Extracorporeal life support in cardiogenic shock: indications and management in current practice
Neth Heart J
Extracorporeal life support in cardiogenic shock: indications and management in current practice
C. L. Meuwese 0 1 2 3 4
F. Z. Ramjankhan 0 1 2 3 4
S. A. Braithwaite 0 1 2 3 4
N. de Jonge 0 1 2 3 4
M. de Jong 0 1 2 3 4
M. P. Buijsrogge 0 1 2 3 4
J. G. D. Janssen 0 1 2 3 4
C. Klöpping 0 1 2 3 4
J. H. Kirkels 0 1 2 3 4
D. W. Donker 0 1 2 3 4
0 Department of Cardiothoracic Surgery, University Medical Center Utrecht , Utrecht , The Netherlands
1 Department of Cardiology, University Medical Center Utrecht , Utrecht , The Netherlands
2 C. L. Meuwese
3 Department of Intensive Care Medicine, University Medical Center Utrecht , Utrecht , The Netherlands
4 Department of Anesthesiology, University Medical Center Utrecht , Utrecht , The Netherlands
Veno-arterial extracorporeal life support (VA-ECLS) provides circulatory and respiratory stabilisation in patients with severe refractory cardiogenic shock. Although randomised controlled trials are lacking, the use of VA-ECLS is increasing and observational studies repeatedly have shown treatment benefits in well-selected patients. Current clinical challenges in VA-ECLS relate to optimal management of the individual patient on extracorporeal support given its inherent complexity. In this review article we will discuss indications, daily clinical management and complications of VA-ECLS in cardiogenic shock refractory to conventional treatment strategies.
Cardiogenic shock; Short-term cardiac mechanical support; Extracorporeal membrane oxygenation (ECMO); Extracorporeal life support (ECLS)
Although survival seems to have improved during recent
years, cardiogenic shock continues to carry a poor
prognosis. After myocardial infarction, mortality rates range from
50 to 75% despite urgent coronary revascularisation [
non-ischaemic cardiac disease, cardiogenic shock carries
a comparably unfavourable outcome [
Cardiogenic shock is encountered in 5–10% of patients
with ST-elevation myocardial infarction (STEMI) and up
to 3% of those with non-STEMI [
]. In non-ischaemic
cardiomyopathy, shock may develop as an acute or acute
on chronic manifestation. In the Netherlands, around 28,000
individuals suffer from acute myocardial infarction annually
and the number of chronic heart failure patients currently
approximates 230,000 and is increasing . This implicates
that, potentially, over 2,000 individuals present with
cardiogenic shock annually.
The shown absence of a survival benefit of the
intra-aortic balloon pump (IABP) compared to conventional
treatment in post-infarction cardiogenic shock without
mechanical complications in the SHOCK II trial [
] in conjunction
with previous evidence [
], has led to a downgrading of
guideline recommendations for IABP use in Europe from
Class I [level of evidence: C] to Class III [A] [
critical evaluation of the IABP has created a new impetus
to reflect on the role of alternative short-term mechanical
support devices [
], such as veno-arterial extracorporeal life
support (VA-ECLS), which can provide partial or full
circulatory support [
]. In addition, VA-ECLS can provide
respiratory support in patients suffering from severe, combined
cardiac and pulmonary failure. Although randomised trials
evaluating VA-ECLS in cardiogenic shock are still lacking
], observational studies have indicated beneficial effects
in patients with cardiogenic shock in acute on chronic heart
failure and cardiac arrest [
In this review we will discuss current indications, clinical
management and potential complications of VA-ECLS in
patients with cardiogenic shock refractory to conventional
Veno-arterial extracorporeal life support, basic concepts
In a VA-ECLS circuit, central venous blood is drained,
relayed through an extracorporeal pump and oxygenator and
then re-infused into the arterial compartment. A modern
ECLS circuit consists of several components including
venous and arterial cannulas, tubing, a membrane oxygenator
with gas blender, a continuous-flow centrifugal pump and
a heat exchanger to compensate for extracorporeal heat loss
(Fig. 1). VA-ECLS was originally derived from
cardio-pulmonary bypass (CPB) but differs in several aspects; firstly,
CPB uses an open reservoir, whereas VA-ECLS is based
on a closed circuit. Secondly, an ECLS circuit actively
drains venous blood with negative pressures on the venous
side of the pump in contrast to a conventional CPB circuit
(using roller pumps) where venous blood is passively
drained into a reservoir. Newer CPB circuits, utilising
centrifugal pumps, also create a negative pressure on the
In cardiogenic shock, arterial and venous femoral
percutaneous cannulation via the Seldinger technique allows
for rapid initiation of VA-ECLS without need for a central
approach via sternotomy. Furthermore, it can be performed
virtually everywhere inside and outside the hospital
]. For optimal vascular access, echographic
asFig. 1 Schematic illustration of a VA-ECLS system
sessment can be used, while echocardiographic and
fluoroscopic guidance allows optimal cannula positioning,
especially for central venous drainage [
Consistent with Poiseuille’s law, narrower, longer
cannulas result in larger resistance, which may in turn reduce
extracorporeal blood flow or necessitate pressures outside
the clinically acceptable range for a given pump speed.
Drainage of central venous blood can best be achieved
through relatively large 21–25 French (Fr) multistage
cannulas. Arterial cannulas are narrower (15–19 Fr) and shorter
and allow injection of oxygenated blood retrogradely into
the descending aorta. Centrifugal pumps, being used in
modern VA-ECLS circuits, are designed to provide a flow
of 60–120 ml/kg/min (range of 2–10 l/min). Maximum
achievable extracorporeal blood flow depends on many
other ECLS circuit and patient characteristics, such as
caval vein diameters, volume status, thoraco-abdominal
pressures, flow capacity of the oxygenator and maximally
tolerable negative and positive pressures (±300 mm Hg).
Membrane oxygenators are made up of selectively
permeable membranes, facilitating blood and gas flow to allow
Indications, contra-indications and prognosis
The main goal of VA-ECLS in refractory cardiogenic shock
is to provide immediate circulatory and respiratory
stabilisation, while accounting for sufficient cardiac unloading.
Although no randomised controlled trials exist on the
effectivity of VA-ECLS, observational studies have shown
survival benefits in comparison to conventional therapy and
Class IIb and Class IIa recommendations have been
specified by European [
] and American [
]. To maximise the potential of cardiac
recovery and prevent impending multi-organ failure, early
initiation of VA-ECLS has been proposed [
evidence further suggests that in Interagency Registry for
Mechanically Assisted Circulatory Support (INTERMACS)
level 1 patients (so called ‘crash-and-burn’ patients),
temporary clinical optimisation with VA-ECLS prior to left
ventricular assist device (LVAD) support improves outcome
as compared to direct implantation of a permanent LVAD
Indications for VA-ECLS can be subdivided according to
cause and setting (Tab. 1; Fig. 2). In the emergency room,
up to 80% of cardiogenic shock states is caused by acute
coronary syndromes with or without ST-segment elevations
]. Within this subgroup of acute coronary syndromes,
cardiogenic shock can be attributed to primary left
ventricular (LV) failure in almost 80% of patients. In the other
20%, cardiogenic shock is caused by acute mitral
regurgitation (6.9%), septal rupture (3.9%), right ventricular failure
(2.8%), and pericardial tamponade (1.4%) secondary to the
myocardial infarction [
Other common causes of cardiogenic shock suitable
for VA-ECLS may relate to acute deterioration of chronic
heart failure (10%), valvular disease (6%), stress-induced
cardiomyopathy (2%), myocarditis (2%), and other causes
such as refractory ventricular tachyarrhythmias (<1%) [
Cardiac arrest refractory to conventional
cardio-pulmonary resuscitation (CPR) forms another potential
indication for VA-ECLS, i. e., extracorporeal-CPR (E-CPR) for
in-hospital and out-of-hospital cardiac arrest. Observational
studies have suggested a favourable outcome in otherwise
refractory in-hospital cardiac arrest [
out-of-hospital cardiac arrest [
]. The current European Resuscitation
Council (ERC) guidelines also advocate considering E-CPR
under favourable clinical circumstances. At present, E-CPR
remains largely an experimental therapy and further
scientific evidence is imperative to clearly identify the subgroup
of patients that may truly benefit from such a demanding
and costly modality.
VA-ECLS is classically used in post-cardiotomy
cardiogenic shock, which occurs in 0.2–6% of cardiac operations
]. In addition to its use in strictly cardiological and
cardio-surgical indications, VA-ECLS has been
successfully applied in patients with acute pulmonary embolism
]. However. evidence remains confined to case reports
and limited series. Furthermore. patients with septic shock
], anaphylaxis [
], severe intoxications [
], or trauma/
multi-trauma with circulatory, cardiac and/or respiratory
failure have been successfully supported with VA-ECLS
]. In these patient subgroups with severe combined
circulatory and respiratory insufficiency the attribute of gas
exchange in VA-ECLS can be of paramount importance.
Before initiation of VA-ECLS, several absolute and more
relative contra-indications should be considered (Tab. 1).
Firstly, VA-ECLS should serve as a bridge to cardiac
recovery or long-term mechanical support. In patients without
such prospects, VA-ECLS should not be used. A
significantly reduced life expectancy due to non-cardiac
morbidities (e. g. metastasised malignancies or severe pulmonary
disease) should also serve as a reason to refrain from
VAECLS. Furthermore, uncontrollable coagulation disorders
or intracranial bleeding should be interpreted as absolute
contra-indications. Other arguments relate to anatomical
or disease-related constraints to the insertion of VA-ECLS
cannulas such as aortic dissection (prior to surgical
correction), extensive multi-trauma, or peripheral artery
disease. In patients with severe aortic regurgitation VA-ECLS
should not be used because of an uncontrollable increase in
regurgitant volume. Older age is a relative contra-indication
although limits are ill-defined.
According to the Extracorporeal Life Support
Organization (ELSO) registry, overall in-hospital survival of
patients treated with VA-ECLS approximates 40% [
Patients with myocarditis have a relatively better prognosis
(in-hospital survival of 62%), whereas patients with
congenital defects demarcate the poorer end of the spectrum
showing average survival rates of 37%. Patients with
nonischaemic heart disease have a better prognosis than those
with ischaemic cardiomyopathy. In cardiac resuscitation,
VA-ECLS has roughly been associated with a 30% hospital
– Recent intracranial haemorrhage or infarction
– Uncontrolled coagulopathy
– Multi-trauma with high risk of bleeding
– Irreversible cardiac disease with no prospect for permanent
ular assist device implantation or heart transplantation
– Aortic dissection and severe aortic regurgitation
– Age >65 years
ECLS extracorporeal life support, eGFR estimated glomerular filtration rate, VT ventricular tachycardia, VF ventricular fibrillation
aWorst value within 6 h prior to cannulation
bCreatinine levels >133 µmol/l (5 mg/dl)
cKidney damage or eGFR <60 ml/min/1.73 m2 for ≥3 months
dWorst value before cannulation
eNeurotrauma, stroke, encephalopathy, cerebral embolism, seizure and epileptic syndromes
fBilirubin ≥33 mcmol/l or elevation of serum aminotransferases (ALT or AST) >70 UI/l at ECLS cannulation
All values prior to cannulation
For assessment of patient-specific prognosis, several
scores have been developed. The Survival After
Venoarterial Extracorporeal membrane oxygenation (SAVE)
score (Tab. 2), available online at www.save-score.com,
was based on 3,846 patients from the ELSO registry and
revealed satisfactory performance at external validation
]. The theoretical risk distribution varies between 10
and 100%, depending on the combination of clinical
characteristics as outlined in Tab. 2 and detailed in the original
]. The ENCOURAGE score, which was
developed based on 138 patients, claimed to have higher
discriminatory abilities than the SAVE score [
the INTERMACS classification was designed for patients
receiving long-term LVADs [
]. With patients qualifying
for VA-ECLS already in a poor clinical condition, reflected
by an INTERMACS level 1 or 2, this score does not seem
to add additional discriminative power.
A broad spectrum of complications can be encountered
during VA-ECLS. These complications are described below.
● Vascular complications:
These include vascular dissection or perforation upon
cannulation, potentially resulting in ischaemia and
compartment syndrome of the lower extremities. Rarely,
perforation of the right atrium may occur which
underscores the importance of periprocedural
trans-oesophageal echocardiographic guidance [
]. Next, limb
ischaemia is often seen as a consequence of
cannularelated impediment of arterial blood flow distal to the
cannulation site [
]. Compression of the vein may also
compromise venous blood flow. Therefore, it is
imperative to closely monitor leg ischaemia and, if suspected,
adequate measures should be taken immediately. These
measures include distal cannulation using a reinforced
sheath connected to the arterial limb of the
extracorporeal circuit or a ‘chimney construction’ using a T-shaped
Dacron tube with bi-directional arterial exit. These
preventive steps should be considered in the use of relatively
large-sized cannulas or in unilateral veno-arterial
]. Ischaemic limb complications occur in less
than 5% of cases and can often be dealt with in an
adequate way but should be recognised in time and not be
● Haemodynamic complications:
Being counterintuitive at first, VA-ECLS increases LV
afterload due to continuous, retrograde infusion of
arterialised blood into the descending aorta. This, in turn,
creates elevated LV end-diastolic pressures and
consequently may cause pulmonary oedema. When LV
overload is not timely recognised, cardiac function and
ventricular mechanics may further deteriorate. Therefore,
close monitoring of an adequate pulsatility of peripheral
arterial pressure tracings (as a measure of LV ejection)
is imperative. Next, close echocardiographic follow-up
of cardiac geometry and function is imperative to
prevent irreversible cavity dilatation and progressive loss of
LV contractility. The clinical significance of pulmonary
oedema in VA-ECLS is underscored by its incidence
exceeding 30% of supported patients and its potential to
deteriorate into acute lung injury (ALI), which in turn
limits long-term outcome even after initially
successful bridging to chronically implanted ventricular assist
● Thromboembolic complications:
The ELSO registry reported a high incidence of 0.5
thrombotic events per case, but this is likely
]. Formation of thrombo-emboli is in part
caused by contact of blood with the artificial surfaces
of the VA-ECLS circuit. Thrombi can form virtually
everywhere in the circuit, grow, migrate and may even
manifest after decannulation [
]. The absence of aortic
valve opening may cause LV cavity and left atrial or
aortic root thrombosis [
]. In order to minimise the risk
of thrombus formation, anticoagulation, classically
unfractionated heparin, is generally advocated during
VAECLS and biocompatible heparin-coated surfaces are
Bleeding may arise at various locations like the
cannulation site, lungs, gastro-intestinal tract, but can also
occur in the pericardium (causing tamponade), or
intra-cranially. The incidence rate is described as being
comparable to thromboembolic events (0.5 events per patient
treatment) but can become significantly higher in certain
settings such as post-cardiotomy syndrome or after lung
transplantation. The pathophysiology of coagulation
disorders in VA-ECLS is extremely complex and includes
direct and indirect effects of anticoagulants,
haemolysis, thrombocytopenia, loss of coagulation factors and the
continuous-flow itself. Controversies exist about the true
clinical significance of acquired von Willebrand disease
and the incidence of heparin-induced thrombocytopenia,
which seems to be rather low [
● Cerebrovascular events:
A cerebrovascular accident is one of the most devastating
complications and may occur as a consequence of
thrombotic or air emboli or due to bleeding [
]. The latter could
also be superimposed on an ischaemic event. Cerebral
ischaemia can also arise due to perfusion with
predominantly desaturated blood, a phenomenon referred to as
‘Harlequin’s syndrome’. As illustrated in Fig. 3,
welloxygenated blood from the membrane oxygenator, is
infused retrogradely into the descending aorta and usually
mixes with blood flow from the heart in the aortic arch.
When significant pulmonary dysfunction prevents
adequate oxygenation of blood in the pulmonary circulation;
the aortic arch, upper right extremity and cerebrum may
receive deoxygenated blood from the left ventricle with
potentially deleterious consequences. Therefore,
mechanical ventilation, if needed, should always be titrated
to an adequate positive end-expiratory pressure (PEEP)
(and oxygen level) to assure optimal pulmonary capillary
oxygenation. In order to timely detect this phenomenon,
continuous pulse oximetry and repeated arterial blood
gas analyses from the right arm should be monitored
closely as they best reflect cerebral oxygenation via the
proximal aortic arch. Finally, cerebral hypoperfusion
may result from vascular spasm, promoted by, for
example, hypocapnia due to inadequate gas flow management.
Currently, the complex brain-ECLS interactions are far
from understood and deserve specific attention in clinical
● Systemic inflammation:
Systemic inflammation as a result of blood contact with
artificial surfaces, infectious complications and
multiorgan failure are well-documented, feared complications
]. Infection (e. g. cannulation site infections,
bacteraemia, pneumonia) is one of the most common
complications in VA-ECLS occurring in up to 13% of adult
]. In this context physicians should realise that
ongoing culture-negative systemic inflammation may
indicate membrane oxygenator colonisation which should
prompt its immediate replacement [
]. The physician
should also take into consideration that significantly
altered pharmacokinetics during VA-ECLS may result in
sub-therapeutic levels of antibiotics [
● Renal complications:
Acute kidney injury is common in patients on VA-ECLS,
but the reported incidence estimates vary greatly (roughly
10–85%) throughout studies [
], in part because of
inconsistencies in definitions of acute kidney injury.
A considerable subset of patients even requires
continuous renal replacement therapy (CRRT), which is reported
to have a significant adverse impact on outcome [
VA-ECLS is a technically sophisticated and expensive
treatment. Adequate management requires expert knowledge of
the extracorporeal circuit, cardiac and vascular
mechanics, as well as mechanical ventilation, coagulation, and
infectious diseases. This implies a 24-hour multidisciplinary
coverage of trained nurses, residents, intensivists,
cardiacsurgeons, cardiologists, anaesthesiologists and
perfusionists. Systematic monitoring should include regular (hourly)
check-ups to screen for potential complications such as
systemic emboli, bleeding, infection, Harlequin’s syndrome
and vascular problems and, last but not least, adequate
systemic perfusion and LV unloading.
Left ventricular unloading
The holy grail of supporting patients in cardiogenic shock
with VA-ECLS is to find an optimal balance between LV
unloading, sufficient residual flow through the pulmonary
circulation and left ventricle, while simultaneously
providing adequate systemic perfusion. Similar to regular heart
failure care, pre- and afterload should be kept as low as
possible. In order to lower preload, circulating volume should
be condensed as much as possible while preventing suction
events because they reduce flow and may cause cavitation.
A low afterload is imperative, but must be balanced against
the maintenance of an adequate systemic perfusion
pressure to ensure optimal organ perfusion. Lowering systemic
blood pressure can be achieved by administration of
afterload-lowering medication, e. g., sodium nitroprusside and
nitroglycerin. On the other hand, during vasoplegia,
noradrenaline may be necessary.
A general VA-ECLS management strategy should aim at
tailoring extracorporeal blood flow to the lowest degree
possible, just exceeding a critical flow preventing circuit
thrombosis (typically >2 l/min). This so called partial support
strategy allows the use of small-sized cannulas (15–17 Fr).
The sum of VA-ECLS flow and native cardiac output (where
the aortic valve opens and a dicrotic notch is visible) should
still meet physiological and/or pathophysiological
requirements. When these targets cannot be met, inotropic drugs
such as dobutamine and milrinone can be used. When all
of these measures provide too little LV unloading,
interventional strategies should be considered. Although routine
use of the IABP in conjunction with VA-ECLS is not
], a mild, but sometimes essential, reduction of
pulmonary capillary wedge pressures may be achieved [
Alternative approaches providing more potent LV
1. simultaneous use of VA-ECLS and a transaortic, axial
2. the creation of an interatrial septostomy to enable
shunting of blood from the left to the right heart;
3. direct surgical venting with a vent from the pulmonary
artery or from the left ventricle using a temporary
cannula connected to the venous side of the ECLS circuit
In this latter system, a so-called hybrid 1 ½ VAD ECLS
circuit is created.
Weaning from VA-ECLS is one of the greatest challenges
in daily management and should already be considered
early in the clinical course of support. Signs of improving
cardiac function during VA-ECLS include increasing blood
pressures (typically mean arterial pressure >65 mm Hg),
increasing pulsatility of the arterial pressure waveform,
and reduced need for inotropics and vasopressors. Several
echocardiographic parameters have been proposed to assess
recovery of LV function on reducing the VA-ECLS flow,
including ejection fraction >30%, and aortic Velocity Time
Integral (VTI) >10 cm [
]. Biomarkers to reflect cardiac
loading conditions [
] and strain imaging have so far not
conveyed advantages in VA-ECLS management [
Removal of VA-ECLS must be considered as soon as the
patient has been clinically stable for 24 h, the inotropic
demand is low and significant fluid overload is absent. Prior
to extraction of the VA-ECLS circuit, a weaning trial is
performed consisting of reducing pump flow to e. g. 50%
or 1 l/min under adequate anticoagulation. When
haemodynamics are maintained in a stable and adequate condition
extraction can be considered after administration of
]. In most patients, successful weaning can be
performed between day 2 and day 5 after treatment
initiation, although this clearly will depend on the nature and
severity of the underlying disease and its individual clinical
Strategies when cardiac function does not recover
When recovery of ventricular function fails to occur or is
deemed unlikely, a decision to withdraw treatment, or to
initiate a long-term support strategy is required. Long-term
treatment options are practically confined to implantation of
a continuous-flow LVAD, while urgent cardiac
transplantation remains preserved for only a few selected cases.
Ideally, a patient would be awake to take part in this decision
making, which is best possible after detubation while on
VA-ECLS, but requires optimal tailoring of extracorporeal
blood flow and gas exchange [
]. Importantly, LVAD
implantation requires a sufficiently preserved right
ventricular function, since long-term mechanical support in right
ventricular or biventricular failure carries an unfavourable
VA-ECLS is an increasingly used cardiac and circulatory
support modality, which can provide immediate
stabilisation in patients with otherwise refractory cardiogenic shock.
In the absence of randomised trials, observational
studies have suggested a reduction in mortality as compared
to conventional treatment. VA-ECLS should be taken into
consideration in well-selected cases. Management of
VAECLS is complex and requires constant support of trained
personnel. For this reason, the application of this support
technique should be confined to centres with sufficient
experience, ongoing exposure and a close and well-organised
Conflict of interest C.L. Meuwese, F.Z. Ramjankhan, S.A.
Braithwaite, N. de Jonge, M. de Jong, M.P. Buijsrogge, J.G.D. Janssen,
C. Klöpping and J.H. Kirkels declare that they have no competing
interests. D.W. Donker has received fees for lectures from Maquet
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