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Thu Jun 11 00:13:37 BST 2009

The NHLBI Halts Study of Concentrated Saline for Patients With Shock
Due to Lack of Survival Benefit

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News

National Heart, Lung, and Blood Institute (NHLBI)
<http://www.nhlbi.nih.gov/>

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 follow-up period.

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 2008.

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

nhlbi_news at nhlbi.nih.gov

To interview Dr. Bulger,
contact Susan Gregg-Hanson at

206-616-6730

to interview Dr. Hoyt, contact John Murray or 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

<http://www.nih.gov>

##

This NIH News Release is available online at:
<http://www.nih.gov/news/health/mar2009/nhlbi-26.htm>

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The NHLBI Halts Study of Concentrated Saline for Patients With Shock