Corticosteroids do not improve survival in patients with late-stage acute respiratory distress syndrome (ARDS), according to new results from the ARDS Clinical Research Network of the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. The study is the first multi-center randomized clinical trial to evaluate the effects of moderate doses of steroids in ARDS patients when treatment is started 7 days or more after the onset of the condition.
ARDS is a sudden, life-threatening lung condition that affects about 150,000 people in the United States each year. ARDS develops in patients who are critically ill with other diseases such as pneumonia or sepsis (severe and widespread bacterial infection), or who have sustained major injuries that result in severe fluid building up in both lungs, leading to breathing failure. An estimated 30 percent to 50 percent of ARDS patients die. Results of the Late Steroid Rescue Study appear in the April 20, 2006, issue of the New England Journal of Medicine.
"These findings provide important information to help us determine the safest and most effective ways to care for patients with this devastating condition," said NHLBI Director Elizabeth G. Nabel, MD. "Whether and how to use steroids to treat ARDS patients have been important questions for years. We now have better evidence of the effect of this treatment to help clinicians and patients make more informed decisions."
There is no specific drug treatment for ARDS. The focus of care is to get enough oxygen into the blood until the lungs are functioning again. Patients are placed in the intensive care unit and supported with mechanical ventilators and fluids. Some patients recover and can breathe on their own within a week or so. Others might need to be on mechanical support to help with breathing for longer periods of time, but they can develop long-term complications from ventilator use or other treatments.
Because ARDS is related to inflammation in the lung, steroids are sometimes used in the hopes of helping the lungs heal. Earlier small or observational studies have suggested that moderate doses of steroids given 7 or more days after the onset of ARDS might improve lung function and increase survival. But a larger randomized clinical trial -- considered the gold standard in medical research -- was needed to determine whether moderate doses of steroids are beneficial for patients with late-stage ARDS.
The new study began in 1997 and involved 180 patients and researchers from 25 hospitals in the U.S. Eligible ARDS patients who had been on mechanical ventilators for 7 to 28 days were randomly selected to receive either a moderate dose of methylprednisolone sodium succinate or placebo intravenously. They were followed for 180 days. Patients or their surrogates provided informed consent to participate in the study.
Overall, there was no difference in mortality at 60 days or 180 days between patients treated with steroids and those who were not treated with steroids. However, when researchers reviewed the data for a small subgroup (23) of patients who began steroid treatment after two weeks or more of ARDS, they found that these participants had a significantly higher risk of death at 60 days and at 180 days than a comparable number in the control group. Although the effect of steroids on survival was linked to how long the patients had ARDS before starting treatment, the researchers report that it remains unclear if there is optimal timing for steroid treatment during the course of ARDS.
The researchers noted some early benefits to steroid treatment, however, which appeared to reduce lung inflammation. They also found that the treatment did not contribute to more secondary infections -- a common side effect of steroids, which are known to suppress the immune system. Participants treated with steroids were able to wean off the mechanical ventilator earlier than participants who did not receive steroids (14 days compared to 27 days), and had fewer days of intensive care during the first 28 days of the study.
However, participants in the treatment group had to return to ventilator use more frequently than patients given placebo (28 percent versus 9 percent). In addition, participants who were treated with the steroids were significantly more likely to develop neuromuscular complications, such as severe muscle weakness that often requires intensive and prolonged rehabilitation, compared to those who did not receive steroid treatment.
"Whether the positive effects of moderate doses of steroids seen in some ARDS patients outweigh the risks of neuromuscular complications is an issue that physicians, patients, and the patients' families will need to grapple with," said Gordon Bernard, MD, director of the Division of Allergy, Pulmonary and Critical Care Medicine at Vanderbilt University in Nashville, and chair of the Steering Committee for the NHLBI ARDS Clinical Research Network.
"The results clearly show that steroids do not prolong survival when given to patients with late-stage ARDS," he added. "We therefore urge great caution in treating these patients with steroids."
"The most effective way to gather enough data on critically ill patients to be meaningful is through the collaboration of several clinical centers," noted Andrea Harabin, PhD, NHLBI project officer for the NHLBI ARDS Clinical Research Network. "Through clinical networks such as NHLBI's ARDS Clinical Research Network, we are able to support rigorous research studies that ultimately direct the best care options for these patients."
The NHLBI ARDS Clinical Research Network was formed in 1994 to hasten the development of effective therapies for ARDS by evaluating new treatments and management practices. The network's first clinical trial, a ventilator management study, was stopped early in 1999 when data showed that death rates were lowered by approximately 25 percent among patients receiving small breaths of air from the mechanical ventilator compared to patients receiving large breaths of air, which were the standard of care at that time. The results have been heralded as signaling a new era of research and management of the critically ill.
ARDS Clinical Research Network scientists have also recently completed studies on the use of pulmonary artery catheter compared to a less invasive alternative, the central venous catheter, and the use of conservative versus liberal fluid management. Results are expected to be released in several weeks.
To interview Dr. Harabin about this study, please contact the NHLBI Communications Office, (301) 496-4236 or firstname.lastname@example.org. To reach Dr. Bernard, please contact John Howser at the Vanderbilt University Medical School Public Affairs Office at (615) 322-4747.