|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
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
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
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
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
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
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,
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
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,
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
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,