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Are Corticosteroids Beneficial in ARDS?

In a large U.S. trial, steroid therapy was not associated with a lower mortality rate.

In 1998, a very small randomized trial suggested that a prolonged course of moderate-dose corticosteroid therapy, starting after at least 1 week of mechanical ventilation, was beneficial for patients with acute respiratory distress syndrome (ARDS; Journal Watch Jul 21 1998). Finally, a larger randomized multicenter U.S. trial has been completed.

The investigators enrolled 180 mechanically ventilated patients with ARDS of least 7 days’ duration, with persistent infiltrates and PaO₂:FIO₂ ratios less than 200. Patients received either intravenous methylprednisolone (starting with 0.5 mg/kg every 6 hours for 14 days and then tapered during the next several weeks) or placebo.

Mortality rates were identical in the 2 groups — 29% at day 60 and 32% at day 180. Among the 132 patients who were enrolled 7 to 13 days after onset of ARDS, the 180-day mortality rate was slightly lower with methylprednisolone than with placebo (27% vs. 39%, P=0.14); in contrast, among the 48 patients who were enrolled at least 2 weeks after onset of ARDS, the mortality rate was higher with methylprednisolone (44% vs. 12%, P=0.01). Several early secondary outcomes favored the methylprednisolone group (e.g., ventilator-free days during the first 28 days), but significantly more methylprednisolone recipients than placebo recipients eventually resumed mechanical ventilation (28% vs. 9%). Infectious complications were not more common in the methylprednisolone group, but methylprednisolone recipients were more likely to develop serious neuropathy or myopathy.

Comment: In this important trial, steroid therapy did not lower 2- or 6-month mortality rates in patients with persistent ARDS. One possible explanation is that early benefits from steroids were negated by steroid-induced neuromuscular weakness when steroids were started too late in the illness. An open question is whether there is a narrow time window — e.g., the second week of illness — during which initiation of steroid therapy is beneficial.

— Allan S. Brett, MD

Published in Journal Watch General Medicine April 21, 2006

Citation(s):

The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006 Apr 20; 354:1671-84.

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