Introduction

Extracorporeal membrane oxygenation (ECMO) is a modified adaptation of

conventional cardiopulmonary bypass techniques for prolonged cardiopulmonary
support using intrathoracic or extrathoracic cannulation. ECMO is currently used at
specialized centers to support patients with respiratory or cardiac failure who are
unresponsive to conventional therapeutic interventions. 1
Extracorporeal membrane oxygenation (ECMO) uses technology derived from
cardiopulmonary bypass (CPB) that allows gas exchange outside the body. In
addition, circulatory support can also be provided. 2
Although long recognized as a successful therapy in neonates,1,2 ECMO has
lately been used increasingly in adults as a rescue therapy for acute lung injury (ALI),
acute respiratory distress syndrome (ARDS), and severe acute respiratory failure. 1-9
It has also been used in the treatment of acute cardiac failure due to cardiogenic shock
(acute myocardial infarction, ischemic and nonischemic cardiomyopa- thy,
myocarditis, pulmonary embolus, and cardiac arrest) and for postcardiotomy
syndromes (failure to wean from cardiopulmonary bypass following cardiac
surgery).3
ECMO is now also used in adults as a rescue therapy to bridge to heart, lung,
or heart-lung trans- plant, as rescue therapy from primary graft dysfunction (PGD)
after trans- plant, and to bridge patients with acute cardiac failure to support with a
ventricular assist device.3

2.1

History
ECLS and the development of the heart-lung machine in cardiac surgery by

Dr. John H. Gibbon Jr. shared a common interwoven history and were primarily
intended for pulmonary support. ECMO was introduced for the treatment of severe
acute respiratory distress syndrome (ARDS) in the 1970s. Dr. Theodore Kolobow
pioneered the perfection of flow patterns in the membrane lung, the method of
layering silicone and the design of vascular access catheters. The concept of heparin
titration helped in reducing the bleeding complications, and the refined design of
circuits with elimination of stagnant flow areas and incorporation of bladder systems
redefined ECMO. Dr. Donald Hill in 1971 reported the survival of a 24-year-old
polytrauma patient with ruptured aorta after a motorcycle accident, who even
according to todays standard would not have been considered a good ECMO
outcome candidate, was successfully treated on ECMO during the acute phase of the
disease. In the following few years, not much success in ECMO outcome and overall
survival was seen in comparison to newer ventilatory management strategies. This
had put ECMO in the backyard of management options with a failing repute. In 1972,
clinical application of ECMO in respiratory failure of newborns and adults was
attempted. There was revival of interest only after Dr. Robert H. Bartlett in 1976
reported the first neonatal ECMO survivor, baby Esperanza. This was the baby of a
poor, illiterate peasant woman from Baja, Mexico. The mother was determined that
her child would have a better life as a United States citizen, crossed the border and
headed for Los Angeles. En route her membrane ruptured and she was taken to
Orange County Medical Centre where her daughter was born. During delivery, the
child had aspirated a large quantity of meconium and developed chemical
pneumonitis. Even with maximal ventilatory support, the baby was unable to sustain
adequate oxygenation. When the PaO2 decreased to 12 mmHg, the situation was
considered so hopeless that there was nothing to lose. Dr. Robert H. Bartlett, a
thoracic surgeon who had been involved in developing the membrane lung, wheeled
in a machine from the laboratory. After 3 days of bypass, Esperanza, which means
hope, was the name that the nurses gave this baby who recovered completely. 1

To monitor the ECMO experience, an ECMO registry was established in 1980

at the University of Michigan. Dr. John Toomasain in 1984 created the Neonatal
ECMO Registry. In 1989, charter for Extracoporeal Life Support Organization
(ELSO) was formed with the purpose of stimulating multi-institutional research in the
field of acute lung injury and its therapy. During the next two decades, the largest case
series experience was registered by the ELSO voluntary case reporting registry.
ECMO today is an accepted treatment modality for neonatal, pediatric and adult
patients with respiratory and/or cardiac failure, failing to respond to maximal medical
therapy or following heart surgery when there is an inability to wean from
cardiopulmonary bypass or as a bridge to definitive therapy. 1
2.2

Definition
ECMO is a form of cardiopulmonary life-support, which can be veno-venous

(VV) or veno-arterial (VA). With VV ECMO, blood is drained from a central vein,
passed through an oxygenator, and pumped back into the venous system of the patient
(Fig. 1).28 When adequate gas exchange can be achieved and there is no substantial
compromise of cardiac function, VV ECMO, due to its generally lower risk of
complications, is often the preferred approach over VA ECMO. Most patients with
respiratory failure refrac- tory to conventional therapies can be supported with VV
ECMO as a mechanism to augment gas exchange while avoiding toxic
ventilator settings. With VV ECMO, the level of mechanical ventilatory support is
decreased to mitigate ventilator-induced lung injury (VILI). While car- bon dioxide
clearance with this approach is easily achieved, oxygenation may be somewhat less
efficient. Gas exchange goals should be set as appropriate for the specific clinical
circumstance. As with mechanical ventilation and most other modes of respiratory
support, VV ECMO does not represent a cure for any underlying disease process(es),
but simply a means to rest the lungs and allow for dis- ease resolution and recovery
of pulmonary function.
In VA ECMO, blood is drained from a central vein in a manner analogous to
VV ECMO, but is returned to the arterial system, generally via the carotid artery in
neonates and children, and the femoral artery in adults (Fig. 2). VA ECMO is
essentially cardiopulmonary bypass for a period of days to weeks, and is extremely

effective at both oxy- genation and ventilation.

For adult respiratory failure, > 80% of ECMO cases reported to the
Extracorporeal Life Support Organization (ELSO) since 1986 have been VV ECMO,
and the per- centage of patients supported with VV ECMO continues to increase each
year.8 We will focus in this paper on the use of VV ECMO in the adult population.

2.3

ECMO Circuit

The components include [Figure 1] a roller or impeller pump, a membrane

oxygenator, a heat exchanger, polyvinylchloride connecting tubing, connectors and a
bladder reservoir. Blood is driven through the membrane by the roller pump or
centrifugal pump and passively drained by gravity from the venous circulation using a
siphon height of 100 cm or more into a collapsible bladder that acts as a compliant
reservoir. The bladder has a proximity switch attached to its surface and acts to
regulate the roller pump by turning it off when the bladder deflates. The roller pump
or centrifugal pump draws blood from the bladder and pushes it through silicone
membrane oxygenator and then a heat exchanger before returning it to the patient.
The bladder and pump are linked by a trip-switch mechanism so that if pump flow
exceeds venous drainage, the bladder collapses to inhibit pump flow. This blood flow
in the extracorporeal circuit requires systemic heparin administration to prevent
thrombus formation within the circuit and membrane oxygenator.

2.4

Anticoagulant on ECMO

Heparin is required after arterial and venous cannulation, 100 IU/kg bolus followed
by infusion of 125 IU/kg/hour to maintain an ACT at 180200 s. Titration of
appropriate anticoagulation with its antecedent clinical implications of bleeding and
thrombosis remains the principal causes of mortality and morbidity. The vast
differences in neonatal and adult anticoagulation and transfusion requirements
demand tremendous clinical knowledge to provide the best care. Methods to
recognize the level of thrombin formation at the bedside could help reduce thrombotic
neurologic complications. ECMO requires an overall multidisciplinary team approach
to achieve the best clinical outcome.

2.5

Type of ECMO

An ECMO circuit can be set up in three ways:

1. veno-arterial ECMO (VA-ECMO): allows gas exchange and haemodynamic

support while blood is pumped from the venous to the arterial side
2. veno-venous (VV-ECMO): facilitates gas exchange; blood is removed from
the venous side and then pumped back into it, but does not provide
haemodynamic support
3. arterio-venous ECMO (AV-ECMO): facil- itates gas exchange by using the
patients own arterial pressure to pump the blood from the arterial to the
venous side.

The circuit setup for VA or VV is almost identical. Blood movement is facilitated

by an external pump that then pushes the blood through a membrane allowing gas
exchange (oxygenation and CO2 removal ), before return- ing the blood to the
patients circulation via a warmer. Due to its configuration, VA-ECMO bypasses the
patients heart and lung and part or all of the blood flow is diverted through the
ECMO circuit. In contrast, VV-ECMO returns the blood before it enters the
pulmonary circulation.

When a pumpless circuit is used (AV-ECMO), blood flows from the femoral
artery through a membrane and is passively returned into the femoral vein, the whole
process dependent on the patients cardiac output.
Indwelling cannulae, either venous or arter- ial, can be placed under direct vision
(surgical cut-down) or via a percutaneous approach, ideally guided by ultrasound or
fluoroscopy. The size and length of the cannula vary depending on the patient surface
area, insertion site, type of circuit, and intended use. Centrifugal pumps are used as
they are reliable and easy to care for.
The gas exchanger (oxygenator) allows more efficient CO 2 removal than O2
addition because of the solubility and better diffusion properties of CO 2 relative to
O2. The most recent models (hollow fibre non-micropore membrane) present less
resistance to blood flow and are less traumatic to blood components than previous
designs. They are also less thrombogenic; therefore, less anticoagulation is required.
2.5.1

Veno-Arterial ECMO
In VA-ECMO, the drainage cannula is com- monly placed in the inferior vena

cava (IVC) or right atrium (RA). This can be done either via a sternotomy or
percutaneously by inserting the cannula via the internal jugular or the femoral vein.
Blood is returned to the patient through a cannula inserted in either the ascending
aorta (central ECMO, inserted surgically; Fig. 1A) or the femoral artery (peripheral
ECMO, either surgically or percutaneously inserted; Fig. 1B). Central ECMO is a
preferred option when used immedi- ately after CPB as the location of the cannulae is
similar to the one used during surgery.
VA-ECMO support decreases cardiac work and reduces cardiac oxygen
consumption while providing adequate systemic organ per- fusion with oxygenated
blood. If cardiac recovery is expected, it is important that distension of the ventricles
is reduced; VA-ECMO can achieve this if the left ventricle continues to eject or a vent
(drainage catheter) is inserted directly into the left ventricle.
The diameter, length, and position of the cannulae used for vas- cular access
determine potential flow that can be achieved. In add- ition, venous filling or patient
preload, systemic vascular resistance or patient afterload, tubing resistance to flow,

and pump properties are important factors.

VA-ECMO operates alongside the native system, and a propor- tion of the
blood flow can continue to go through the lungs. Therefore, in a patient with impaired
gas exchange, the proportion of blood going through the lungs will mix with welloxygenated blood provided by the ECMO circuit in the aorta. The final content of
oxygen depends on the combination of ECMO and patients blood flows. This means
that when using peripheral VA-ECMO, the neck vessels or coronaries may receive
relatively poor oxygenated blood while the lower body receives better oxygenated
blood.
2.5.2

Veno-Venous ECMO
When the cardiac function is preserved, VV-ECMO is used to improve gas

exchange. Traditionally, VV-ECMO required the in- sertion of at least two cannulae in
large veins ( jugular, femoral, or both), sometimes more to facilitate drainage and flow
and therefore oxygenation. A recently introduced dual-chamber cannula (Avalon
Laboratories, Rancho Dominguez, CA, USA) allows efficient drainage from the
inferior and superior vena cava and return of the blood through the RA into the
tricuspid valve (Fig. 1C). This new cannula decreases the incidence of recirculation
(when oxygenated blood injected by the return cannula is drained immediately back to
the ECMO by the drainage cannula), bleeding issues, and allows for greater patient
mobilization.2

2.5.3

AV pumpless assist device

This system is characterized by a membrane gas exchange device integrated

into a pumpless AV circuit, established by cannulation of the femoral artery and vein.
The circuit allows a small amount of oxygenation but predominantly CO 2 removal, as
arterial blood is returned to the venous side. AV-ECMO requires the patient to have a
cardiac index of at least 2.5 litre min 21 m22 that must be confirmed with
echocardiography, invasive monitoring before insertion, or both.
2.6

ECMO indications
VA-ECMO is indicated in patients with refractory cardiogenic shock who have

an underlying potentially reversible heart condi- tion, although it can also be used as a
bridge to a ventricular assist device or cardiac transplantation. VA-ECMO can also be
used as a salvage technique during cardiac arrest, and the current data support its use
after 10 min of adequate but unsuccessful Advanced Life Support (ALS).3
In-hospital survival rate of patients with VA-ECMO varies from 30% to 50%
according to the cause of the cardiac dysfunction.4 VA-ECMO can be considered in

patients with systolic arterial pres- sure lower than 85 mm Hg, cardiac index lower
than 1.2 litre min21 m22, despite adequate preload, more than two inotropes in use,
intra-aortic balloon counterpulsation, and systemic signs of low cardiac output. The
paucity of data in the literature makes it difficult to determine which patients will
benefit from VA-ECMO and when ECMO support will be futile. Thus, it is strongly
recom- mended to discuss all possible cases with the nearest ECMO centre in these
circumstances (Table 1).
The aim of VV-ECMO in adult patients is to provide oxygen- ation and rest
the lungs, decreasing the insult caused by mechanic- al ventilation. Hence, VV-ECMO
should be considered as an alternative to conventional therapy for adults with ARDS
and patients with graft dysfunction after lung transplantation 5 (Fig. 2). VV-ECMO
has a lower risk of thromboembolic complications and lung perfusion allows
endocrine pulmonary function in comparison with VA-ECMO. It is sometimes
necessary to use VA-ECMO if significant haemodynamic compromise becomes
apparent or if oxygenation that is provided is not sufficient; this may require changes
of the cannulae position.
ECMO is associated with significant inherent risks, and benefit compared with
conventional therapies is still unclear. ECMO gained popularity during the
H1N1/2009 pandemic, when clini- cians were confronted with severe, refractory, and
rapidly progres- sive hypoxaemia in young and fit patients. It made clinical sense to
use the new generation of safer ECMO circuits in this situation. This was
substantiated by the release of the Cesar trial results and no doubt catalysed by the
media, influencing political choices.6, 7 The Cesar trial is the third randomized
controlled trial evaluating the benefits of ECMO in ARDS. The endpoint of the trial
was to compare the survival at 6 months in the absence of severe disabil- ity, in
patients who had developed ARDS and been randomized to be treated either in their
original centre or in the treatment centre. The trial demonstrated that patients
transferred to a centre with ECMO available had a better outcome than those treated
at the ori- ginal hospital with conventional therapy, and that this approach was costeffective.
Whether ECMO can really replace conventional treatment of adult ARDS is

still unknown. Studies to determine the group that may benefit most are still lacking
but patients mechanically venti- lated for longer than 7 days or in multiorgan failure
are considered poor candidates as underlying lung damage might then be irreversible, and ECMO is generally not offered.8 ECMO therapy in ARDS allows a decrease
in the stress imposed on the lung by ven- tilation at high airway pressure that may
eventually damage the lung, and should be offered to patients with refractory
hypoxaemia or hypercapnia despite optimal ventilation (Table 1).
The best survival rates are observed in patients with non- necrotizing viral
pneumonia and associated respiratory failure, probably because (i) these are often
younger patients, (ii) they have fewer co-morbidities, and (iii) the associated lung
injury is often reversible.
AV-ECMO is particularly useful in patients with severe hypercapnia,
respiratory acidosis, and moderate hypoxaemia. The absence of a pump makes this
device simpler to use, but it means that cardiac function must be preserved for the
blood to be effectively pumped. However, mortality has been reported to be high in
patients with ARDS who had AV-ECMO, and some patients may require conver- sion
from AV-ECMO to VV- or even VA-ECMO.9 It does allow however easier
transportation than other ECMO modes as no source of energy is required and it is
smaller in size and weight.

2.7

Contraindications
Patients with irreversible organ damage, multiorgan failure, or those who are

not candidates for transplantation will usually not benefit from ECMO support.
ECMO is not generally recommended in patients who cannot be anticoagulated, but
this is not an absolute contraindication.
Severe aortic regurgitation or aortic dissections are contraindi- cations for VAECMO. ECMO therapy is continuously evolving and it is preferable to involve an
ECMO specialist in discussing indications and contraindications in each instance.
2.8

Cardiovascular Respons on ECMO

Systolic and diastolic pressures decrease with decrease in aortic pulse

pressure. Preload and afterload parameters are the most affected. Peak and mean
blood flow velocities decrease by 3050% after ECMO. They return to normal after
72 hours of ECMO run, concurrent with the reduction in pump flows. Blood pressure
abnormalities occur frequently following the initiation of ECMO. Systemic
hypertension is more frequent than hypotension. Initial management on ECMO
requires the weaning of inotropes with aggressive treatment for hypertension, as there

is a risk of intracranial hypertension and bleed (especially in neonates). Hypotension

is less frequent, but is secondary to decrease in systemic vascular resistance and the
most common cause is hypocalcemia. Arrhythmias are commonly encountered during
cannulation for ECMO, particularly bradyarrythmias secondary to vagal stimulation,
hypoxia or acidosis. Other arrhythmias include atrial and ventricular ectopics from
mechanical irritation. Atrial fibrillation and supraventricular tachycardia are less
common but are usually responsive to cannulae repositioning. Electrolyte
abnormalities of calcium and potassium can occur during the first hour of ECMO
support and can contribute to rhythm abnormalities. Cardiac Stun, complete or nearcomplete absence of ventricular contractions in response to ECMO support
(predominantly seen in VA ECMO), may spontaneously resolve, but carries a high
mortality. Seen as pulse pressure becoming <5 mmHg with a marked increase in PaO2
which almost equals membrane lung PaO 2 and is hypothesized as reperfusion injury
or mismatch of preload or afterload or contractility. This can also result from incorrect
positioning of cannulae. In such scenarios, cannulae repositioning usually solves the
issue.[7-9]
2.9

Physiology Of Oxygen Exchange On ECMO

Oxygen delivery on ECMO is determined by a combination of blood

oxygenation within membrane lung, flow through the extracorporeal circuit, oxygen
uptake through the native lung and cardiac output through the native heart. The final
oxygen gradient at tissue level is determined by extracellular tissue partial pressure of
O2 (normal 30 mmHg) to reach cell cytoplasmic partial pressure of oxygen (normal
610 mmHg) required for optimal metabolic requirement. Oxygen transport in the
oxygenator occurs across a semipermeable membrane, from the gas interface to blood
interface. Here, the oxygen gradient is relatively large, making the diffusion across the
thin silicone membrane relatively swift. The critical factor for oxygen delivery is the
blood phase. The longer the blood is in contact with the membrane, the better is the
saturation of hemoglobin with oxygen. Therefore, a minimum time is required for
oxygenation. Also, a laminar flow will cause better oxygenation of blood at the sides
of membrane than the blood at center column. Hence, any mechanism disrupting the
laminar flow would result in better oxygenation efficiency. Finally, larger the surface

area, larger is the area for oxygenation. As the blood path thickness and surface area
of membrane is fixed, this makes a limitation for achieving maximal blood flow,
ultimately restricting the O2 transmission across the membrane. Rated flow is the
pump flow at which maximal oxygen delivery is achieved and is unique to each
membrane oxygenator device. Tables 12 and 13 show important variables for oxygen
exchange that relate to oxygen gradient between the blood and gas phases. In
critically ill patients, particularly the pediatric group, oxygen consumption may
increase from 68 ml/kg/min to about 1012 ml/kg/min or higher during seizures,
sepsis and with infusion of catecholamine drugs. This may require higher flows on
ECMO run to meet the oxygen requirement.[13-15]
CO2 transport- CO2 transport is 20 times more efficient than the oxygenation
in the lungs; this principle applies even to artificial lungs. The most important factor
limiting the transfer of CO 2 [Table 14] is the relative concentration of CO 2 on either
side of the membrane. Here, the CO 2 transfer is 6 times faster than that of O 2 for
equivalent membrane thickness and pressure gradient. The pressure gradient for CO 2
will not exceed the gradient of O 2 (as pump venous blood PvCO2 is 4550 mmHg
and PvO2 is 0). This pressure gradient and membrane thickness of 36 mm limits
CO2 transfer up to 200 ml/min/m2 for most of the devices. At lower blood flow rates,
the removal of CO2 from the blood is more post-oxygenator effective than is the
transfer of oxygen to the blood. Therefore, CO2 removal can be maintained in
circumstances with severe respiratory dysfunction unlike O2. This has a clinical
implication when ECMO is used for total gas exchange, where hypocapnea invariably
results. A marked respiratory alkalosis therefore can occur, requiring the addition of
25% CO2 during ventilation. Gas exchange is very much dependent on membrane
surface area and relatively independent of blood flow rate. Any malfunction
decreasing the membrane surface area will affect CO 2 removal before it affects
oxygenation. Any rise in post-membrane CO 2 is a sensitive indicator of loss of
functioning membrane area. Like normal lungs, oxygenator membranes are also

subject to pulmonary edema, ventilation perfusion (V/Q) mismatch, pulmonary

embolism, minor and major thrombosis (inlet header and distribution ports), gas
embolism and hemorrhage (blood leak into gas phase). In addition, cumulating water
or blood in the gas phase results in abnormalities of ventilation. This leads to full
saturation of water with O2 from ventilating gas, maintaining the oxygenation of
perfusing blood, whereas the CO2 clearance is selectively decreased. In this scenario,
the sweep gas flow rate is selectively increased with the intention of forced blowing
the water droplets, simultaneously avoiding high pressure in the gas phase in
comparison to blood phase, which leads to CO2 and H2O clearance and return the
normal function of membrane. The sole advantage with artificial membrane lung is
the ease and liberty to simply discard and replace the lung unit when it malfunctions,
unlike the human lungs

2.10

ECMO Management
Haemodynamic management can be particularly challenging. Initially, most

patients require intravascular volume expansion. However, the institution of ECMO

can lead to a rapid reduction in the doses of inotropic and vasoconstrictor drugs, as
gas ex- change improves and intrathoracic pressures are decreased.
During ECMO, the goal is often to reduce the excess fluid that has
accumulated in the extracellular space as a result of sepsis, in- flammation, or cardiac
failure. Fluid restriction and diuretics may be effective, although many patients will
require extracorporeal haemofiltration. This can often be performed on blood from the
ECMO circuit.
Anticoagulation is critical, to avoid the formation of clots in the ECMO
circuit, while balancing the patients risk of bleeding. Heparin is commonly used to
keep the whole-blood activated clot- ting time (ACT) at a designated level (usually
1.5 times normal for the ACT measurement system). Thrombocytopenia is a common
problem and regular platelets transfusions may be necessary to keep the platelets
account over an arbitrary limit to decrease the risk of spontaneous bleeding (.150 000
ml21). If heparin-induced thrombotic thrombocytopenia is diagnosed, the use of
alternative anticoagulant is required. It is possible to run ECMO without heparin, but

this increases substantially the thrombotic risk.

2.11

Complications
Haemorrhage and infection are the two main complications related to ECMO.

Most patients require continuous anticoagulation and more than 50% of them will
suffer at least one haemorrhagic com- plication. Half of these relate to the cannulation
site and it is hoped that the development of new cannulae will reduce this risk.
Arterial cannulation is related to higher risk of bleeding. Haemorrhage can occur in
any organ, with intracranial bleeding being the most devastating. Improvement in
heparin-bounding techniques and other materials allows interruption of systemic
anticoagulation, sometimes for some days. The pathogenesis of thromboembolism
during ECMO is multifactorial (i.e. blood acti- vation after contact with foreign
surfaces, blood stasis in the cardiac chambers and the systemic veins, and
disseminated intra- vascular coagulation). Thrombus in the circuit can affect the function of the pump or the oxygenator. In VA-ECMO, it can lead to stroke or leg
ischaemia. Interruption of blood flow distally to a femoral arterial cannula is a major
issue that can be prevented by the insertion of a small cannula distally to the main
cannula that allows part of the flow to be directed to the leg. ECMO manage- ment
includes close coagulation monitoring, ensuring the best pos- sible balance in
coagulation homeostasis.
Infective complications can be related to the indwelling lines, access sites, or
primary pathology. Strict aseptic handling of lines is required.
ECMO circuit failure or breakage may lead to catastrophic failure, but this is
unusual as long as all components are secure. Bedside staffs are trained to check the
circuit integrity regularly to prevent problems and to react promptly in the case of
acute failure. Cannula displacement or malposition is a major issue as this affects
blood flow and ECMO efficiency.

Reference

1. Extracorporeal membrane oxygenation, an anesthesiologists perspective:

Physiology and principles. Part 1

2. Extracorporeal membrane oxygenation in adults

3. DISCHARGE
OUTCOME
IN
ADULTS

TREATED

EXTRACORPOREAL MEMBRANE OXYGENATION

WITH