Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.
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.).
Steinberg
Kenneth P
KP
Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, Box 359762, 325 Ninth Ave., Seattle, WA 98104, USA. steinkp@u.washington.edu
Hudson
Leonard D
LD
Goodman
Richard B
RB
Hough
Catherine Lee
CL
Lanken
Paul N
PN
Hyzy
Robert
R
Thompson
B Taylor
BT
Ancukiewicz
Marek
M
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D003131:Combined Modality Therapy; D016638:Critical Illness; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017052:Hospital Mortality; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007275:Injections, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D018908:Muscle Weakness / Q000139:chemically induced; D010100:Oxygen / Q000097:blood; D011014:Pneumonia / Q000209:etiology; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012772:Shock, Septic / Q000209:etiology; D016019:Survival Analysis; D016896:Treatment Outcome
D001786:Blood Glucose; D005938:Glucocorticoids; D010100:Oxygen; D008775:Methylprednisolone