|Steroids Do Not Prolong Survival in Intensive
Care Patients with ARDS on Life Support, Finds NHLBI Study
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.
For more information:
Acute Respiratory Distress Syndrome (for patients and the public)
ARDS Clinical Research Network
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.
Part of the National Institutes of Health, the National Heart,
Lung, and Blood Institute (NHLBI) plans, conducts, and supports
research related to the causes, prevention, diagnosis, and treatment
of heart, blood vessel, lung, and blood diseases; and sleep disorders.
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on women and heart disease, healthy weight for children, and
other topics. NHLBI press releases and other materials are available
online at: www.nhlbi.nih.gov.
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