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Journal of Cardiothoracic and Vascular Anesthesia 000 (2019) 1
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Contents lists available at ScienceDirect

Journal of Cardiothoracic and Vascular Anesthesia

journal homepage: www.jcvaonline.com

Review Article
Extracorporeal Membrane Oxygenation: The New
Jack-of-All-Trades?
1
Jenny Kwak, MD , Michael B. Majewski, MD,
W. Scott Jellish, MD, PhD
Division of Cardiothoracic Anesthesia, Loyola University Medical Center, Maywood, IL

The role of extracorporeal membrane oxygenation in the adult patient population still is evolving. Technologic advancements have improved the
ability to provide extracorporeal life support. The miniaturization and durability of these systems have made extracorporeal membrane oxygen-
ation more convenient and mobile than ever. Because of these improvements, its use has increased steadily. The indications for use also have
diversified. In this review, the authors provide a panoramic view of extracorporeal membrane oxygenation to provide a foundation of knowledge
for anesthesiologists.
Ó 2019 Elsevier Inc. All rights reserved.

Key Words: extracorporeal membrane oxygenation; ECPR; respiratory failure; cardiogenic shock; postcardiotomy; mobile ECMO; neurologic complications;
bridge to transplant

Background The role of ECMO in the adult patient population is expand-

Extracorporeal life support (ECLS) is a broad term that
includes extracorporeal membrane oxygenation (ECMO), car-
diopulmonary bypass (CPB), and extracorporeal cardiopulmo-
nary resuscitation (ECPR). The term ECMO is used
predominantly in this review to distinguish it from CPB. The
term ECLS is used where appropriate.
The Extracorporeal Life Support Organization (ELSO) is an
international registry that collects data on adults and children.
Since its inception, ELSO has collected data on 78,397
patients with a 58% survival to hospital discharge (Table 1).1
In the past 10 years, the number of ECMO cases has increased
steadily each year with the largest growth occurring in the
adult population.1,2 The miniaturization and durability of
ECMO systems have made it more convenient and mobile
than ever. However, ECMO-related morbidity and mortality
remain high (Table 2).1
ing and evolving. Indications typically are classified by respi-
ratory or cardiac failure. Extracorporeal membrane
oxygenation for bridge to transplantation (BTT) is increasing,
and ECPR has become its own category.1 There are increasing
case reports about ECMO being used for temporary support
during procedures and a mobile service not unlike ST-eleva-
tion myocardial infarction and stroke programs.
This is a new era of ECLS in which the question is: Is
ECMO the new jack-of-all-trades, the master of none, or some-
where in between? In this review, the authors offer a pan-
oramic view of ECMO to provide a foundation of knowledge
for anesthesiologists. The authors provide an overview of tech-
nology, indications for use, and patient selection in addition to
a review of current trends and literature. Anesthetic considera-
tions and potential complications are discussed throughout the
review. Also included is a special contribution on neurologic
complications.

1 ECMO Circuit and Technology3
5

Address reprint requests to Jenny Kwak, MD, Department of Anesthesiol-
ogy and Perioperative Medicine, Loyola University Medical Center, 2160
South First Ave, Maywood, IL 60153. Since the first successful application, numerous advances
E-mail address: jkwak@lumc.edu (J. Kwak). have improved the ECMO circuit. Circuits have 3 fundamental

https://doi.org/10.1053/j.jvca.2019.09.031
1053-0770/Ó 2019 Elsevier Inc. All rights reserved.
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Table 1 allow for longer and safer use owing to advances in bearing-
ECLS Cases and Survival to Discharge From the ELSO Registry free pump designs that are also more compact and portable
Number of Survived ECLS Discharged
than roller pumps.
Cases N (%) N (%) Additional technology found on ECMO circuits includes
heat exchangers, the ability to measure line pressures, ultra-
Neonatal
Respiratory 29,153 24,488 (84) 21,545 (74)
sonic flow detectors, and measurement of oxyhemoglobin sat-
Cardiac 6,475 4,028 (62) 2,695 (42) uration. Normal inlet pressures are negative 100 to 200
ECPR 1,336 859 (64) 547 (41) mmHg. Cavitation can occur when pressures exceed negative
Pediatric 750 mmHg, which can lead to hemolysis. Outlet pressure
Respiratory 7,552 5,036 (67) 4,371 (58) should not exceed 400 mmHg. Hemolysis, turbulent line flow,
Cardiac 8,374 5,594 (67) 4,265 (51)
ECPR 2,996 1,645 (55) 1,232 (41)
and overheating all become concerns at higher outlet pres-
Adult sures. Saturations should be measured before and after gas
Respiratory 10,601 6,997 (66) 6,121 (58) exchanger to monitor for oxygenator failure. Although the cur-
Cardiac 9,025 5,082 (56) 3,721 (41) rent generation of hollow fiber oxygenators minimizes plasma
ECPR 2,885 1,137 (39) 848 (29) leak, it is still a concern, especially with longer use. A device
Total 78,397 54,866 (70) 45,345 (58)
for continuous renal replacement therapy can be introduced to
NOTE. Reproduced with permission from Thiagarajan et al.1 the ECMO circuit, typically post-pump and pre-oxygenator.
Abbreviations: ECLS, extracorporeal life support; ECPR, extracorporeal
cardiopulmonary resuscitation; ELSO, Extracorporeal Life Support Types of ECMO and Cannulation Options
Organization.

Venovenous (VV)-ECMO is indicated for primary hypox-

Table 2 emic respiratory failure and does not provide hemodynamic
Adverse Events During ECLS for Adults by Indication support. Common cannulation strategies include femoral-
Percent (%)
atrial, femoral-femoral, and the use of a single dual-lumen
catheter (Fig 1). Venous cannula positions should be con-
Respiratory firmed by transesophageal echocardiography or other imaging
Mechanical: pump malfunction 1.5
Mechanical: oxygenator failure 9.1
modality such as fluoroscopy. Even with proper positioning,
Cannula site hemorrhage 13.2 recirculation can occur (oxygenated blood returned to the right
Surgical site hemorrhage 10.5 atrium enters the drainage cannula rather than the right ventri-
Pulmonary hemorrhage 6.1 cle). Recirculation reduces the efficiency of VV-ECMO and
CNS hemorrhage 3.9 should be minimized. See Table 3 for a list of factors that
CNS infarction 2.0
Renal failure 9.3
increase recirculation and options for quantification. Trends by
Hyperbilirubinemia 8.7 quantification and arterial saturation can be used to monitor
Infection 17.5 for recirculation. A properly placed dual-lumen cannula has
Cardiac been shown to reduce recirculation.6 However, larger dual-
Mechanical: pump malfunction 0.8 lumen cannulas have been associated with intracranial hemor-
Mechanical: oxygenator failure 6.6
Cannula site hemorrhage 18.5
rhage thought to be related to increased intracranial venous
Surgical site hemorrhage 20.2 pressure.7 Thus the smallest cannula should be used when pos-
Pulmonary hemorrhage 3.1 sible.
CNS hemorrhage 2.2 Echocardiography guidance is paramount to proper posi-
CNS infarction 3.8 tioning of a dual-lumen cannula. Blood returning to the right
Renal failure 12.3
Hyperbilirubinemia 12.2
atrium must be directed toward the tricuspid valve or
Infection 13.0 else recirculation can occur. During placement, TEE guidance
reduces the risk of vessel or cardiac injury, both of which have
NOTE. Reproduced with permission from Thiagarajan et al.1 been reported.8
11 From a midesophageal bicaval view,
Abbreviations: CNS, central nervous system; ECLS, extracorporeal life
support.
the wire should be followed from the superior vena cava
(SVC) to the inferior vena cava (IVC). Echocardiography can
be used to confirm positioning of the distal cannula tip within
components: a blood pump, gas exchange device, and heat the final 4 to 5 cm of the IVC. If needed, slightly withdrawing
exchanger. Blood pumps are categorized as occlusive (roller) the cannula can remove any anterior curvature. Rotation of the
or nonocclusive (axial and centrifugal). Considerations for cannula to move the tip posteriorly helps to avoid crossing the
roller pumps include the possibility of tubing rupture and tricuspid valve or catching on the Eustachian valve.12 Confir-
release of emboli. The mechanical stress placed on red blood mation that the return orifice is in the upper right atrium and is
cells and tubing by roller pumps has led to the preference for directed toward the center of the TV will minimize recircula-
nonocclusive pumps. Considerations for nonocclusive pumps tion. If adjustment is necessary, the cannula should be rotated
include hemolysis from shear stress and turbulent flow as well in the same direction as the TEE probe when switching from a
as localized heat generation. Newer nonocclusive devices bicaval view to a modified bicaval view, which shows the
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Fig 1. Cannulation options for venovenous ECMO. (A) Femoral-atrial cannulation. Drainage is achieved through the femoral cannula with tip in the IVC, and oxy-
genated blood is returned to the right atrium via a cannula placed in the internal jugular vein. (B) Femoral-femoral cannulation. Drainage is identical to (A). Oxy-
genated blood is returned to the right atrium via a cannula placed in the opposite femoral vein and advanced until the tip lies within the right atrium. (C) Dual
lumen cannula placed in right internal jugular vein with tip within the IVC. Drainage occurs from the IVC (via the tip) and from the SVC (via side ports) and oxy-
genated blood is returned through an outlet port that is directed toward the tricuspid valve. Reproduced with permission from Sidebotham et al.4 ECMO, extracor-
poreal membrane oxygenation; IVC, inferior vena cava; RA, right atrium; SVC, superior vena cava; TV, tricuspid valve.

tricuspid valve from a view that shows the return jet. Before
Table 3 ECMO initiation, saline can be injected into the return lumen
List of Factors That Increase Recirculation and Available Methods of to visualize the outflow jet. Although technically challenging
Quantification6 to place, using a dual-lumen cannula requires access to only 1
vessel, thus reducing bleeding risk, and increases the possibil-
Factors That Increase Recirculation Quantification Options
ity of ambulation while on VV-ECMO. Some centers have
Close proximity of drainage and Calculations based on saturation reported success with rehabilitation, including ambulation, in
return cannulae
patients on ECMO with femoral cannulation.13 This approach
Elevated intrathoracic pressure Ultrasound-detected dilution of blood in
the drainage limb requires a highly trained multidisciplinary team that includes a
Higher pump speeds Thermodilution of blood in drainage limb perfusionist to monitor for changes in ECMO flow.
High blood flow Trending pre-oxygenator blood saturation Selective extracorporeal CO2 removal is a variant of VV-
Malposition of return cannula ECMO in which the goal is CO2 removal rather than oxygen
NOTE. Any quantification method can be used regardless of the cause of delivery. Much lower flows (<1 L/min) are required to provide
recirculation. None of the listed quantification methods ever have been shown sufficient CO2 removal when oxygen delivery is unnecessary.14
to give a “percentage of recirculation” definitively and accurately. Treatment Indications include hypercapnic respiratory failure such as
of problematic recirculation depends on the cannulation strategy and etiology. chronic obstructive pulmonary disease and supplementation of
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Table 4
Types of ECLS, Cannulation, and Indications

Type of Most Common Cannulation Indications Common Disease States Treated

ECLS Options
VV Femoral-jugular Hypoxemic § hypercarbic respiratory ARDS
Dual-lumen jugular failure End-stage lung disease as BTT
VA Femoral-femoral Cardiac circulatory failure Postcardiotomy heart failure
Right atrial-aortic Acute heart failure
Jugular-subclavian Acute decompensated heart failure
ECPR
High-risk PCI
VVA Femoral + jugular-femoral Upper-body hypoxemia despite Persistent hypoxemia due to intracardiac shunt despite full
VA-ECMO VA-ECMO
VAV Femoral-femoral + jugular Hypoxemic respiratory failure in the Persistent hypoxemia due to worsening pulmonary function
setting of cardiac circulatory failure despite full VA-ECMO
ECCO2R Femoral-jugular Hypercarbic respiratory failure Status asthmaticus
Dual-lumen jugular COPD
Arterial-venous* ARDS with lung ultra-protective strategy

Abbreviations: ARDS, acute respiratory distress syndrome; BTT, bridge to transplant; COPD, chronic obstructive pulmonary disease; ECCO2R, extracorporeal
carbon dioxide removal; ECLS, extracorporeal life support; ECMO, extracorporeal membrane oxygenation; ECPR, ECLS to support cardiopulmonary
resuscitation; PCI, percutaneous coronary intervention; VA, venoarterial; VAV, venoarterial-venous; VVA, veno-venoarterial.
* When arterial-venous ECCO2R is used, no circulation pump is used. Flow is determined by mean arterial pressure and requires sufficient cardiac output.

CO2 removal in ultra-protective ventilation strategies for acute
respiratory distress syndrome (ARDS). Cannulation can be
identical to VV-ECMO, but an appropriate pump should be
used to deliver the low flows required for extracorporeal CO2
removal. Alternatively, arterial-venous cannulation can be used.
In this instance, blood is sent to an oxygenator from an artery,
flow through the oxygenator is driven by arterial pressure rather
than a pump, CO2 is removed, and then blood is returned to a
vein. An arterial-venous gradient of at least 60 mmHg and a suf-
ficiently large cardiac output to avoid hypotension are
required.14
Venoarterial (VA)-ECMO is indicated for cardiac failure.
Venoarterial ECMO using femoral artery cannulation can lead
to different oxygen saturations in the upper and lower body
known as differential hypoxia. Arterial oxyhemoglobin satura-
tion measured from the right radial artery most closely approx-
imates blood flow to the coronary and carotid arteries. A
significant difference between oxygen content of radial arterial
and femoral arterial suggests differential hypoxia and should
be addressed. This can occur with insufficient VA-ECMO
flows, malposition of a cannula, or recovery of cardiac func-
tion. Persistent upper-body hypoxemia despite normal ECMO
flows may necessitate the placement of a third cannula (see tri-
ple cannulation below) or conversion to VV-ECMO.15 In addi-
tion, if femoral artery cannulation is used, distal limb ischemia
is a concern. The risk can be minimized with placement of a
distal perfusion cannula or by cannulating the femoral artery
via a chimney graft.16
In veno-venoarterial ECMO, a second venous drainage can-
nula is placed (such that there are now drainage cannulae
within both the IVC via the femoral vein and the SVC via the
internal jugular vein), and the 2 venous cannulae are connected
via a Y-adapter. In venoarterial-venous ECMO, oxygenated
blood is returned to both an arterial cannula and a separate
venous delivery cannula commonly placed via the jugular
vein. The theoretical advantages of either technique over tradi-
tional VA-ECMO include treatment of differential hypoxia
and additional cardiac unloading. No study data exist for
veno-venoarterial ECMO, so it cannot be recommended for
routine use at this time.17 In the instance of venoarterial-
venous ECMO, no survival benefit has been realized.18
Lastly, safe cannulation of the jugular vein or pulmonary
arterial catheterization of a patient on ECMO can be challeng-
ing. Any catheter that can reach the right atrium, especially
one with a flow-directed balloon such as a pulmonary artery
catheter, can be sucked up by the drainage cannula. In addi-
tion, reduced right atrial pressure from blood drainage can
increase the risk of air embolism. Aspiration of the guidewire
into the venous drainage line has been reported.19 If feasible,
turning down the ECMO flow during placement would reduce
these risks.
Types of ECMO and cannulation strategies are listed in
Table 4. The hemodynamic consequences of each type of
ECMO are summarized in Table 5. A typical VA-ECMO setup
is pictured in Figure 2.
Anesthetic Considerations
The pharmacodynamics and pharmacokinetics of medica-
tions given on ECMO are complex due to characteristics
related to the patient (critically ill with end-organ dysfunc-
tion) and to ECMO itself. Considerations related to ECMO
include the larger volume of distribution and adsorption of
medications to polyvinyl chloride tubing or the membrane
oxygenator (lipophilic and highly protein-bound medica-
tions). The use of renal replacement therapy also contributes
to the complexity. Thus, therapeutic drug monitoring should
be used when possible to monitor for efficacy and toxicity.
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Table 5
Hemodynamic Consequences of Different Types of ECMO

Strategy Right Atrial Pressure Left Ventricular End Diastolic Pressure* Systemic Blood Pressure LV Afterload Catecholamine Dosing
Vasopressors Inotropes
y
VV $ $ $ $ $-# $
VA #-## Varies (should decrease) "" "" # #
VVA ## Varies (should decrease) "" "" # #
VAV Varies " " " Varies Varies

NOTE. Although VV-ECMO is largely neutral in this context, all cannulations with arterial access profoundly influence venous and arterial pressures by modified
flow. Much of the information in this table is based on experience and requires formal confirmation by dedicated studies. Reproduced under CC BY 4.0 (Open
Source publication) from Napp LC et al.17
Abbreviations: VA, venoarterial; VAV, venoarterial-venous; VV, venovenous; VVA, veno-venoarterial.
* Effects vary upon function of the aortic valve.
y May decrease with improvement of metabolic status by enhanced gas exchange.

Fig 2. Venoarterial extracorporeal membrane oxygenation setup. Typical “ECMO cart” configuration using the Maquet Cardiohelp (Maquet Holding B.V. & Co.
KG, Rastatt, Germany). The pump (A) and oxygenator (B) sit atop a mobile cart, allowing for easy movement. The oxygenator is positioned behind the pump. The
display panel (C) shows revolutions per minute of the centrifugal pump, measured blood flow through the pump, venous and arterial saturation and temperature,
and hemoglobin (Hb) and hematocrit (Hct). ECMO, extracorporeal membrane oxygenation.

For anesthesia maintenance, intravenous medications are pre-
ferred to volatile anesthetics. The delivery of volatile anes-
thetics may not be reliable owing to reduced pulmonary
blood flow (VA-ECMO) or pulmonary failure. Lung-protec-
tive ventilation strategies should be used to minimize baro-
trauma, avoid oxygen toxicity, reduce pulmonary edema, and
reduce the presence of inflammatory mediators.20
23 This
includes tidal volumes <6 mL/kg and plateau pressure
<30 cm H20. A positive end-expiratory pressure of 10 to
15 cm H20 may be need for patients with pulmonary failure.
Additional ventilation modes to be considered for patients
with respiratory failure include prone positioning, bilevel air-
way pressure mode, airway pressure release ventilation, and
high-frequency oscillatory ventilation.20
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Table 6
Anticoagulant Dosing and Monitoring for ECMO

Drug Typical Dosing Monitoring Additional Information

UFH 50-100 units/kg IV bolus
7.5-50 units/kg/h infusion
Bivalirudin 0.05-0.5 mg/kg/h infusion
Argatroban 0.1-0.7 mg/kg/min infusion
ACT or aPTT to 1.5-2.0 £ baseline value Recommended if no contraindication
anti-Xa 0.3-0.7 IU/mL
aPTT goal 50-60 s 20% undergoes renal elimination
ACT also can be used t1/2 approximately 25 min
Use documented in clinical studies as well as case series
aPTT goal 50-60 s Primary hepatic elimination
ACT also can be used t1/2 approximately 45 min
Use documented by case reports and case series

NOTE. UFH is the recommended first-line agent. If a contraindication exists, bivalirudin has been studied as the anticoagulant for ECMO and is the recommended
alternative agent for cardiopulmonary bypass in the setting of HIT, according to the Society of Thoracic Surgeons.26 Argatroban is recommended in the context of
significant renal dysfunction.
Abbreviations: ACT, activated clotting time; aPTT, activated partial thromboplastin time; HIT, heparin-induced thrombocytopenia; IV, intravenous; UFH,
unfractionated heparin.

Anticoagulation and Transfusion anticoagulation, but Buscher et al. had one-third of their
ECMO cases occur without any heparin administration and
During ECLS, blood comes into contact with a foreign sur- found no statistical difference in survival to discharge.25 Anti-
face, necessitating anticoagulation to prevent thrombosis of coagulant-free ECMO should be reserved only for instances
the circuit. Baseline laboratory values, including activated par- where severe bleeding is occurring.
tial thromboplastin time (aPTT), prothrombin time/interna- Transfusion thresholds and protocols vary from center to
tional normalized ratio, D-dimer, fibrinogen, complete blood center. Extracorporeal Life Support Organization guidelines
count, activated clotting time (ACT), and thromboelastogra- recommend fresh frozen plasma to maintain INR to less than
phy or rotational thromboelastometry ideally should be mea- 1.5 to 2.0, platelet count > 100,000 cells/mm3, and fibrinogen
sured before ECMO initiation. The most widely used greater than 100 to 150 mg/dL.24 Antifibrinolytics can be con-
anticoagulant is unfractionated heparin (UFH) owing to its pre- sidered for patients with active bleeding or evidence of
dictable, dose-dependent half-life, ease of monitoring with increased fibrinolysis and those undergoing surgical proce-
aPTT and ACT, and reversibility with protamine. Typical dures. Recombinant activated factor VII (15-50 mg/kg) and
goals are elevating the ACT or aPTT to 1.5 £ to 2.0 £ their prothrombin complex concentrates (25-50 IU/kg) have been
normal values (180-220 seconds and 50-70 seconds, respec- used to treat refractory bleeding.24 Prothrombin complex con-
tively) and are achieved with an initial heparin bolus at the centrates are potentially less likely than recombinant activated
time of cannulation followed by continuous infusion.24,25 factor VII to cause thrombosis.
Unfractionated heparin dosing protocols vary by institution
and by patient age, but generally fall within 50 to 100 units/kg
bolus followed by 7.5 to 50.0 units/kg/h and titration to aPTT
Table 7
or ACT goals. In instances where additional heparin doses fail ECMO for Respiratory Failure30,39
41
to achieve antithrombotic goals, antithrombin (AT) replace-
ment may be indicated via fresh frozen plasma or recombinant Indications Conditions Associated With
Poor Outcomes
AT concentrates. Centers that routinely test for AT levels tar-
get AT levels greater than 50%.24 At this time, the lack of reli- Hypoxic respiratory failure Prolonged mechanical ventilation
able monitoring, time to therapeutic effect, and availability of > 7 d at extreme settings
Hypercapnic respiratory failure Severe neutropenia
an antidote make oral and intravenous direct thrombin inhibi-
Severe air leak syndromes Immunosuppression
tors, oral Xa inhibitors, vitamin K antagonists, prostaglandins, Bridge to lung transplantation Acute CNS hemorrhage
and other anticoagulants less appealing than UFH. In instances ECPR Non-recoverable terminal disease
where heparin is contraindicated, such as in the case of hepa- (eg, diffuse malignancy)
rin-induced thrombocytopenia, intravenous direct thrombin Advanced age
Late initiation of ECMO
inhibitors have been shown to be safe.26 See Table 6 for rec-
ommended dosing and monitoring. Conditions associated with
In instances of ongoing bleeding or worsening coagulop- improved mortality
athy, interruption of UFH may be appropriate until hemostasis Viral pneumonia
can be achieved. Due to advances in ECMO circuit technology H1N1 influenza
and heparin coating of tubing, withholding anticoagulation for Prone ventilation before ECMO
Early initiation of ECMO
as many as 8 days has been reported without significant
complication.25 There is currently no recommendation on how Abbreviations: CNS, central nervous system; ECMO, extracorporeal
long a patient can be safely on ECMO and without membrane oxygenation; ECPR, extracorporeal cardiopulmonary resuscitation.
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Table 8
Scores to Help Predict Outcomes in Patients With Respiratory Failure33
35

Murray Score APPS AOI

Parameters Consolidation on CXR Age (y) Oxygenation index = plateau pressure £ FIO2/PaO2
PaO2/FIO2 (mmHg) PaO2/FIO2 (mmHg)
PEEP (cmH20) Plateau pressure (cmH20)
Lung compliance (mL/cmH20)
Significant scores >2: consider transfer to center with ECMO 8: consider ECMO >80: consider ECMO
3-4: consider ECMO

Abbreviations: AOI, age-adjusted oxygen index; APSS, age, PaO2/FIO2, plateau pressure score; CXR, chest X-ray; ECMO, extracorporeal membrane oxygenation;
PEEP, positive end-expiratory pressure.

ECMO for Pulmonary Failure Data suggest that survival differs when the cause of ARDS
and patient comorbidities are considered. For example, viral
Extracorporeal membrane oxygenation was relatively pneumonia, H1N1 influenza, and prone ventilation prior to
underused owing to poor outcomes until 2 articles in 2009 induction of ECMO are associated with lower mortality, and
showed promising data for patients with severe respiratory immunocompromised state, advanced age, and malignancy are
failure refractory to conventional support.27,28 Between 2008 associated with higher mortality (Table 7).39
41
and 2014 in the United States, the most common indications
were respiratory failure (n = 8,062 cases) and postcardiotomy
(n = 6,583 cases).29
Extracorporeal membrane oxygenation for respiratory fail- Table 9
The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction
ure should be considered in cases when mortality is 50% or
(RESP) Score38
greater and is indicated when mortality is 80% or greater. Indi-
cations are summarized in Table 7. There are no absolute con- Parameter Score
traindications to ECMO, but conditions associated with poor Age (y)
outcomes are listed in Table 7.30 There is no agreed-upon, spe- 18-49 0
cific age that prohibits the use of ECMO, but increasing age 50-59 -2
comes with increasing risk. Mendiratta et al. did a review of  60 -3
Immunocompromise -2
all patients within the ELSO database above age 65 placed on Mechanical ventilation prior to initiation of ECMO
ECMO for respiratory failure. Survival to hospital discharge <48 h 3
was 41% in this group compared to 55% in all adults.31 48 h to 7 d 1
Scoring systems help providers identify patients in the high >7 d 0
mortality category. The ECMOnet score was developed using Acute respiratory diagnosis
Viral pneumonia 3
data from influenza A (H1N1)-associated respiratory failure to Bacterial pneumonia 3
assess for appropriateness and timing of VV-ECMO.32 The Asthma 11
ELSO references the Murray score,33 age-adjusted oxygen- Trauma and burn 3
ation index (AOI) score,34 and APPS (age, PaO2/FIO2, plateau Aspiration pneumonitis 5
pressure) score35 as viable metrics of the severity of respira- Other acute respiratory diagnoses 1
Non-respiratory and chronic respiratory diagnoses 0
tory failure (Table 8).30 The Murray score for acute lung injury CNS dysfunction -7
stratifies the severity of acute lung injury and is used to help Acute associated infection (nonpulmonary) -3
select patients for ECMO.33 The AOI originally was designed Neuromuscular blockade before ECMO 1
to predict the outcome in neonatal respiratory failure. Dechert Inhaled nitric oxide use before ECMO -1
et al. validated the AOI to 28-day mortality using the ARDS- Bicarbonate infusion before ECMO -2
Cardiac arrest before ECMO -2
Net database.34 The APPS is a system for scoring patients at PaCO2  75 mmHg -1
24 hours after ARDS diagnosis to predict outcomes.35 Mortal- Peak inspiratory pressure  42 cmH20 -1
ity in excess of 80% is associated with a Murray score of 3 to Total score -22 to 15
4, AOI > 80, and APSS 8, and ELSO encourages the consider- Total RESP Risk Survival (%)
ation of ECMO after supportive care of 6 hours or less.30 Early Score Class
initiation (1-2 days) leads to better outcomes.30,36,37 The
6 I 92
Respiratory ECMO Survival Prediction (RESP) score was 3-5 II 76
developed by the ELSO and the Alfred Hospital to assist in the -1 to 2 III 57
prediction of survival for adult patients on ECMO for respira- -5 to -2 IV 33
tory failure (Table 9).38 The PRedicting dEath for SEvere -6 V 18
ARDS on VV-ECMO mortality risk score is calculated using Abbreviations: CNS, central nervous system; ECMO, extracorporeal
parameters at the time of ECMO initiation (Table 10).39 membrane oxygenation.
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Table 10
The PRESERVE Mortality Risk Score
Parameter
Age (y)
<45
45-55
>55
Body mass index > 30
Immunocompromised
SOFA > 12
MV > 6 d
No prone positioning before ECMO
PEEP < 10 cmH20
Plateau pressure > 30 cmH20
Total score
PRESERVE Class 6-Month Probability of Survival (%)
0-2 97
3-4 79
5-6 54
7 16
NOTE. The PRESERVE score is calculated using parameters at the time of
ECMO initiation. Reproduced with permission from Schmidt et al.39
Abbreviations: ECMO, extracorporeal membrane oxygenation; MV,
mechanical ventilation; PEEP, positive end-expiratory pressure; PRESERVE,
PRedicting dEath for SEvere ARDS on VV-ECMO; SOFA, sepsis-related
organ failure assessment.
The ECMO to Rescue Lung Injury in Severe ARDS trial
group performed a prospective randomized trial to assess
ECMO versus aggressive conventional treatment for severe
ARDS. Although the primary endpoint was not statistically
different between the 2 groups, the trial reached premature ter-
mination criteria. Therefore, the study was underpowered to
identify a 20% difference in mortality, the criteria for cross-
over into the ECMO group. Further, 28% of the control group
crossed over to ECMO and resulted in a benefit in favor of
ECMO in the predetermined secondary endpoint of death plus
crossover into ECMO.42
When weaning from VV-ECMO, ventilator settings and
FIO2 must be optimized. Extracorporeal membrane oxygen-
ation gas flow then can be decreased gradually to 0 while the
patient is monitored for signs of weaning failure: decrease in
oxygen saturation, hypoxemia, acidosis (metabolic or respira-
tory), and right heart failure.
ECMO for Lung Transplantation
Lung transplantation has become the standard of care for
many causes of end-stage lung disease.43,44 Extracorporeal
membrane oxygenation as BTT has increased and with excel-
lent results.45 There is also a trend for using ECMO instead of
CPB for patients who need circulatory support during lung
transplantation. The introduction of the lung allocation score
in 2005 changed organ allocation to a system based on medical
urgency rather than time on the waiting list.46 Before the revi-
sion, outcomes for ECMO as BTT were poor. Since the revi-
sion, patients on ECMO as BTT receive a higher urgency,
greatly increasing the chances of identifying a suitable organ
in a much shorter time frame. Hakim et al. showed an 87%
success rate in survival to transplantation in patients placed on
Score ECMO as BTT.47 One-year and 3-year survival in this cohort
were 85% and 80%, respectively, which is comparable to
nationally published lung transplantation survival data of 82%
0
2 (1-year) and 69% (3-year) for bilateral lung recipients.48
3 Extracorporeal membrane oxygenation as BTT is consid-
-2 ered for potential transplant candidates with rapid deterioration
2 in pulmonary function that is refractory to medical manage-
1
ment. Conditions associated with poor outcomes also should
1
1 be considered (Table 7).30,39
41,44
2 There is significant variability among transplant centers
2 regarding perioperative management and the use of ECLS.
0-14 Some centers use ECLS, in 30% to 50% of lung transplanta-
tion cases.49,50 Recent data suggest that patients undergoing
lung transplantation with ECMO as their ECLS have better
short-term outcomes, such as shorter intensive care unit and
hospital length of stay, lower mechanical ventilation require-
ments, and less high-grade primary graft dysfunction, com-
pared to those receiving CPB.51
53 In a retrospective review,
Biscotti et al. showed that patients undergoing lung transplan-
tation with CPB received more volume from cell salvage
(1123 mL v 814 mL), fresh frozen plasma (3.64 units v 1.51
units), platelets (1.38 units v 0.43 units), and cryoprecipitate
(4.89 units v 0.85 units) compared to patients undergoing lung
transplantation with ECMO (approximately 90% VA-ECMO,
10% VV-ECMO).51 Postoperatively there was more bleeding,
platelet transfusion, need for reoperation, and primary graft
dysfunction in the CPB group.51 Despite these differences, a
statistically significant difference in mortality between patients
supported with CPB and those supported with ECMO was not
shown.51,53 Hoetzenecker et al. showed improved survival for
patients transplanted with intraoperative ECMO support (with
and without postoperative support) compared to patients trans-
planted without any ECLS, supporting the use of prophylactic
ECMO during lung transplantation rather than it being
reserved for hemodynamic instability.54 Primary graft dys-
function continues to be the leading cause of early death after
lung transplantation.48 The reduction in primary graft dysfunc-
tion with ECMO is promising, especially since other authors
have shown an increase in mortality with patients who develop
high-grade primary graft dysfunction.55
ECMO for Cardiac Failure
Venoarterial ECMO is used for cardiogenic shock and also
can be used for acute cardiopulmonary failure. Venoarterial
ECMO is used for cardiogenic shock from various causes that
include acute myocardial infarction, myocarditis, acute
decompensated heart failure, pulmonary embolism, post-
cardiotomy cardiogenic shock, early or acute graft dysfunc-
tion, and refractory cardiac arrest. It can be used as a bridge to
recovery, heart transplantation, or more durable mechanical
circulatory support. Although the number of patients bridged
to heart transplantation is small, it may increase with the
implementation of changes to the adult heart allocation sys-
tem.56,57 Adults supported with ECMO will be eligible for the
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Table 11 Table 12
Simple Cardiac ECMO Score76 The Survival After Veno-arterial ECMO (SAVE) Score

Parameter Score Parameter Score

Postcardiotomy 2 Acute cardiogenic shock diagnosis group (select 1 or more)
Lactate > 2 mmol/L 2 Myocarditis 3
RIFLE score injury or above 1 Refractory VT/VF 2
Post-heart or -lung transplantation 3
Simple Cardiac ECMO Score Mortality (%) Congenital heart disease -3
0 0 Other diagnosis leading to cardiogenic shock requiring 0
1 20 VA-ECMO
2 29 Age (y)
3 50 18-38 7
4 71 39-52 4
5 100 53-62 3
63 0
NOTE. Permission falls under STM guidelines (adapted from another Elsevier Weight (kg)
article). <65 1
Abbreviations: ECMO, extracorporeal membrane oxygenation; RIFLE: 65-89 2
kidney risk, injury, failure, loss of function, end-stage renal disease. 90 0
Acute pre-ECMO organ failures (select 1 or more if required)
highest status listing for the first 7 days and status 2 for days 7 Liver failure* -3
CNS dysfunctiony -3
through 14 and will be renewable thereafter.58,59
Renal failurez -3
The mortality of patients supported with VA-ECMO for car- Chronic renal failurex -6
diac failure remains high with 40% to 50% of patients surviving Duration of intubation prior to initiation of ECMO (h)
to hospital discharge (Table 1).1,60,61 There is a worse prognosis 10 0
for patients who experience cardiac arrest and require cardiopul- 11-29 -2
30 -4
monary resuscitation (CPR) before initiation of ECMO.60
65 It
Peak inspiratory pressure  20 cmH20 3
seems that survival is dependent on the underlying cause for Pre-ECMO cardiac arrest -2
cardiogenic shock. Patients with more reversible causes of myo- Diastolic blood pressure before ECMO  40 mmHg|| 3
cardial injury (eg, myocarditis, primary graft failure) have better Pulse pressure before ECMO  20 mmHg|| -2
survival than patients with post-cardiotomy cardiogenic shock HCO3 before ECMO 15 mmol/L|| -3
Constant value to add to all calculations of SAVE score -6
or acute myocardial infarction.66
71
Total score -35 to 17
Factors associated with worse outcomes include increasing
age, female sex, higher body mass index, ischemic heart dis- Hospital Survival by Risk Class Survival (%)
SAVE Score Risk Class
ease, diabetes mellitus, chronic renal disease, and chronic
obstructive lung disease.61,65,66,72 The degree of acidosis and >5 I 75
severity of end-organ failure at the time of ECMO initiation 1-5 II 58
-4 to 0 III 42
are also predictors of long-term survival.61,66,70,72,73 In patients
-9 to -5 IV 30
with post-cardiotomy shock, ischemic heart disease and level -10 V 18
of arterial lactate before initiation of VA-ECMO were inde-
NOTE. An online calculator is available at www.save-score.com. Reproduced
pendent risk factors for 90-day mortality.74 For patients with with permission from Schmidt et al.70,77
acute decompensated chronic systolic heart failure, diabetes Abbreviations: CNS, central nervous system; ECMO, extracorporeal membrane
mellitus and mineralocorticoid receptor antagonist use were oxygenation; VA, venoarterial; VF ventricular fibrillation; VT, ventricular
found to be independent predictors of mortality.75 tachycardia.
Risk scores have been developed to assess the likelihood of * Liver failure was defined as bilirubin  33 mmol/L or elevation of serum
aminotransferases (alanine transaminase or aspartate aminotransferase) >
survival to discharge and potentially improve patient selection. 70 UI/L.
Peigh et al. developed a simple cardiac ECMO score to pro- y CNS dysfunction combined neurotrauma, stroke, encephalopathy, cerebral
vide survival predictability (Table 11).76 The Survival After embolism, as well as seizure and epileptic syndromes.
Veno-arterial ECMO score was developed using ELSO data to z Renal dysfunction is defined as acute renal insufficiency (eg, creatinine >
stratify patients into 5 risk categories that correlated with sur- 1.5 mg/dL) with or without renal replacement therapy.
x Chronic kidney disease is defined as either kidney damage or glomerular
vival after VA-ECMO (Table 12).70,77 filtration rate < 60 mL/min/1.73 m2 for 3 months.
Weaning from VA-ECMO depends on the indication. || Worse value within 6 h prior to ECMO cannulation.
Mechanical ventilation may or may not be needed with VA-
ECMO. If pulmonary recovery lags cardiac recovery, bridging dose pharmacologic support, and recovery from metabolic aci-
to VV-ECMO can be considered. Success of weaning from dosis. Weaning from VA-ECMO is facilitated by echocardio-
VA-ECMO depends on the etiology of cardiac failure (eg, graphic assessment of cardiac recovery and function. Specific
end-stage dilated cardiomyopathy v acute or chronic heart fail- echocardiographic parameters have been studied and
ure). Weaning can be considered when there is recovery of a described. Aissaoui et al. reported that aortic velocity time
pulsatile arterial line tracing, hemodynamic stability with low- interval greater than or equal to 12 cm, left ventricular ejection
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10 J. Kwak et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2019) 1
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fraction > 20% to 25%, and tissue Doppler of lateral mitral
annulus peak systolic velocity greater than or equal to 6 cm/s
were associated with successful weaning.78 Cavarocchi et al.
reported that an increase in strain and strain rate of 20% at
minimal ECMO flows with concomitant increase in ejection
fraction could predict successful weaning.79
Trends in VA-ECMO Use
Extracorporeal CPR and mobile ECMO for out-of-hospital
arrests are being used increasingly. Extracorporeal CPR is the
use of VA-ECMO for patients who remain in refractory car-
diac arrest. Neurologically favorable survival is poor for both
out-of-hospital (2%-11%) and in-hospital (22%) cardiac
arrest.80 Neurologically favorable survival after ECPR varies
in different observational studies and ranges from 15% to 25%
for out-of-hospital arrest to 35% for in-hospital arrest.80 In an
analysis of ELSO data, overall survival to discharge after
ECPR was 29%.81 There is no consensus on indications and
contraindications for ECPR. See Table 13 for a summary of
available published criteria for ECPR.80,82 Age continues to be
a controversial criterion. The American Heart Association
states that there is insufficient evidence to recommend the rou-
tine use of ECPR.63
The formation of a mobile ECMO program for out-of-hospi-
tal or emergency department arrests is a complex process that
may take years of planning. Consultation and patient selection
are critical parts of the program.64,82,83 Organizational require-
ments, ECPR recommendations, and algorithms have been
published.80,82 Through initial experiences by mobile ECMO
teams, data are emerging on the profile of patients who will ben-
efit more from mobile ECMO: younger patients (<60 years);
patients with no flow time of fewer than 5 minutes; and patients
with a shockable rhythm, sufficient CPR, and ECMO implanta-
tion time of 60 minutes.82,84
There are also case reports and reviews describing the use of
ECMO for temporary circulatory support during procedures
Table 13
Ideal Criteria and Exclusion Criteria for ECPR80,82
Ideal Criteria for ECPR
Witnessed sudden arrest
Assumption of cardiac etiology and/or reversible cause (eg, acute coronary
syndrome, pulmonary embolism, myocarditis, shockable rhythm)
High-quality CPR initiated immediately after witnessed sudden arrest
Intermittent ROSC
No major comorbidities
Age under 70 y (with individual, case-by-case consideration)
Exclusion Criteria for ECPR
Age greater than 75 y and frailty
Unwitnessed cardiac arrest
Clinical signs of irreversible brain damage
Comorbidities with reduced life expectancy
Patient refusal (advanced directive)
Conscious patient
Contraindication to anticoagulation
Abbreviations: CPR, cardiopulmonary resuscitation; ECPR, extracorporeal
cardiopulmonary resuscitation; ROSC, return of spontaneous circulation.
such as ventricular tachycardia ablation, percutaneous valve
replacement, and resection of a thoracic mass.85
88 Also
described is the use of VA-ECMO to optimize patients with
advanced structural heart disease before proceeding with
surgery.89 Another group describes ECMO support of brain-
dead organ transplant donors.90
Distention and Venting Strategy for VA-ECMO
Venoarterial ECMO flow rates can be as high as 3 to
4 L/min.72 Initial goals are flow of 50 to 70 mL/kg/min and
mean arterial pressure > 60 mmHg.66 Regardless of high VA-
ECMO flow rates, there is still blood that returns to the left
ventricle (LV): residual flow from pulmonary circuit, Thebe-
sian drainage of coronary blood flow, flow from any aortic
regurgitation, and return of bronchial blood flow to the left
atrium.72 Blood in the LV must exit through the aortic valve,
necessitating the struggling LV to eject against arterial pres-
sure that is increased by VA-ECMO flow.91 With increasing
ECMO flows, the stroke volume may decrease to a volume
less than the volume returning to the left ventricle.72 Stasis
of blood in the LV can lead to thrombosis (LV, aortic,
pulmonary).92 Left ventricle distention can increase diastolic
filling pressures, which reduce coronary perfusion and worsen
or create myocardial ischemia. Left ventricle distention and
increased diastolic filling pressures also can increase left atrial
pulmonary artery pressures, which can worsen or cause pulmo-
nary edema. Thus LV venting strategies to avoid events related
to LV distention are an essential component of VA-ECMO and
are listed in Table 14.72,91,93,94
Intra-aortic balloon pump improves LV distention by
increasing stroke volume with some unloading effect, which
could be beneficial in the setting of a persistently non-ejecting
LV.94 The challenge of atrial septostomy is creating an appro-
priately sized, well-defined defect.94 A well-defined defect
allows for potential future use of a percutaneous closure
device. Left atrial or left ventricular cannulation allows for
controlled decompression but comes with the challenges of
managing an indwelling catheter: cannula movement, kinking,
thrombosis, and patient immobility.
Table 14
Strategies for Left Ventricular Venting With VA-ECMO
Strategies for Left Ventricular Venting With VA-ECMO
Reduction of ECMO flow
Inotropes
Vasodilators
Intra-aortic balloon pump
Atrial septostomy
LA venting (LA cannula connected to ECMO circuit)
Surgical LV venting (LV cannula connected to ECMO circuit)
Percutaneous LV venting (pigtail catheter connected to ECMO circuit)
Percutaneous transaortic ventricular assist device (Impella)
Abbreviations: LA, left atrial; LV, left ventricular; ECMO, extracorporeal
membrane oxygenation; VA, venoarterial.
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The Impella device (Abiomed, Danvers, MA), which is
capable of providing 2.5 to 5.0 L/min of flow, is emerging as a
successful, though expensive, strategy to manage LV venting
on VA-ECMO.93,95
97 In a limited study, Fiedler et al. found
that patients with peripheral VA-ECMO and Impella implanta-
tion had improved survival compared to patients with VA-
ECMO alone.93 They also report a trend in their experience
that patients with improved LV function and reduced LV
cavity size visualized by echocardiography after Impella
implantation may benefit the most from the combination of
VA-ECMO and Impella implantation.93
Neurologic Injury and ECMO
Despites advances in technology, there still is considerable
mortality and morbidity from neurologic complications. These
injuries range from neurocognitive dysfunction with subtle
neuropsychological impairment to seizures, stroke, intracere-
bral hemorrhage, paralysis, ischemic encephalopathy, and
brain death. Studies have demonstrated that complications of
acute ischemic stroke or hemorrhage are associated with cog-
nitive impairment, prolonged hospitalization, increased costs,
and higher rates of discharge to a long-term care facility. There
is also greater long-term mortality in ECMO patients with neu-
rologic complications.98,99 The reported incidence of neuro-
logic complications is highly variable.99
104 In one study of
VA-ECMO patients, an estimated rate of 13.3% was noted for
all reported neurologic complications and 5.9% to 7.8% for
ischemic or hemorrhagic stroke.105 In a recent review of VV-
ECMO patients, neurologic complications were reported in
7.1% of patients. Of these complications, 42.5% were intracra-
nial hemorrhage, 23.5% were brain deaths, 19.9% were
strokes, and 14.1% were seizures.99 Another study of patients
receiving ECMO (69% VA and 31% VV) found the combined
neurologic complication rate to be 47% (intracranial hemor-
rhage, embolic or ischemic stroke, seizures, or generalized
encephalopathy).102 Another broad review noted the complica-
tion rate from intracranial bleeding or infarction to be
<10%.103 A meta-analysis of 20 studies with 1,866 patients
supported with ECMO for cardiac arrest or cardiogenic shock
found a stroke rate of 5.9% and an overall neurologic compli-
cation rate of 13.3%.106
Extracorporeal membrane oxygenation approaches and indi-
cations may have different outcomes. Neuroradiological out-
comes consistent with cerebral injury were more frequent after
VA-ECMO (75%) compared to VV-ECMO (17%).107 The lead-
ing cause of death in VA-ECMO patients was cerebral injury
secondary to either cerebral infarction or hemorrhage.107 Intra-
cranial hemorrhage was the most common cause of mortality in
H1N1 influenza patients supported with VV-ECMO.
Factors that contribute to neurologic complications are com-
plex and divided into events that happened before initiation of
ECMO or those that occurred while on ECMO (Table 15).104
Contributing factors before ECMO include severe hypotension
or hypertension (loss of cerebral autoregulation), severe hyp-
oxia, pyrexia, hypoglycemia or hyperglycemia, metabolic

Table 15
Summary of Risk Factors for Neurologic Injury With ECMO

Risk Factors With VV-ECMO Risk Factors With VA-ECMO

Before ECMO
Loss of cerebral autoregulation
Severe hypoxia
Pyrexia
Hyperglycemia/hypoglycemia
Metabolic acidosis
Electrolyte disturbances
Hypertension/hypotension
In pediatric populations:
Preterm births
Low birth weight
Congenital conditions (eg, congenital cardiac defects, bronchopulmonary dysplasia)
During ECMO
Recirculation leading to hypoxemia Solid or gaseous microemboli and thrombosis
Blood returned to a major artery
Differential hypoxia
Hyperoxia; increasing generation of free oxygen radicals
Loss of pulsatile flow leading to vascular hyperactivity or hypoactivity
Rapid reductions/alterations in carbon dioxide levels and resultant vasoconstriction and acute reductions in cerebral blood flow
Hemodynamic instability requiring inotropes
Use of potent sedatives leading to reduction in mean arterial pressure due to peripheral vasodilation
Systemic inflammatory response due to contact between blood and circuit
Imbalance between intrinsic procoagulant and anticoagulant regulatory systems
Mechanical damage of circulating blood cells
Exogenous anticoagulation

NOTE. Reproduced with permission from Xie et al.104 Permission falls under STM guidelines (reproduced from another Elsevier article).
Abbreviations: ECMO, extracorporeal membrane oxygenation; VA-ECMO, venoarterial ECMO; VV-ECMO, venovenous ECMO.
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acidosis, electrolyte abnormalities, cerebral vascular injury,

and emboli. There are several ECMO-related factors that could
produce neurologic injury. In VA-ECMO, cerebral infarction
can occur due to solid and/or gaseous microemboli and throm-
bosis. Hypoperfusion with mean arterial pressure less than
30% of baseline is associated with perioperative stroke.108
Outflow cannula placement could affect cerebral blood flow
by directing flow away from the brain. In addition, internal
jugular vein occlusions owing to inflow cannulation can cause
cerebral venous hypertension, resulting in decreased cerebral
blood flow velocity with possible cerebral ischemia. In patients
with hypercapnic respiratory failure, rapid reduction in carbon
dioxide levels has been implicated as a possible cause of neu-
rologic injury owing to vasoconstriction of the cerebral vascu-
lar bed. Rapid reversal of hypercapnia may lead to impaired
cerebral autoregulation, which increases the risk of cerebral
injury. In patients with impaired cerebral autoregulation,
agents that may reduce mean arterial pressure, such as sedating
medications, should be used with caution.109
Intracranial hemorrhage is a major cause of morbidity and
mortality. The systemic inflammatory response to the ECMO
circuit may contribute to the risk of cerebral hemorrhage by
disrupting the blood
brain barrier and damaging neurons. Fig 3. Axial T2-weighted turbo spin-echo image shows presence of blood
Absorption of plasma proteins and activation of factor X may products in both frontal lobes (arrows). Reproduced with permission pending
contribute further to an increased risk for abnormal bleeding from Risnes et al.107 Permission falls under STM guidelines (reproduced from
or thrombosis. The inflammatory response also causes another Elsevier article).
increased release of cytokines that can result in thrombocyto-
penia and activation of the coagulation system. As previously
discussed, the ECMO pump and circuit can produce mechani- cannot be used in conjunction with ECMO owing to ferromag-
cal damage and functional impairment of blood and clotting netic parts associated with the ECMO system.
factors. Bleeding also can be exacerbated by the anticoagulants Cerebral near-infrared spectroscopy (NIRS) offers a vali-
used to facilitate ECMO. A pediatric center created and initi- dated, continuous, noninvasive means to measure variations in
ated a protocol targeting coagulation issues related to ECMO regional oxygen saturation (rSO2). A potential cause for the
that was associated with reduced blood product transfusions development of cerebral ischemia in patients on VA-ECMO is
and decreased hemorrhagic complications.110 The protocol from deoxygenated blood being ejected from the patient’s LV.
included anti-factor Xa assays, thromboelastography, and anti- This should be considered when a decrease in rSO2 values,
thrombin measurement at specific intervals. unilateral or bilateral, is detected. In another study of VA-
A less common, but devastating, neurologic complication is ECMO patients, acute brain injury was associated with the fre-
spinal cord infarction. Samadi et al. proposed that the mecha- quency, duration, and burden of desaturation noted on NIRS
nism for spinal injury was hypoperfusion of the spinal cord cerebral oximetry.113 NIRS also can be used to detect hypoper-
from low cardiac output state, high vasopressor requirements fusion during ECMO cannulation. One study demonstrated
causing vasospasm of the spinal cord arteries, occlusion of ret- that rSO2 decreased to either 40% or 25% lower than baseline
rograde oxygenated blood flow from peripheral VA-ECMO, values in all patients, and all responded to increasing pressure,
and possible thromboembolism.111 oxygenation, and ECMO flow rates.114
Monitoring for neurologic injury during ECMO support can Continuous electroencephalogram (EEG) monitoring is
be problematic. Subtle signs of neurologic injury such as common in pediatric ECMO patients.115 It is used to detect
mydriasis or anisocoria may be missed if patients are sedated. pathologic changes such as nonconvulsive seizures or status
The onset of hemiplegia, confusion, coma, and malignant epilepticus. EEG is not used to monitor awareness or awaken-
hypertension associated with intracranial hemorrhage also ing. Severe EEG abnormalities before and/or during ECMO
may be missed on clinical exam, especially if there is a slow have been shown to predict death or significant intracranial
and insidious onset. neurologic complications.
Computerized tomography (CT) is the main imaging modal- Transcranial Doppler (TCD), which measures blood flow
ity used to assess acute intracranial complications in ECMO velocity and pulsatility of middle cerebral artery blood flow,
patients (Fig 3).107 Studies that have evaluated the utility of has been used as a tool in ECMO patients to detect cerebral
CT in patients on ECMO found this modality to be particularly microemboli (solid and gaseous), which have been associated
useful in determining cerebral hemorrhage or infarction and independently with poorer outcomes in patients with ischemic
predictive of poor prognosis.112 Magnetic resonance imaging stroke.116 TCD to diagnose cerebral circulatory arrest has been
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reviewed and is limited to patients with pulsatility.117,118 In
neonates, TCD is more useful for detecting intracranial hemor-
rhage than cerebral ischemia.
Biochemical blood markers also have been used as indicators
for stroke and traumatic brain injury. Plasma glial fibrillary acid
protein is associated with acute brain injury and death. Neuron-
specific enolase is released in the setting of injury and has been
noted to correlate directly with the severity of neurologic injury
(high levels associated with more severe injury).119 Another
serum marker of neuronal injury, S100 calcium-binding protein
B, has been proposed to be associated with cerebral complica-
tions and an early marker of intracranial hemorrhage, especially
in neonatal intracranial hemorrhage. A study by Gazzolo et al.
demonstrated that S100 calcium-binding protein B levels were
elevated 48 to 72 hours before intracranial hemorrhage was
detected on cranial ultrasound.120 When these biochemical
blood markers were used in combination, their elevation was
associated with poor neurologic outcomes. Although monitoring
these markers of neurologic injury is not currently standard of
care, there is growing potential for the role in assessing and fol-
lowing neurologic damage while on ECMO.
Factors that contribute to neurologic injury include genetic
predisposition, hypoperfusion, embolism, hemodilution, and
inflammation. Clinical examination, CT, NIRS, TCD, EEG,
and serum markers are all methods to detect these injuries, but
there are sparse data on the ideal monitor. With the expanding
role of ECMO in critical illness, greater insight is needed into
the pathophysiology of ECMO-associated neurologic injuries
and methods to detect and prevent neurologic damage.
Conclusion
Advances in ECMO technology have contributed to the
increased utilization of ECMO. There is room for improve-
ment in patient outcomes, likely through patient selection and
ECMO management. Indication for ECMO, patient risk fac-
tors, anticipated duration of support, and an exit strategy
should be considered. Further challenge arises from the ethical
and legal issues of studying the use of ECMO. It is paramount
to learn from experience through registries and publication of
outcomes.
Conflict of Interest
The authors do not have any conflicts of interest to disclose.
Acknowledgments
This article is dedicated to W. Scott Jellish, MD, PhD, for-
mer professor and chairman of the Department of Anesthesiol-
ogy and Perioperative Medicine at Loyola University Medical
Center. Dr. Jellish was an expert and leader in the field and a
mentor to many.
13
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