PULSE: Finding Cardiac Resuscitation Strategies, Interventions
That Save Lives
Richard
J. Traystman, Ph.D
This short article is meant to inform ASA members
of a recent research initiative called the “Post-resuscitative
and Initial Utility in Life-Saving Efforts,”
otherwise known as PULSE. Each year, some 500,000
Americans will suffer cardiac arrest and require cardiopulmonary
resuscitation (CPR). One-half of these arrests result
in immediate death, and of the remaining, only about
5 percent are successfully resuscitated to the extent
that they are returned to productive lives. Neurological
and neuropsychological deficiencies remain prevalent
in the remaining 95 percent of patients.
The chance of survival after cardiac arrest decreases
7 percent to 10 percent for each minute of no flow,
and for cardiac arrests longer than 12 minutes, only
2 percent to 5 percent of patients achieve long-term
survival. Good neurological outcomes occur even less
frequently. These dismal results persist despite 50
years of work attempting to improve outcome from cardiac
arrest.
Accordingly, a PULSE Workshop was convened in June
2000 in recognition of the grave public health consequences
resulting from poor cardiopulmonary and trauma resuscitation
outcomes. The purpose of the PULSE Workshop was to
provide an interdisciplinary forum on promising and
novel life-saving therapies in settings of cardiac,
asphyxial and traumatic arrest and to identify the
most promising new directions in cardiopulmonary and
trauma resuscitation research. The PULSE Workshop
was organized under a multiagency initiative with
participation by the National Heart, Lung and Blood
Institute (NHLBI), the National Institute of Child
Health and Human Development (NICHHD), the National
Institute of General Medical Sciences (NIGMS) and
the National Institute of Neurological Disorders and
Stroke (NINDS) of the National Institutes of Health
(NIH) together with the Food and Drug Administration
(FDA) and the Department of Defense (DOD). This workshop
provided a unique opportunity to convene national
and international experts to chart a new course for
future CPR research.
The PULSE Workshop sought opportunities for major
improvements in clinical outcomes after CPR and after
resuscitation from serious traumatic injury. The panel
of experts focused on scientific research that would
yield major advances in life-saving care, including
measurable increases in survival and functional recovery.
However, unless research support is prioritized to
address CPR, it is unlikely that these opportunities
will soon be realized. The basic science of resuscitation
medicine has promise of evolving in parallel with
major medical advances, but additional focus on resuscitation
is required. Resuscitation should therefore be prioritized
for appropriate funding of research by federal and
voluntary organizations. The PULSE leadership attempted
to implement a consortium of societies for resuscitation
research. At the PULSE Workshop, the participants
discussed funding resuscitation research and even
attempted to prioritize this research in the area
of resuscitation from clinical to basic science.
The workshop participants unanimously felt that we
stand at the verge of new therapies and technologies
that, when implemented, could save thousands of lives
currently lost following circulatory arrest. Two broad
strategies should be aggressively pursued. First,
the participants identified the need for focused basic
and applied research. Second, many existing therapies
that are known to save lives can be refined so that
they can be implemented more rapidly, thereby reducing
the duration of global ischemia. Earlier and better
CPR, rapid defibrillation and early control of hemorrhage
will lead to improved survival. There was great optimism
that new resuscitation strategies and therapeutic
interventions will be life-saving for patients who
fall outside the “effectiveness window”
of current interventions. Human data from survivors
of intractable ventricular fibrillation and demonstration
that cell survival could be extended following previously
lethal ischemia suggest that novel therapies will
increase the number of lives saved. The participants
applauded earlier emphasis on focal or regional ischemia,
including myocardial infarction and stroke, but recognized
the increasing need to address global ischemia involving
multiple regions and, actually, the entire body.
New therapeutic interventions are likely to come from
the frontiers of molecular medicine, basic cardiovascular
sciences, neurosciences, pharmacology, epidemiology,
new diagnostic techniques and technological advances,
including miniaturization of devices. Diverse disciplines,
the basic sciences, clinical sciences and biotechnology
should be integrated to improve understanding of resuscitation
physiology and the translation of new insights into
life-saving medical practices. PULSE defined resuscitation
science as the study of the epidemiology, pathophysiology,
mechanisms and improved management of the sudden states
of illnesses or injuries that result in impending
or actual cessation of oxygen delivery. Resuscitation
science especially addresses mechanisms, diagnoses
and management of clinical and experimental pathophysiological
states of whole-body oxygen consumption. These clinical
events typically occur without prior warning, and
they affect age groups ranging from neonates to senior
adults. Thus, resuscitation research encompasses investigations
of mechanisms with a focus on conditions that initiate,
mediate and result from whole-body hypoxia and multiorgan
ischemia. This research will require basic laboratory
investigations, utilization of animal models, clinical
trials and epidemiological investigations. The goal,
of course, is to decrease mortality and morbidity
in both human and monetary costs of cardiopulmonary
arrest and traumatic injuries such as to significantly
improve individual and public health.
The PULSE leadership attempted to prioritize research
initiatives. There were eight working groups convened
that considered the following: acute myocardial rescue,
neurological preservation, pharmacotherapeutics, ventilatory
management, mechanical circulatory adjuncts and bioengineering
of new devices, epidemiology and trauma care. During
and after the PULSE Workshop, five areas of resuscitation
research were identified, including: mechanisms, pharmacology,
translational studies, bioengineering and clinical
evaluative research. The PULSE group made specific
recommendations to NIH for implementation of the PULSE
Strategic Plan.
To summarize:
1. Develop a national center
for resuscitation research represented by a
broad-based initiative among institutes and
partnering with other governmental agencies.
NHLBI, NICHHD, NIGMS, NINDS, FDA and DOD have
already demonstrated effective collaboration
in their support of the PULSE initiative.
2. Recognize the need for and implement programs
that prioritize support for resuscitation research.
This should include grants and/or contracts
as support to consortia of investigators who
collaborate throughout the spectrum from basic
science, applied and bioengineering research
and clinical investigations and preferably all
three.
3. Prioritize the development of a multicenter
network to support clinical trials. To the extent
that it is possible, both basic and translational
research deserve priority consideration.
4. Prioritize specific programs of support for
the development of strategies and devices in
support of biosensor technology to guide diagnoses,
monitoring and response to resuscitation intervention.
5. Support the development and maintenance of
registries of clinical cases on resuscitation.
Current registries should be expanded to include
trauma and cardiac arrest, especially in the
prehospital/emergency medical setting.
6. Extend education and training opportunities
for both laboratory and clinical researchers
on resuscitation, including fellowships and
developmental support for junior faculty. Focused
training grants and institutional research training
awards in resuscitation medicine are recommended.
7. Ensure that organized panels of qualified
experts on resuscitation, and/or ensure the
appropriate inclusion of reviewers from such
panels, participate on Study Sections to which
applications are directed. Clinical investigators
who have experience and expertise in the conduct
of clinical trials, including federal regulations,
should be enlisted.
8. Direct appropriate agencies of government
to promote public education and enhance public
awareness of acute, life-threatening conditions
and therapies and to acknowledge the need of
support for research and development on resuscitation.
NIH would best take a leadership role in addressing
the current state of resuscitation research
and identify opportunities for supporting novel
initiatives. |
The bottom line idea of the PULSE initiative is to
convince funding agencies that resuscitation research
deserves a high priority because resuscitation represents
such a poor outcome in the community. For those who
would like to read the full PULSE initiative, please
refer to Circulation 2002; 105:2562-2570.
We have already seen fruits of the PULSE initiative
in the request for applications (RFA) for cardiopulmonary
resuscitation research, which had a deadline due date
of February 2002. I urge all individuals interested
in resuscitation science to be aware of these initiatives
and to look carefully for these RFAs as they are produced
through NIH. They represent important funding programs
and have the potential to resolve many problems in
resuscitation research from the gene and molecular
level to the bedside to epidemiological studies.
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Richard
J. Traystman, Ph.D., is Distinguished University
Professor, Senior Vice-Chair for Research, Anesthesiology
and Critical Care Medicine, and Director of
Anesthesiology and Critical Care Medicine Laboratories,
Johns Hopkins Medical Institutions, Baltimore,
Maryland. He received the ASA Award for Excellence
in Research in 1997. |
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