The NHLBI Halts Study of Concentrated
Saline for Patients with Shock Due to Lack of Survival Benefit
The National Heart, Lung, and Blood Institute (NHLBI) of the
National Institutes of Health has stopped a clinical trial studying
the benefits and safety of administering a highly concentrated
form of saline solution in the ambulance (before hospital arrival)
to trauma patients suffering from shock due to severe bleeding.
The trial was stopped because patients who received the concentrated
saline solutions were no more likely to survive than those who
received a normal saline solution. A parallel study of concentrated
saline for traumatic brain injury without shock continues.
Typically, in the crucial early minutes before blood transfusions
can be safely administered in the hospital, trauma patients receive
normal saline solution intravenously in the field to compensate
for blood loss and buy time. Concentrated saline solution is believed
to compensate for blood loss more effectively, lessen excessive
inflammatory responses, and prevent brain swelling.
The trials of concentrated saline solutions are conducted through
a network of clinical research sites in the United States and Canada
called the Resuscitation Outcomes Consortium (ROC). A major focus
of the ROC is to conduct randomized trials of promising new treatments
for severe traumatic injury in real-world settings.
“Survival from traumatic injury is a critical public health issue
and the large clinical trials under way in this effort are needed
to improve the treatment of patients. Of course, it is always disappointing
when new therapies, such as concentrated saline for shock, fail
to offer added benefit to patients. However, we look forward to
results from the other ongoing studies that are part of this important
research consortium,” said Elizabeth G. Nabel, M.D., director of
the NHLBI, the lead federal sponsor of the research effort.
The NHLBI suspended enrollment into the concentrated saline (hypertonic)
shock study on Aug. 25, 2008, due to concerns raised by ROC’s Data
and Safety Monitoring Board (DSMB), an independent group monitoring
the study. In the shock trial, the DSMB observed no difference
among the treatment groups in 28-day mortality. However, more of
the patients receiving hypertonic saline died before reaching the
hospital or in the emergency department, while more of the patients
receiving normal saline died during the remainder of the 28-day
The DSMB requested further analysis of these observations. The
additional analysis looked at in-hospital data (following saline
administration in the field) from 545 patients in the largest enrolling
hospital from each site. The results, presented to the DSMB on
Feb. 25, 2009, confirmed the previous findings that deaths occurred
earlier in patients who received hypertonic saline and that there
was no significant difference in cumulative mortality between the
hypertonic and normal saline groups at 28 days. However, the new
analysis did not fully explain the mortality findings. The investigators
are completing analyses of these results and will submit them for
publication in a peer-reviewed scientific journal.
Although there were no similar concerns about earlier mortality
in the traumatic brain injury trial, this trial was also temporarily
and voluntarily suspended last August so that emergency medical
service (EMS) personnel could be retrained to enroll only brain
injury patients, not those who would have been eligible for the
shock study. The traumatic brain injury study resumed in late November
ROC is a research network of nine major regional clinical centers
in the United States and Canada focusing on treating patients who
collapse with cardiac arrest or with life-threatening traumatic
injury before they reach the hospital. Under the various research
protocols, participating EMS providers give standard emergency
care to all patients, with some patients eligible to receive the
experimental treatment in addition to usual care. The clinical
trials are conducted under strict FDA and well defined Canadian
guidelines that allow for patients in life-threatening situations
to participate in research under an exception to informed consent,
according to U.S. and Canadian law.
In both the shock and traumatic brain injury ROC hypertonic saline
trials, patients were randomly selected to receive either approximately
8 ounces of intravenous normal saline, which has nearly the same
concentration of salt as blood and is considered standard care;
approximately 8 ounces of hypertonic saline, which has a higher
salt concentration; or about 8 ounces of hypertonic saline with
dextran, a carbohydrate which can prolong the effect of the hypertonic
saline. The stopped trauma shock study tested whether hypertonic
solutions improve survival by 28 days after injury, compared to
usual care with normal saline.
The now-resumed trial of brain- injured patients continues to
investigate whether the hypertonic solutions improve both survival
and brain function in patients 6 months after traumatic injury.
As the traumatic brain injury study continues, ROC investigators
hope that hypertonic saline will prove beneficial for this application. "Patients
with traumatic brain injury have significant swelling of the brain,
and hypertonic fluids are known to be very effective at reducing
this swelling, which may improve recovery," said Eileen Bulger,
M.D., the University of Washington, Seattle, and co-principal investigator
of the hypertonic saline studies.
"Hypertonic saline has also been shown to improve blood
flow to the brain after injury and to protect nerve cells from
increased intracranial pressure," added David Hoyt, M.D.,
University of California, Irvine, the other co-principal investigator
of the hypertonic saline studies.
The NHLBI is the lead sponsor of the ROC studies with additional
funding provided by the NIH’s National Institute of Neurological
Disorders and Stroke, the Institute of Circulatory and Respiratory
Health of the Canadian Institutes of Health Research, U.S. Army
Medical Research & Materiel Command, American Heart Association,
Defence Research and Development Canada, and the Heart and Stroke
Foundation of Canada.
For additional information about ROC, see: https://roc.uwctc.org/tiki/tiki-index.php.
To interview an NHLBI spokesperson, contact the NHLBI Communications
Office at 301-496-4236 or at email@example.com.
To interview Dr. Bulger, contact Susan Gregg-Hanson at 206-616-6730;
to interview Dr. Hoyt, contact John Murray /Tom Vasich at 714-456-7759.
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.
The Institute also administers national health education campaigns
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.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.