New Federally Funded Research Program
Aims to Improve Survival from Cardiac Arrest and Severe Trauma
A young mother is unconscious and bleeding from internal injuries
caused by a highway accident. A soldier is severely injured in a
roadside explosion. A 50-year-old man suffers a cardiac arrest as
he gets ready for work. For the “real” counterparts
of these made-up case histories, the chance of survival from life-threatening
injury and cardiac arrest is dismally low. Many more could survive
if only they could be sustained long enough to reach a hospital
alive. However, most cardiac arrest victims die before they reach
the hospital, and traumatic injury is a top killer in North America.
With the launch of a massive research program funded by the National
Institutes of Health (NIH) and other federal and Canadian agencies,
scientists hope to learn the best ways to improve survival chances
from cardiac arrest and severe trauma.
The “Resuscitation Outcomes Consortium” (ROC) will
conduct collaborative clinical trials of promising new treatments
for cardiac arrest (the stopping of the heartbeat) and severe traumatic
injury. Along with Emergency Medical Services (EMS) agencies, ROC
will involve public safety agencies, regional hospitals, community
healthcare institutions and medical centers in 11 regions in the
United States and Canada and as many as 15,000 patients over a 3-year
period. Communities involved in ROC will learn about the study in
a comprehensive community education effort to be conducted over
the next 6 months to a year.
“Surviving traumatic injury and cardiac arrest is a serious
public health issue. Tens of thousands of Americans die each year
from sudden cardiac arrest and trauma. The good news is that there
is a growing body of research – basic research and small studies
-- that suggests a significant number of these people can be saved,”
said Elizabeth G. Nabel, M.D., director of the National Heart, Lung,
and Blood Institute (NHLBI) of the NIH, the lead federal sponsor
of the research effort.
Other funding agencies include the U.S. Department of Defense,
the NIH’s National Institute of Neurological Disorders and
Stroke, the Institute of Circulatory and Respiratory Health of the
Canadian Institutes of Health Research, Defence Research and Development
Canada, the Heart and Stroke Foundation of Canada, and the American
Heart Association. The initial funding commitment to the Consortium
is $50 million.
“This is the first time we have used large-scale clinical
trials to improve the treatment of patients with traumatic injury
and cardiac arrest. Similar studies in patients with heart attack
and heart failure have answered questions about the best treatments.
As a result, we’ve seen greatly improved survival for these
disorders. That’s what we want to do with cardiac arrest and
traumatic injury,” said Myron Weisfeldt, M.D., professor and
chair of internal medicine at Johns Hopkins University and chair
of the steering committee for the research effort.
All of the interventions to be tested in the new program will have
been shown in smaller, single center studies to be safe and to potentially
have a life-saving effect. According to Weisfeldt, the Consortium’s
testing of new techniques will provide the large-scale proof of
effectiveness needed to support widespread adoption and use.
An important goal of the ROC will be the evaluation of interventions
in terms of benefit to cognitive outcomes, as the ultimate goal
of resuscitation is to return victims to their prior functional
capacity.
The first treatments to be tested will be highly concentrated forms
of a saline solution similar to the body’s own fluids. Typically,
in the crucial early minutes before blood transfusions can be safely
administered in hospital, trauma patients receive normal saline
solution intravenously in the field to compensate for blood loss
and buy time. In the new trial, trauma patients with either signs
of blood loss or severe brain injury will receive one of three saline
solutions -- standard normal saline, high concentration saline,
or high concentration saline with dextran, a circulation-enhancing
substance. The two concentrated solutions are designed to compensate
for blood loss more effectively, lessen excessive inflammatory responses
and prevent brain swelling. These effects in turn could potentially
lead to a reduction in organ failure for patients with major blood
loss and improved function for patients with brain injury.
The second study will test a device to enhance blood flow during
CPR. This device is a one-way valve that fits between the airbag
used to introduce air into a person in cardiac arrest and the flexible
plastic tube that goes through the nose or mouth and into the lungs
to help with breathing. The valve can also be used with a facemask
that goes over the patient’s nose and mouth. During CPR, the
one-way valve creates a small vacuum inside the patient’s
chest, which increases the return flow of blood to the heart.
Other possible future studies include testing of new drug approaches
to aid resuscitation from cardiac arrest and evaluation of novel
strategies to control hemorrhage.
There are an estimated 330,000 out-of-hospital cardiac deaths
each year in the United States. Most of these are from sudden cardiac
arrest, although the exact numbers are not known. In cardiac arrest,
the heart stops beating effectively, blood does not circulate and
no pulse can be felt. The victim collapses suddenly into unconsciousness.
Heart attacks, which are caused by a blockage of a coronary artery,
can sometimes lead to cardiac arrest. A common underlying cause
of sudden cardiac arrest is an abrupt disorganization of the heart’s
rhythm called ventricular fibrillation, which can be triggered by
a heart attack or can just represent a catastrophic rhythm disturbance.
Unless cardiac arrest victims are treated within minutes (by defibrillation
to shock an abnormally beating heart back into normal rhythm or
CPR followed by or in conjunction with other procedures), they will
die.
Severe injury is also a major public health problem. It is the
number one killer of both children and young adults up to age 44.
As a disease of young people, it is also the leading cause of life
years lost. In 2002, there were over 161,000 fatal injuries in the
United States. The leading causes of death following injury are
brain injury, blood loss, and organ failure from excessive inflammation.
In addition to rigorous review by an NHLBI-convened independent
review group, the clinical trials of the new Consortium will be
conducted under strict FDA guidelines that allow for patients in
life- threatening situations to participate in research without
individual consent at enrollment. The guidelines specify criteria
that must be followed for a study to have an exception from informed
consent. These include:
- Approval by an institutional review board (IRB), a committee
of experts and lay people established to review research.
- Consultation with the community.
- Public disclosure of the study’s design before the study
begins and when the study is over to share results.
- Notification of patients who were involved in the research.
- Oversight by an independent group of experts charged with monitoring
the research for safety.
Each site’s IRB will decide how best to inform the community,
recommending approaches that might include town meetings, newspaper
notices, random digit dialing surveys, and meetings with groups
at high risk of either cardiac arrest or trauma – such as
local motorcycle clubs. In order to inform future studies involving
exceptions from informed consent, the community consultation process
used in ROC will be evaluated in at least one ancillary study.
“There is a high probability of benefit for patients participating
in these trials,” said Joseph Ornato, M.D., the Consortium’s
co-chair for cardiac arrest and chairman of the Department of Emergency
Medicine at the Virginia Commonwealth University Medical Center
in Richmond, VA. “Not only have these therapies been shown
to be potentially life-saving, but also EMS personnel involved in
the research will be trained in the most up-to-date and effective
methods of emergency treatment.”
According to Tracey Hoke, M.D., Sc.M., NHLBI project officer for
the ROC, “A federal exception of informed consent can only
be granted when patients are in a life-threatening situation, when
obtaining individual informed consent is impossible, and when current
therapy is unproven or unsatisfactory. The most critical stipulation
of the exception is that there must be the potential for direct
benefit to the patients enrolled. In the case of ROC, this means
that preliminary evidence of direct survival benefit must be shown
prior to the development of any trial.”
“These initial studies, and those that follow, will change
the way all providers of trauma care, military and civilian, care
for the most critically injured,” said COL John Holcomb, MD,
the consortium co-chair for trauma, and the Commander of the US
Army Institute of Surgical Research, San Antonio, TX. “For
the first time we will know, based on large and well designed studies,
what interventions really make a difference.”
In a typical study scenario, a first responder will arrive at the
scene of the cardiac arrest or trauma and confirm the patient’s
diagnosis. The emergency medical technician (EMT) will then assess
whether the patient meets the entrance criteria for the study and
if so, treat the patient with the study intervention.
Since the studies will be blinded, the EMTs in the field will not
know which treatment the patient receives. For example, in the first
consortium study testing the concentrated saline solutions, all
solutions of saline to be administered to patients will look alike,
although they will be numbered for later identification and analysis
by the study’s scientists.
In addition to the clinical trials, the Consortium is also currently
enrolling patients into a database of all cardiac arrest and trauma
events. “This is the first multi-city comprehensive database
with information about how field treatment leads to patient survival,”
said George Sopko, M.D., deputy project officer on the study and
a medical officer with NHLBI.
The study is coordinated by investigators at the University of
Washington, Seattle, Principal Investigator: Al Hallstrom, Ph.D.
The participating cities include:
- Birmingham, AL: The Alabama Resuscitation Center is coordinated
through the University of Alabama at Birmingham (Central and possibly
Northern Alabama). Principal Investigator: Tom Terndrup, M.D.
- Dallas, TX: The Dallas Center for Resuscitation Research is
coordinated through the University of Texas Southwestern Medical
Center (Dallas and surrounding cities to participate). Principal
Investigator: Ahamed Idris, M.D.
- Iowa City, IA: The University of Iowa Carver College of Medicine-Iowa
Resuscitation Network is coordinated through the University of
Iowa (includes 10 cities throughout Iowa). Principal Investigator:
Richard Kerber, M.D.
- Milwaukee, WI: The Milwaukee Resuscitation Research Center is
coordinated through the Medical College of Wisconsin. Principal
Investigator: Tom Aufderheide, M.D.
- Ottawa, Ontario/Vancouver, BC (counts as two regions): The University
of Ottawa/University of British Columbia Collaborative RCC is
coordinated through the Ottawa Health Research Institute, University
of Ottawa, Ontario and St. Paul’s Hospital, University of
British Columbia (includes additional 20 cities). Principal Investigator:
Ian Stiell, M.D., Co-Principal Investigator: Jim Christenson,
M.D.
- Pittsburgh, PA: The Pittsburgh Resuscitation Network is coordinated
through the University of Pittsburgh Medical Center (includes
several suburbs). Principal Investigator: Clif Callaway, M.D.,
Ph.D.
- Portland, OR: The Portland Resuscitation Outcomes Consortium
is coordinated through the Oregon Health and Science University
(includes 4 counties). Principal Investigator: Jerris R. Hedges,
M.D., MS.
- San Diego, CA: The UCSD-San Diego Resuscitation Research Center
is coordinated through the University of California, San Diego
(entire county). Principal Investigator: David Hoyt, M.D.
- Seattle and King County, WA: Seattle-King County Center for
Resuscitation Research at the University of Washington. Principal
investigator: Peter Kudenchuk, M.D.
- Toronto, Ontario: The Toronto Regional Resuscitation Research
out of hospital Network is coordinated through the University
of Toronto (includes areas surrounding Toronto). Principal Investigator:
Arthur Slutsky, M.D., Co-Principal Investigators: Laurie Morrison,
M.D. and Paul Dorian, M.D.
To interview NHLBI’s Dr. Tracey Hoke, ROC project officer
or NHLBI’s Dr. George Sopko, ROC deputy project officer, contact
the NHLBI Communications Office at 301-496-4236. To interview Dr.
Weisfeldt or Dr. Jeremy Sugarman, ROC ethicist and Harvey M. Meyerhoff
Professor of Bioethics and Medicine with the Phoebe R. Berman Bioethics
Institute and Department of Medicine Johns Hopkins University, call
David March, Media Relations and Public Affairs, Johns Hopkins Medicine
at 410-955-1534. To interview Dr. Ornato, call 804-828-7184. To
interview COL Holcomb, call 210--916-2720.
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.
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