Circulation

IN DEPTH
Veno-Arterial Extracorporeal Membrane
Oxygenation for Cardiogenic Shock
An Introduction for the Busy Clinician

ABSTRACT: Extracorporeal membrane oxygenation has evolved, from a Peter M. Eckman, MD

therapy that was selectively applied in the pediatric population in tertiary Jason N. Katz, MD, MHS
centers, to more widespread use in diverse forms of cardiopulmonary Aly El Banayosy, MD
failure in all ages. We provide a practical review for cardiovascular Erin A. Bohula, MD, DPhil
clinicians on the application of veno-arterial extracorporeal membrane Benjamin Sun, MD
oxygenation in adult patients with cardiogenic shock, including Sean van Diepen, MD,
epidemiology of cardiogenic shock, indications, contraindications, and MSc
the extracorporeal membrane oxygenation circuit. We also summarize
cannulation techniques, practical management and troubleshooting,
prognosis, and weaning and exit strategies, with attention to end of life
and ethical considerations.
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E
xtracorporeal membrane oxygenation (ECMO) has evolved from a therapy
that was selectively applied in the pediatric population in tertiary centers,
to more widespread use in diverse forms of cardiopulmonary failure in all
ages. This contemporary review aims to provide a review of the application in
adult patients, including a summary of indications, contraindications, the circuit,
cannulation techniques, key practical management considerations, prognosis,
models of care, weaning and exit strategies, and end of life and ethical topics.
Herein, we provide a summary to ensure that clinicians, who may be considering
initiating or expanding the use of veno-arterial-ECMO (VA-ECMO) for cardiogen-
ic shock in their practice, have a basic understanding of the modality, including
associated risks.

EPIDEMIOLOGY OF SHOCK AND ECMO

Acute myocardial infarction (MI) is the most common underlying cause of car-
diogenic shock (CS), accounting for more than 80% of cases, though there is
a growing recognition that the pathophysiology of hypotension and end-organ
failure can be multifactorial.1 In the postrevascularization era, the incidence of
MI-associated CS ranges from 4% to 10% and is declining in most longitudinal
studies.2,3 After the publication of the SHOCK trial (Should We Emergently Revas-
cularize Occluded Coronaries for Cardiogenic Shock), an early invasive approach
in MI-associated CS has been associated with a substantial decline in mortality, Key Words:  cardiogenic shock
◼ extracorporeal membrane
though not all studies have supported these conclusions, and contemporary mor- oxygenation
tality rates remain high (30% to 50%) in observational studies and randomized
© 2019 American Heart Association, Inc.
trials.2–4 Heart failure is complicated by CS in 4% of hospitalized patients and is
the second leading cause of CS (11%).5 https://www.ahajournals.org/journal/circ

Circulation. 2019;140:2019–2037. DOI: 10.1161/CIRCULATIONAHA.119.034512 December 10, 2019 2019

 Eckman et al
In the context of persistently poor CS outcomes
and technological improvements in VA-ECMO, pa-
STATE OF THE ART
tients treated with cardiovascular mechanical circula-
tory support (MCS) have exponentially increased over
the last decade (Figure 1).6,7 An analysis of the Nation-
wide Inpatient Sample in the United States showed a
1511% increase in percutaneous device support (in-
cluding ECMO) between 2004 and 2011.6 A similar
temporal increase in use of ECMO was reported in the
ELSO Registry (Extracorporeal Life Support Organiza-
tion) with CS (60.6%), cardiomyopathy (20.5%), and
congenital defects (12.2%) being the top 3 indica-
tions among adults.7
INDICATIONS AND CONTRAINDICATIONS
Indications
The overarching purpose of VA-ECMO is to provide
temporary cardiopulmonary support for patients with
refractory shock as a bridge to recovery from the acute
incident or to allow for transition to, or candidacy for,
long-term advanced therapies, such as surgical ven-
tricular assist device or transplant. In general, the in-
dication for the use of VA-ECMO is circulatory failure,
with or without concomitant respiratory failure. Al-
though it is not mandatory for VA-ECMO, concurrent
respiratory failure may necessitate the choice of VA-
ECMO over other temporary MCS options. Also, the
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advantage of VA-ECMO over other modalities of tem-
porary MCS is that it provides robust biventricular, as
opposed to univentricular support. VA-ECMO is most
frequently used in cases of shock with predominantly
cardiogenic or obstructive physiology, and less com-
monly for distributive shock.
It is important to emphasize that indications are not
based on prospective randomized clinical trials, and de-
2020 December 10, 2019
VA-ECMO for Cardiogenic Shock
ployment is often driven by a clinical judgment that a
patient is unstable with a risk of imminent death from
cardiopulmonary failure. Specific indications for VA-EC-
MO include, but are not limited to, refractory CS attrib-
utable to myocarditis, acute MI, acute cor pulmonale
from massive pulmonary embolism, primary transplant
graft failure, postcardiotomy CS, acute exacerbation of
chronic heart failure, toxic ingestions, and intractable
arrhythmias (Table  1). In addition, certain health care
systems and centers have begun to use VA-ECMO in
the setting of in-hospital or out-of-hospital cardiac ar-
rest, or so-called extracorporeal cardiopulmonary re-
suscitation (eCPR), such as with refractory ventricular
fibrillation arrest. eCPR has been incorporated into the
most recent advanced cardiac life support guidelines,
and now “may be considered as an alternative to con-
ventional CPR for select patients with refractory cardiac
arrest when the suspected etiology of the cardiac arrest
is potentially reversible during a limited period of me-
chanical cardiorespiratory support.”8 VA-ECMO can be
considered for procedural support, such as extreme-risk
percutaneous coronary intervention or hemodynami-
cally unstable catheter ablation of ventricular or atrial
tachyarrhythmias.9,10
Short-Term Outcomes By Indication
Although outcomes data are limited to observational
studies, there does appear to be differential short-term
outcomes according to indication. The ELSO registry
reported overall survival to discharge of 41% for adult
VA-ECMO (Figure 1).7 In general, it appears that short-
term outcomes are most favorable in patients requiring
ECMO in the setting of either acute fulminant myocar-
ditis or primary graft failure after cardiac transplant, in
whom, reported survival to discharge is 70% to 80%
and are independent predictors of survival in the ELSO
Figure 1. Recent trend in extracorporeal
membrane oxygenation (ECMO) use and
survival in adult cardiac patients (from
Thiagarajan et al,7 reprinted with permis-
sion).
ECLS indicates extracorporeal life support.
Circulation. 2019;140:2019–2037. DOI: 10.1161/CIRCULATIONAHA.119.034512
 Eckman et al VA-ECMO for Cardiogenic Shock

Table 1.  Common Indications and Contraindications for VA-ECMO treated with conventional CPR. There is a rich literature
on eCPR, and adequate review of this particular subset

STATE OF THE ART

Common Indications Selected Contraindications
Refractory cardiogenic shock Relative:
of patients is beyond the scope of the present review.
secondary to: Readers with further interest are referred to recent work
   Acute myocardial infarction   Uncontrollable bleeding or on the topic for more information.22,23
contraindication to systemic
anticoagulation
  Acute exacerbation of chronic   Severe peripheral arterial Contraindications
heart failure disease
Patients with an underlying cause of CS that can be
   Fulminant myocarditis   Aortic dissection quickly corrected may be best served without VA-ECMO.
   Massive pulmonary embolism   Adverse prognostic score (such Relative contraindications to VA-ECMO include uncon-
as modified SAVE or PREDICT
   Intractable arrhythmias trollable bleeding or other contraindications to systemic
VA-ECMO)
anticoagulation. Severe peripheral arterial disease may be
   Postcardiotomy syndrome   Severe AI
a contraindication to peripheral cannulation, but central
   Primary transplant graft failure Absolute: and axillary cannulation can be considered as alterna-
  Toxins   Irrecoverable condition tives. Unrepaired aortic dissection, in which VA-ECMO
Periprocedural Support   Unwitnessed asystole flow may cause additional fenestrations or propagate
ECPR   Goals of care not in keeping dissection flaps, should be undertaken cautiously, and
with temporary mechanical acute aortic insufficiency that cannot be surgically cor-
support
rected almost immediately is prohibitive. There are few
ECMO indicates extracorporeal membrane oxygenation; ECPR, extracorporeal absolute contraindications, which include goals of care
cardiopulmonary resuscitation; SAVE, Surviving After Veno-Arterial ECMO trial;
and VA, veno-arterial.
that are not in keeping with cardiopulmonary or intensive
care support, and preexisting or acute conditions that are
registry.11–13 Observational studies of patients undergo- incompatible with recovery, such as neurologic injury or
ing VA-ECMO and percutaneous coronary intervention end-stage malignancy that preclude a meaningful chance
for CS complicating acute MI have reported short-term of intermediate-term survival or functional recovery.
survival rates of 60% to 70%, which appeared to be im-
proving compared with the 30% survival among histori-
CIRCUIT AND CANNULATION
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cal controls.14,15 Survival rates are generally lower for the

use of VA-ECMO in the setting of postcardiotomy shock,
where single-center registries report survival ranging
from 20% to 60%.16,17 Poor prognostic indicators in pa-
tients with postcardiotomy shock included older age, a
requirement for continuous renal replacement, hepatic
failure, and a prolonged duration of VA-ECMO.17
eCPR
Patients undergoing eCPR have invariably had the worst
outcomes; the ELSO registry reported 29% survival to
discharge in patients undergoing eCPR.7 As might be
expected, survival to discharge is particularly poor in pa-
tients experiencing out-of-hospital cardiac arrest with
rates of 15% to 22%. Predictors of survival and favor-
able neurologic outcomes were younger age, witnessed
arrest, initial rhythm other than asystole, and early re-
covery of blood pressure.18,19 Interestingly, 2 studies
identified an association between use of eCPR and im-
proved survival and neurologic outcomes for in-hospital
cardiac arrest compared with propensity-matched pa-
tients undergoing conventional CPR, with survival to
discharge of ≈30% versus 12% and good neurologic
outcomes of ≈24% to 28% versus 7% to 11%, respec-
tively.20,21 These poor outcomes nevertheless represent a
substantial absolute improvement compared with those
ECMO Circuit
The ECMO circuit is a sealed system without a blood
reservoir that can be configured to address variable
physiological needs. There are 4 components to the
ECMO circuit (Figure  2): cannulas, tubing, pump, and
oxygenator with a heater/cooler for blood. Common di-
rectional nomenclature for the circuit describes the flow
of blood as it relates to the pump apparatus and not the
patient. The inflow cannula is where the blood leaves
the patient going to the pump, and the outflow can-
nula or graft returns the blood to the patient. Standard
configurations are: (1) Veno-arterial, the inflow is from
the venous system, and the outflow is into an arterial
vessel, this configuration is used for CS and shunts the
blood around the heart and lungs; (2) Veno-veno, the
inflow and outflow are into the venous system, this
configuration, used typically for respiratory failure or as
a right ventricular assist device, oxygenates the blood
before entering the lungs; and (3) Veno-arterial-venous,
the inflow is from the venous system with outflow go-
ing to both the venous and arterial systems, this con-
figuration is commonly used for patients who develop
Harlequin syndrome (see below) on VA-ECMO and in
patients with pulmonary hemorrhage.
The tubing is a plasticized polyvinyl chloride 3/8-inch
or 1/2-inch internal diameter that has heparin covalently

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 Eckman et al
STATE OF THE ART
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bonded on the blood-contacting inner surface. The
heparin bonded tubing reduces complement activation,
inflammation, and platelet adhesion and activation.24 It
does not leach into the bloodstream and has been re-
ported to be safe for use in patients with heparin-induced
thrombocytopenia.25 The tubing can be spliced to permit
dialysis access on the venous side of the circuit, although
this can add turbulence, risk of air embolism, and increase
risk of infection; thus, many centers avoid this practice.
Circuit monitoring typically includes bubble detec-
tion, flow/pump stop detectors, and measurement of
withdrawal and outflow pressures. A roller pump was
2022 December 10, 2019
VA-ECMO for Cardiogenic Shock
Figure 2. Schematic of extracorporeal membrane
oxygenation (ECMO) circuit.
Blood is withdrawn from the venous system through
a 21- to 25-Fr venous cannula, renal replacement
therapy (RRT) may be optionally added, inflow pres-
sure (Pi) is measured, blood is sent through a pump,
oxygenator with sweep gas blender, heater/cooler, and
outflow pressure (Po) is measured before infusion into
the arterial system through a 15- to 21-Fr arterial can-
nula. Optional distal perfusion cannula (DPC, 4–7- Fr)
can be connected to the outflow cannula. Monitoring
includes right upper extremity arterial line, pulmonary
artery catheter, and cerebral and distal perfusion near-
infrared spectroscopy (NIRS). An additional outflow
return through the right jugular vein may be added
for veno-arterio-veno configuration. EEG indicates
electroencephalogram; ETT, endotracheal tube; and
PAC, pulmonary artery catheter.
initially used for all ECMO circuits. Because of the wear
on the tubing as well as trauma to the blood, centrifu-
gal pumps have replaced them as the energy source
used to drive the circuit. Though there are different
centrifugal pump designs, power, and efficiency, there
are no reported differences in clinical safety.26
Oxygenators
Historically, microporous polypropylene hollow fi-
ber oxygenators were used for ECMO. Unfortunately,
they had limitations, such as the development of early
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 Eckman et al
plasma leakage. The ensuing consumptive coagula-
tion limited the time of support and relegated ECMO
to salvage therapy. The development of the hollow fi-
ber polymethylpentene oxygenator alleviated this plas-
ma leak and has facilitated the potential for weeks of
ECMO support. This innovation in oxygenator design
is arguably the most important innovation facilitating
development of ECMO as a clinically safe and effective
therapeutic technique. Pressure lines pre- and postoxy-
genator monitor pressure changes. The oxygenation
is adjusted by increasing or decreasing the fraction of
inspired oxygen to the oxygenator. The ventilation (car-
bon dioxide removal) is adjusted by increasing or de-
creasing the sweep, or liters per minute, of gas passing
through the oxygenator.
A heater/cooler unit is often attached to the oxygen-
ator to facilitate targeted temperature management in
cardiac arrest patients treated, or conversely, treatment
of accidental hypothermia.
ECMO Cannulation
Cannulation for ECMO can be separated into central or
peripheral approaches. Central cannulation is defined
when at least 1 of the cannulas or grafts is placed by
access through the chest wall. Inflow cannula is typi-
cally placed in the right atrium. An outflow cannula or
vascular graft can be attached to the aorta, subclavian/
innominate artery, or pulmonary artery. Typically, the
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outflow cannulation is placed centrally. By sewing an
appropriately sized graft (≥10 mm) to the ascending
aorta, blood flow and hemolysis are rarely problematic
in central cannulation.
Advantages to central VA-ECMO include antegrade
blood flow, no flow limitations, no limb complica-
tions, ability to immediately place LV vent if necessary,
and potential mobilization/ambulation. Key disadvan-
tages include sternotomy for implant and often for
explant, higher chance for bleeding, and increased
risk of sternal infection.
Femoral artery outflow cannulation has become very
common and can be placed percutaneously or through
a surgical cut down; some centers use a side graft to
preserve distal perfusion. Percutaneous access is often
preferred, and surgical cutdown is increasingly reserved
for centers without prompt access to operators experi-
enced in the less invasive technique. Ultrasound guid-
ance facilitates vessel identification, diameter estimation
and confirmation of access. Arterial cannula sizes range
from 15 French (Fr) to 21 Fr. Many centers find that 15 Fr
will work for most women and 17 Fr for most men. The
risks for vascular limb complications are greater with
larger cannulas (>20 Fr), in women, in young patients,
and in the presence of peripheral arterial disease.27 Dis-
tal limb perfusion cannulation can be performed via
antegrade placement in the femoral artery (5-7 Fr wire
Circulation. 2019;140:2019–2037. DOI: 10.1161/CIRCULATIONAHA.119.034512
VA-ECMO for Cardiogenic Shock
reinforced sheath), antegrade through the superficial
femoral artery, or retrograde through the posterior tibial
STATE OF THE ART
artery. Limb perfusion monitoring with clinical exams,
Doppler assessment, and limb saturations are required
even with distal perfusion in place, as these smaller can-
nulas may kink or thrombose. The inflow (venous return)
cannula is most often a dual-stage wire-wound cannula
sized 25 Fr that is positioned at the junction of the intra-
hepatic portion of the inferior vena cava and the right
atrium, which optimizes blood drainage into the system.
The venous cannula is a strong determinant of the flow
that can be achieved, and 25 Fr can be safely placed in
almost all patients. It is often placed centrally directly
into the right atrium or peripherally through either an
internal jugular or femoral vein.
Advantages to peripheral VA-ECMO include the
ability to cannulate while undergoing CPR, that it can
be performed in multiple areas (operating room, cath-
eterization lab, intensive care unit [ICU], emergency
department, and prehospital),28 and femoral decan-
nulation is less morbid. Disadvantages can include dif-
ficult cannulation with arterial spasm or small femoral
artery diameter, patient immobility on support, risk of
limb complications, and potential need for distal limb
perfusion cannulation.
MANAGEMENT
Venous Chatter
Venous chatter is one of the most common patient-
circuit management issues. An ECMO circuit has a
maximum blood flow rate that is determined, in part,
by patient volume status, patient size, venous cannula
size, and pump speed. Blood flow rates above an upper
limit will cause venous/caval collapse, which can stop or
slow circuit flow rates. When sufficient pressure or vol-
ume is restored, the circuit flow resumes. This cyclical
pattern produces venous circuit chatter, which is clini-
cally evident as minor oscillations of the venous can-
nula (Video in the online-only Data Supplement). Left
uncorrected, this could result in loss of hemodynamic
support, hemolysis, or venous caval damage. Potential
patient causes include low patient volume status, hem-
orrhage, tamponade, or excessive intraabdominal or in-
trathoracic pressure. ECMO circuit causes include high
pump rates, a small cannula, cannula malposition, cir-
cuit kinking, or clot. In emergency situations with a loss
of hemodynamic support, initial management often
entails volume resuscitation and lowering pump speeds
followed by identification of the underlying cause.
Anticoagulation
A comprehensive review of the coagulation pathways,
their interaction with the exogenous material, and
December 10, 2019 2023
 Eckman et al
anticoagulant physiology is beyond the scope of this
review. This section will focus, instead, on the rationale
STATE OF THE ART
for anticoagulation, therapeutic options, and targets.
The goals of anticoagulation are to inhibit the coagu-
lation system’s interaction with the ECMO circuit; pre-
vent clotting within the heart, coronaries, and aorta
(particularly in patients with minimal cardiac function);
and minimize the risk of systemic bleeding. Although
bleeding and clotting are the 2 most common VA-
ECMO complications, reported rates vary significantly
by VA-ECMO indication, cannulation strategy, intensity
of anticoagulation, and individual patient variables.29
Significant clot formation within the VA-ECMO circuit
or oxygenator occurs in approximately 10% of adult
cases, whereas patient thrombotic events including
stroke (3.8–6.8%) and limb ischemia (3.6%) are less
frequent.7,30 Hemorrhagic complications occur in 27%
to 44% of patients and include a 2.2% risk of intracra-
nial hemorrhage.7,29
The optimal anticoagulation strategy for ECMO has
not been established.29 Currently, guidelines suggest
unfractionated heparin bolus of 50-100 U/kg at the
time of cannulation.31 Key advantages of unfractionat-
ed heparin include familiarity to clinicians, widespread
availability, point of care testing, and the availability
of an inexpensive reversal agent (protamine). Its dis-
advantages include the potential for heparin-induced
thrombocytopenia and dependence on anti-thrombin
III for clinical efficacy. ELSO guidelines suggest titrating
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unfractionated heparin to an activated clotting time or
activated partial thromboplastin time at least 1.5 times
the upper limit of normal, or anti-factor Xa activity lev-
els of 0.5 IU/ml, but optimal therapeutic ranges were
not defined.31,32 No recommendation for a testing tech-
nique or frequency was provided, but ELSO suggests
that every program develop an anticoagulation moni-
toring approach that “works best for their patients in
their individual center.”31 Thromboelastography and
thromboelastometry are theoretically attractive moni-
toring techniques that provide a more comprehensive
evaluation of the coagulation system. However, avail-
able studies in this population have only demonstrated
testing feasibility and not efficacy or safety.33
Direct thrombin inhibitors, bivalirudin and argatro-
ban, are used as the primary anticoagulant in some
centers and in patients with heparin-induced throm-
bocytopenia. They have the advantage of working in-
dependently of antithrombin III. Disadvantages include
higher drug costs and the lack of a reversal agent.
Guidelines recommend titration to an activated clotting
time or activated partial thromboplastin time of 1.5
times the upper limit of normal.32
There are insufficient data to guide the role of rou-
tine adjuvant antiplatelet agents, though antiplatelet
therapy is often required in patients with a recent per-
cutaneous coronary intervention. In patients with poor
2024 December 10, 2019
VA-ECMO for Cardiogenic Shock
myocardial contraction and intra-cardiac flow, left ven-
tricular venting strategies (see below) may help prevent
intracardiac thrombus formation. In some patients, the
therapeutic balance between bleeding and clotting may
be narrow or not achievable with bleeding and clotting
occurring concurrently. In these difficult cases, antico-
agulation initiation and therapeutic ranges require an
individualized approach.
Pharmacotherapy in ECMO
ECMO can alter the pharmacokinetics and pharmaco-
dynamics of several medications used in critically ill pa-
tients, including sedatives and antimicrobials, through
sequestration,34 for example. There are fewer data
available in adults than neonates and children, but this
is an important area of active investigation. Readers
with further interest are referred to a contemporary re-
view on the topic.35
Clot and Fibrin Formation in Circuit and
Oxygenator
Clots appear as dark spots on connectors, the oxygen-
ator, or low flow areas, whereas fibrin deposits ap-
pear white.32 Common causes include subtherapeutic
anticoagulation, heparin resistance, heparin-induced
thrombocytopenia, and slow pump speeds (≤2–2.5L/
min) for prolonged periods. The potential sequelae of
clotting includes oxygenator failure (6.6%) and isch-
emic stroke (3.8%).7 Thus, clinical practice guidelines
recommend regular monitoring of the circuit and
oxygenator with a flashlight.32 Measurement of pre-
and postoxygenator pressures provides important di-
agnostic information, as outlined in Table  2. For ex-
ample, increased transmembrane pressure (increased
pre- and low postoxygenator) suggests changes with-
in the oxygenator, usually owing to development of
thrombus. Parallel increases in pressures often sug-
gest increased resistance (for example, hypertension
or outflow cannula obstruction), and decreased pres-
sures may be caused by hypotension, hypovolemia,
or pump occlusion. Perfusionist or ECMO specialist
expertise can be essential in circuit management and
troubleshooting.
Small circuit fibrin deposits and clot formation (Fig-
ure 3) preoxygenator side of the ECMO circuit are com-
mon and pose little risk to the patient as embolized ma-
terial will be captured by the oxygenator. These deposits
are typically observed and treated by maintaining thera-
peutic anticoagulation.32 Visual inspection for thrombus
formation and postoxygenator arterial blood gases are
regularly required to monitor performance. Declines
in efficiency may necessitate oxygenator exchange. A
sectional or circuit change is often required for rapidly
growing or large preoxygenator fibrin/clots that may
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 Eckman et al VA-ECMO for Cardiogenic Shock

Table 2.  Circuit Pressure Troubleshooting clinical sequelae, which include anemia, hyperkalemia,
renal failure, or jaundice. Laboratory monitoring and de-

STATE OF THE ART

High Inflow Pressure
Causes
 Obstruction
  Cannula kink or malposition
Thrombosis
Cannula undersized
Tamponade (central)
Abdominal compartment
syndrome (peripheral)
Increased venous pressure (eg,
transient – Valsalva)
 Hypovolemia
 High outflow pressure
 Sensor failure
Evaluation and treatment
 Confirm cannula position(s)
 Consider upsizing to larger cannula
or adding second inflow cannula
 Evaluate volume status –
consider volume challenge
Transmembrane pressure should be <50 mm 
Hg; if elevated, consider
oxygenator exchange.
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High Outflow Pressure
Causes
 Cannula undersized
 Outflow obstruction (kink,
malposition, tip in dissection flap,
dislodgement)
 Arterial spasm or systemic
hypertension
 Cannula thrombosis
Evaluation and Treatment
 Imaging to confirm appropriate
outflow position
 Decrease systemic blood pressure
 Decrease speed/flow
 Upsize cannula
tection include daily lactate dehydrogenase and plasma-
free hemoglobin measurements. Common causes of EC-
MO-associated hemolysis include pump thrombosis, clot
formation in the circuit or oxygenator, venous chatter or
excessive negative access pressure, or high pump speeds.
Prevention includes maintaining therapeutic anticoagu-
lation and acceptable circuit pressures, as well as timely
management of venous chatter; treatment is focused on
addressing the underlying cause.
Circuit Air and Air Embolism
Entrainment of air into the ECMO circuit is a rare com-
plication (1.1%) that can occur either through periph-
eral venous access or via the circuit itself (loose con-
nections, open Luer locks, or oxygenator membrane
rupture).30 Air entrapment is an emergency that must
be addressed immediately, as air bubbles can result
in cerebral or peripheral air emboli. The circuit should
be equipped with bubble detection, and pump stop
mechanism enabled. Emergency management includes
clamping the ECMO circuit, placing the patient in
Trendelenburg to promote caudal migration of the air
bubbles, and initiating appropriate hemodynamic and
ventilatory patient support. Delivering 100% oxygen
may promote nitrogen gas resorption and reduce air
bubble size. Circuit management includes de-airing and

re-priming, or entire circuit changes depending on the

threaten circuit flow, causing significant hemolysis, and
for postoxygenator circuit deposits ≥ 5 mm.32
Excessive clot formation in the oxygenator may lead
to oxygenator failure. Signs of poor oxygenator func-
tion include a postoxygenator low oxygen pressure
(PO2) and elevated carbon dioxide pressure (PCO2), a
widened transmembrane pressure, low central venous
oxygenation (ScvO2), and increased hemolysis. When
oxygenator failure is progressive, the timing of a non-
emergent oxygenator change must be individualized
based on the oxygenator membrane function, rate of
decline, level of cardiopulmonary support required by
the patient, and anticipated duration of ECMO support.
Oxygenator exchange is typically performed at the bed-
side by a perfusionist or ECMO specialist.
Hemolysis
A small amount of hemolysis is common during ECMO
support. However, clinically significant hemolysis, defined
as plasma free hemoglobin levels >50 mg/dl, occurs in
approximately 5.5% of cases and merits further inves-
tigation.30,32 Clinical manifestations include dark or red
urine or continuous renal replacement therapy effluent,
which must be distinguished from rhabdomyolysis, and
air bubble burden.
Left Heart Venting
Adequate unloading of the left ventricle (LV) after CS
is essential for myocardial recovery. Depending on LV
function and ECMO flow, aortic retrograde blood flow
during VA-ECMO can increase LV afterload, which
in turn decreases LV output and increases LV end-
diastolic pressure, left atrial pressure, and pulmonary
wedge pressure. This is observed as LV distention and
pulmonary edema, often with hemoptysis and poor
gas exchange.36 Oxygenation may become severely
compromised, and poorly oxygenated blood from the
LV perfuses cerebral and coronary circulation, leading
to neurologic dysfunction and worsening myocardial
function (see Harlequin syndrome below). In a recent
meta-analysis, it was reported that 16% of patients
receiving VA-ECMO had required some form of LV
venting to mitigate this phenomenon.37 Another po-
tential consequence of high afterload is impaired LV
output, which may prevent aortic valve opening, and
increase the likelihood of clot formation within the LV
or aortic root.38
Patients receiving VA-ECMO support should be close-
ly monitored, which often includes a pulmonary artery

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 Eckman et al
STATE OF THE ART
Figure 3. Chest x-ray following shortly after peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO; left upper), 1 day later with
development of pulmonary edema (middle upper), and after atrial septostomy for venting (right upper).
Examples of white fibrin deposition in oxygenator (left lower) and thrombus in oxygenator (right lower), more evident after decannulation and saline flush.
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catheter to monitor left-sided filling pressures and a
right radial arterial pressure line to assess LV contrac-
tility and aortic valve opening with the pulse pressure
and presence of a dicrotic notch, respectively. A low
or absent pulse pressure and no aortic valve opening
indicates that VA-ECMO flow and LV afterload exceeds
the ability of the LV to eject blood. Echocardiography
should be used liberally to assess aortic valve opening,
LV and left atrial (LA) size, and to aid in intravascular
volume management. The decision of when to address
inadequate LV unloading is typically driven by a com-
prehensive assessment of filling pressures, LV contrac-
tion by waveform, aortic valve and ventricular function
by echocardiography, and pulmonary edema by level of
oxygen support and appearance on chest x-ray.
Avoiding high LV afterload is important but is sec-
ondary to ensuring sufficient ECMO flow to achieve
optimal systemic perfusion. VA-ECMO flow should be
titrated to a level that achieves adequate systemic per-
fusion and acceptable afterload, as assessed by lactate
level, arterial pH, central venous oxygen saturation,
careful dosing of vasodilators, inotropes, and intravas-
cular volume maintenance.
There is no consensus on the optimal approach for LV
venting. Diuretics or renal replacement therapy are usu-
ally necessary but are rarely sufficient. Inotropes, such
2026 December 10, 2019
VA-ECMO for Cardiogenic Shock
as dobutamine and epinephrine, may help promote
contractility and left heart decompression and may be
considered in most patients, whereas intravenous vaso-
dilators may help reduce high systemic afterload.
Mechanical unloading techniques include afterload
reduction with an intra-aortic balloon pump39 or Impel-
la 2.5, CP, or 5.0 (Abiomed Inc, Danvers, MA), LA drain-
age, atrial septostomy, pulmonary artery drainage, or
direct LV cannulation. LA drainage is accomplished by
placement of an 8- to 15-Fr cannula into the LA trans-
septally, with blood drained into the venous inflow of
the ECMO circuit. Balloon septostomy can be used to
create a left-to-right shunt that facilitates and decrease
LA volume via the preexisting right atrial cannula, but
may require surgical closure after termination of VA-
ECMO.40 Decreasing left heart volume by draining the
pulmonary artery into the ECMO inflow through a per-
cutaneously placed 15-Fr cannula has been shown to
be effective in 2 reported cases.41 The LV can be decom-
pressed by direct cannulation at the LV apex through a
mini-thoracotomy or a subcostal approach, with place-
ment of a 21- to 23-Fr cannula in the LV.38,42 Surgical
LV vent placement is indicated when more conservative
methods are ineffective, in the setting of severe cardiac
arrhythmias or cardiac standstill, or based on institu-
tional experience and preference. When VA-ECMO is
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 Eckman et al
initiated with central cannulation through a sternoto-
my, venting of the left heart can be accomplished by
direct cannulation with a 16- to 20-Fr cannula through
the LV apex or cannulation into the LA via the pulmo-
nary vein, with blood diverted by a Y connection into
the venous return of the VA-ECMO circuit.
The Impella 2.5, CP, 5.0 devices may be used for ei-
ther primary mechanical support in CS or LV unloading
during VA-ECMO. Concurrent use of VA-ECMO and
Impella is colloquially referred to as ECPELLA. Single-
center studies have shown improved hemodynam-
ics and better outcomes when the Impella is used for
LV venting.43,44 However, controlled multicenter trials
evaluating this technique have not been conducted.
The technique used should be based on the level of
expertise and training at the individual center. Identifi-
cation of the optimal threshold to trigger additional de-
compression and method of treatment remain unmet
clinical needs as we strive to define best practices for LV
decompression.
Limb Ischemia
Limb ischemia is a serious complication of femoral ar-
terial cannulation that requires careful monitoring.
This complication occurs in 3.6% of cases and can be
avoided with proper cannulation planning. Ultrasound
studies should be performed on the target cannulation
vessel to measure its diameter, allowing for optimal se-
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lection of cannula size. A properly selected cannula may
allow sufficient blood flow to the leg and avoid isch-
emia. Placement of a distal limb perfusion cannulation
should be strongly considered for use in most cases.
Distal limb perfusion cannulation is performed by inser-
tion of a 5- to 7-Fr sheath that is connected to the arte-
rial outflow of the VA-ECMO circuit. Retrograde and
antegrade cannulation may also be accomplished with
placement of a T-shaped Dacron graft on the femoral
artery. Maintaining flow through the sheath is also im-
portant to minimize the risk of sheath thrombosis, and
consideration should be given to a configuration that
permits relatively high flow or local anticoagulant infu-
sion. Leg ischemia should be monitored using near-in-
frared spectroscopy and nursing protocols that include
Doppler pedal pulse evaluation. Early recognition and
prompt treatment usually results in good outcomes.36
Harlequin Syndrome
Harlequin syndrome during VA-ECMO with peripheral
cannulation may occur when gas exchange in the lungs
is severely impaired, and deoxygenated blood from the
left ventricle enters the aorta and may be the primary
blood flow source to the coronary, right subclavian, and
carotid arteries (Figure 4).36 This is only operative with
retrograde aortic flow, such as with femoral cannula-
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VA-ECMO for Cardiogenic Shock
tion, and is not observed with central cannulation and
the resulting antegrade flow. In severe cases that go
STATE OF THE ART
undetected, myocardial recovery is hindered, and cere-
bral ischemia results in neurologic deficit.
The presence of Harlequin syndrome is detected by
monitoring the arterial oxygen saturation from the right
radial artery, as this is the most distal point from the
VA-ECMO blood flow. A pulse oximeter placed on the
fingers of the right hand may give an early indication of
desaturation. Measures to avoid severe Harlequin syn-
drome include mechanical ventilation with a sufficient
fraction of inspired oxygen and positive end-expiratory
pressure to maintain an oxygen saturation of at least
90% in the blood from the left heart. When the right
radial oxygen saturation is <88%, the VA-ECMO flow
may be low and should be increased when possible.
Inotropic support is decreased, and left heart venting
should be assessed. When these measures fail to re-
solve the low radial artery saturation, cannulation of
the ascending aorta to establish antegrade outflow can
resolve the problem, although it requires sternotomy.
Also, conversion to veno-arterio-veno–ECMO where
the outflow is split between the femoral artery and a
new cannula is placed in the superior vena cava may be
effective. In the case of splitting the outflow, cannula
clamps and outflow flow probes can be used to direct
the flow between the 2 paths, as needed.
PROGNOSIS AFTER VA-ECMO
Contemporary survival to hospital discharge after VA-
ECMO ranges from 30% to 45%,13,45–50 but can be
highly variable. Mortality reports are influenced by het-
erogeneity in patient presentation, therapeutic appli-
cation, and institutional resources. Age is perhaps the
most commonly reported risk predictor among ECMO
cohorts, and advanced age (often defined as ≥70 years)
is associated with greater mortality.48,49 In a review of
the ELSO registry, Lorusso et al49 specifically examined
the elderly population. They found that older ECMO
patients were not only more likely to die in the hospital
but also had significantly greater rates of multisystem
organ failure complicating their care. However, despite
their higher risk, these same elderly patients represent-
ed the most rapidly growing group of ECMO-supported
individuals within the entire registry.49
Short-term survival on VA-ECMO is also influenced
by the indication for MCS. There is considerable vari-
ability in reported patient outcomes for ECMO in
acute MI, end-stage heart failure, and postcardiotomy
shock,13 consistently worse outcomes are seen when it
is used as an adjunct to active cardiopulmonary resusci-
tation (eg, eCPR),50,51 although additional recent reports
have been encouraging.52–54 The eCPR score is a risk
prediction model for survival to discharge in cardiac ar-
rest patients undergoing VA-ECMO and may be helpful
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 Eckman et al
STATE OF THE ART
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in estimating early prognosis.55 Likewise, the timing of
the ECMO cannulation appears to be associated with
both morbidity and mortality. Several investigators have
found that a longer delay to support initiation is as-
sociated with a much higher risk of end-organ injury
and patient death among those with refractory CS.13,48
End-organ dysfunction has also been consistently asso-
ciated with an increased risk of mortality among ECMO
patients.13,56 In particular, the development of renal
failure and the need for renal replacement therapy is
associated with an approximately 50% reduction in
survival.13,48,56 Additionally, biochemical markers of pro-
tracted shock, such as elevations in serum lactate, are
associated with greater rates of patient death.46,56
Several risk scores have been constructed to predict
survival after ECMO placement. Among these are the
Surviving After Veno-Arterial ECMO (SAVE) and modi-
fied SAVE scores (http://www.save-score.com), each
purporting better discriminatory performance than tra-
ditional ICU prediction models.13,57 The SAVE score was
derived from the aforementioned ELSO registry, then
2028 December 10, 2019
VA-ECMO for Cardiogenic Shock
Figure 4. Harlequin syndrome occurs when deoxy-
genated blood exiting the left ventricle mixes in
the aorta with oxygenated blood from the veno-
arterial extracorporeal membrane oxygenation
(VA-ECMO), resulting in hypoxia in the brain and
right side of the body.
validated from a cohort of VA-ECMO patients admit-
ted to Alfred Hospital in Melbourne, Australia. Using a
derivation cohort of nearly 4000 patients, Schmidt and
colleagues risk-stratified patients into 5 classes. A SAVE
score of zero represents a predicted mortality of 50%,
whereas positive scores indicate a higher chance of sur-
vival.13 The modified SAVE score leveraged the prog-
nostic capabilities of the original SAVE data but also
incorporated serum lactate to enhance the model’s pre-
dictive capacity (from an area under the curve of 0.68
to 0.84).46 More recently, the PREDICT VA-ECMO score
reported a prognostic model using lactate, pH, and bi-
carbonate concentration over 12 hours of support.58
Prognostic scores such as SAVE and PREDICT VA-ECMO
can be helpful in making decisions about initiating or
withdrawing support but are rarely used in isolation.
Though short-term survival is frequently addressed in
the contemporary literature, very few studies have re-
ported on longer-term sequelae of ECMO cannulation
and patient functional capacity after ECMO support. In
one such study, a retrospective, single-center review of
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 Eckman et al
VA-ECMO patients, >40% of survivors were ultimately
dependent upon others for their activities of daily living
or were left in a persistent vegetative state at a me-
dian of 31 months.59 Neurologic and neuropsychiatric
sequelae are, in fact, common after ECMO.47,60,61 Long
term sequelae among survivors include the spectrum of
physical and cognitive features of post-ICU syndrome
(intensive care myopathy/neuropathy, cognitive dys-
function, anxiety, depression, and posttraumatic stress
disorder).62 In a study of psychiatric outcomes after
ECMO, the authors found that 39% of surviving pa-
tients developed 1 or more mental health disorders.60
Screening for cognitive deficits and mental health dis-
orders, as well as physical and occupational therapy
evaluation, should be considered for all survivors.
Rates of 1-year survival range from 24% to 38%,
with no difference in survival between ECMO and non-
ECMO patients after the first year.45,50,57 Aubin and
colleagues45 reported favorable neurologic outcomes
among long-term survivors and high rates of re-inte-
gration into the workplace. These findings were cor-
roborated by Rückert et al59 in a study of mobile ECMO,
but not supported by other investigators who have de-
scribed persistently diminished mental health and social
functioning among long-term ECMO survivors.47 In ag-
gregate, the inconsistency of these findings argues for
greater and more focused appraisal of patient quality-
of-life after VA-ECMO in contemporary cohorts.
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MODELS OF CARE FOR THE ECMO
PATIENT
Many institutions have leveraged hub-and-spoke mod-
els of care for the CS and ECMO patient. These net-
works often use a mobile team to assist in the transpor-
tation of patients to the hub (or receiving) hospital, in
some cases directing on-site cannulation before travel.
Single-center studies have consistently highlighted the
feasibility of these efforts,56,63,64 though more rigorous
investigation focusing on the superiority of these mod-
els over routine care is needed. Nonetheless, many be-
lieve that the potential to use established regional sys-
tems of care, like those used for stroke,65 trauma,66 and
acute MI67 at high-volume institutions, may ultimately
lead to similarly improved outcomes for ECMO patients.
It also has been consistently shown that the complex
management of these individuals requires coordinated,
multidisciplinary care, and collaboration.1,63,68,69 ECMO
teams should include cardiac surgeons, heart failure
and interventional cardiologists, intensive care practitio-
ners, perfusionists, respiratory therapists, pharmacists,
and nurses. Nephrologists may be required to evaluate
and treat acute kidney injury and use renal replacement
therapies. Vascular surgeons are essential for the com-
mon vascular complications from emergency peripheral
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VA-ECMO for Cardiogenic Shock
access. Neurologists may help with neuroprognostica-
tion and management if brain injury occurs. Palliative
STATE OF THE ART
care practitioners, already integrated as part of durable
MCS programs, should also be considered essential
contributors to the care of the ECMO patient.70 Among
their many benefits, palliative care practitioners can
help with the assessment and management of pain
and anxiety, the development of optimal goals of care,
and can enhance communication between patients,
families, and the entire care team. Reports have also
highlighted the benefits of dedicated cardiovascular in-
tensivists (as opposed to general critical care providers)
in the management of critically ill patients within the
cardiac ICU.71 This was particularly true among cardiac
ICU patients admitted with a diagnosis of CS, many of
whom are managed with temporary MCS. A preference
for using cardiac intensivists in closed models of car-
diac ICU care has also been championed within several
international scientific statements.72–74 A closed model
of care describes a unit in which an ICU-based physi-
cian and dedicated critical care team assumes primary
responsibility for all aspects of patient care. Additional
studies, however, are still needed to corroborate these
findings and recommendations.
Team-Based Approach to Care
Guidelines now support a team-based approach to
managing shock to deliver comprehensive, collabora-
tive, and multi-disciplinary care.1 It is also advisable that
decisions regarding VA-ECMO candidacy and subse-
quent management be addressed via a multi-disciplin-
ary, team-based approach.
WEANING AND SEPARATION
Weaning Protocol
For patients treated with VA-ECMO, there are 3 poten-
tial outcomes: recovery permitting weaning and decan-
nulation, persistent need for MCS requiring conversion
to durable support, or deterioration or death. Timeli-
ness is paramount, given the potential for catastrophic
complications while on support (see Figure 5).
Although there is no universal method for determin-
ing whether VA-ECMO can be successfully weaned and
decannulated, some general principles apply. A holis-
tic evaluation of clinical status is the first step. Namely,
have derangements in end-organ function from the
previous low-flow state improved or resolved? Stable
pulmonary status and euvolemia are particularly impor-
tant. Recall that the oxygenator can perform substantial
gas exchange, even at low sweep gas rates. Neurologic
assessment can be delayed if therapeutic hypother-
mia is used, and distinguishing injury from persistent
encephalopathy from sedation and multi-organ failure
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 Eckman et al
STATE OF THE ART
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may not be possible in a short time frame. Evaluation
of myocardial function is typically done with a combi-
nation of echocardiography and hemodynamics. Serial
echocardiography will typically provide clues as to im-
provement, assuming adequate ventricular unloading,
although ejection fraction may not reflect contractility
on ECMO.75 Turndown echocardiograms, in which the
ECMO flow is decreased, can be performed frequently
in a protocolized fashion76 and provide compelling evi-
dence of function. LV ejection fraction (>20% to 25%),
aortic velocity time integral (≥10 cm), and lateral mitral
annulus peak systolic velocity (≥6 cm/s) have been re-
ported to predict successful weaning.77 Maintenance of
systemic blood pressure at lower flow is also an encour-
aging sign that the heart sufficiently recovered without
the substantial assistance of VA-ECMO. An alternative
approach has been described in which the pump flow
is gradually reversed until low (0.5–1 L) retrograde flow
is achieved, described as a pump controlled retrograde
trial off.78 An advantage is an evaluation under more
physiologic loading conditions, albeit with the pres-
ence of an extracorporeal arteriovenous shunt. Risk of
thrombosis increases with lower circuit flow, so particu-
2030 December 10, 2019
VA-ECMO for Cardiogenic Shock
Figure 5. Algorithm for determining suit-
ability for decannulation.
Echocardiography parameters may include left
ventricular (LV) and right ventricular (RV) func-
tion, aortic outflow velocity time integral (VTI),
and lateral mitral annulus peak systolic velocity
(TDSa). BP indicates blood pressure, and MCS,
mechanical circulatory support.
lar attention must be given to anticoagulation during
weaning, such as maintaining therapeutic anticoagula-
tion when flow rates are below 2.5 to 3 L/min.79,80
Decannulation
Once the decision has been made that VA-ECMO sup-
port is no longer needed, decannulation should be ac-
complished as soon as possible, to minimize the risk
of thrombotic complications. Anticoagulation can be
held, and the circuit flow can be increased until co-
agulation parameters are suitable for the anticipated
procedure. The location (central versus peripheral) and
method (surgical versus percutaneous) of cannulation,
along with the specific local personnel and expertise
available, typically dictate the operational details. For
peripheral decannulation, some amount of vascular re-
pair is common, and complications are similar to those
seen after peripheral cannulation for cardiopulmonary
bypasses, such as lymphocele and delayed wound
healing requiring vacuum-assisted closure. Removal
of large venous cannulae is typically performed with a
purse-string suture.
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 Eckman et al
Conversion to Durable MCS
If a patient supported on ECMO for CS has not dem-
onstrated sufficient recovery to permit decannulation,
conversion to durable MCS is an essential manage-
ment option. Evaluation for medical and psychosocial
suitability for durable MCS can take several days, and
centers that do not offer this modality may limit access
if there is a delay in consideration; early consultation
with centers able to provide this option should be con-
sidered routinely.
Most patients would be characterized as high-risk
for adverse outcomes after durable MCS, given acuity
of illness, and frequent end-organ impairment. How-
ever, acceptable outcomes have been reported by sev-
eral groups.81–83 Furthermore, temporary circulatory
support with VA-ECMO can improve the medical stabil-
ity of CS patients in support of excellent durable MCS
outcomes.84,85 A recent report has also highlighted the
potential for durable MCS implant from VA-ECMO sup-
port without the use of cardiopulmonary bypass.86
Heart Transplant From ECMO
Heart transplant from VA-ECMO is uncommon. Only
1.0% of transplants between 2009 and 2016 were per-
formed from ECMO, according to the International So-
ciety of Heart and Lung Transplant Registry Data.87 High
early mortality (30% to 50%) has been reported,88–90
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although recent work suggests that risk scores may
help stratify those patients who can be transplanted
with an acceptable outcome.70,91 In the United States,
the Organ Procurement and Transplantation Network/
United Network for Organ Sharing changed the Heart
Allocation System in October 2018.92 Under the new
policy, support with VA-ECMO merits highest priority
(Status 1) for 7 days, with regional review board re-
view for possible extension every 7 days. Coupled with
broader geographic sharing, it is anticipated that heart
transplant from VA-ECMO will be more common in the
future, at least in the United States.
Withdrawal of Support
If significant myocardial recovery has not been observed
and neither durable MCS nor heart transplant is an op-
tion, terminal withdrawal of support should be consid-
ered. Devastating complications, such as catastrophic
intracranial hemorrhage, may lead to a decision to
withdraw VA-ECMO support and permit death. Surro-
gate decision-makers may also request terminal with-
drawal if the level of aggressive care provided exceeds
what the patient would have elected under the circum-
stances. Appropriate pretreatment of pain, anxiety, and
ensuring an appropriate level of sedation is essential to
avoid potential dyspnea or discomfort from pulmonary
edema. Flow may alternatively be decreased gradually,
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VA-ECMO for Cardiogenic Shock
or the circuit clamped, and the pump stopped by the
ECMO team. Patients are typically kept intubated with
STATE OF THE ART
nominal oxygen (21%) and some positive end-expira-
tory pressure to minimize the risk of pulmonary edema
or discomfort. Death should be anticipated within min-
utes to hours after stopping device support, and ECMO
team involvement should continue until death. Pallia-
tive medicine specialists and clinical ethicists can be an
integral part of such difficult decision-making and pro-
vide medical support to the ECMO team and ensure
analgesia and anxiolysis.
FUTILITY, ETHICS, AND COST
CONSIDERATIONS
Futility
The initial decision of whether to initiate VA-ECMO
support is challenging, and the decision to forgo based
on futility is often made at this point. Patients present-
ing in asystole have been reported to have 0% survival
from VA-ECMO, but the presenting circumstances are
rarely so clear-cut.93 The decision if and when to termi-
nally withdraw VA-ECMO for futility poses a different
challenge than the decision of whether to initiate, in
part because there is now time for myriad perspectives
to develop and be expressed. Tensions both within the
interdisciplinary medical team and within patient fami-
lies and friends are common in the care of such criti-
cally ill patients, and the risk of moral distress is high
for all involved.94 Efforts to build shared understanding
and consensus are merited, both for peace of mind for
next of kin, but also to ensure professional relationships
within the medical team are respectfully maintained.
The myriad factors that contribute to a medical deter-
mination of futility are beyond the scope of this review,
but some common markers in the VA-ECMO popula-
tion include neurologic injury that precludes return to a
minimally acceptable level of function or contraindicates
conversion to durable MCS, ineligibility for an immedi-
ate heart transplant, or refractory end-organ dysfunc-
tion. Acute kidney injury is common in this population,
and the inability to maintain sufficient blood pressure to
permit even continuous renal replacement therapy may
be a milestone defining futility in some cases.
A recent survey of 179 physicians evaluated opin-
ions on whether the medical team should have the
right to discontinue VA-ECMO over the objection of
a patient surrogate.95 Seventy-six percent of attending
physicians responding were supportive, in contrast to
the more normative practice of shared decision-mak-
ing. An important difference with VA-ECMO, however,
is that technological and practical limitations prevent
prolonged use so that long-term support of a patient
with devastating but not fatal neurologic injury is sim-
ply not possible.
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 Eckman et al VA-ECMO for Cardiogenic Shock

Table 3.  Future Research and Development Needs

STATE OF THE ART

ECMO Research Sphere Clinical Research Need

Efficacy and safety
Cannulation and circuit
Patient management
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Evaluating whether ECMO improves survival in common indications including cardiogenic shock, cardiac arrest,
hypothermia, drug overdose, acute pulmonary thromboembolism, and quantification of benefit
Defining appropriate patient selection, timing and evidence-based contraindications with attention to the challenging
circumstances in which emergency decisions are often made
Evaluating the optimal cannulation strategy for patients in centers without ECMO (mobile cannulation teams versus
hospital-based cannulation)
Comparison with other mechanical circulatory support devices in cardiogenic shock
Examining the relationship between cannulation location (femoral, central, axillary), access (cannula, side grafts), and
complications including limb ischemia, bleeding, and patient mobility
Anti-coagulation therapeutic targets, agents, and role of adjuvant anti-platelet agents
Technical improvements in cannulas
 Reduction in thrombogenicity
 Improvement in durability
 Role of antimicrobial coatings to reduce infection
 Improved interface with blood vessels to minimize risk of bleeding, facilitate safe insertion, and stabilization to
promote patient mobility
 Techniques to obviate need for separate distal perfusion
Technical improvements in oxygenator
 Improvement in durability
 Reduction in thrombogenicity
Ventilatory management including ventilation modes, pressure or volume goals, oxygenation targets
Fluid management goals, choices (crystalloid versus colloid), and therapeutic goals
Defining optimal transfusion thresholds
Testing medical and mechanical left ventricular decompression strategies (triggers, methods of treatment)

Inotrope/Inopressor selection and hemodynamic targets

Timing and intensity of renal replacement therapy
Optimal sedation agents, duration, and therapeutic targets
Pharmacokinetic and pharmacodynamic data for commonly used agents
Testing of ECMO weaning strategies and protocols
Defining the role of adjuvant monitoring techniques including cerebral/peripheral saturation, pulmonary arterial
catheters, distal perfusion, and continuous EEG monitoring
Care systems Defining minimal provider, care unit, and hospital practice volumes for cannulation and management
Evaluating if multi-disciplinary ECMO teams can improve outcomes and reduce complications
Testing if mobile ECMO systems or regional hub-and spoke care systems can improve outcomes
Prognosis and care transitions Derivation and external validation of dynamic prognostic models that be used at the time of cannulation decision and
throughout ECMO support to determine appropriateness for transition to destination therapies or decannulation
Development of recognized treatment futility standards of care
Cost Improve cost effectiveness of ECMO

ECMO indicates extracorporeal membrane oxygenation.

Ethical Considerations threats to each pillar. Disputes in the decision-making

The 4 most commonly cited pillars of medical ethics,
autonomy (informed consent), beneficence, nonmalef-
icence, and justice, are all themes that arise in the care
of mortally ill patients who typically require VA-ECMO,
as recently reviewed.96,97 There is seldom time to obtain
first-hand consent, determining who will benefit dur-
ing a crisis (sometimes without any medical history) is
challenging, the risk of catastrophic complications is
omnipresent, and VA-ECMO is resource-intensive; clear
and care of this population are common between the
surrogate(s) and the medical team, within groups of
caregivers/families, and within the medical team itself.
Palliative care and ethics consultants can help provide
support to all involved, even if no specific ethical ques-
tion or dilemma has been identified.98 Disputes are of-
ten focused on whether enough time has passed to
predict an outcome accurately; has treatment passed
the point of benefit and entered the realm of harmful?

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 Eckman et al
Many caregivers involved in the care of VA-ECMO pa-
tients exclusively provide inpatient care, and thus see
a disproportionate share of adverse outcomes without
the benefit of seeing the long-term survivors, a factor
which may increase risk for burnout and informs per-
sonal opinions about when the line from beneficence
to maleficence has been crossed.
Some outstanding provocative questions might
include: (1) Withdrawing and withholding treatment
are generally regarded as ethically and legally equiva-
lent. Is this different for an awake patient who will
not recover and is ineligible for durable support op-
tions, but declines removal in the face of near-certain
and prompt death?96 (2) In the setting of substantial
therapeutic uncertainty, under what circumstances
can clinicians decline to initiate VA-ECMO? (3) Does
the ability of VA-ECMO to provide adequate cardio-
pulmonary support despite complete cardiac arrest,
and without using the lungs for gas exchange, alter
the concept of cardiac death? (4) Should care of VA-
ECMO patients after cannulation be regionalized to
centers with durable support options such as ven-
tricular assist device or transplant akin to the system
of trauma centers? (5) How are triage decisions made
when a center is unable to provide this resource-in-
tensive therapy to additional patients, whether at-
tributable to insufficient facilities, staffing, cost, or
lack of local/regional alternatives? (6) Should EMS
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systems preferentially incorporate centers able to
provide this level of support into triage and transport
decisions, and do hospitals without ECMO capability
have an obligation to partner with systems that can
provide timely access for initially unsuccessful resus-
citation efforts?
Cost Considerations
Cost to provide VA-ECMO can vary substantially and is
determined by a combination of equipment, person-
nel, and the costs typically associated with hospital
stay (medications, laboratory, radiology, blood prod-
ucts). A recent single program retrospective financial
review found that ICU charges were by far the larg-
est expense and comprised almost one-third of total
charges;99 international experience has also noted that
the ECMO-attributable charges were a small propor-
tion of total hospital costs.100 Charges directly attribut-
able to ECMO averaged $74 500±61 400 per patient.
One substantial cost that can be directly attributable
to ECMO is if full-time perfusionist coverage is man-
dated at the bedside. Of note, published experience
has demonstrated that experienced intensive care unit
nurses or ECMO specialists can manage extracorporeal
life support circuits with excellent outcomes and at a
lower cost.68,101 Avoiding the requirement for continu-
ous perfusionist presence may also help ensure that
Circulation. 2019;140:2019–2037. DOI: 10.1161/CIRCULATIONAHA.119.034512
VA-ECMO for Cardiogenic Shock
hospital cardiothoracic surgical procedures do not
need to be canceled or delayed because of a lack of
STATE OF THE ART
perfusionists. Despite the significant cost, reimburse-
ment for VA-ECMO in the United States is proportion-
ally high; the current payment system has historically
provided adequate support for hospitals and health
systems to provide this complex care without major fi-
nancial losses. Payment system evolution is a perpetual
topic of great interest, and the Center for Medicare
Services changed codes and diagnosis-related group
for ECMO significantly in October 2018; the Inpatient
Prospective Payment System (IPPS) rule returned to the
prior designation in August 2019 for fiscal year 2020.
FUTURE NEEDS
Despite the significant advances in VA-ECMO for car-
diogenic shock, a number of important research needs
remain, as summarized in Table 3.
CONCLUSION
VA-ECMO has rapidly evolved from a rarely used treat-
ment at few centers to a conventional, aggressive op-
tion for suitable candidates with severe cardiopulmo-
nary failure at a growing number of centers. Many
patients who would historically not survive now have
a powerful treatment option, albeit with a risk of sub-
stantial complications and posing ethical and financial
challenges. VA-ECMO has transformed the clinical care
of patients with severe cardiogenic shock, and cardio-
vascular specialists need to have a basic understanding
of this treatment option.
ARTICLE INFORMATION
The online-only Data Supplement is available with this article at https://www.
ahajournals.org/doi/suppl/10.1161/circulationaha.119.034512.
Correspondence
Peter M. Eckman, MD, Minneapolis Heart Institute, 920 E 28th Street, Suite
300, Minneapolis, MN 55407. Email peter.eckman@allina.com
Affiliations
Minneapolis Heart Institute, MN (P.M.E., B.S.). Department of Medicine, Duke
University Medical Center, Durham, NC (J.N.K.). Department of Advanced
Cardiac Care, INTEGRIS Baptist Medical Center, Oklahoma City, OK (A.E.B.).
Thrombosis in Myocardial Infarction Study Group, Department of Medicine,
Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical
School, Boston, MA (E.A.B.). Department of Critical Care Medicine and Divi-
sion of Cardiology, Department of Medicine, University of Alberta, Edmonton,
Canada (S.V.D.).
Disclosures
Dr Eckman discloses the following: Abbott Laboratories – Honoraria (Modest,
all donated), Medtronic – Honoraria (Modest, all donated). Dr Katz discloses
the following: Abbott Laboratories – Research (Modest). Dr Sun discloses the
following: Abbott Laboratories – Consulting (Modest). The other authors re-
port no conflicts.
December 10, 2019 2033
 Eckman et al
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