N Engl J Med. 2006 Apr 20;354(16):1671-84.

Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT,
Ancukiewicz M; National Heart, Lung, and Blood Institute Acute Respiratory
Distress Syndrome (ARDS) Clinical Trials Network.

Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, Box
359762, 325 Ninth Ave., Seattle, WA 98104, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

BACKGROUND: Persistent acute respiratory distress syndrome (ARDS) is
characterized by excessive fibroproliferation, ongoing inflammation, prolonged
mechanical ventilation, and a substantial risk of death. Because previous reports
suggested that corticosteroids may improve survival, we performed a multicenter,
randomized controlled trial of corticosteroids in patients with persistent ARDS.
METHODS: We randomly assigned 180 patients with ARDS of at least seven days'
duration to receive either methylprednisolone or placebo in a double-blind
fashion. The primary end point was mortality at 60 days. Secondary end points
included the number of ventilator-free days and organ-failure-free days,
biochemical markers of inflammation and fibroproliferation, and infectious
complications. RESULTS: At 60 days, the hospital mortality rate was 28.6 percent
in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and
29.2 percent in the methylprednisolone group (95 percent confidence interval,
20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95
percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent
confidence interval, 22.8 to 41.7 percent; P=1.0), respectively.
Methylprednisolone was associated with significantly increased 60- and 180-day
mortality rates among patients enrolled at least 14 days after the onset of ARDS.
Methylprednisolone increased the number of ventilator-free and shock-free days
during the first 28 days in association with an improvement in oxygenation,
respiratory-system compliance, and blood pressure with fewer days of vasopressor
therapy. As compared with placebo, methylprednisolone did not increase the rate
of infectious complications but was associated with a higher rate of
neuromuscular weakness. CONCLUSIONS: These results do not support the routine use
of methylprednisolone for persistent ARDS despite the improvement in
cardiopulmonary physiology. In addition, starting methylprednisolone therapy more
than two weeks after the onset of ARDS may increase the risk of death.
(ClinicalTrials.gov number, NCT00295269.). Copyright 2006 Massachusetts Medical
Society.