Background Persistent acute respiratory distress syndrome (ARDS)is characterized by excessive fibroproliferation, ongoing inflammation,prolonged mechanical ventilation, and a substantial risk ofdeath. Because previous reports suggested that corticosteroidsmay improve survival, we performed a multicenter, randomizedcontrolled trial of corticosteroids in patients with persistentARDS.
Methods We randomly assigned 180 patients with ARDS of at leastseven days' duration to receive either methylprednisolone orplacebo in a double-blind fashion. The primary end point wasmortality at 60 days. Secondary end points included the numberof ventilator-free days and organ-failure–free days, biochemicalmarkers of inflammation and fibroproliferation, and infectiouscomplications.
Results At 60 days, the hospital mortality rate was 28.6 percentin the placebo group (95 percent confidence interval, 20.3 to38.6 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 confidenceinterval, 23.2 to 42.0 percent) and 31.5 percent (95 percentconfidence interval, 22.8 to 41.7 percent; P=1.0), respectively.Methylprednisolone was associated with significantly increased60- and 180-day mortality rates among patients enrolled at least14 days after the onset of ARDS. Methylprednisolone increasedthe number of ventilator-free and shock-free days during thefirst 28 days in association with an improvement in oxygenation,respiratory-system compliance, and blood pressure with fewerdays of vasopressor therapy. As compared with placebo, methylprednisolonedid not increase the rate of infectious complications but wasassociated with a higher rate of neuromuscular weakness.
Conclusions These results do not support the routine use ofmethylprednisolone for persistent ARDS despite the improvementin cardiopulmonary physiology. In addition, starting methylprednisolonetherapy more than two weeks after the onset of ARDS may increasethe risk of death. (ClinicalTrials.gov number, NCT00295269
[ClinicalTrials.gov]
.)
Source Information
The members of the Writing Committee (Kenneth P. Steinberg, M.D., Leonard D. Hudson, M.D., Richard B. Goodman, M.D., and Catherine Lee Hough, M.D., University of Washington, Seattle; Paul N. Lanken, M.D., University of Pennsylvania, Philadelphia; Robert Hyzy, M.D., University of Michigan, Ann Arbor; and B. Taylor Thompson, M.D., and Marek Ancukiewicz, Ph.D., Massachusetts General Hospital, Boston) of the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network assume responsibility for the overall content and integrity of the article.
Address reprint requests to Dr. Steinberg at the Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, Box 359762, 325 Ninth Ave., Seattle, WA 98104, or at steinkp{at}u.washington.edu.
Corticosteroids in ARDS
Marik P., Pastores S., Annane D., Speich R., Schmid C., Stocker R., Okamoto H., DiNubile M. J., Steinberg K. P., Hudson L. D., Thompson B. T., the NHBLI ARDS Clinical Trials Network
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N Engl J Med 2006;
355:316-319, Jul 20, 2006.
Correspondence
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