ARTIFICIAL LUNG

Artificial Lung
Often called blood oxygenators.
Replace entirely the pulmonary gas exchange function (when the
natural organ is totally disabled or, while still sound, must be
taken out of commission for a limited time to allow a surgical
intervention) or to assist the deficient gas transfer capacity of the
natural organ, either temporarily, with the hope that the healing
process will eventually repair the diseased organ, or
permanently, when irreversible lung damage leaves the patient
permanently disabled.
Since most artificial lungs cannot be placed in the anatomical
location of the natural lung, venous blood must be diverted from
its normal path through the central veins, right heart, and
pulmonary vascular bed and rerouted, via catheters and tubes,
through an extracorporeal circuit which includes the artificial
lung before being returned, by means of a pump, to the arterial
system.
The procedure in which the pulmonary circulation is temporarily
interrupted for surgical purposes and gas exchange is provided
by an artificial lung is often referred to as extracorporeal
circulation (ECC) because, for convenience sake in the operating
room, the gas exchange device as well as the pumps which
circulate the blood are located outside the body.
 Gas exchange systems
Stationary film oxygenator: a bulky device in which
venous blood was evenly smeared over a stack of
vertical wire screen meshes in an oxygen
atmosphere, flowing gently downward to accumulate
in a reservoir from where blood could be returned to
a systemic artery.
Problems: cumbersome dimensions, blood
streaming, maintaining a constant blood-gas
exchange area.
 Gas exchange systems
Replacing the stationary film support with rotating
screens or rotating discs partly immersed in a pool of
blood:
 Allowed some control of gas transfer performance by changing
the rotational speed.
 Foaming and hemolysis were encountered at high disc
spinning velocity.
 Gas exchange systems
Technical advances:
 The discovery that hydrophobic microporous membranes,
through which gas can freely diffuse, have a high enough
surface tension to prevent plasma filtration at the moderate
pressures prevailing in the blood phase of an artificial lung.
 The large-scale fabrication of defect-free hollow fibers of
microporous polypropylene, which can be assembled in
bundles, potted and manifolded at each extremity to form an
artificial capillary bed of parallel blood pathways immersed in
a cylindrical hard shell through which oxygen circulates.
Plasma proteins were denatured at the gas interface, leading to blood trauma
associated with platelet activation and aggregation, complement activation, and
hemolysis.
Manifolding and blood distribution system could match the fluid dynamic efficiency of the pulmonary
circulation, where a single feed vessel – the pulmonary artery – branches over a short distance and with
minimal resistance to flow into millions of tiny gas exchange capillaries the size of an erythrocyte.
In chemistry, hydrophobicity (from the combining form of water in Attic Greek
hydro- and for fear phobos) is the physical property of a molecule (known as a
hydrophobe) that is repelled from a mass of water.[1]
Hydrophobic molecules tend to be non-polar and thus prefer other neutral
molecules and nonpolar solvents. Hydrophobic molecules in water often cluster
together forming micelles. Water on hydrophobic surfaces will exhibit a high
contact angle.
Examples of hydrophobic molecules include the alkanes, oils, fats, and greasy
substances in general. Hydrophobic materials are used for oil removal from water,
the management of oil spills, and chemical separation processes to remove non-
polar from polar compounds.
Basic principles of operation

Hollow
fiber
membranes

Oxygen diffuses down its

concentration gradient across the
fiber wall into blood, while carbon
dioxide (CO2) diffuses down its
concentration gradient from the
blood into the sweep gas flowing
through the fibers and is removed
when the sweep gas exits the device.

In most artificial lung Small polymer tubes

applications, an oxygen (O2)
“sweep gas” flows through the
with microporous walls
inside lumens of the hollow of 20 to 50 µm thickness
fibers, while blood flows outside and with outer
the hollow fibers through the
interstitial spaces in the hollow diameters from 200 to
fiber bundle. 400 µm.

Made from hydrophobic The wall pores have

polymers (often characteristic sizes typically
polypropylene), so that the below about 0.1 µm, and
membrane wall pores the porosity or volume
remain gas-filled and fraction of the fiber wall
respiratory gases can diffuse can vary from about 40% to
readily across it. 50%.
 Determinants of gas exchange

The overall O2 exchange rate, VO2, is related to the

O2 permeance, KO2 (overall mass transfer coefficient
for O2 exchange), according to

 Where PO2g and PO2b = average O2 partial pressures in the

sweep gas and blood phases, respectively, flowing through the
artificial lung.
 A = total membrane area of the hollow fiber bundle.
 Determinants of gas exchange

The overall CO2 exchange rate, VCO2, is related to the

CO2 permeance, KCO2 (overall mass transfer
coefficient for CO2 exchange), according to

 Where PCO2g and PCO2b = average CO2 partial pressures in the

sweep gas and blood phases, respectively, flowing through the
artificial lung.
 A = total membrane area of the hollow fiber bundle.
 Permeance
Inverse of a diffusional resistance.
Overall transfer resistance in an artificial lung device has 2 principal
components:

 Km and Kb = the membrane and blood-side permeances for each gas (O2 and CO2).
 1/Km = diffusional resistance for the membrane itself.
 1/Kb = resistance for gas diffusing between the membrane and the flowing blood stream.
Figure 5 illustrates the membrane and blood-side diffusional
resistances to gas exchange in artificial lungs by showing the
general gradient in CO2 partial pressure from the sweep gas to
the blood pathway. Transfer resistance within the sweep gas
pathway is negligible. Most of the diffusional resistance resides
within a blood-side diffusional boundary layer, and
secondarily within the membrane itself. The blood-side and
membrane permeances dictate overall gas exchange in
artificial lungs and represent serial transport processes whose
resistances add directly to determine overall resistance, as in
Eq. 3. As serial “resistors” the smallest permeance or largest
resistance controls overall gas exchange in an artificial lung.
 Membrane permeance

Most artificial lungs use microporous hollow fiber

membranes.
 Gas exchange occurs by diffusion through these gas-filled pores.
The hydrophobic nature of the polymers (e.g.
polypropylene) used to make the fiber membranes
prevents intrusion of blood plasma into the fiber pores
under normal conditions.
Most artificial lungs, including standard blood oxygenators, use
microporous hollow fiber membranes. Microporous hollow fibers
have fixed submicron pores within the wall that are contiguous
from outer to inner lumen, and gas exchange occurs by diffusion
through these gas-filled pores. The polymer used does not dictate
gas exchange through the membrane as much as the pore
characteristics and the fiber wall porosity. In artificial lungs the
hydrophobic nature of the polymers (e.g. polypropylene) used to
make the fiber membranes prevents intrusion of blood plasma
into the fiber pores under normal conditions. Most microporous
hollow fiber membranes for artificial lungs are manufactures by
Celgard (Charlotte, NC), Membranea (Germany), and Mitsubishi
Rayon (Japan).
 Membrane permeance

The membrane diffusional resistance of a microporous

hollow fiber depends on the permeance, Km, of the fiber
membrane.
 Its effect on the overall gas exchange performance of artificial lungs
is negligible compared to blood-side permeance.
 Can be estimated using simple diffusion principles or measured
using gas-gas test systems.
Example:
 If membrane permeance dictated overall gas exchange, an artificial
lung with 2 m2 membrane area perfused with blood at a PCO2 of 50
mmHg would remove CO2 at a theoretical rate of __60__ L/min.
Km = 1.47 x 10 ml/cm /s/cm Hg
-2 2

The gas exchange rate of artificial lungs is much
smaller than this because overall gas exchange is
dictated by diffusional boundary layers that arise on
fiber surfaces n the flowing blood stream. In practice,
therefore, K~Kb unless hollow fibers are coated with
nonporous polymers (true membranes) to resist
plasma wetting.
 Membrane permeance

In practice, K~ Kb unless hollow fibers are coated with nonporous

polymers (true membranes) to resist plasma wetting.
Plasma wetting
 A process in which blood plasma infiltrates the microporous walls of hollow
fibers.
 A common problem when extracorporeal oxygenators are used in extended
respiratory support and can lead to device failure within days.
 Results primarily from phospholipids, lipoproteins and/or proteins in blood
that absorb onto the fiber polymer surfaces at the plasma interface, rendering
the interface hydrophilic and allowing for wetting of the pores by either
partial or complete plasma infiltration.
 Plasma infiltration markedly diminishes the membrane permeance, K m,
because relatively rapid gas phase diffusion is replaced by diffusion through
stagnant plasma within fiber pores.
 Membrane permeance

Composite hollow fibers

incorporate a thin nonporous
polymer layer as a true membrane
or “skin” on the microporous fiber
surface.
 Blocks infiltration of plasma into pores
and is a key functional requirement of
artificial lungs for longer-term respiratory
support.
 Made either by coating an existing
microporous fiber with a thin nonporous
polymer (a true composite hollow fiber) or
by modifying the fabrication of the
microporous fiber itself to seal off pores at
the surface (an asymmetric hollow fiber).
 Membrane permeance

The membrane permeance of a composite hollow

fiber is essentially dominated by the nonporous
polymer layer:

 αP and DP are the solubility and diffusivity of the gas within the
nonporous polymer.
 δ is the polymer layer thickness.
The design of composite hollow fiber membranes for
artificial lungs requires a Km that does not
significantly reduce overall gas exchange.
Nonporous polymer skin that prevents plasma wetting also
diminishes membrane permeance because a nonporous
polymer can present an impediment to gas diffusion. Pm =
polymer permeability to specific gases.
As an example, if coated or composite fibers are to exert no
more than a 5% reduction in overall gas exchange for a
particular artificial lung design, then Km needs to be greater
than 20 times Kb. For this reason, composite hollow fiber
membranes for artificial lungs require nonporous polymers
with relatively high gas permeabilities (~100 Barriers or
greater) that can be coated in a continuous layer of 1 um
thickness or less on microporous hollow fiber surfaces.
 Diffusional Boundary Layers

 The blood side permeance, Kb, accounts for gas movement through the diffusional boundary
layers that exist adjacent to the fiber surfaces, where fluid velocity is reduced by drag forces.

 αb and Db are the effective solubility and diffusion coefficient of the diffusing gas in blood.
 δbl is the average boundary layer thickness.
 The boundary layer thickness on a flat surface grows with distance along the surface in the
direction of flow according to

 where ν is the kinematic viscosity

 Db is the species diffusion coefficient
 V is the bulk flow velocity past the surface.
The blood-side permeance of an artificial lung, Kb, accounts for gas movement through the diffusional boundary
layers that exist adjacent to the fiber surfaces, where fluid velocity is reduced by drag forces. Gas molecules traverse
the boundary layer by molecular diffusion before being exposed to sufficient convection by the blood flowing past
fiber surfaces. The blood-side permeance can be expressed as

Where are the effective solubility and diffusion coefficient of the diffusing gas in blood and is an average boundary
layer thickness. For O2 and CO2 the effective solubility accounts for increased solubility due to hemoglobin binding
(for O2) or carriage as bicarbonate ion (for CO2).
The boundary layer thickness, , depends on the local interaction between diffusional and velocity fields in the flowing
blood phase subjacent to the fiber surfaces of the artificial lung. The nature of these diffusional boundary layers is
complex, but the simple boundary layer paradigm of laminar flow past a flat membrane surface can be instructive.
Boundary layer thickness on a flat surface grows with distance along the surface in the direction of flow according to

Where v is the kinematic viscosity, Db is the species diffusion coefficient, and V is the bulk flow velocity past the
surface. An important concept is that boundary layer thickness can be decreased by increasing the blood flow velocity
past the fiber surfaces, and the resulting increase in gas exchange permeance varies as the square root of flow velocity.
Furthermore, because boundary layers grow along the fiber surface, permeance and gas exchange are less with
longitudinal flow, parallel to the fiber axes, than with transverse or cross flow, perpendicular to the fiber axes. The
simple boundary layer paradigm predicts that Kb for transverse versus longitudinal flow would be Kbtran/Kblong ~
sqrt(L/d), where L and d are fiber length and diameter, respectively. Since L/d in hollow fiber bundles can vary from
100 to 1000, an appreciable mass transfer benefit exists for transverse compared to parallel blood flow through hollow
fiber bundles.
 The blood oxygenator
 Membrane blood oxygenators consisting of either microporous polypropylene hollow
fiber membranes or, as in one design, silicone sheets.
 Blood enters the oxygenator through an inlet port and flows either along the outside of the
hollow fibers or the outside of the silicone sheet. The blood is then collected in a
manifolded region, flows through a heat exchanger, and then exits the device through an
outlet port.
 The gas, which can be pure oxygen or a mixture of oxygen and room air, enters the
oxygenator through a gas inlet port, flows through the inside of the hollow fibers/silicone
sheets, and exits the device via an outlet port.
Artificial lungs that are used currently are membrane blood oxygenators
consisting of either microporous polypropylene hollow fiber membranes
or, as in one design, silicone sheets. The general anatomy of the
oxygenator is similar between the two types of devices despite the differing
gas exchange surfaces. Blood enters the oxygenator through an inlet port
and flows either along the outside of the hollow fibers or the outside of the
silicone sheet. The blood is the collected in a manifolded region, flows
through a heat exchanger, and then exits the device through an outlet port.
The gas, which can be pure oxygen or a mixture of oxygen and room air,
enters the oxygenator through a gas inlet port, flows through the inside of
the hollow fibers/silicone sheets, and exits the device via an outlet port.
The key design considerations in blood oxygenators include minimizing
the resistance to blood flow, reducing the priming volume, ensuring easy
debubbling at setup, and minimizing blood activation and
thrombogenicity.
 The blood oxygenator

 Key design considerations: minimizing the resistance to blood flow,

reducing the priming volume, ensuring easy debubbling at setup, and
minimizing blood activation and thrombogenicity.
 Most current blood oxygenators have fiber membranes with outer
diameters of 200-400µm and wall thickness of 20-50µm, total
membrane surface area of 2-4m2, and blood priming volume of 135-
340mL.
Most current blood oxygenators (Fig. 9) have fiber
membranes with outer diameters of 200–400 mm and wall
thickness of 20–50 mm, total membrane surface area of 2–
4 m2, and blood priming volume of 135–340 ml.[17] The
hollow fibers are wound or matted within a hard plastic
outer shell to produce fiber packing densities in the bundle
of 40–60%, and the arrangement of the fiber bundle and
blood flow patterns differ between devices.[32] For example,
fibers are helically wound in the Medtronic Affinity
NT oxygenator. Blood enters the device through a central
core channel and is then distributed radially through the
fiber bundle. Fibers in the Jostra Quadrox oxygenator are
aligned so that blood flow is perpendicular to the gas
pathways. Hollow fiber oxygenators with intraluminal
blood flow have been designed but are rarely used due to a
generally unfavorable high resistance to blood flow.
 Rated flow

Rated flow: the flow rate through the oxygenator at

which an inlet blood saturation of 70% can be
oxygenated to an outlet blood saturation of 95%.
 Measure of the gas exchange capacity of the device.
The rated flow can range from 1 -1 1.8L/min for a
neonatal oxygenator and up to 7 L/min for an adult
oxygenator.
The fabrication or wrapping of the fiber bundle in a blood oxygenator can be
important as the geometry obtained impacts diffusional boundary layers,
secondary flows, and gas exchange efficiency. A blood oxygenator is often
characterized by its rated flow as a measure of the gas exchange capacity of the
device. Rated flow is the flow rate through the oxygenator at which an inlet
blood saturation of 70% can be oxygenated to an outlet blood saturation of 95%.
The rated flow can range from 1-1.8L/min for a neonatal oxygenator and up to 7
L/min for an adult oxygenator with increased gas exchange capacity.

As flow through the membrane increases, actual O2 transfer increases

proportionally until the residence time of the venous return prevents complete
hemoglobin saturation. At this point, the absolute O2 transfer becomes fixed,
but as the flow continues to increase, a smaller percentage of the venous return
becomes saturated. R represents the rated flow, which is the flow at which the
blood leaving the membrane is 95% saturated.
 Silicone membrane oxygenators vs. microporous hollow
fiber oxygenators

 Silicone membrane oxygenators are often used in extracorporeal

membrane oxygenation for respiratory support since plasma leakage
does not occur as it does in microporous hollow fiber oxygenators.
 Because diffusion occurs across a nonporous silicone sheet, the
thickness of these sheets was reduced to 100-200µm. Nevertheless, the
gas exchange efficiency of silicone oxygenators is substantially below
that of hollow fiber oxygenators.
 Silicone membrane oxygenators are often used in extracorporeal membrane oxygenation
for respiratory support since plasma leakage does not occur as it does in microporous
hollow fiber oxygenators. Kolobow[33] is generally credited with developing the first spiral-
wound silicone membrane oxygenators in 1963. The oxygenator contains two silicone
sheets sealed around the edges, which are wound around a polycarbonate core. Gas flows
within the sealed sheets and blood flows countercurrently between the spiral wraps. The
surface area of silicone membrane oxygenators ranges from 0.4 to 4.5 m2 and the priming
volumes range from 90 to 665 ml.[33] Because diffusion occurs across a nonporous
silicone sheet, the thickness of these sheets was reduced to 100–200 mm.
 Nevertheless, the gas exchange efficiency of silicone oxygenators is substantially below that
of hollow fiber oxygenators. The Avecor 0800 silicone oxygenator (a descendant of the
Kolobow silicone oxygenator) has an O2 transfer efficiency of 88 ml/min/m2 compared to
150 ml/ min/m2 for the Affinity hollow fiber device.[33] Them resistance to blood flow is
also higher in silicone sheet oxygenators compared with hollow fiber oxygenators, and
debubbling the sheet oxygenators can be more difficult.
 Cardiopulmonary bypass (CPB)

A procedure that allows the temporary replacement of the gas

exchange function of the lungs and the blood-pumping function
of the heart (bypass the heart cavities and the pulmonary
circulation).
Equipment used: pump oxygenator and heart-lung machine.
On the blood side – hemodilution, some degree of hypothermia,
nonpulsatile arterial perfusion at a flow rate near the resting
cardiac output, and continuous recirculation of blood in an
extracorporeal circuit in series with the systemic circulation of the
patient.
On the gas side – oxygen or an oxygen-enriched gas mixture (with
or without a low concentration of CO2) flows from a moderately
pressurized source in a continuous, nonrecycling manner and is
vented to the room atmosphere.
 Oxygenators in Cardiopulmonary Bypass

 Cardiopulmonary bypass (CPB) uses an external flow circuit

incorporating a blood oxygenator.
 Components of CPB: heat exchanger, flowmeters & blenders, suction
devices, cardiotomy reservoir, pressure and temperature monitors,
sampling ports, filters, tubing, and cannulae.
In CPB, blood is drained by gravity from the inferior/superior vena cava or the right
atrium into a venous reservoir and is then pumped through the oxygenator by
either a roller or centrifugal pump back into the ascending aorta.
Blood flow during CBP is kept low (2–2.4 l/m2/min) to minimize bleeding.[35] A
heat exchanger is required to cool and rewarm the patient and is typically
incorporated into the oxygenator. Oxygen, or a mixture of oxygen and carbon
dioxide, is fed through flowmeters and blenders
into the oxygenator at flow rates of 5–10 l/min, which is 2–3 times the flow rate
of blood.[36] The oxygenator must be capable of transferring up to 250 ml/min
of oxygen and 200 ml/min of carbon dioxide during cardiopulmonary bypass in
order to meet the metabolic needs of the patient.[36] The bypass circuit also
includes suction devices that are used to maintain a blood-free surgical field. The
suctioned blood is collected and filtered in a cardiotomy reservoir and is then
pumped into the venous reservoir. Other components of the bypass circuit
include pressure and temperature monitors, sampling ports, filters, tubing, and
cannulae.
 Typical operating conditions for a CPB

Blood from Venous reservoir Cardiotomy reservoir Blood from

central veins coronary suction

Ice water 0 – 5 oC 10 – 20 oC
Heat exchanger

pO2 40 mmHg
mmHg pCO2 45 mmHg mmHg
pO2 713 Oxygenator 675 5 – 10 L/min
Gas
pCO2 0 30
pH2O 47 47
Blood to patient
5L/min

Typical Operating Parameters for Cardiopulmonary Bypass in an Adult

Oxygen transfer requirement 250 mL/min
CO2 elimination requirement 200 mL/min
Respiratory gas exchange ratio (respiratory quotient) 0.8
Blood flow rate 5 L/min
Gas flow rate 5-10 L/min
Gas partial pressures (in mmHg)
Blood in pO2 = 40 pCO2 = 45
Blood out pO2 = 100-300 pCO2 = 30-40
Gas in (humidified) pO2 = 250-713 pCO2 = 0-20
Gas out pO2 = 150-675 pCO2 = 10-30
The respiratory quotient (or RQ or respiratory
coefficient), is a unitless number used in
calculations of basal metabolic rate (BMR) when
estimated from carbon dioxide production. Such
measurements, like measurements of oxygen uptake,
are forms of indirect calorimetry. It is measured
using Ganong's Respirometer.

RQ = CO2 eliminated / O2 consumed

 Complications with CPB

Activation of the coagulation cascades and

thrombosis.
 Thrombus formation in the oxygenator can cause an increase
in resistance to blood flow and a decrease in gas transfer.
 To reduce the risk of clot formation, oxygenators are designed
to minimize regions of blood flow stasis, which typically
promote thrombus formation.
 High level of anticoagulation: increased risk of bleeding.
 Oxygenators and the entire bypass circuit are now being coated
with heparin in order to prevent clotting in the circuit while
reducing the required amount of systemic anticoagulation.
There are several different heparin coatings
currently available on the market.[38] The Carmeda
Bioactive Surface has been used for more than a decade
and utilizes a covalent end-point attachment of heparin to
the surface. The BioLine Coating by Jostra first coats the
surface with polypeptides and then with a low-molecularweight
heparin, Liquemin. The coating is available in
two types, one for CBP and one for long-term use in
extracorporeal membrane oxygenation. Other more recent
coatings include AOThel by Artificial Organ Technology,
Corline by Corline Systems AB, and the Trilium Biopassive
Surface by Avecor. Many studies have been
performed on the efficacy of the heparin coatings and the
required level of systemic heparin with the coatings.
Aldea et al.[39] compared noncoated circuits and an ACT
of 480 seconds with coated circuits and an ACT of 280
seconds. The heparin coating resulted in a 34% decrease
in the need for blood products, 13.8% less bleeding,
43.6% shorter intubation time, 41.7% less time in the
intensive care unit, and 17.8% less time in the hospital
compared with noncoated circuits.
Extracorporeal Membrane Oxygenation (ECMO)

Uses blood oxygenators in pump-driven external circuits to

provide respiratory support and lung rest and recovery for
prolonged periods of time (1-30 days).
 Used in patients with severe lung failure who fail traditional
mechanical ventilation.
 ECMO circuit contains a pump, a heat exchanger, an oxygenator (no
venous reservoir and suctioning equipment).
Extracorporeal membrane oxygenation (ECMO) uses blood oxygenators in pump-driven
external circuits to provide respiratory support and lung rest and recovery for prolonged
periods of time (1–30 days).[40] ECMO is used in patients with severe lung failure who fail
traditional echanical ventilation. Similar to CPB circuits,
the ECMO circuit contains a pump, a heat exchanger, and an oxygenator, but unlike CPB
circuits, a venous reservoir and suctioning equipment is not used. In ECMO, the patient is
continuously anticoagulated with heparin to achieve an ACT of 160–240 seconds, much
less than that found in CPB.[41] The required blood flow in ECMO is 120 ml/kg/min for
neonates, 75 ml/kg/min for pediatric, and 50 ml/kg/min for adults.[33] Extracorporeal
membrane oxygenation is used to treat neonatal, pediatric, and adult patients with lung
failure, and the effectiveness of ECMO differs in each of these groups. ECMO is most
commonly used in neonates with a survival rate of 80%.[42] Indications for neonatal
ECMO include meconium aspiration syndrome, respiratory distress syndrome, persistent
fetal circlation, persistent pulmonary hypertension, and hyaline membrane disease.[43]
Pediatric and adult patients have lower survival rates of 53% and 41%, respectively.[42]
Indications for ECMO in pediatric or adult patients are viral, bacterial, or aspiration
pneumonia and acute respiratory distress syndrome (ARDS), which can be caused by
trauma, pneumonia, or sepsis.[44]
 Cannulation techniques

Cannulation
techniques

Venovenous Venoarterial
 Venovenous (VV) ECMO

Drains and returns to the venous system.

Most commonly used cannulation techniques.
Sites for cannulation: internal jugular, saphenous,
femoral veins or the right atrium.
Provides no cardiac support and is not used in
patients with cardiac arrest, arrhythmias, or
myocardial failure.
The cannula must be designed to reduce recirculation of
returned blood directly back into the ECMO circuit.
 Cardiac output, pump flow rate, cannula position, and right atrium
size are all factors that can affect recirculation.
Venovenous ECMO drains and returns to the venous system, venoarterial ECMO drains from
the venous system and returns into the arterial system, and arteriovenous ECMO is the
opposite. Venovenous (VV) ECMO was established in the 1960s and 1970s and is now
the most commonly used cannulation technique.[33,45] VV ECMO has several different sites
for cannulation including the internal jugular, saphenous, or femoral veins or the
right atrium. In neonates, VV ECMO can use a single dual-lumen cannula or two cannulae.
The single doublelumen cannula is used in the jugular vein, and the septum
offset produces a larger channel for venous inflow into the ECMO circuit. The cannula must
be designed to reduce recirculation of returned blood directly back into the
ECMO circuit. Cardiac output, pump flow rate, cannula position, and right atrium size are all
factors that canaffect recirculation. Single double-lumen cannulation
cannot be used in pediatric and adult ECMO due to inadequate venous inflow into the circuit
and also high levels of hemolysis, recirculation, and pressure with flow
rates greater than 600 ml/min.
 Venoarterial (VA) ECMO

Drains from the venous system and

returns into the arterial system.
Original cannulation technique used
in ECMO.
Indicated when cardiac support is
required in addition to respiratory
support.
Disadvantages of VA ECMO:
 Cannulation of a major artery.
 Lack of pulmonary perfusion.
 Decreased cardiac output due to a higher
afterload.
 Increased risk of neurological events.
Venoarterial (VA) ECMO was the original cannulation technique used in ECMO and is
indicated when cardiac support is required in addition to respiratory support. In contrast,
VV ECMO provides no cardiac support and is not used in patients with cardiac arrest,
arrhythmias, or myocardial failure.[45] The disadvantages of VA ECMO include
cannulation of a major artery, lack of pulmonary perfusion, decreased cardiac output due
to a higher afterload, and increased risk of neurological events. VV ECMO has several
advantages over VA ECMO including preserving pulsatility and avoiding the cannulation
of a major artery. Neurological events can also be reduced since thromboemboli from the
circuit travel to the lungs instead of the brain. VV ECMO also prevents ischemic injury to
the lungs since the lungs remain perfused with blood, but blood flow must be carefully
regulated in order to prevent an imbalance in the central venous system.[45]
Given its advantages compared to VA ECMO, several institutions are now using VV
ECMO and comparing results with VA ECMO. Knight et al.[46] found an increased
survival rate of 91% with VV ECMO compared to 80% with VA ECMO in neonates. Zahraa
et al.[47] performed a retrospective study from 1986–1997 comparing VV and VA ECMO
in pediatric patients and found a trend for improved survival with VV ECMO with survival
rates of 60% and 56%, respectively.
 Advantages of VV ECMO over VA ECMO

Preserving pulsatility.
Avoiding the cannulation of a major artery.
Neurological events can also be reduced since
thromboemboli from the circuit travel to the lungs
instead of the brain.
Prevents ischemic injury to the lungs since the
lungs remain perfused with blood, but blood flow
must be carefully regulated in order to prevent an
imbalance in the central venous system.
Given its advantages compared to VA ECMO, several
institutions are now using VV ECMO and comparing
results with VA ECMO. Knight et al.[46] found an
increased survival rate of 91% with VV ECMO compared
to 80% with VA ECMO in neonates. Zahraa et al.[47]
performed a retrospective study from 1986–1997
comparing
VV and VA ECMO in pediatric patients and found
a trend for improved survival with VV ECMO with
survival rates of 60% and 56%, respectively.
 Complications with ECMO

Plasma wetting of hollow fiber membranes from

the longer-term exposure of the ECMO oxygenator
to blood.
 Plasma wetting decreases gas exchange, can occur quickly
and unpredictably, and requires replacement of the
oxygenator.
 Microporous hollow fiber membranes can be coated with
thin siloxane layers to prevent plasma wetting and
increase the biocompatibility.
 The inflammatory and thrombogenic complications associated with cardiopulmonary
bypass are exacerbated in ECMO due to the longer blood exposure to the extracorporeal
circuit. As for CPB circuits, ECMO circuits and oxygenators are heparin-coated to help
minimize systemic heparinization, decrease inflammatory responses, and prevent
thrombosis. One complication of ECMO not seen in CPB is plasma wetting of hollow fiber
membranes from the longer-term exposure of the ECMO
 oxygenator to blood. Plasma wetting decreases gas exchange, can occur quickly and
unpredictably, and requires replacement of the oxygenator. Microporous hollow fiber
membranes can be coated with thin siloxane layers to prevent plasma wetting and
increase the biocompatibility.[ 48–52] New polymer coatings are also being developed to
resist plasma leakage while attenuating the inflammatory
 response. Saito et al.[52] coated CBP circuits with poly(2-methoxyethylacrylate) (PMEA)
and compared the inflammatory response with that caused by uncoated circuits in swine.
Protein adsorption was significantly less on the PMEA circuits compared with control
(0.3±0.03
 mg/cm2 versus 3.42±0.04 mg/cm2). Peek et al.[53] performed an initial clinical trial with
the Medos Hilite 7000LT oxygenator, which uses a polymethyl pentene (PMP)
asymmetric hollow fiber membrane, which was also coated with heparin. Additional
studies are needed to fully evaluate the effectiveness of these new coated fiber
oxygenators.
 Artificial Lung vs. Natural Lung
Natural lung Hollow fiber oxygenator
Performance
Must meet demand at rest and during exercise, fever, etc. Must meet demand at rest and under anesthesia.
Constant temperature process around 37oC. Can be coupled with heat exchanger to lower body temperature.
O2 and CO2 transfer are matched to achieve the respiratory quotient O2 and CO2 transfer are largely independent of each other and must be
imposed by foodstuff metabolism (around 0.8). controlled by the operator.
Continuous over a life time Usually limited to few hours.
Exchange surface area
Wide transfer are (~70m2). Limited transfer area (1-3m2).
Highly permeable alveolar-capillary membrane Diffusion barriers in synthetic membrane and blood oxygenation
boundary layer
Short diffusion distances (1-2 μm) Relatively thick membranes (50-100 μm).
Hydrophilic membrane Hydrophobic polymers
No hemocompatibility problems Hemocompatibility problems
Self-cleaning membrane Protein-build-up on membrane
Gas side
To-and-fro ventilation Steady cross flow gas supply
Operates with air Operates with oxygen-rich mixture
Membrane structure sensitive to high oxygen partial pressure Membrane insensitive to high oxygen partial pressure
Pressure below that in blood phase to avoid capillary collapse Pressure below that on blood side to avoid bubble formation
Operates under water vapor saturation conditions Can be clogged by water vapor condensation
Ventilation linked to perfusion by built-in control mechanisms Ventilation dissociated from perfusion, with risks of hyper- or
hypoventilation
Can be used for gaseous anesthesia Can be used for gaseous anesthesia
Blood side
Short capillaries (0.5-1 mm) Long blood path (10-15cm)
Narrow diameter (3-7 μm) Thick blood film (150-250 μm)
Short exposure time (0.7 s) Long exposure time (5-15 s)
Low resistance to blood flow Moderate to high resistance to blood flow
Sophisticated branching Crude manifolding of entry and exit ports
Minimal priming volume Moderate to large priming volume
Capillary recruitment capability Fixed geometry of blood path
No recirculation Possibility of recirculation
Limited venous admixture Risk of uneven perfusion of parallel beds
No on-site blood mixing Possibility of blood stirring and mixing
Operates with normal hemoglobin concentration Hemodilution is common
Does not require anticoagulation Requires anticoagulation.
In the natural lungs, the factors underlying exchange across the alveolo-capillary barrier and transport by the blood can be
grouped into four classes:
1)The ventilation of the lungs (the volume flow rate of gas) and the composition of the gas mixture to which mixed venous
(pulmonary artery) blood will be expored.
2)The permeability of the materials which separate the gas phase from the blood phase in the pulmonary alveoli.
3)The pattern of pressure and flow through the airways and through the pulmonary vascular bed and the distribution of inspired
air and circulating blood among the various zones of the exchange system.
4)The gas carrying capacity of the blood as regards oxygen and carbon dioxide (and secondarily nitrogen and anesthetic gases).

In an artificial lung, replacing the gas transfer function of the natural organ implies that blood circulation can be sustained by
mechanical pumps for extended periods of time to achieve a continuous, rather than a batch process, and that venous blood
can be arterialized in that device by exposure to a gas mixture of appropriate composition. The external gas supply to an
artificial lung does not pose particular problems, since pressurized gas mixtures are readily available. Similarly, the
components of blood which provide its gas-carrying capacity are well identified and can be adapted to the task at hand. In
clinical practice, it is important to minimize the amount of donor blood needed to fill the extracorporeal circuit, or priming
volume. Therefore a heart-lung machine is generally filled with an electrolyte or plasma expander solution (with or without
donor blood), resulting in hemodilution upon mixing of the contents of the extracorporeal and intracorporeal blood circuits.
The critical aspects for the operating of an artificial lung are blood distribution to the exchanger, diffusion resistances in the
blood mass transfer boundary layer, and stability of the gas exchange process.
Artificial lungs are expected to perform within acceptable limits of safety and effectiveness. The most common clinical situation
in which an artificial lung is needed is typically of short duration, with resting or basal metabolism in anesthetized patients.
Table 66.3 compares the structures and operating conditions of the natural lung and standard hollow fiber artificial
membrane lungs with internal blood flow.
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