size in this study was quite small, making the confidence interval wide. Larger trials are needed to confirm the findings of this study and to determine the optimal dosage, duration and timing of methylprednisolone therapy in patients hospitalized with ARDS.

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Copyright © 1998 by the American Academy of Family Physicians.

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