Extracorporeal CPR: Now a standard of care?

Abstract

Despite significant improvements in the field of resuscitation, overall survival after out-of-hospital cardiac arrest (OHCA) remains low, 1,2 and many survivors have persistent neurological damage. Refractory OHCA, defined as the failure to achieve return of spontaneous circulation (ROSC) despite conventional cardiopulmonary resuscitation (CPR), is associated with an even worse prognosis. In fact, after ten minutes of conventional CPR, chances of survival start to decline rapidly. 3 After 35 minutes, less than 1% of patients achieve ROSC and survive with a favourable neurological outcome. 4,5 One of the most recent interventions applied and investigated in the resuscitation of patients with OHCA is extracorporeal membrane oxy-genation (ECMO). Extracorporeal CPR (E-CPR), the rapid deployment of veno-arterial ECMO during ongoing CPR, is a promising approach for patients with refractory OHCA. 6 Evidence supporting E-CPR is now compelling. After many observational studies, 7-13 two randomised trials demonstrated the feasibility and possible benefits of early transport to the hospital for initiation of E-CPR in patients with refractory OHCA. 14,15 In addition, a recent meta-analysis showed an improved rate of survival with good neurological outcomes. 16 In this issue of Resuscitation Plus, Mørk et al. 17 described the performance of a tertiary cardiac arrest centre (CAC) in Denmark in treating patients with OHCA with a particular focus on the role of E-CPR. The authors analysed three groups of OHCA patients managed at their institution: patients admitted with ROSC, patients receiving E-CPR for refractory OHCA, and patients who arrived with refractory OHCA but were not treated with E-CPR. The rate of survival at hospital discharge was 64% in patients admitted with ROSC. While such a rate of survival may appear high compared with the literature , it probably reflects the very selected population of patients referred to a CAC characterised by favourable prognostic factors such as cardiac cause, witnessed arrest, bystander CPR, and initial shockable rhythm. In refractory OHCAs, survival at hospital discharge occurred in 27% of patients receiving E-CPR and only 1% of patients without E-CPR, confirming the very low survival of patients with prolonged refractory OHCA who do not proceed with E-CPR. 4,5 Patients with refractory OHCA were considered eligible for E-CPR after 15 minutes of conventional CPR without ROSC and if the following criteria were met: age 18-65 years, witnessed arrest, bystander CPR and preferably initial shockable rhythms, no-flow time less than ten minutes, and absence of severe comorbidity. When interpreting studies on E-CPR, it is essential to remember that E-CPR is part of a bundle of treatments that begins in the pre-hospital setting, continues during transport, and is completed in the hospital (Fig. 1). This must be considered when trying to generalise the findings of studies conducted in successful E-CPR programs to other cities. In fact, survival rates in patients treated with E-CPR are highly variable, between 8% and 40% among studies. 13,18,19 Such high variability can be mainly explained by differences in emergency medical services (EMS) response times, quality of bystander CPR, availability of citizen first responders defibrillation, 20 patient selection, time to support on veno-arterial ECMO and post-resuscitation care. A prolonged no-flow time, the time between collapse and initiation of bystander CPR, is one of the main factors contributing to poor survival. 21 Early bystander-initiated CPR is the most important modifi-able factor in decreasing the no-flow time and increasing survival. 22 Denmark, the country of the study by Mørk et al., 17 is one of the European countries with the highest rate of bystanders' interventions. Thanks to multiple initiatives 23 including mandatory CPR education in schools, dispatcher-assisted CPR, and a citizen first responders smartphone app, 24 bystander-initiated CPR reached 80% in 2020. 25 In fact, in the study by Mørk et al., 17 98% of refractory OHCAs treated with E-CPR received bystander-initiated CPR before EMS arrival and no-flow time was virtually zero. In the two recent randomised trials, rates of bystander-initiated CPR were 98% in the Prague OHCA study 15 and 87% in the ARREST trial 14 but such performances are still very far from being reached in many countries. Low-flow time, the time between initiation of CPR and commencement of ECMO, is another crucial factor contributing to poor survival. 26 An optimal time interval for ECMO has been proposed to lie between 30 and 60 minutes after OHCA. However, the survival benefit of E-CPR can also be extended beyond 60 minutes for carefully selected patients. 13 Impressively, more than 20% of patients receiving E-CPR for refractory OHCA in the study by Mørk et al. 17 had a good neurological outcome despite low-flow times higher than R E S U S C I T A T I O N P L U S 1 0 (2 0 2 2) 1 0 0 2 3 5 Available online at www.sciencedirect.com Resuscitation Plus journal homepage: www.elsevier.com/locate/resuscitation-plus

Full text

Editorial
Extracorporeal CPR: Now a standard of care?
Keywords: Extracorporeal cardiopulmonary resuscitation, Extracorporeal membrane oxygenation, Refractory cardiac arrest, Out-of-hos-
pital cardiac arrest, Cardiac arrest centres
Despite significant improvements in the field of resuscitation,
overall survival after out-of-hospital cardiac arrest (OHCA) remains
low,
1,2
and many survivors have persistent neurological damage.
Refractory OHCA, defined as the failure to achieve return of sponta-
neous circulation (ROSC) despite conventional cardiopulmonary
resuscitation (CPR), is associated with an even worse prognosis.
In fact, after ten minutes of conventional CPR, chances of survival
start to decline rapidly.
3
After 35 minutes, less than 1% of patients
achieve ROSC and survive with a favourable neurological
outcome.
4,5
One of the most recent interventions applied and investigated in the
resuscitation of patients with OHCA is extracorporeal membrane oxy-
genation (ECMO). Extracorporeal CPR (E-CPR), the rapid deploy-
ment of veno-arterial ECMO during ongoing CPR, is a promising
approach for patients with refractory OHCA.
6
Evidence supporting
E-CPR is now compelling. After many observational studies,
7–13
two
randomised trials demonstrated the feasibility and possible benefits
of early transport to the hospital for initiation of E-CPR in patients with
refractory OHCA.
14,15
In addition, a recent meta-analysis showed an
improved rate of survival with good neurological outcomes.
16
In this issue of Resuscitation Plus, Mørk et al.
17
described the
performance of a tertiary cardiac arrest centre (CAC) in Denmark
in treating patients with OHCA with a particular focus on the role of
E-CPR. The authors analysed three groups of OHCA patients man-
aged at their institution: patients admitted with ROSC, patients
receiving E-CPR for refractory OHCA, and patients who arrived with
refractory OHCA but were not treated with E-CPR. The rate of sur-
vival at hospital discharge was 64% in patients admitted with ROSC.
While such a rate of survival may appear high compared with the lit-
erature, it probably reflects the very selected population of patients
referred to a CAC characterised by favourable prognostic factors
such as cardiac cause, witnessed arrest, bystander CPR, and initial
shockable rhythm. In refractory OHCAs, survival at hospital dis-
charge occurred in 27% of patients receiving E-CPR and only 1%
of patients without E-CPR, confirming the very low survival of
patients with prolonged refractory OHCA who do not proceed with
E-CPR.
4,5
Patients with refractory OHCA were considered eligible
for E-CPR after 15 minutes of conventional CPR without ROSC
and if the following criteria were met: age 18–65 years, witnessed
arrest, bystander CPR and preferably initial shockable rhythms, no-
flow time less than ten minutes, and absence of severe comorbidity.
When interpreting studies on E-CPR, it is essential to remember
that E-CPR is part of a bundle of treatments that begins in the pre-
hospital setting, continues during transport, and is completed in the
hospital (Fig. 1). This must be considered when trying to generalise
the findings of studies conducted in successful E-CPR programs to
other cities. In fact, survival rates in patients treated with E-CPR
are highly variable, between 8% and 40% among studies.
13,18,19
Such high variability can be mainly explained by differences in emer-
gency medical services (EMS) response times, quality of bystander
CPR, availability of citizen first responders defibrillation,
20
patient
selection, time to support on veno-arterial ECMO and post-resuscita-
tion care.
A prolonged no-flow time, the time between collapse and initiation
of bystander CPR, is one of the main factors contributing to poor sur-
vival.
21
Early bystander-initiated CPR is the most important modifi-
able factor in decreasing the no-flow time and increasing
survival.
22
Denmark, the country of the study by Mørk et al.,
17
is
one of the European countries with the highest rate of bystanders’
interventions. Thanks to multiple initiatives
23
including mandatory
CPR education in schools, dispatcher-assisted CPR, and a citizen
first responders smartphone app,
24
bystander-initiated CPR reached
80% in 2020.
25
In fact, in the study by Mørk et al.,
17
98% of refractory
OHCAs treated with E-CPR received bystander-initiated CPR before
EMS arrival and no-flow time was virtually zero. In the two recent
randomised trials, rates of bystander-initiated CPR were 98% in
the Prague OHCA study
15
and 87% in the ARREST trial
14
but such
performances are still very far from being reached in many countries.
Low-flow time, the time between initiation of CPR and com-
mencement of ECMO, is another crucial factor contributing to poor
survival.
26
An optimal time interval for ECMO has been proposed
to lie between 30 and 60 minutes after OHCA. However, the survival
benefit of E-CPR can also be extended beyond 60 minutes for care-
fully selected patients.
13
Impressively, more than 20% of patients
receiving E-CPR for refractory OHCA in the study by Mørk et al.
17
had a good neurological outcome despite low-flow times higher than
RESUSCITATIONPLUS10 (2022) 100235
Available online at www.sciencedirect.com
Resuscitation Plus
journal homepage: www.elsevier.com/locate/resuscitation-plus

75 minutes. It is clear how bystanders play a significant role
27
:
thanks to their intervention, the time window within which successful
resuscitation manoeuvres can be performed and tolerated is
extended. In the absence of bystander CPR, severe irreversible
damage to the brain and other organs occurs, and any advanced
treatments like E-CPR would likely have little or no effect on out-
comes. Another important consideration, given the very long median
low-flow time, is whether E-CPR increases the number of survivors
with neurological impairment. In the study by Mørk et al.,
17
a good
neurological outcome was found in 93% of patients discharged alive
from the hospital after a refractory OHCA treated with E-CPR. Rates
of patients surviving with significant neurological impairment (a score
on the cerebral performance category scale of 3 or 4) were similar
between patients treated with E-CPR and patients admitted with
ROSC. Patient-centred outcomes such as long-term neurological
outcomes and quality of life are important but were not assessed
in the study by Mørk et al.
17
Studies demonstrating the feasibility and benefits of E-CPR indi-
rectly increase the supportive evidence for transporting and treating
OHCA patients in designated CACs.
27–29
In the study by Mørk
et al.,
17
92% of patients received coronary angiography and 75%
percutaneous coronary intervention. Post-arrest temperature control,
easily achievable through the ECMO circuit, was also provided in
97% of patients. Percutaneous left ventricular assist devices, such
as the Impella, were used in a small proportion of patients, alone
or in combination with ECMO. As peripheral veno-arterial ECMO
may increase left ventricular afterload with subsequent distension
and pulmonary congestion, Impella can be useful for unloading
and supporting the left ventricle.
30
Availability of temporary and
long-term mechanical circulatory support and access to heart
transplantation are also necessary. Expertise in neurological prog-
nostication is also required in a CAC. Finally, organ donation in
patients who proceed to irreversible, severe brain injury may also
benefit the community.
In conclusion, Mørk et al.
17
should be congratulated for
addressing this important area of research. Systems already provid-
ing E-CPR as a part of a well-organised system are now supported
by further evidence. Conversely, systems considering the implemen-
tation of E-CPR must carefully reflect if the necessary services are
available or can be implemented. As recent studies on E-CPR taught
us, to implement a successful E-CPR program, it is imperative to
have an optimised chain of survival with early bystander-initiated
CPR, rapid EMS response time, high-performance CPR on-scene,
mechanical CPR devices for transport of patients in refractory arrest
with ongoing chest compressions, availability of high-volume CAC
for immediate E-CPR, rigorous post-arrest care and careful selection
of patients to undergo this expensive yet effective treatment.
Declaration of interests
TS is the Social Media Editor of Resuscitation and Resuscitation
Plus and member of the ERC BLS Science and Education Commit-
tee. SB has no competing interests to declare.
Fig. 1 – Schematic representation of the ideal structure and performance of a successful extracorporeal
cardiopulmonary resuscitation (E-CPR) program for refractory out-of-hospital cardiac arrest.
CPR = cardiopulmonary resuscitation, ALS = advanced life support, EMS = emergency medical services,
CAC = cardiac arrest centre, VA-ECMO = veno-arterial extracorporeal membrane oxygenation, CA = cardiac arrest.
2RESUSCITATIONPLUS10 (2022) 100235

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Tommaso Scquizzato
*
Department of Anesthesia and Intensive Care, IRCCS San Raffaele
Scientific Institute, Milan, Italy
Stephen A Bernard
Intensive Care Unit, The Alfred Hospital, Melbourne, Australia
* Corresponding author at: Department of Anesthesia and Intensive
Care, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132
Milan, Italy. Fax: +39 02 2643 6152.
scquizzato.tommaso@hsr.it (T. Scquizzato).
RESUSCITATIONPLUS10 (2022) 100235 3

Received 7 April 2022
Accepted 7 April 2022
https://doi.org/10.1016/j.resplu.2022.100235
Ó2022 The Author(s). Published by Elsevier B.V.This is an open access
article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).
4RESUSCITATIONPLUS10 (2022) 100235