LUCAS (Lund University Cardiac Arrest System) In Hospital Cardiac Arrest Antonius Hospital

BACKGROUND AND RATIONALE
Annual incidence of resuscitation for out-of-hospital cardiopulmonary arrest of
cardiac etiology is 49.5*66 per 100,000 population based on data from Scotland
and from five cities in other parts of Europe [1].The incidence of in-hospital
cardiac arrest is difficult to assess because it is influenced heavily by
factors such as the criteria for hospital admission and implementation of a
do-not-attempt-resuscitation (DNAR) policy. In a general hospital in the UK,
the incidence of primary cardiac arrest (excluding those with DNAR and those
arresting in the emergency department) was 330/100,000 admissions [2]. using
the same exclusion criteria, the incidence of cardiac arrest in a Norwegian
University hospital was 150/100,000 admissions [3]. The likelihood of a
successful resuscitation without neurologic compromises depends mainly on time
of onset cardiac arrest till restoration of adequate systemic circulation. The
European resuscitation council (ERC) defined stepwise actions in *the chain of
survival* for optimizing survival of a sudden cardiac arrest [4]. They include
early recognition of the emergency and activation of the emergency services,
early CPR, early defibrillation and early advanced life support. One problem
that militates against greater success is the difficulty to perform effective
and uninterrupted compressions over time. Although the artificial maintenance
of blood flow (by chest compressions) is essential for survival if a shock
cannot be given very quickly, the theoretical 25% of normal cardiac output that
might be obtained by compressions are unlikely to be achieved during the great
majority of resuscitations. Computer print-outs from automated defibrillators
show that compressions are given on average only during 36% of the available
resuscitation time even when performed by experienced rescuers [5].Trained
first responders who compress at a rate of 120/min when providing CPR still end
up with only 38 compressions per minute over the resuscitation time because of
ventilatory and other interruptions [6]. Moreover, the depth of compressions,
even when given by healthcare professionals, is generally appreciably less than
what is recommended in guidelines [7, 8]. Whatever quality is achieved over the
first minute or so rapidly deteriorates if a single rescuer is involved [9].
New methods to achieve consistent and high quality compressions are needed for
in en out of hospital cardiac arrests.

Alternative methods of delivering compressions
Mechanical devices can offer one way to achieve good quality resuscitations in
terms of both rate and depth of compressions. Such methods have been in use in
some centers for many years. The first publication comparing manual and
mechanical compressions was published in 1978 [10], when devices had already
been in use for at least 10 years. One device (Thumper, Michigan Instruments
Inc., US) was shown to provide compressions comparable to those delivered
manually *under ideal conditions* [10], whilst several others attest to the
ability of mechanical CPR to be a successful life support technique [11, 12,
13, 14]. The hemodynamic advantages of mechanical compression have been well
summarized by Wik [15].

Mechanical compression can be achieved in several ways: by simple piston-type
devices that press in the chest in the area usually covered by the hands during
manual compressions, by circumferential inflating vests, by devices that
compress alternately the chest and abdomen, and by others that alternately
compress and decompress. The equipment in the first two groups have - until
recently - been cumbersome and heavy, difficult to apply, unstable when
positioned, unsuitable for use during transport of patients, and expensive to
purchase and run. Recently, two retrospective studies with AutoPulse (ZOLL,
US), a device using circumferential chest compressions, were published with
promising results [16, 17]. This was followed by a prospective cluster
randomized multicenter trial that, however, was early terminated due to lack of
benefit in 4 hrs survival, worse neurological outcome and a trend towards worse
survival [18]. Problems with the study was that the application time for the
tested device was prolonged resulting in delayed compressions. Another issue
was study protocol violation by one of the major centers.
Lucas Chest Compression System
LUCAS Chest Compression System (JOLIFE AB, Sweden) is a pneumatic gas-driven
device that provides automatic mechanical chest compressions. LUCAS Chest
Compression System delivers sternal compression at a constant rate to a fixed
depth by a piston with the added feature of a suction cup that helps the chest
return back to the normal position. It compresses 100 times per minute to a
depth of 4-5cm in adherence with International scientific guidelines on CPR
(ref). It is easy to apply, stable in use, relatively light weighted (6.5 Kg),
and well adapted to use during patient movement on a stretcher and during
ambulance transportation. The device has been on the market since 2002 in
Europe. Detailed descriptions of the device and experimental data showing
increased cardiac output and cortical cerebral flow compared to manual
standardized CPR have been published [19, 20].

The first human, cluster-controlled pilot study, published in 2006, in a 2 tier
ambulance system, could not manage to show any advantage when replacing manual
chest compressions in the recommended ACLS algorithm. The delay to treatment
with LUCAS Chest Compression System was substantial with a median time of 18
minutes from the alarm. Furthermore, in this study defibrillation was not
delivered during ongoing mechanical compressions [21]. A second randomized
pilot study in Uppsala, Sweden, was closed in April 2007. Preliminary results
are more encouraging [22]. LUCAS Chest Compression System has the additional
advantages that it can be used during movement of a patient on a stretcher and
can be used easily within any ambulance, an environment that is notoriously
difficult for manual compressions and indeed one that carries a real risk of
injury to healthcare professionals attempting to deliver them effectively [23].
No randomized studies have been published regarding LUCAS Chest Compression
System for In-Hospital cardiac arrest.
The need for compressions before and after defibrillation
Even in the recent past, one of the tenets that has been considered beyond
debate is the need to defibrillate the cardiac arrest victim as soon as the
opportunity exists, provided a *shockable rhythm* is present. However, over the
last years, new data have challenged this dogma. Observations from Seattle
based on comparisons with historical data and published in 2000 [24] suggested
that benefit might come if compressions were given electively before
defibrillation if more than four minutes had passed after the collapse This
study was followed by a randomized study from Oslo in 2003 which confirmed the
benefit of compressions prior to *late defibrillation* [25]. In the latest
international consensus on resuscitation it is thus recommended to give chest
compressions before attempting defibrillation in unwitnessed out-of-hospital
cardiac arrest, where prolonged arrest might be the fact [26].

Both experimental [27,28] and clinical [29,30] evidence exists that *hands-off*
time (time without compressions) causing a deterioration in the waveform of
ventricular fibrillation that is associated with a fall in coronary perfusion
pressure. At the same time, it has long been known that equilibration of
pressures on the arterial and venous sides of the circulation occurs relatively
slowly [31], accompanied by dilatation of the right ventricle and constraint of
the left ventricle - a finding that has been stressed recently in animal
experiments [32] and confirmed by both autopsy [33] and post-mortem
radiological findings [34]. Even successful defibrillation of a heart with a
constrained left ventricle with a seriously impaired effective diastolic
filling pressure (influenced by intra-pericardial pressure [35]) cannot restore
an effective circulation. Moreover, effective contraction of a dilated right
ventricle does not occur sufficiently quickly to relieve pericardial pressure
and permit an effective contractile force in the left ventricular myocardium
(that depends on fiber stretch) before complete cardiac arrest is likely to
recur.

A second reason why late defibrillation is unlikely to be successful unless
supported by compressions is metabolic rather than hemodynamic but it is likely
to exacerbate the loss of contractile power of the left ventricle. The fall in
myocardial ATP resulting from ischemia has a predominant effect on the
extrusion calcium pump which causes calcium overload [36]. Indeed this leads
to contracture rather than contraction, and without early relief causes an
irreversible condition known to surgeons as *stone heart*.
Thus delay in resuscitation is associated with decreasing prospects of a
successful outcome after a defibrillatory shock even if a coordinated waveform
is achieved briefly (pulseless electrical activity). The findings add a
convincing hemodynamic explanation for the empirical observations of the value
of cardiopulmonary resuscitation given as a prelude to defibrillation unless
defibrillation can be provided very quickly after the onset of circulatory
arrest. The current *window of opportunity* for a good prospect of effective
resuscitation from ventricular fibrillation has been clearly shown to be
approximately 5 minutes from call to shock [37], an interval widely accepted as
a high priority goal for EMS care [26]. The concept has developed into
different phases of management and priority of resuscitation attempts, with the
first being the electrical phase lasting four minutes and the second being the
circulatory phase over another six minutes [38]. The electrical phase matches
very persuasively the time taken in experimental work for equilibration of the
arterial and venous pressures after induction of fibrillation [28], after which
the hemodynamics militate strongly against any return of an effective
circulation unless compressions are given. The time course of this
equilibration is matched very closely over the first 30 seconds for which human
data are now available from measurements at the time of implantation of
automatic implantable cardioverter defibrillators (AICDs) [39].
We have no evidence from randomized trials, including the one cited above [25],
that compressions given before defibrillation even for very recent cardiac
arrest has any adverse effect on overall survival. The interval from collapse
to defibrillation - or the possibility thereof - is always very hard to judge
and estimates are unreliable. We believe, therefore, that a policy of primary
compressions is best tested for all cardiac arrest cases unless the arrest is
monitored and occurs when a defibrillator and a trained operator are
immediately at hand.
Uninterrupted compressions may also be useful after defibrillation. There may
be risk to ultimate survival in leaving the newly defibrillated left ventricle
unsupported by compressions during the procedures to check for an effective
cardiac output. A small retrospective study of downloads from defibrillators
has showed that a median time of more than 40 seconds may elapse between shock
given by an AED and first compressions, half of which was due to human factors
and not analysis time [40]. The surest way of providing support when it is
needed would be to provide chest compressions as a routine for a set period
before attempting to discover whether or not there had been a return of
spontaneous circulation. The advantages are likely to outweigh any
arrythmogenic hazard from mechanical stimulation of a vulnerable heart.

Cardiac Magnetic Resonance Imaging after resuscitation
Predicting functional improvement of myocardial function after acute MI is well
established with Magnetic Resonance Imaging (MRI). Contrast-enhanced (CE) MRI
can characterize acute myocardial infarction with 2 well-defined CE patterns as
follows: (1) First-pass images performed immediately after contrast injection
often demonstrate areas of reduced CE MRI or hypoenhancement in the endocardial
core of the infarct, corresponding to microvascular obstruction[44,45]. (2)
Delayed images (10 to 20 minutes after contrast injection) demonstrate regional
signal hyperenhancement, corresponding to myocardial necrosis. Improvement of
segmental circumferential shortening late after infarction can be predicted by
CE patterns early after MI. Regions with normal CE pattern display the most
improvement in circumferential shortening, whereas regions with early
hypoenhancement do not improve regional contractility. In regions with delayed
hyperenhancement, improvement in circumferential shortening is inversely
related to the degree of transmural involvement [46]. Although multiple studies
are preformed with MRI focusing on brain injury after a successful
resuscitation, no studies are involved in analyzing residual myocardial
function after a successful resuscitation.

The primary objective is to show superiority in survival of the modified method
with the LUCAS Chest Compression System, compared to the conventional manual
resuscitation method in patients suffering from witnessed In-hospital cardiac
arrest

Primary endpoint is ROSC more than 20 minutes

LIHA is a randomized single centre non-blinded clinical trial. Inclusion starts
from April 2009 until April 2013. During this time 400 patients will be
included.

Mechanical chest compression vs conventional manual chestcompressions in a
resuscitation. see appendix 1 and 2 from LIHA protocol

Benefits & Risks
Potential benefits and risk from mechanical chest compressions on survival and
neurologic outcomes are studied. A two centre randomized trial and a pilot
trial for conventional manual and LUCAS resuscitation in out of hospital
cardiac arrest showed an increased ROSC for LUCAS and no better nor worse
survival to discharge [21, 22]. A prospective autopsy study revealed a similar
incidence of sternum and rib fractures and no increased side-effects patterns
due to LUCAS.
* Expected injures. Ref; 1. 2005 International Concensus on Cardiopulmonary
Resuscitation and Emergency Cardiovascular Care Science with Treatment
Recommendations. Resuscitation 2005;67:195. 2. Englund E, Kongstad PC. Active
compression-decompression CPR necessitates follow-up post mortem. Resuscitation
2006; 68:161-162. 3. Rubertsson S, Covaciu L. Mechanical chest compressions
with the LUCAS device does not increase the incidence of injuries in cardiac
arrest vicitims. In press AHA 2007.

Assessment of safety
Autopsy will performed according to a specified CRF to investigate injuries in
both study groups. Number of injuries possibly affecting survival will be
studied. This study will be done in a limited number of patients. The goal will
be to get autopsy results from a total of 100 study patients.
Adverse events
There will be no non-serious adverse event reporting in this study. Events like
rib fractures, sternum fractures and skin bruises are common after CPR using
either method and are not needed to be reported as adverse events. However, if
events including the above mentioned occur that fall under the Serious Adverse
Event definition, they should be reported as serious adverse events.
serious adverse events
SAE is defined as an event directly related to CPR, as judged by
investigator/co-investigator and assumed to occur after the randomization in
the study, such as incidents that have resulted in:
· Death
· Serious deterioration of health in patient. This may include
- life threatening illness or injury
- permanent deterioration of body function or structure
- prolongation of hospitalization
-conditions that require medical or surgical treatment to prevent any of the
above

reporting of serious adverse events
The Investigator should report all serious AE:s by using a Serious Adverse
Event Report form.