REVIEW ARTICLES

Paul G. Barash, MD,

Giovanni Landoni, MD
Section Editors

Venovenous Extracorporeal Membrane Oxygenation in Adults: Practical

Aspects of Circuits, Cannulae, and Procedures
David Sidebotham, MBChB, FANZCA,* Sara Jane Allen, BHB, MBChB, FANZCA,*
Alastair McGeorge, MBChB, FANZCA,* Nathan Ibbott, CCP, and Timothy Willcox, CCP

NTEREST IN extracorporeal membrane oxygenation

(ECMO) for treating severe respiratory failure in adults has
increased substantially in the last 5 years. There are several
reasons for this increase. The first reason is the publication of
the CESAR study in 2009, which showed improved survival in
adults with severe acute respiratory distress syndrome (ARDS)
randomized to consideration of ECMO compared with patients
treated conventionally.1 Second is the H1N1 influenza pandemic of 2009 and 2010, which resulted in a substantial increase in the use of ECMO for treating severe respiratory
failure.2 The outcome from ECMO in this group of patients was
excellent, with reported survival rates of 68% to 77%.3-5 The
third factor has been improvements in the equipment used for
ECMO; in particular, the introduction of polymethylpentene
(PMP) oxygenators, second-generation centrifugal pumps, and
cannulae specifically designed for ECMO. Finally, ECMO increasingly is being used for patients undergoing surgical correction of critical airway obstruction (eg, tracheal papilloma).6,7
There are 2 basic forms of ECMO: venoarterial (VA) and
venovenous (VV). VA ECMO supports the lungs and the heart
(left and right ventricles), whereas VV supports the lungs only.
In adults, VA ECMO is used for treating acute cardiac and
cardiorespiratory failure. For acute cardiac failure, ECMO may
be used instead of a ventricular assist device (VAD), as a
bridging technique either to recovery or to a long-term VAD.
Historically, VA ECMO also was used for treating respiratory
failure in adults8 and is still used commonly for treating neonatal respiratory failure.2 However, VV ECMO is now the
preferred mode of extracorporeal support for adults with ARDS
because it avoids 2 important disadvantages associated with
VA ECMO: the need for arterial cannulation and upper-body
hypoxemia. Upper-body hypoxemia occurs in patients with
respiratory failure but good cardiac function who are supported
with peripheral VA ECMO in which the arterial cannula is
placed in the femoral artery. Oxygenated blood from the
ECMO circuit perfuses the lower body, but deoxygenated
blood, passing through the nonfunctioning lungs and ejected
from the left ventricle, perfuses the upper body (coronary
arteries and cerebral circulation).
Although VV ECMO provides no direct cardiac support, the
institution of ECMO allows ventilator settings to be reduced to
rest levels, which resolves much of the hemodynamic instability associated with ARDS. In the CESAR study, all the

patients treated with ECMO received VV support.1 Fewer than

10% of patients requiring ECMO for respiratory failure require
VA support4 although occasionally, when there is concomitant
septic shock, VA ECMO is required.9
For these reasons, the focus of this article is VV ECMO for
treating respiratory failure. The technical considerations of VV
ECMO using centrifugal pumps, PMP oxygenators, and
ECMO-specific cannulae are described. Additionally, the physiology of VV ECMO, circuit complications, and practical procedures related to the circuit are outlined. The use of VA
ECMO for treating cardiac and cardiorespiratory failure is
outlined in a previous review.10
With respect to terminology, the phrase extracorporeal gas
exchange more accurately describes the form of extracorporeal life support under discussion than extracorporeal membrane oxygenation because carbon dioxide exchange also occurs. Likewise, the term gas exchanger more accurately
describes the function of the oxygenator than oxygenator.
However, in deference to common usage, familiarity, and esthetics, the terms ECMO and oxygenator are used here.
PHYSIOLOGY OF ECMO

With VV ECMO, deoxygenated blood is drained from a

cannula placed in a large central vein, typically the inferior
vena cava (IVC), and oxygenated blood is returned via a
cannula whose tip lies in or close to the right atrium (RA).
Ideally, all the blood from the return cannula passes through the
tricuspid valve into the pulmonary circulation. By passing

From the*Cardiothoracic Intensive Care Unit and Department of

Clinical Perfusion, Auckland City Hospital, Auckland, New Zealand.
Address reprint requests to David Sidebotham, MBChB, FANZCA,
Cardiothoracic Intensive Care Unit (Ward 48), Auckland City Hospital, Building 32, Park Road, Grafton, Auckland, New Zealand. E-mail:
dsidebotham@adhb.govt.nz
2012 Elsevier Inc. All rights reserved.
1053-0770/2605-0026$36.00/0
doi:10.1053/j.jvca.2012.02.001
Key words: adult, human, extracorporeal membrane oxygenation/
adverse effects, extracorporeal membrane oxygenation/instrumentation, extracorporeal membrane oxygenation/methods, catheterization,
peripheral/methods, respiratory insufficiency/therapy, pumps, heart assist, heart-assist devices, oxygen, oxygenators, oxygen/physiology, carbon dioxide, carbon dioxide/physiology, complications

Journal of Cardiothoracic and Vascular Anesthesia, Vol 26, No 5 (October), 2012: pp 893-909

893

894

through the pulmonary circulation, oxygenated blood from the

ECMO return cannula contributes to arterial oxygenation. Oxygenated blood from the return cannula that passes into the
ECMO drainage cannula does not contribute to arterial oxygenation, and is termed recirculation.
Because oxygenated blood from the return cannula mixes
with deoxygenated blood from the patients systemic venous
return, it usually is not possible to achieve normal arterial
oxygen saturation (SaO2) during VV ECMO, particularly if the
lungs are not contributing to gas exchange. A common target
for SaO2 during VV ECMO is 86% to 92%. If ECMO circuit
flow is at least 70% of cardiac output and most of the ECMO
return blood passes into the pulmonary circulation (thereby
avoiding recirculation through the ECMO circuit), an SaO2
within this range usually can be achieved, even if the lungs are
not contributing to gas exchange. Thus, for most adults, circuit
flows of 3.0 to 6.0 L/min are required to achieve an SaO2 above
86%.
This point is shown with a simple example of a patient with
a cardiac output of 5 L/min and a systemic venous oxygen
saturation of 70% who is supported with VV ECMO at 3.5
L/min. Assuming all the ECMO blood passes through the
tricuspid valve and the oxygen saturation (SO2) in the ECMO
return blood is 100%, then of the blood entering the pulmonary
artery, 3.5 L/min is from the ECMO circuit (SO2 100%) and
1.5 L/min is native venous return (SO2 70%). Using simple
ratios, the resulting oxygen saturation of pulmonary arterial
blood is 91%, which, if the lungs are not contributing to gas
exchange, also will be the SaO2. Higher circuit flows would be
required to achieve the same SaO2 if cardiac output was higher
or systemic venous oxygen saturation was lower. Furthermore,
in practice, some recirculation through the ECMO circuit always occurs.

SIDEBOTHAM ET AL

Recirculation is influenced by the relative positions of the

drainage and return cannulae, ECMO flow, intravascular volume, cardiac output, and patient position. Recirculation can be
assessed clinically by comparing the oxygen saturation on the
venous side of the oxygenator (preoxygenator SO2) with the
patients SaO2. A high preoxygenator SO2 (75%) in combination with a low SaO2 (85%) suggests clinically significant
recirculation is occurring. Conversely, a low preoxygenator
SO2 (60%) in combination with a low SaO2 (85%) indicates that the patients cardiac output (or oxygen consumption)
is abnormally high and/or the ECMO flow is too low. Recirculation also can be assessed by comparing the pre- and postoxygenator PO2. A high separation between the 2 suggests
there is minimal recirculation. With the FIO2 of the sweep gas
at 1.0 L/min, a preoxygenator PO2 10% of the postoxygenator PO2 suggests that clinically significant recirculation is not
occurring.11
The concept of systemic venous oxygen saturation is confusing during VV ECMO. Normally, the average oxygen saturation of the systemic venous return is quantified by the
mixed venous oxygen saturation, the SO2 of pulmonary arterial blood. However, with VV ECMO, pulmonary arterial
blood is a combination of systemic venous return and oxygenated blood from the return cannula. Preoxygenator SO2 often is
used as a surrogate for the patients systemic venous oxygen
saturation. However, because some recirculation is virtually
always present, preoxygenator SO2 typically is higher than the
SO2 of systemic venous blood.
THE ECMO CIRCUIT

The basic circuit design for VV ECMO using a centrifugal

pump and a PMP oxygenator is shown in Figures 1 and 2. The
circuit can be divided into 3 functional limbs: (1) the drainage

Fig 1. A photograph of an ECMO circuit. Arrows indicate the direction of blood flow. Note that all connections are secured with cable ties,
and all access ports are protected by 2-way and 3-way taps. In this example, an adapter plate is shown allowing a Rotaflow pump (MAQUET
Cardiovascular) to interface with a Bio-Medicus pump drive.

VENOVENOUS EXTRACORPOREAL MEMBRANE OXYGENATION

895

Fig 2. A schematic of the ECMO circuit shown in Figure 1. The only major difference between the circuits shown in Figures 1 and 2 is that
the preoxygenator (venous) oximeter is positioned in the drainage limb (region 1) in the photograph and between the pump and the
oxygenator (region 2) in the schematic. Additionally, an air filter is present in the sweep gas tubing in Figure 1 but is not shown in Figure 2.

limb, which extends from the drainage cannula to the pump

(region 1); (2) the limb between the outflow of the pump and
the venous side of the oxygenator (region 2); and (3) the
return limb, which extends from the arterial side of the
oxygenator to the return cannula (region 3).
A negative pressure (20 to 100 mmHg), generated by the
centrifugal pump, exists in the drainage limb (region 1). By
contrast, a large positive pressure exists in the 2 limbs distal to
the pump (regions 2 and 3). This positive pressure may be as
little as 100 to 200 mmHg or as high as 500 mmHg depending
on the circuit flow and resistance. A pressure drop of 30 to 150
mmHg normally occurs across the oxygenator (ie, between
regions 2 and 3), the magnitude of which depends on oxygenator type and blood flow. Breaches in the circuit where the
pressure is negative lead to air entrainment; breaches in the
circuit where the pressure is positive lead to blood loss.
Regions 1 and 2, which are proximal to the oxygenator,
contain deoxygenated venous blood; region 3, which is distal
to the oxygenator, contains oxygenated arterial blood. The

circuit may be modified to include a bridge, access ports, flow

sensor, and inline oxygen saturation monitors. The potential benefit of additional circuit components (and their associated tubing
connections) must be weighed against the risk associated with
increasing circuit complexity. Tubing connections can rupture or
leak and are sites of turbulent flow, which can lead to thrombus
formation and cell damage. The authors advocate using simple
circuits with a minimum number of connections and access ports.
All tubing connections should be reinforced with cable ties, and all
access ports should be protected by both a 2-way and a 3-way
connector (Fig 3). The priming volume of the circuit is 400 to 500
mL depending on the oxygenator type and the tubing length.
The Oxygenator
Three types of oxygenators have been used for ECMO: (1)
silicone membrane, (2) microporous hollow fiber, and (3) PMP
hollow-fiber membranes. Silicone oxygenators formed the
mainstay of ECMO oxygenators for more than 20 years. They

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Fig 3. A photograph of a 2-way and 3-way connector system used

to protect access ports from inadvertent opening to air.

contain a nonmicroporous silicone membrane in a rolled flat

sheet construction. Silicone membrane oxygenators are durable
but, compared with hollow-fiber oxygenators, have a large
priming volume and a high resistance to flow, provide less
efficient gas exchange, are associated with higher transfusion
requirements, and may induce more pulmonary injury.12-14
Microporous hollow-fiber oxygenators are the standard oxygenators used for cardiopulmonary bypass. They are small and
easy to prime and provide efficient gas exchange. However, the
hollow fibers contain millions of micropores through which gas
exchange takes place. Over the course of several days of use,
these micropores become permeable to fluid, causing plasma to
leak into the gas phase. Plasma leak can develop rapidly, over
a few hours, and necessitates changing the oxygenator.
PMP oxygenators are also highly efficient, but because the
hollow fibers are a true membrane, in which the blood and gas
phases are separate, they are far less prone to plasma leak than
microporous oxygenators,15,16 although this complication has
been reported.17 Compared with microporous hollow-fiber oxygenators, PMP oxygenators last longer and have lower rates of
thrombus formation and hemolysis.15,16 Additionally, failure of
a PMP oxygenator typically develops slowly over several days.
The mechanism of failure of PMP oxygenators is deposition of
a fibrous network of red blood cells and platelets onto the
surface of the membrane, causing increased resistance to blood
flow and impaired gas diffusion.18
Several PMP oxygenators are available for adult ECMO
including the Quadrox PLS (MAQUET Cardiovascular, Hirrlingen, Germany), the Medos Hilite 7000 LT (Medos, Stolberg, Germany), and the Eurosets ECMO (Eurosets, Medolla,
Italy). All are designed for prolonged use (weeks), contain a
biocompatible surface coating to reduce activation of blood,
have a low priming volume (200-300 mL) and a large surface
area for gas exchange (1.5-2 m2), and provide efficient gas
transfer at blood flow rates between 1 and 7 L/min.
Functionally, the oxygenator has blood and gas phases separated by the membrane. The blood phase has a venous and
an arterial side. The pressure drop across the oxygenator
refers to the pressure difference between the arterial and venous

SIDEBOTHAM ET AL

sides of the blood phasenot the pressure difference across the

membrane.
Oxygenators contain inflow and outflow connections for the
circuit blood, the sweep gas, and water from the heater unit
(Figs 1 and 2). Deoxygenated blood from the pump enters on
the venous side and exits on the arterial side. The exhalation
port for the sweep gas usually is downward facing to minimize
the chance of obstruction. Blockage of the outflow port can lead
to pressurization of the gas phase, potentially rupturing the
membrane and causing gas embolism.
The FIO2 and flow rate of the sweep gas control the postoxygenator PO2 and PCO2, respectively. The oxygen and carbon
dioxide transfer characteristics of the Quadrox PLS oxygenator
are shown in Figures 4 and 5. During normal clinical care, it is
usual to have the FIO2 of the sweep gas at 1.0 and to titrate the
gas flow to the patients pH, targeting a value of 7.3 to 7.4.
Before initiating ECMO for ARDS, patients often have a partially compensated severe respiratory acidosis; titrating gas
flow to PaCO2 may result in a marked respiratory alkalosis,
which may adversely affect the cerebral blood flow. A sweep
gas flow 1 to 2 times the circuit blood flow usually is required
to achieve a normal PaCO2. With an FIO2 of 1.0, the postoxygenator PO2 should be 40 to 80 kPa (300-600 mmHg).
A low postoxygenator PO2 (10-15 kPa, 75-110 mmHg) or
a high postoxygenator PCO2 may be caused by the buildup of
water vapor in the gas phase or may indicate that the oxygenator is failing because of thrombus deposition. Rarely, a low
postoxygenator PO2 (or a high postoxygenator PCO2) indicates
that the gas transfer capabilities of the oxygenator are exceeded. This situation can occur in hypermetabolic patients
who are receiving high ECMO flows. As can be seen from

Fig 4. Oxygen transfer at different blood flow rates for the

Quadrox PLS oxygenator. (Modified from ECMO and Life Support
Systems Quadrox PLS and Rotaflow RF 32 Hardware and Accessories
product brochure).

VENOVENOUS EXTRACORPOREAL MEMBRANE OXYGENATION

897

The Pump

Fig 5. Carbon dioxide transfer at different blood flow and sweep

gas flow rates for the Quadrox PLS oxygenator. (Modified from
ECMO and Life Support Systems Quadrox PLS and Rotaflow RF 32
Hardware and Accessories product brochure).

Figures 4 and 5, increasing circuit flow increases gas transfer

by the oxygenator. However, at a circuit flow of 6 L/min and a
sweep gas flow of 12 L/min, the transfer of oxygen and carbon
dioxide of the Quadrox PLS oxygenator are each about 400
mL/min, which may be less than the oxygen consumption and
carbon dioxide production by a hypermetabolic patient.
In the first instance, a low postoxygenator PO2 or a high
postoxygenator PCO2 should be treated by coughing the
oxygenator. Coughing the oxygenator involves turning the
sweep gas up to the maximum flow (eg, 15 L/min) for 60
seconds to remove accumulated water vapor from the gas
phase. If this maneuver does not solve the problem, consideration should be given to changing the oxygenator or adding a
second oxygenator in parallel with the first.
It can be difficult to distinguish between a failing oxygenator
because of thrombus formation and a hypermetabolic patient
who is exceeding the gas transfer capabilities of the device.
Visible thrombus and an abnormally large pressure drop across
the oxygenator (typically more than twice normal) usually
accompany oxygenator failure. Failure of a PMP oxygenator is
very rare in the first few days of use. If doubt exists as to the
cause of a low postoxygenator PO2 (or a high postoxygenator
PCO2), the oxygenator should be changed and the situation
reassessed. If a second oxygenator is added to facilitate carbon
dioxide clearance, a second gas blender dedicated to the second
oxygenator also should be included.
The normal pressure drop between the arterial and venous
sides of the oxygenator varies with the blood flow rate and the
oxygenator type. At blood flow rates of 6 L/min, the normal
pressure drop varies between 50 and 150 mmHg for the 3
oxygenators listed previously. The normal pressure drop, at
different flow rates, across the Quadrox PLS oxygenator is
shown in Figure 6.

Both roller and centrifugal pumps are used for ECMO.

However, centrifugal pumps have several advantages over
roller pumps, which have led to centrifugal pumps becoming
the preferred choice for ECMO. Roller pumps are afterload
independent. Thus, in the presence of obstruction distal to the
pump (eg, kinking of the tubing), extremely high pressures can
develop, potentially causing circuit rupture. It is usual with a
roller pump to include a blood-filled bladder proximal to the
pump to allow continuous pumping in the presence of reduced
drainage (eg, because of hypovolemia), which adds to the
complexity of the circuit. Roller pumps also cause spallation of
the plastic tubing with prolonged use, resulting in microemboli
of tubing debris.19,20
Centrifugal pumps contain a magnetically driven impella
inside a spiral housing. The impella spins rapidly, up to 5,000
rpm (rpm), creating a negative upstream pressure and positive
downstream pressure, forcing blood through the pump. Centrifugal pumps are small, very easy to prime, and have a very
low volume (32 mL in the case of the Rotaflow, MAQUET
Cardiovascular).
Centrifugal pumps are both pre- and afterload dependent.
Hypovolemia (low preload) or circuit obstruction (high afterload/low preload) reduces blood flow. Thus, there is no fixed
relationship between pump speed and blood flow. Therefore, a
flow sensor must be included in the circuit. When a centrifugal
pump is turned off, there is the potential for reverse flow to
occur in the circuit. This is a very real concern with VA ECMO
because arterial pressure is higher than venous pressure, but is
less of a problem with VV ECMO. To prevent reverse flow

Fig 6. The pressure drop at different blood flow rates across the
Quadrox PLS oxygenator. (Modified from ECMO and Life Support
Systems Quadrox PLS and Rotaflow RF 32 Hardware and Accessories
product brochure).

898

occurring, the circuit always should be clamped before turning

off the pump. (By contrast, with roller pumps, the pump should
be turned off before clamping the circuit to avoid generating
very large positive pressures distal to the pump.) The circuit
should be clamped downstream from the pump (ie, in regions
2 and 3). Clamping upstream from the pump (ie, region 1), with
the pump still spinning, will transiently generate a large negative pressure in the drainage limb, with the potential for cavitation of dissolved gases.
A particular concern during extended support with centrifugal pumps is the potential for hemolysis, as indicated by a high
plasma hemoglobin concentration (50 mg/dL). Hemolysis is
caused primarily by thrombus-induced turbulence in the pump
but is exacerbated by obstruction and turbulence elsewhere in
the circuit. Hemolysis also is influenced by the pump design,
and is less with second-generation centrifugal pumps (eg, Rotaflow, MAQUET Cardiovascular; Revolution, Sorin Cardiovascular, Milan, Italy; and CentriMag, Thoratec Corp, Pleasanton, California, US) than with older style centrifugal pumps
(eg, Bio-Medicus; Medtronic, Inc, Eden Prairie, MN) and roller
pumps.15,21-23
The Pump Drive, Heater Unit, Gas Blender,
and Console
In addition to the circuit, a pump drive, gas blender, heater
unit, and controller console are required. Several integrated
pump drive/controller console units are available commercially, including the Bio-Medicus Bio-Console (Medtronic,
Inc), the MAQUET Rotaflow, the MAQUET Cardiohelp, and
the Sorin centrifugal pump system. Pumps are designed for use
with specific pump drives. However, adapter plates are available that allow pumps and pump drives from different manufacturers to interface together.
The heater unit controls the patients temperature by heating
water that flows through the oxygenator. In hypermetabolic
patients, in whom active cooling is required, it may be necessary to use a separate heater-chiller unit to control the patients
temperature.
The ECMO unit should be plugged into an essential power
source. In the event of power failure, an inbuilt battery provides
temporary power to the pump and console. A hand-crank pump
drive should be included in the ECMO cart as a contingency in
the event of total power failure. The gas blender should be
connected to wall oxygen and air supplies. Full gas bottles and
gas flow regulators should be included in the ECMO cart to
provide emergency gas in the event of failure of the wall supply
or failure of the gas blender.
Access Ports and Inline Oxygen
Saturation Monitoring
Access ports are used for priming the circuit, emergency
deairing, pressure monitoring, blood sampling, and administering heparin. Figure 2 shows the common site for access ports
within the circuit. Some centers routinely measure the negative
pressure in the drainage limb (region 1) as an early indicator of
impending suction events (described later). However, monitoring this pressure is inherently dangerous because if the access

SIDEBOTHAM ET AL

port is inadvertently opened air will be entrained rapidly into

the circuit.
Several access ports are built into the housing of the oxygenator. On the Quadrox PLS oxygenator, there are 4 such
ports, 2 each on the venous and arterial sides (Fig 2). The lower
ports on each side are used for measuring the pressure drop
across the oxygenator (when clinically indicated) and for sampling pre- and postoxygenator blood gases. The upper port on
the arterial side of the oxygenator is used for emergency deairing. Additionally, a gas venting port, containing a hydrophobic membrane, is present on the arterial aspect of the oxygenator. Theoretically, this port can be used for deairing the circuit.
However, after 1 to 2 days of use, the hydrophobic membrane
becomes coated with fibrin and loses its deairing function.
Thus, this port should be capped to avoid it wetting out,
which can cause a plasma leak and be a source of circuit
contamination.
The authors practice is to include an additional access port
between the pump and the oxygenator (region 2) to facilitate
priming and emergency deairing. The heparin infusion should
be connected into region 2 (ie, preoxygenator in a positivepressure part of the circuit). Depending on the manufacturer,
access ports may be built into the tubing connectors on the
cannulae.
Inline oximeters on the arterial and venous side of the
oxygenator may be included for continuous measurement of
pre- and postoxygenator SO2 and hematocrit. Because oxygenator failure usually evolves slowly and is relatively uncommon,
a continuous recording of postoxygenator SO2 is not necessary.
By contrast, changes in the preoxygenator SO2 occur rapidly in
response to changes in the recirculation fraction or the patients
cardiac output and metabolic oxygen requirements. Thus, continuous inline measurement of preoxygenator SO2 is useful.
Bridge
A bridge is a tubing connection between the drainage and
return limbs of the circuit. It allows the patient to be eliminated
from the circuit while still maintaining blood flow in the circuit,
which theoretically is beneficial during emergency deairing.
Various options are used to manage the bridge during routine
care including (1) allowing continuous blood flow through the
bridge using a variable occluder, (2) clamping and intermittent
release (eg, for a few seconds every hour) of the bridge, and (3)
flushing the bridge with saline and then double clamping each
end. None of these techniques is without risk. Continuous flow
or intermittent releasing can both lead to embolism of clots that
have formed in the bridge. Flushing with saline and clamping
can lead to thrombus formation in the region of stasis on the
blood side of the clamps. A bridge creates extra connections in
the circuit, with the potential for disconnections and leaks.
Furthermore, deairing the circuit can be performed without
using a bridge, as described later. The authors do not recommend including a bridge.
Surface Coatings
Manufacturers use surface coatings on the pump, connector
tubing, oxygenator, and cannulae to improve biocompatibility
and, therefore, to potentially reduce the activation of blood and

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899

Fig 7. Cannula configurations for

VV ECMO. (A) Femoroatrial cannulation: drainage is via a large multiport
cannula introduced into a femoral
vein and advanced to the mid-IVC; return is via a short cannula introduced
into the right internal jugular vein and
advanced to the SVC-RA junction. (B)
Femorofemoral cannulation: drainage
is via a large multiport cannula introduced into a femoral vein and advanced to the mid-IVC; return is via a
long cannula introduced into the contralateral femoral vein and advanced
to the RA. (C) Double-lumen cannulation: drainage and return are via a
double-lumen cannula introduced
into the right internal jugular vein.
The cannula is advanced until the tip
lies in the mid-IVC, just distal to the
hepatic vein. Drainage is from the IVC
and the SVC, and return is to the RA.
See text for details. TV, tricuspid
valve.

reduce fibrin/platelet deposition.24 These coatings typically involve covalently bonding heparin to the blood contact surface.
Examples include Bioline (MAQUET Cardiovascular), Rheoparin (Medos), and Carmeda Bioactive Surface (Medtronic,
Inc). Alternative biocompatibles are also used, such as phosphorylcholine (Eurosets), in which the surface is coated with
phospholipids that mimic natural cell membranes. Data on the
clinical benefit of these surface coatings during prolonged
ECMO support are lacking.
CANNULAE, CANNULATION, AND COMMENCING ECMO

ECMO cannulae are constructed from wire-reinforced polyurethane and come with a guidewire/dilator kit to facilitate
percutaneous insertion via the Seldinger technique. Cannulae
should be resistant to collapse and kinking and be specifically
designed for either drainage or return. Wire reinforcing should
extend to the cannula tip to minimize the chance of wrinkling
the cannula tip as it passes through the skin or vessel wall
during percutaneous insertion. The introducer should fit snugly
inside the cannula with a smooth transition between the cannula
tip and the introducer. Guidewires should be long (2 m) and
kink resistant. Two systems that meet these criteria are HLS

Cannulae (MAQUET Cardiovascular) and Avalon Elite

(Avalon Laboratories, Rancho Dominquez, CA).
Cannula Configurations
The goal of any cannula configuration for VV ECMO is to
maximize flow and minimize recirculation. High flow rates are
best achieved by positioning a large drainage cannula in the
IVC. Recirculation is minimized by returning oxygenated
blood in or near to the RA, ideally with the jet of blood directed
through the tricuspid valve. Several possible cannula configurations may be used (Fig 7).
Two-cannulae techniques
There are 2 commonly used techniques for a 2-cannulae
configuration:
1. Femoroatrial: blood is drained from the IVC via a
cannula introduced into the femoral vein and advanced
so the tip lies 5 to 10 cm below the RA-IVC junction.
Blood is returned to the RA via a cannula introduced
into the right internal jugular vein and advanced so the
tip lies at the RA-superior vena cava (SVC) junction.
This is the authors preferred 2-cannulae technique.

900

2. Femorofemoral: blood is drained from the IVC via a

cannula introduced into a femoral vein and advanced so
the tip lies 5 to 10 cm below the RA-IVC junction. Blood
is returned to the RA via a cannula introduced into a
femoral vein and advanced so the tip lies in the RA.
A third 2-cannulae configuration has been termed atriofemoral,25
in which deoxygenated blood is drained from the RA via a
cannula introduced into the right internal jugular vein and
oxygenated blood returned to the IVC via a cannula introduced into a femoral vein and advanced to the mid-IVC.
Atriofemoral cannulation is associated with more recirculation than femoroatrial cannulation26 and is therefore not
recommended. A 17F or 19F cannula is suitable for return in
most adults. A short (20 cm) cannula is suitable for return
via the right internal jugular vein (femoroatrial technique).
A long (50 cm) cannula is required for return via the
femoral vein (femorofemoral technique).
For drainage, a long (50 cm) 23F to 29F cannula is suitable
for most adults. The authors preference is to use a large
(25F-29F) multiport cannula, which has multiple side holes as
well as an end hole. Large multiport cannulae allow higher
flows (typically 6 L/min) than is possible with smaller cannulae that have only an end hole. Higher flow may be obtained
by advancing the tip of the cannula closer to the IVC-RA
junction, but this may result in more recirculation. Conversely,
withdrawing the cannula may reduce recirculation but limit
flow.
If recirculation is suspected or a low-flow state exists, adjustments to the cannula positions should be performed under
echocardiographic (or fluoroscopic) imaging. It may be necessary to advance, withdraw, or twist the return cannula to direct
the jet of oxygenated blood through the tricuspid valve and
away from the IVC. Similarly, it may be necessary to advance
or withdraw the drainage cannula to improve flow or minimize
recirculation.
When withdrawing a multiport cannula, it is critical to know
how far the side holes extend from the cannula tip to ensure
side holes are not withdrawn out of the vein because this will
rapidly cause air entrainment into the circuit. Important differences exist between cannulae in this regard: side holes extend
31 cm from the tip of an Avalon Elite multiport drainage
cannula but extend only 20 cm from the tip of a MAQUET
HLS multiport cannula.
Single-cannula technique
Recently, a family of double-lumen cannulae (Avalon Elite,
Bi-caval Dual Lumen Catheters, Avalon Laboratories) designed for placement in the right internal jugular vein have
been introduced into clinical practice. These cannulae have an
inner membrane that separates the cannula into 2 lumens. The
return lumen opens 10 cm from the cannula tip and is designed
to return blood to the RA. The tip of the (larger) drainage lumen
should be positioned in the IVC just distal to the origin of the
hepatic vein (Fig 7). The drainage lumen has an end hole and
side holes at the tip as well side holes proximal to the exit site
of the return lumen, thus allowing drainage from the both SVC
and the IVC. A 27F or 31F cannula is used for adults.27
During insertion of the Bicaval cannula, it is essential to
show that the guidewire and the cannula pass into the IVC and

SIDEBOTHAM ET AL

not through the tricuspid valve or into the hepatic vein. Imaging
of the guidewire and cannula may be done with fluoroscopy or,
more commonly, echocardiography.27 Once inserted, it may be
necessary to rotate the cannula to direct the jet of return blood
through the tricuspid valve. If the cannula is inserted too far or
the jet of return blood is not directed through the tricuspid
valve, significant recirculation and/or low flow can occur.
Potential advantages of the Avalon Elite Bi-caval Dual Lumen cannulae include only having to cannulate 1 vein, minimal
recirculation when correctly positioned, and the potential to
wake and mobilize patients who require long-term ECMO
support. Initial experience with these cannulae indicates a high
rate of successful cannulation, minimal need for repositioning,
and few complications.27,28 However, in the authors limited
experience of 5 patients (all of whom received a 31F cannula),
3 patients needed extensive manipulation of the cannula to
avoid recirculation, and 3 required placement of a second
drainage cannula to achieve adequate flow.
Three-cannulae technique
In large patients or when cardiac output is increased, maximum circuit flow to keep SaO2 in the goal range may be
insufficient with a single or 2-cannula technique. In this case,
the addition of a second drainage cannula allows higher flows
and may reduce recirculation.29 For femoroatrial or doublelumen cannulation, the second drainage cannula may be placed
in a femoral vein and advanced into the distal IVC; for femorofemoral cannulation, the second drainage cannula may be
placed in the right internal jugular vein and advanced to within
2 cm to the SVC/RA junction. A 19F or 21F short (20 cm)
cannula is suitable as a second drainage cannula.
Technique of Cannula Insertion
There are 2 approaches to cannulation for VV ECMO: surgical cutdown or percutaneous insertion. Percutaneous insertion via a modified Seldinger technique is well described in
adults,30,31 children,32 and neonates.33 However, when using
modern purpose-designed cannula/dilator kits, an unmodified
Seldinger technique, in which the guidewire, dilators, and cannulae are inserted without any (or minimal) cutting of the skin,
can be performed. The major advantage of an unmodified
Seldinger technique is that, if performed correctly, there is little
or no bleeding at the insertion site. The authors have used an
unmodified Seldinger technique (described later) using purpose-designed cannulae for the last 40 patients treated with VV
ECMO in their institution. There have been no technical failures, but there was 1 serious complication, a late presentation
of a femoral arterial injury that required surgical repair and
lower-limb fasciotomy.
There are limited data on cannula-related complications for
VV ECMO in adults. However, in 2 series involving 638
patients undergoing percutaneous large-bore venous cannulation (of the internal jugular, femoral, or subclavian veins) for
VV bypass for liver transplantation, a total of 11 cannulation
complications were reported, including 4 cases of hemomediastinum requiring thoracotomy and 1 death.34,35

VENOVENOUS EXTRACORPOREAL MEMBRANE OXYGENATION

Cannulation Using an Unmodified

Seldinger Technique
The authors preferred technique involves intensivist-led
cannulation performed in the intensive care unit (ICU). Preparation involves cross-matching 2 units of blood, resiting any
venous catheters that are in the planned ECMO cannulation
sites, ensuring peripheral venous access is in place for fluid
administration, and placing defibrillator pads (in the event of
guidewire-induced arrhythmias). The authors use 2 operators
and an assistant for cannulation: 1 operator for the femoral
drainage cannula, 1 operator for the right internal jugular return
cannula, and a scrubbed assistant. Additional personnel include
a perfusionist, a bedside nurse, and a clinician to perform
transesophageal echocardiography. Full sterile precautions are
observed, including draping the entire patient and sterilization
of the operative sites with 2% chlorhexidine solution. Operators
wear gown, gloves, masks, and surgical hats. The jugular and
femoral veins are identified with surface ultrasound. Guidewires are inserted via the Seldinger technique under ultrasound
guidance. The guidewires are confirmed to be in the vena cavae
with transesophageal echocardiographic imaging. Once the
guidewires are positioned correctly, heparin (5,000 IU) is given
intravenously, aiming for an activated coagulation time (ACT)
above 160 seconds. Serial dilation of the vessels is then performed. It is important to ensure the guidewire moves freely
inside the dilator at all times to prevent kinking of the wire or
the creation of a false passage. During the passage of each
dilator and the introducer/cannula unit, it is helpful for the
assistant to gently pull back on the wire to ensure the wire is
tensioned against the dilator tip and moving freely. If kinking
of the guidewire does occur, the kinked segment should be
withdrawn a few centimeters into the dilator. Cutting the skin
is avoided if possible.
Once the vessel is dilated, the cannula/introducer unit is
advanced into the vein over the wire. It is usual for there to be
some resistance as the lip between the cannula tip and the
introducer passes through the skin and the vessel wall. This
situation should be managed by the operator applying gentle
forward pressure and a twisting motion to the cannula/introducer unit as the assistant gently pulls back on the wire.
Passage of the cannula into the vein is often indicated by a
give. The cannula/introducer unit is then advanced into the
vessel, and the correct position of the cannula is confirmed
using transesophageal echocardiography. The guidewire and
then the introducer are withdrawn from the cannula, and the
cannula is clamped. It is essential that the cannulae not be
clamped in the region of wire reinforcing because this will
permanently deform the cannula.
Sedation and Analgesia During Cannulation
The vast majority of patients undergoing cannulation for
ECMO are already mechanically ventilated and deeply sedated.
In this circumstance, a neuromuscular blocker and an opioid
should be administered before cannulation. However, there are
2 circumstances in which cannulation may need to be performed awake: (1) patients undergoing VV ECMO for surgical
resection of an obstructed airway and (2) patients with cardiogenic shock (eg, because of fulminant myocarditis) who require

901

VA ECMO. In the latter situation, the induction of anesthesia

not infrequently precipitates a cardiac arrest.
Cannulation in patients who are awake is not straightforward. The procedure should be explained to the patient, and the
cannulation sites should be extensively infiltrated with local
anesthetic (eg, 1% lidocaine without epinephrine). Generally,
no conscious sedation should be given during the procedure,
but equipment and drugs for the induction of general anesthesia
should be immediately available. Once cannulation is performed and the circuit connected, low-flow ECMO support
should be instituted and shown to be effective before the
induction of general anesthesia and endotracheal intubation.
Sweep gas flow should be kept low (eg, half blood flow) in
awake patients to avoid inducing symptomatic respiratory alkalosis.
CIRCUIT PROCEDURES

Commencing ECMO for the First Time

In most EMCO centers, including the authors center, perfusionists provide a primed, clamped (with the clamp placed
between the pump and the oxygenator) ECMO circuit, with a
wrapped sterile section of tubing. In adults, it is usual to prime
the circuit with a crystalloid solution; however, for anemic or
extremely unstable patients, a blood prime may be used. After
cannulation and heparinization, the perfusionist hands off the
unwrapped sterile tubing into the operative field. It is essential to
correctly distinguish the drainage and return limbs of the circuit.
Drainage tubing typically is marked with blue (venous) tape and
return tubing marked with red (arterial) tape. The appropriate
limbs of the new circuit are aligned with the appropriate cannula. Both limbs of the circuit are clamped, and the tubing is
cut 10 cm distal to the clamps. The cut ends of the circuit and
the cannulae are held upward and backfilled to the clamps using
a 50-mL saline-filled syringe. Saline should continue to be
dribbled over the cannulae and tubing as they are joined together to ensure no air is trapped in the circuit. Wetting the
outside of the connectors makes it easier to connect the tubing.
Once connected, all clamps are released apart from the clamp
between the pump and the oxygenator. The pump is turned on
to 1,000 to 1,500 rpm, and the final clamp is released slowly.
The sweep gas should initially set to the same flow as the
ECMO circuit flow, ie, 3-6 L/minute. ECMO should be established slowly over 2 to 3 minutes. It is common for the patient
to become hypotensive as ECMO is commenced. A bolus dose
of calcium chloride or phenylephrine and intravenous fluids
should be available for treating this problem.
Once ECMO is established and the patients SaO2 is in the
target range, the ventilator should be set to rest settings (eg,
FIO2 of 0.4, peak inflation pressure (PIP) of 20 cmH2O, respiratory rate (RR) of 10 breaths/min, and positive end-expiratory
pressure (PEEP) of 10 cmH2O). If SaO2 is low despite reasonable ECMO flow (3-6 L/min) or if ECMO flow is low despite
adequate pump speed (flow 4 L/min, pump speed 4,000
rpm), transesophageal echocardiographic examination of the
flow patterns in the cannulae should be performed using color
Doppler imaging to exclude recirculation and cannula obstruction. Once ECMO support is satisfactory, the cannulae are
secured using fixation clips, sutures, and tape. The authors

902

approach is to suture the cannulae at 3 separate points, ensuring

the sutures do not tension the skin. The entry site is covered
with a chlorhexidine-impregnated patch and covered with a
transparent occlusive dressing.
Changing the Circuit
For a failing oxygenator or pump, an important decision is
whether to change out the individual component or the entire
circuit. The oxygenator, by virtue of its large blood-contact
surface area, is the major source of the inflammatory response
to ECMO. Furthermore, when thrombus forms in the oxygenator, there is often thrombus elsewhere in the circuit. Thus, if
the oxygenator needs changing, it is best to exchange the entire
circuit. Occasionally, for isolated thrombus in the pump, it may
be appropriate to exchange the pump only although this is rare.
To change the entire circuit, the old circuit must be cut out
and the new circuit connected. This process involves a brief
period of ECMO support, which should be 1 minute. Before
changing the circuit, all clinicians involved in the procedure
should agree on the sequence of events. The ventilator should
be set to the following emergency settings: FIO2 of 1.0, PIP of
35 to 45 cmH2O, RR of 20 breaths/min, and PEEP of 10
cmH2O. Ideally, 3 operators are required, 1 each for managing
the drainage and return limbs plus 1 to backfill the cut ends of
tubing. The following sterile equipment is required: 6 tubing
clamps, two 50-mL saline-filled syringes, 2 straight tubing
connectors, and 2 pairs of shears for cutting the tubing.
Full sterile precautions are observed. Thirty- to 50-cm
lengths of the drainage and return tubing of the old circuit are
swabbed with 2% chlorhexidine solution and included in the
sterile field. The sterile segment of the new circuit, handed off
by the perfusionist, also is included in the sterile field. The
drainage and return limbs of the old circuit are identified and
aligned with the same limbs of the new circuit. The procedure
is performed in the following sequence:
1. The drainage and return limbs of the new circuit are
clamped (Fig 8A), and the tubing is cut 10 cm distal to
the clamps. Straight tubing connectors are inserted
into the cut ends of the new circuit (Fig 8B).
2. The return limb and then the drainage limb of the old
circuit are double-clamped, 20 cm apart (Fig 8B), and
the pump is turned off. Each limb of the old circuit is
cut midway between the clamps.
3. The cut ends of the new circuit are connected to the
appropriate patient ends (Fig 8C) as described in the
Commencing ECMO for the First Time section.
4. All clamps are released from the circuit, and ECMO is
slowly restarted.
As noted previously, the return limb should be clamped before
the drainage limb; however, in practice, the 2 limbs may be
clamped simultaneously.
Adding a Second Oxygenator
Adding a second oxygenator is most easily performed using
an entirely separate circuit, from which the oxygenator is cut
out and then connected into the original circuit in parallel to the
first oxygenator (Fig 9). The procedure requires 2 brief periods
of ECMO support as follows:

SIDEBOTHAM ET AL

1. The new circuit is double clamped on the venous and

arterial sides of the oxygenator (Fig 9A). The primed
oxygenator is cut out of the new circuit.
2. The original circuit is double clamped in region 2 (ie,
preoxygenator), and the pump is turned off. The circuit
is cut between the clamps, and a 3-way tubing connector is inserted between the 2 clamps (Fig 9B). The new
oxygenator is then connected into the original circuit in
region 2 with the cut ends of tubing backfilled with
saline.
3. All clamps, except the clamp on the arterial side of the
new oxygenator, are removed, and ECMO is restarted
slowly (Fig 9C).
4. A period of patient recovery is provided.
5. The circuit is double clamped in region 3 (ie, postoxygenator), and the pump is turned off. A 3-way tubing
connector is inserted between the 2 clamps.
6. The new oxygenator is then connected into the original
circuit in region 3, with the cut ends of tubing backfilled with saline (Fig 9D).
7. All clamps are removed, and ECMO is restarted slowly
(Fig 9E).
Emergency Deairing of the Circuit
Circuit gas embolism is an uncommon but life-threatening
ECMO complication, which necessitates immediate clamping
and deairing the circuit, both to re-establish ECMO flow and to
prevent gas embolism to the patient. Literature regarding gas
embolism is limited to case reports and registry data.2,36 The
incidence of circuit gas embolism, reported by the Extracorporeal Life Support Organization, is 1.6% in adult VA ECMO and
1.8% in adult VV ECMO.2 The incidence of patient gas embolism is significantly lower (ie, 0.2%) for adult ECMO. A
higher incidence of circuit gas embolism is reported in neonatal
and pediatric ECMO, with 2.9% to 3.6% in pediatric ECMO
and 3.0% to 4.9% in neonatal ECMO. Rates of patient gas
embolism in neonatal and pediatric ECMO are significantly
lower (ie, 0.8%).
Because centrifugal pumps generate a large negative pressure in the drainage limb of the circuit, this region is uniquely
vulnerable to gas entrainment. Four potential sources of circuit
gas embolism exist: (1) entrainment of air via taps, connectors,
or damaged tubing in the drainage limb; (2) withdrawal of a
multiport drainage cannula exposing side holes to air; (3)
kinking or occlusion of circuit tubing, which can cause cavitation of dissolved gases out of solution; and (4) rarely, obstruction of the sweep gas outlet port, resulting in pressurization of
the gas phase of the oxygenator, potentially causing membrane
rupture and transfer of gas into the circuit.
The most common consequence of circuit gas embolism is
the immediate loss of circuit flow due to an air lock forming in
the pump. This necessitates immediate institution of emergency
ventilator settings and clamping of the circuit to prevent patient
gas embolism. (The formation of an air lock in the pump is
protective against patient gas embolism because the resulting
loss of circuit flow prevents further movement of gas through
the circuit.) If patient gas embolism does occur, the consequences vary with the type of ECMO support. With VV

VENOVENOUS EXTRACORPOREAL MEMBRANE OXYGENATION

Fig 8.

A schematic showing technique for changing the circuit. See text for details.

903

904

Fig 9.

SIDEBOTHAM ET AL

A schematic showing the technique for adding a second oxygenator to the circuit in parallel with the first. See text for details.

VENOVENOUS EXTRACORPOREAL MEMBRANE OXYGENATION

ECMO, gas transfer to the patient results in venous embolism

with the potential for hemodynamic compromise; with VA
ECMO, arterial embolism occurs with the potential for devastating cerebral, visceral, and limb ischemia.
Most commonly, when gas is entrained into the circuit, it
accumulates in the drainage tubing, the pump, the tubing of
region 2, and the oxygenator. The technique for deairing depends on the circuit components and ports. A suggested approach to deairing the circuit is shown in Figure 2, containing
a Quadrox PLS oxygenator as follows:
1. The circuit is double clamped, and the pump is turned
off. The first clamp is applied to the return limb, and
the second clamp is applied to the drainage limb (Fig
10A).
2. An empty reservoir bag is attached to the upper port on
the arterial side of the oxygenator and the port is
opened, allowing drainage of air from the circuit (Fig
10B).

Fig 10.

905

3. The pump is unclipped from the pump drive. The

clamp attached to the drainage limb is removed, allowing blood from the patient to flow into the drainage
tubing and pump. Air is walked along the circuit
tubing, through the pump, toward the oxygenator (Fig
10B).
4. Once the pump is deaired, a clamp is placed on the
circuit just distal to the pump. A fluid-filled bag then is
attached to the access port in region 2. This bag allows
further deairing of the circuit distal to the pump by
infusing fluid into the tubing and further walking air
along the tubing into the oxygenator. The reservoir bag
attached to the oxygenator slowly fills with air and
blood (Fig 10C). The use of this additional fluid bag is
not always necessary because satisfactory deairing may
be achieved by blood draining from the patient. Complete deairing of the oxygenator usually is not possible
(or necessary). The venous side of the oxygenator

A schematic showing the technique for deairing the circuit. See text for details.

906

SIDEBOTHAM ET AL

usually deairs completely; however, some gas usually

remains on the arterial side.
5. Once all the gas has been removed from the tubing
and pump and the oxygenator is more than threequarters deaired, the pump head is reattached to the
pump drive, and the pump turned on at low speed
(1,000-1,500 rpm). The clamp positioned distal to
the pump is removed, allowing a small amount of
additional air to be expelled into the drainage bag by
the pump (Fig 10D).
6. The access port on the arterial side of the oxygenator is
closed, and the clamp attached to the return limb of the
circuit is released. The pump speed is then increased
slowly to re-establish ECMO flow.
7. If a small amount of air remains in the oxygenator, the
authors recommend a complete circuit change (as previously described) after a suitable period of patient
recovery.
OTHER PROCEDURES

Because of the high risk of causing serious bleeding, extreme

caution should be exercised when deciding to perform procedures unrelated to the circuit, such as chest drain insertion and
percutaneous tracheostomy. The authors approach is to avoid
draining simple pneumothoraces or pleural effusions and to use
a no-cut, Seldinger technique for draining tension pneumothoraces or large hemothoraces. The authors avoid performing
percutaneous (or surgical) tracheostomy until ECMO has been
discontinued. Surgeons familiar with operating on anticoagulated patients should perform any surgeries required (eg, thoracotomy for drainage of loculated collections of blood or pus
and laparotomy for suspected mesenteric ischemia).
OTHER ASPECTS OF CARE

Many aspects of ongoing care of ECMO-supported patients

are similar to that of any critical ill patient; however, 3 issues
warrant special mention: sedation, anticoagulation, and fluid
management. The authors recently have reviewed these and
other aspects of care;10 therefore, only limited discussion is
provided here. Because ECMO support for respiratory failure
may extend for several weeks, maintaining appropriate sedation
can be problematic because of the development of marked
tolerance to opioids and benzodiazepines. The authors initial
approach is to use intravenous infusions of midazolam and
morphine (or fentanyl if renal function is impaired), aiming for
the lightest depth of sedation that avoids interference with
ECMO support (eg, causing suction events, described later) and
other cares (eg, tracheal suctioning and turning). If high doses
of morphine and midazolam are required (10-20 mg/h),
which is common in young patients, the authors introduce other
sedating drugs, such as phenobarbitone, ketamine, and clonidine. Unstable patients typically require neuromuscular blockade although the routine use of these drugs is not necessary or
appropriate. Some centers wake up and extubate patients during
long-term ECMO support;37 however, in the authors experience,
this has proven to be difficult. During recovery from a prolonged
ECMO run, benzodiazepines and opioids must be weaned slowly
to avoid withdrawal syndromes. The authors use enterally admin-

istered morphine (or methadone) and lorazepam (or diazepam) in

combination with clonidine tapered over 2 to 4 weeks.
Anticoagulation for the ECMO circuit is with unfractionated
heparin administered into region 2 of the circuit (see earlier).
The authors measure the ACT every 2 hours and the activated
partial thromboplastin time (APTT) every 6 hours, aiming for
values of 160 to 180 seconds for the ACT and 60 to 80 seconds
for the APTT. If there is discordance between the ACT and
APTT or evidence of bleeding or thrombus formation, the
authors measure an anti-Xa level, which provides a direct
measure of heparin activity, aiming for an activity level 0.3 to
0.6. If the required heparin dose is high (eg, 20 U/kg/h), the
authors measure an antithrombin III level. An antithrombin III
level below 50% of normal in combination with high heparin
dose requirements is an indication for fresh frozen plasma or
recombinant antithrombin III therapy.
Pathologic bleeding (eg, gastrointestinal, cannula insertion site,
and chest drain) may be caused by overanticoagulation, thrombocytopenia (eg, because of heparin-induced thrombocytopenia or
sepsis), disseminated intravascular coagulation (eg, because of
circuit thrombus or sepsis), or gastrointestinal stress ulceration or
erosions. Investigations include coagulation testing (ie, ACT,
APTT, anti-Xa level, D-dimer level, and platelet count), measuring the plasma hemoglobin concentration, performing a thromboelastogram, and, if indicated, gastrointestinal endoscopy. For
serious bleeding, in addition to administering blood products and
treating the underlying cause, it may be appropriate to discontinue
or reverse heparin anticoagulation. The authors have safely run the
ECMO circuit heparin free for more than 48 hours without adverse
effects. If pathologic bleeding is caused by disseminated intravascular coagulation secondary to circuit thrombus (as evidenced by
a high D-dimer, fibrinolysis on the thromboelastogram, visible
thrombus in the circuit, and a high plasma hemoglobin concentration), the circuit should be changed out. During the first 48
hours of ECMO support, the authors routinely target a platelet
count above 100,000/mm3, which thereafter is reduced to
50,000/mm3 if there is no pathologic bleeding.
During initial presentation with acute lung injury or ARDS,
patients typically require (or are given) significant fluid resuscitation. A similar period of increased fluid requirements often follows
the institution of ECMO. However, once ARDS has developed, a
restrictive fluid strategy is associated with improved lung function
and shortened duration of mechanical ventilation and ICU stay.38
Thus, the authors try to limit fluid administration and use loop
diuretics to try to maintain a negative fluid balance, even if this
results in the increased use of vasopressors and causes some
degree of acute kidney injury. The authors target a hemoglobin
concentration between 90 and 100 g/L. A higher hemoglobin
target may be necessary for treating hypoxemia for which no other
cause is identified (see later).
TROUBLESHOOTING AND COMPLICATIONS

Suction Events
A suction event occurs when the IVC collapses onto the
drainage cannula, resulting in an immediate loss of ECMO
flow. Increased chatter of the drainage tubing provides an
early warning sign of an impending suction event. Suction
events are common in patients who are hypovolemic and when

VENOVENOUS EXTRACORPOREAL MEMBRANE OXYGENATION

907

Table 1. Causes, Symptoms, and Treatment of Low Circuit Flow

Cause

Symptoms

Thrombus in the pump

Thrombus in the
oxygenator

Obstruction of the drainage

cannula

Treatment

Change in sound of pump

Rising plasma hemoglobin
Visible thrombus in pump
Increasing pressure drop across the
oxygenator
Low postoxygenator PO2; high postoxygenator
PCO2 (for a given sweep gas flow)
Visible thrombus in the oxygenator
Increased chatter in drainage limb
Echocardiographic signs of problems with
drainage cannula (thrombus/malposition)

high circuit flows are used and may be precipitated by turning

the patient, suctioning the airway, coughing, or ventilator
dysynchrony.
A suction event is treated by immediately reducing pump
speed to 0 (to relieve the suction) and then slowly reestablishing ECMO at a flow rate below that which precipitated the
event. Treatment of the underlying cause may include fluid
administration, sedation and paralysis, and repositioning the
cannula.
Low Circuit Flow
Low circuit flow for a given pump speed (or high pump
speed to obtain normal flow) implies there is an obstruction
within the circuit. Common causes of flow limitation are thrombus in the oxygenator, thrombus in the pump, malposition of
the drainage cannula, and kinks in the circuit (Table 1). Inves-

Change the pump or entire circuit

Increase anticoagulation
Change the oxygenator or the entire
circuit
Increase anticoagulation

Reposition drainage cannula

Place a second drainage cannula

tigation of low flow includes inspecting the circuit for kinking

and thrombus, measuring the plasma hemoglobin concentration, measuring the pressure drop across the oxygenator, and
examining the position and flow patterns of the drainage cannula with echocardiography.
Hypoxemia
The factors that contribute to arterial hypoxemia during VV
ECMO are (1) ECMO flows that are too low relative to the
patients cardiac output or metabolic oxygen requirements, (2)
recirculation, (3) deteriorating pulmonary function, (4) oxygenator failure, and (5) when the gas transfer capabilities of the
oxygenator are exceeded (Table 2). Any factor that increases
the patients cardiac output (eg, sepsis, aggressive fluid administration, inotropic agents, or anemia) or metabolic oxygen

Table 2. Causes, Investigations, and Treatment of Hypoxemia During VV ECMO

Cause

Recirculation

High cardiac output or high

metabolic oxygen
requirements
Deteriorating pulmonary
function
Oxygenator failure

Capabilities of the
oxygenator exceeded

Symptoms

High preoxygenator SO2 (70%); low separation

between preoxygenator SO2 and patient SaO2
(20%)
Evidence of flow between the drainage and
return cannulae on echocardiographic
imaging
Low preoxygenator SO2 (60%)
Other signs of sepsis or hypermetabolism
Reduced tidal ventilation
Deteriorating chest radiograph
Low postoxygenator PO2; high postoxygenator
PCO2 (for a given sweep gas flow)
Increasing pressure drop across the oxygenator
(for a given circuit flow); visible thrombus in
the oxygenator
High circuit flow (6 L/min)
Low postoxygenator PO2; high postoxygenator
PCO2
Low preoxygenator SO2
Normal pressure drop across the oxygenator
(for the circuit flow); no visible thrombus
Signs of hypermetabolism: sepsis, fever,
hyperdynamic circulation

Treatment

Reposition the cannulae under echocardiographic

imaging

Treat underlying cause; increase circuit flow; sedate and

paralyze patient; actively cool the patient; increase
hemoglobin concentration; increase circuit flow
Increase circuit flow; diagnose and treat nosocomial
sepsis
Replace oxygenator or circuit

Add second oxygenator into circuit, in parallel with the

first.
Treat the underlying cause of hypermetabolism

908

SIDEBOTHAM ET AL

requirements (eg, sepsis or hyperthermia) reduces SaO2 for a

given circuit flow.
Deteriorating pulmonary function is an interesting cause of hypoxemia. As noted previously, an SaO2 in the target range usually can be
achieved even when the lungs are noncontributory to gas exchange.
However, a common response to recovering pulmonary function is to
reduce circuit flows. Then, if secondary pulmonary dysfunction occurs (eg, nosocomial pneumonia or large pneumothorax) and ECMO
flows are not increased, SaO2 falls.
Low SaO2 should be investigated by checking pre- and
postoxygenator blood gases measuring the hemoglobin concentration and obtaining a chest radiograph. The patient should be
evaluated for signs of sepsis, including assessing their circulation, their need for vasopressors, and their hematology and
coagulation panels. Specimens for microbiologic analysis
should be obtained, including sputum, urine, and blood. Blood
cultures should be obtained from both the patient and the
circuit.
Assuming oxygenator failure is not the cause, low SaO2 is
most easily corrected by increasing circuit flows. However,
depending on the positions of the cannulae, increasing circuit
flow may increase the recirculation fraction, mitigating the
beneficial effect of higher flows. If recirculation is suspected,
the position and flow patterns of the ECMO cannulae should be
investigated with echocardiography. In the presence of increased cardiac output and high metabolic oxygen demands, it
may be necessary to actively cool the patient (eg, to 35C) and
boost their hemoglobin concentration (eg, 100 g/L). If these
measures are not effective, adding a second drainage cannula
and/or a second oxygenator may be necessary.
WEANING AND DISCONTINUING ECMO

Signs of pulmonary recovery are indicated by reduced

ECMO flow to maintain SaO2, an improving chest radiograph,
and increased tidal volumes. ECMO flows of 2 L/min for
prolonged periods should be avoided to reduce the risk of
thrombus forming in the circuit. However, maintaining normal
circuit flow with the sweep gas turned off prevents thrombus

forming in the circuit but allows the patient to be tested off

extracorporeal support.
When the required circuit flows to maintain an SaO2 above
92% has reduced to 3L/min and tidal volumes on rest
ventilator settings have increased to 200 mL, a trial period on
standard ventilator settings (eg, FIO2 0.4, PIP 30 cmH2O,
PEEP 5-10 cmH2O, RR 15 breaths/min) off extracorporeal support should be performed. If, after 2 to 4 hours of no
ECMO support, tidal volume and gas exchange are adequate
(ie, tidal volume 5 mL/kg, PaO2 10 kPa [75 mmHg], and
PaCO2 7 kPa [52 mmHg]), ECMO may be discontinued and
the patient decannulated.
ECMO is stopped by first clamping the return limb and then
the drainage limb and turning off the pump. Full sterile precautions are observed during the removal of the cannulae. If an
unmodified Seldinger technique has been used for insertion, the
cannulae simply can be removed and manual pressure applied
to the insertion site for 10 to 15 minutes. If the cannulae were
inserted by a cut-down technique, formal surgical removal and
repair of the veins are indicated. Heparin is reversed with
protamine, 50 to 100 mg, and an ACT checked aiming for a
value in the normal range (140 seconds).
CONCLUSIONS

ECMO is a potentially lifesaving intervention for treating

severe ARDS. As a consequence of recent trial data and the
introduction of new equipment, notably PMP oxygenators
and purpose-designed cannulae, the use of ECMO is increasing. However, ECMO is a complex intervention with the
potential for substantial patient harm. As such, a thorough
understanding of the circuit, pump, oxygenator, and cannulae is essential. ECMO clinicians also must be able to
manage the complications associated with ECMO, such as
cannula malposition, circuit gas embolus, and hypoxemia.
Furthermore, a good team approach with excellent communication among intensivists, cardiac anesthesiologists, surgeons, perfusionists, nurses, and other personnel are essential for success.

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