Introduction

The term extracorporeal membrane oxygenation (ECMO) was initially used to describe long-term
extracorporeal support that focused on the function of oxygenation. Subsequently, in some patients, the
emphasis shifted to carbon dioxide removal and the term extracorporeal carbon dioxide removal was coined.
Extracorporeal support was later used for postoperative support in patients following cardiac surgery. Other
variations of its capabilities have been tested and used over the last few years, making it an important tool in
the armamentarium of life and organ support measures for clinicians. With all of these uses for extracorporeal
circuitry, a new term, extracorporeal life support (ECLS), has come into vogue to describe this technology.

The differences between ECMO and cardiopulmonary bypass are as follows:

• ECMO is frequently instituted using only cervical cannulation, which can be performed under local
anesthesia. Standard cardiopulmonary bypass is usually instituted by transthoracic cannulation under
general anesthesia.
• Unlike standard cardiopulmonary bypass, which is used for short-term support measured in hours,
ECMO is used for longer-term support ranging from 3-10 days.
• The purpose of ECMO is to allow time for intrinsic recovery of the lungs and heart; a standard
cardiopulmonary bypass provides support during various types of cardiac surgical procedures.

Extracorporeal membrane oxygenation (ECMO) system.

History of Extracorporeal Membrane Oxygenation

In May 1953, Gibbon used artificial oxygenation and perfusion support for the first successful open heart
operation.1 In 1954, Lillehei developed the cross-circulation technique by using slightly anesthetized adult
volunteers as live cardiopulmonary bypass apparatuses during the repair of certain congenital cardiac
disorders.2 In 1955, at the Mayo Clinic, Kirklin et al improved on Gibbon's device and successfully repaired an
atrial septal defect.3

In 1965, Rashkind and coworkers were the first to use a bubble oxygenator as support in a neonate dying of
respiratory failure.4 In 1969, Dorson and colleagues reported the use of a membrane oxygenator for
cardiopulmonary bypass in infants.5

In 1970, Baffes et al reported the successful use of extracorporeal membrane oxygenation (ECMO) as support
in infants with congenital heart defects who were undergoing cardiac surgery.6 In 1975, Bartlett et al were the
first to successfully use ECMO in neonates with severe respiratory distress.7
Mechanics of Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation apparatus

The extracorporeal membrane oxygenation (ECMO) apparatus consists of a blood pump with raceway tubing,
a venous reservoir, a membrane oxygenator, and a countercurrent heat exchanger (see Media file 1).

Extracorporeal membrane oxygenation (ECMO) system.

The blood pump is either a simple roller pump (most common) or a constrained vortex centrifugal pump. The
roller pump causes less hemolysis and is used for neonatal ECMO. The venous reservoir is used with the roller
pump for neonatal ECMO. The oxygenator is responsible for exchanging both oxygen and carbon dioxide and
is central to the successful performance of prolonged ECMO. Three types of commercial artificial lungs are
available: bubble, membrane, and hollow-fiber devices. The heat exchanger warms the blood using a
countercurrent mechanism. Blood is exposed to warm water that circulates within metal tubing.
Safety devices and monitors

• Air bubble detectors can identify microscopic air bubbles in the arterialized blood and automatically
turn off the blood pump.
• Arterial line filters between the heat exchanger and the arterial cannula are used to trap air, thrombi,
and other emboli.
• Pressure monitors, which are placed before and after the oxygenator, measure the pressure of the
circulating blood and are used to monitor for a dangerous rise in circuit pressure. This can occur with
thrombosis of the oxygenator or occlusion of the tubing or cannulae. Pressure monitors are critical in
preventing circuit disruption in the face of distal occlusion.
• A continuous venous oxygen saturation monitor and temperature monitor are other important safety
features.

Extracorporeal Membrane Oxygenation Procedure

The extracorporeal membrane oxygenation (ECMO) circuit is primed with the freshest blood available. The
acid-base balance and blood gas of the primer are adjusted appropriately. Differences between venoarterial
ECMO and venovenous ECMO are presented below.

The standard ECMO procedure used in most neonatal ICUs is venoarterial bypass. In this situation, a cannula
is placed through the right jugular vein into the right atrium. Blood is drained to a venous reservoir located 3-4
feet below heart level. The blood is actively pumped by a roller pump through the oxygenator, where gas
exchange occurs via countercurrent flow of blood and gas. Next, the blood is warmed to body temperature by
the heat exchanger before returning to the patient through a cannula placed through the right carotid artery into
the aortic arch. Systemic anticoagulation therapy with heparin is administered throughout the bypass circuit,
with frequent monitoring of activated clotting time (ACT), which should be maintained at 180-240 seconds.

In venovenous bypass, a double-lumen cannula is placed through the right jugular vein into the right atrium.
Desaturated blood is withdrawn from the right atrium through the outer fenestrated venous catheter wall, and
oxygenated blood is returned through the inner lumen of the catheter and is angled to direct blood across the
tricuspid valve.

Differences Between Venoarterial and Venovenous Extracorporeal Membrane Oxygenation

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Venoarterial ECMO Venovenous ECMO

Higher PaO2 is achieved. Lower PaO2 is achieved.

Lower perfusion rates are needed. Higher perfusion rates are needed.

Bypasses pulmonary circulation Maintains pulmonary blood flow

Decreases pulmonary artery pressures Elevates mixed venous PO2

Provides cardiac support to assist systemic Does not provide cardiac support to assist systemic
circulation circulation

Requires arterial cannulation Requires only venous cannulation

Venoarterial ECMO Venovenous ECMO

Higher PaO2 is achieved. Lower PaO2 is achieved.

Lower perfusion rates are needed. Higher perfusion rates are needed.

Bypasses pulmonary circulation Maintains pulmonary blood flow

Decreases pulmonary artery pressures Elevates mixed venous PO2

Provides cardiac support to assist systemic Does not provide cardiac support to assist systemic
circulation circulation

Requires arterial cannulation Requires only venous cannulation

In certain patients with cardiac or respiratory failure who have recently undergone cardiac surgery,
transthoracic cannulation of the right atrial appendage and the aortic arch can be used as an alternative to neck
cannulation. Transthoracic cannulation allows left heart decompression by cannulation of the left atrium. This is
useful in patients with primary left heart failure.

Indications and Contraindications

Neonatal Extracorporeal Membrane Oxygenation

Indications
Patients with the following 2 major neonatal diagnoses require the use of extracorporeal membrane
oxygenation (ECMO):

• Primary diagnoses associated with primary pulmonary hypertension of the newborn (PPHN), including
idiopathic PPHN, meconium aspiration syndrome, respiratory distress syndrome, group B
streptococcal sepsis, and asphyxia
• Congenital diaphragmatic hernia (CDH)

Selection criteria

• Gestational age of 34 weeks or more*

• Birth weight of 2000 g or higher*
• No significant coagulopathy or uncontrolled bleeding
• No major intracranial hemorrhage (grade 1 intracranial hemorrhage)*
• Mechanical ventilation for 10-14 days or less*
• Reversible lung injury
• No lethal malformations
• No major untreatable cardiac malformation
• Failure of maximal medical therapy

*Failure to meet these criteria is a relative contraindication for ECMO.

Qualifying patient criteria for extracorporeal membrane oxygenation

Qualifying criteria are applied only when the infant has reached maximal ventilatory support of 100% oxygen
(fraction of inspired oxygen [FiO2] equals 1) with peak inspiratory pressures (PIP) often as high as 35 cm H2 O.

• Alveolar-arterial (A-a) gradient of 600-624 mm Hg for 4-12 hours at sea level, which may be computed
as follows (where 47=partial pressure of water vapor): (A-a)(Diffusing capacity [D] of O2 equals
atmospheric pressure - 47 - (PaCO2 + PaO2])/FiO2
• Oxygenation index (OI) greater than 40 in 3 of 5 postductal gas determinations obtained 30-60
minutes apart, which may be computed as follows (where MAP is mean airway pressure): OI = (MAP x
FiO2 x 100)/ PaO2 PaO2 = 35-50 mm Hg for 2-12 hours

• Acute deterioration
o PaO2 less than or equal to 30-40 mm Hg for 2 hours
o pH less than or equal to 7.25 for 2 hours
o Intractable hypotension

Pediatric Extracorporeal Membrane Oxygenation

Indications

• Low cardiac output resulting from right, left, and biventricular failure following repair of congenital heart
defect
• Pulmonary vasoreactive crisis following repair of congenital heart defect leading to severe hypoxemia,
low cardiac output, or both
 • Rarely, as a bridge to cardiac surgery in patients with serious end-organ damage resulting from
profound low cardiac output related to congenital heart disease
• As a bridge to cardiac transplant
• Possibly, as a bridge to recovery in temporary cardiomyopathy secondary to renal failure, myocarditis,
and burns

Today other indications or less strict selection of patients in certain institutions have made the use of this
technology more diverse, not only in acute cardiac problems but also in primary pulmonary diseases.8,9,10

Unlike the situation in neonates, when ECMO is considered in a pediatric patient, no clear set of inclusion or
exclusion criteria exists. Evaluation of a pediatric patient for ECMO support is largely based on an assessment
of the patient's condition and the institutional experience with pediatric ECMO.

Management

Pulmonary system

Extracorporeal membrane oxygenation (ECMO) is used temporarily while awaiting pulmonary recovery. In the
classic use of neonatal ECMO, the typical ventilator settings are FiO2 of 21-30%, PIP of 15-25 cm H2 O, a
positive end-expiratory pressure (PEEP) of 3-5 cm H2 O, and intermittent mechanical ventilation (IMV) of 10-20
breaths per minute. In some centers, a high PEEP of 12-14 cm H2 0 has been used to avoid atelectasis; this
has been found to shorten the bypass time in infants. Pulmonary hygiene is strict and requires frequent
positional changes, endotracheal suctioning every 4 hours depending on secretions, and a daily chest
radiograph.

Cardiovascular system

Systemic perfusion and intravascular volume should be maintained. Volume status can be assessed clinically
by urine output and physical signs of perfusion and by measuring the central venous pressure and the mean
arterial blood pressure. Native cardiac output can be enhanced with inotropic agents. Echocardiography should
be performed to exclude any major congenital heart anomaly that may require immediate intervention other
than ECMO (eg, obstructed total anomalous pulmonary venous connection).

CNS

CNS complications are the most serious and are primarily related to the degree of hypoxia and acidosis.
Avoiding paralytic agents and performing regular neurologic examinations are recommended. If feasible, head
ultrasonography should be performed before beginning ECMO in a neonate. Reevaluation with serial head
ultrasonography may be needed on a daily basis, especially after any major event. In patients with seizures or
suspected seizures, aggressive treatment is recommended (eg, phenobarbital).

Renal system

During the first 24-48 hours on ECMO, oliguria and acute tubular necrosis associated with capillary leak and
intravascular volume depletion are common because ECMO triggers an acute inflammatorylike reaction. The
diuretic phase, which usually begins within 48 hours, is often one of the earliest signs of recovery. If oliguria
persists for 48-72 hours, diuretics are often required to reduce edema. When renal failure does not improve,
hemofiltration or hemodialysis filters may be added to the circuit.
Hematologic considerations

To optimize oxygen delivery, the patient's hemoglobin should be maintained at 12-15 g/dL using packed RBCs
(pRBCs). As a result of platelet consumption during ECMO, platelet transfusions are required to maintain
platelet counts above 100,000/mcL. Activated clotting time (ACT) should be maintained at 180-240 seconds to
avoid bleeding complications.

Infection control

Strict aseptic precautions are required. The presence of infection is monitored by obtaining cultures from the
circuit at least once a week. Based on institutional experience, the protocol frequency may vary. Other
appropriate cultures (eg, fungal and viral) should be obtained as needed.

Fluids, electrolytes, and nutrition

Patients on ECMO require close monitoring of fluids and electrolytes. The high-energy requirements should be
met using hyperalimentation techniques. The patient's weight increases in the first 1-3 days on ECMO because
of fluid retention.

Medications

• Doses of most inotropic medications, such as dopamine, dobutamine, and epinephrine, can usually be
decreased once the patient is on ECMO.
• Diuretics, such as furosemide (Lasix) and chlorothiazide (Diuril), may be required for mobilization of
tissue fluids.
• Antacids and H2 antagonists are usually administered for GI tract bleeding.
• Only minimal sedation with fentanyl, midazolam, or morphine is required after stabilization.
• Phenobarbital can be used if the patient has seizures.
• Aminocaproic acid may be required to reduce bleeding during surgery.
• Antibiotics, such as ampicillin and cefotaxime, are used initially in the typical septicemic dosages;
dosage modification may be needed, depending on the pathogen and sensitivity.

Complications

Mechanical Complications

• Clots in the circuit are the most common mechanical complication (19%). Major clots can cause
oxygenator failure, consumption coagulopathy, and pulmonary or systemic emboli. More recently,
heparin-coated extracorporeal membrane oxygenation (ECMO) systems have been used to decrease
the frequency of this complication.
• Cannula placement can cause damage to the internal jugular vein, which causes massive mediastinal
bleeding. Dissection of the carotid arterial intima can lead to lethal aortic dissection.
• Air in the circuit can range from a few bubbles to a complete venous air lock. This air can originate in
the dislodgement of the venous cannula, a small tear in the membrane, or high partial pressure of
oxygen in the blood. A large bolus of air can be fatal.
• Oxygenator failure is defined either as decreased oxygen or carbon dioxide transfer or as presence of
consumptive coagulopathy. A failing membrane should be replaced immediately.
• Cracks in the connectors and tube rupture have become less serious problems since the introduction
of Tygon raceway tubing.
 • Pump malfunction may be a manifestation of inadequate venous return to the pump.
• Heat exchanger malfunction can cause severe hypothermia.
• Failure of the entire circuit, including the oxygen source and oxygen blenders, may occur.
• Failure of circuit-monitoring equipment may occur.

Management of circuit failure

• Immediately clamp the venous line, open the bridge, and clamp the arterial line to remove the patient
from the ECMO.
• Because the patient is ventilator dependent, immediately bag the patient with 100% oxygen (FiO2 =1)
or shift the patient back to pre-ECMO ventilator settings.

Complications in Patients
Neurologic complications

• Seizures may occur.

• Intracranial bleeds and infarction may be due to ligation of the carotid artery and internal jugular vein,
systemic heparinization, thrombocytopenia, coagulopathies, or systolic hypertension.

Hemorrhagic complications

• Hemolysis and consumption coagulopathy may occur.

• Hemorrhage at the surgical site, cannula site, or into the site of a previous invasive procedure is a
frequent complication because of systemic heparinization.
• Intrathoracic, abdominal, or retroperitoneal hemorrhage may occur.
• Decreases in platelet count occur because of decreased production, increased consumption,
sequestration, or dilution.

Cardiac complications

• Myocardial stun is defined as a decrease in the left ventricular shortening fraction by more than 25%
with initiation of ECMO that returns to normal after 48 hours of ECMO.
• Hypertension is a dangerous complication because of the risk of hemorrhage and stroke. Arrhythmia
may occur as a result of hypoxia and electrolyte imbalance.
• Symptomatic patent ductus arteriosus may occur.
• Pericardial tamponade may occur.

Pulmonary complications

• Pneumothorax is a potential complication.

• Pulmonary hemorrhage may occur.

Renal complications

• Oliguria is commonly observed during the early part of ECMO.

• Acute tubular necrosis is observed in some patients and may require hemofiltration and dialysis.
GI tract complications

• Hemorrhage may occur as a result of stress, ischemia, or bleeding tendencies.

• Direct hyperbilirubinemia and biliary calculi occur secondary to prolonged fasting and total parenteral
nutrition (TPN), hemolysis, and diuretics.

Complications resulting from infection and sepsis

• The ECMO circuit represents a large intravascular foreign body; frequent manipulation increases the
risk of sepsis.

Metabolic complications

• Acidosis or alkalosis
• Hyperkalemia or hypokalemia
• Hypernatremia or hyponatremia
• Hypercalcemia or hypocalcemia
• Hyperglycemia or hypoglycemia

Drug serum concentrations

• ECMO may alter serum concentration of drugs due to increased volume of distribution.
• Caution is warranted when narrow therapeutic drugs are administered. Dose alterations may be
necessary.

Differential Diagnoses of Acute Cardiorespiratory Decompensation in Patients

on Extracorporeal Membrane Oxygenation

• Pericardial tamponade (from blood or air)

• Tension pneumothorax or hemothorax
• Respiratory failure
• Myocardial ischemia
• Electrolyte imbalance
• Massive hemorrhage (especially intracranial hemorrhage)
• Drug effects
• Overwhelming sepsis

Weaning or Trial Period Without Extracorporeal Membrane Oxygenation

• In patients with a principal pre-ECMO diagnosis of respiratory failure, a trial period without ECMO is
scheduled if (1) the patient demonstrates adequate gas exchange and is on reasonable ventilatory
settings and (2) the patient tolerates a pump flow of 10-20 mL/kg/min with the minimum of 200 mL/min.

Mortality, Morbidity, and Legal Issues

Mortality
Mortality statistics of extracorporeal membrane oxygenation (ECMO)-treated patients have remained stable
over the past decade. Predictors of death include the following:

• Patients with a primary diagnosis of congenital diaphragmatic hernia (CDH) and total anomalous
pulmonary venous returns (TAPVR) have a mortality rate of 50%.
• Approximately 50% of reported deaths are due to severe bleeding complications.
• The mortality rate is high in infants with a birth weight less than 2000 g.

Morbidity
Medical morbidity

• Difficulty in establishing full oral feeding is common after ECMO decannulation. Feeding difficulty is
reported in as many as one third of babies, even in the presence of normal suck and swallow reflexes.
• Somatic growth is normal in infants who survive following ECMO. Poor growth should be evaluated for
another underlying cause.
• Approximately 15% of infants still require oxygen at 28 days after ECMO. These children have a higher
rate of rehospitalization for pulmonary indications, particularly in the first 6 months after ECMO. These
children have a slightly higher prevalence of bronchial asthma.
• Infants who survive following ECMO have a higher rate of rehospitalization for nonpulmonary and
surgical conditions.
• The rate of sensorineural disabilities in infants who survive following ECMO averages 6% (range, 2-
18%); developmental delay occurs in 9% (range, 0-21%).
• Abnormal brainstem auditory-evoked response (BAER) with mild-to-moderate threshold elevation is
seen in 25% of children following ECMO at discharge. This condition usually resolves. Sensorineural
hearing loss is documented after age 1 year in 9% (range, 4-21%) of children following ECMO.
• Routine ophthalmic examinations during ECMO are not recommended because studies in term babies
have not shown any occurrence of retinopathy. In the rare neonate with birth weight less than 2 kg in
whom ECMO is used, ophthalmic examination is required prior to discharge. Some degree of cortical
visual impairment has been seen after posterior brain injury. However, in the long term, visual function
has been shown to improve.
• Both clinical and electroencephalographic seizure activity is reported in 20-70% of neonates while on
ECMO. Epilepsy is reported in 2% of patients at age 5 years.
• Neuromotor deficits range from mild hypotonia to gross motor delay and spastic quadriparesis.
• Glass and colleagues compared the neurodevelopmental outcome of 103 neonates following ECMO
and 37 neonates without ECMO at 5 age years.11 Major disability, which was defined as mental
disability, motor disability, sensorineural impairment, or seizure disorder, was present in 17 of children
in whom ECMO had been used. The mean full-scale, verbal, and performance intelligence quotient
(IQ) scores of children who received ECMO treatment were within the normal range; however, as a
group, the scores were significantly lower than in children who had not had ECMO (96 vs 115). Other
studies have proven that the neurodevelopmental outcome of the ECMO cohort is comparable to other
high-risk neonatal groups and similar to neonates with the same condition managed conventionally.

Psychosocial morbidity

• Increased frequency of social problems, academic difficulties at school age, and higher rates of
attention deficit disorder are reported in children who received ECMO.
• The ECMO procedure is dramatic and highly invasive.
• Families can feel isolated if no other patients are on ECMO in the same institution. At age 1 year, the
stress level of the mother of an infant previously on ECMO is the same as the stress level in the family
of a preterm infant. By age 5 years, the family stress level is the same as that of the family of a healthy
child in whom ECMO was not used.