Out of hospital cardiac arrest (OOHCA) is the sudden cessation of effective
cardiovascular circulation in the pre hospital setting. This is sadly a common occurrence
within the UK with approximately 60,000 OOHCAs per year. In 30,000 of these,
resuscitation is attempted by the ambulance service. Survival remains poor (2-12%) within
the UK and even the best performing regions still lag someway behind exemplar global
systems (Seattle 21%, Norway 25%). There are a plethora of reasons for variation in
outcome, not limited to the availability of community defibrillators, the education and
ability of bystanders to provide effective CPR, the response times of the emergency
medical personnel, the training of emergency services personnel and their individual
exposure to cardiac arrest, the availability of primary percutaneous coronary
intervention, and even the availability of extracorporeal resuscitation.
Despite poor outcomes from OOHCA for decades, there exists promising data from animal and
cadaver studies that new technological devices could improve the currently poor blood
flow generated by chest compressions during CPR, particularly cerebral blood flow. The
current standard of care for patients with an OOHCA includes manual CPR delivered at a
rate of 100-120 compressions per minute with a depth of 5 cm (maximum 6 cm). In turn,
periodic inflation of the lungs using positive pressure ventilation to maintain
oxygenation is mandated during CPR. Animal data have shown that blood flow to the heart
and brain using this method is approximately 15-30% of normal. Conventional CPR is
therefore unphysiological by definition, with intracerebral pressures being too high in
the compression phase and intrathoracic pressure being too high in the release phase for
adequate blood flow to the brain and heart respectively. Mechanisms and tools to improve
this have been available for some time but using them synergistically to achieve improved
cerebral and coronary blood flow is a relatively recent advance.
It is now possible to mimic a more physiologically normal situation by combining 3 pieces
of technology. These may lead to better organ perfusion during CPR and therefore better
rates of survival. The 3 devices in question do this in different complementary ways, in
turn;
Head up position- gradated elevation of the head after CPR has been initiated,
improves cerebral blood flow during CPR. This has been studied predominantly in
porcine models. HUP-CPR enhances venous return, and reduces intracranial pressure
during the decompression phase of CPR. This results in improved cerebral perfusion
pressure and improves cerebral blood flow.
Active compression/decompression CPR uses a device with a suction cup placed on the
thorax that via active decompression generates a negative intrathoracic pressure on
each upward stroke, meaning that venous return to the heart improves during each
cycle of CPR, allowing more blood to then be pumped to the brain on the next
compressive cycle.
Combined with an impedance threshold device which works by limiting air entry into
the lungs during chest recoil between chest compressions thereby enhancing the lower
intrathoracic pressure achieved by active decompression, as described above.
The first retrospective study examining the combination of active compression
decompression CPR with an ITD and HUP-CPR in humans was published in 2022, concluding
that rapid initiation of bundle of care-CPR was associated with a higher likelihood of
survival to hospital discharge after OHCA when compared with conventional CPR. 9. The
first prospective human study using this triple bundle approach is currently ongoing in
France.
The 3 devices described above are all CE marked meaning that this trial is not a trial of
an experimental device and therefore does not need to be reported to the MHRA for their
regulatory approvals.
Justification for undertaking the trial
Survival from OOHCA in the UK remains extremely poor (2-12%). The fact that this has not
changed over many decades is of concern. Additionally, the global health disparity that
exists in survival from OOCHA between different healthcare systems is stark.
The published animal data has created a plausible biological signal that improvements
with cerebral blood flow are indeed possible using a bundle approach to neuroprotective
CPR. The practicalities of performing this in human subjects in cardiac arrest is already
being done in certain emergency medical systems globally. One study has published
retrospective data with a signal to suggest that improved outcomes are possible using
this approach. As far as the investigators are aware, no randomised control trial is
currently being undertaken to test this hypothesis.
The proposed treatment bundle holds the potential to change this, the investigators are
of the opinion that this should be tested scientifically within the remit of a clinical
trial and this is the first necessary stage of that process. The individual components
have shown promise in animal studies but this has not been borne out in the human trials
that have followed. The synergistic and complementary effect of the 3 devices that make
up the bundle of care in this study have the potential to change outcomes.
In parts of the USA (Seattle and Phoenix Fire departments) this bundle of care has been
brought in due to the marked improvements in survival that have been seen. The
investigators are of the opinion that an adequately powered randomised trial is essential
to confirm these possible benefits.
Research statement
Out-of-hospital cardiac arrest (OOHCA) is a common event with poor long-term survival
rates, often resulting in poor neurological outcomes. While there are several
interventions that may improve survival and neurological outcomes, single interventions
alone have not consistently demonstrated significant improvements in outcomes. The
combination of head up cardiopulmonary resuscitation (CPR), active compression
decompression CPR, and the use of an impedance threshold device has not yet been tested
in a pragmatic randomised controlled trial. Therefore, the objective of this study is to
assess the feasibility of conducting a randomized trial comparing usual care with a
"bundle of care" approach incorporating the above interventions to improve patient
outcomes after OOHCA.