Principles of

cardiopulmonary bypass
David Machin BSc ACP
Chris Allsager MB ChB FRCA

Key points The use of cardiopulmonary bypass (CPB) during gas exchange in the natural lung
technology allows cardiac surgical procedures also apply to the artificial lung. However,
Membrane oxygenators are
to be performed in a motionless, bloodless gas exchange is less efficient. Diffusional
commonly used for gas
exchange during surgical field. It incorporates an extracorpor- distances are greater (approximately 200 mm
cardiopulmonary eal circuit to provide physiological support. in comparison with 10 mm in the human
bypass (CPB). Typically, blood is gravity drained from alveolus) and surface area for gas exchange is
the heart and lungs to a reservoir via venous 1.7–3.5 m2 compared with 70–100 m2 in the
Roller or centrifugal pumps
are utilized in CPB. cannulation and tubing, and returned oxy- human lung. Gas exchange obeys Fick’s law
genated to the cannulated arterial system by of diffusion:
Confirm adequate patient
utilizing a pump and artificial lung (oxy- ADdP
anticoagulation before V gas a
genator or gas-exchanger). The tubing and T
initiation of CPB.
cannulae are manufactured of clear polyvinyl
CPB is performed over a Sol
chloride, while the oxygenator casing and Da pffiffiffiffiffiffiffiffiffiffi
range of temperatures MW
connectors consist of polycarbonate (Fig. 1).
(37–15
C).
where the amount of gas transferred (Vgas)
Cardiac surgery with CPB can is proportional to the area (A), a diffusion
promote a systemic Gas exchange constant (D) and the partial pressure differ-
inflammatory response ence (dP) and is inversely proportional to the
Three basic types of blood oxygenators for
syndrome.
CPB have been developed. Historically, oxy- membrane thickness (T). D is proportional to
genators provided gas exchange by contact of the specific gas solubility (Sol) and inversely
a blood film to an oxygen rich atmosphere proportional to the square root of its mole-
(e.g. disc oxygenators) or by bubbling oxygen cular weight (MW).
through blood (e.g. bubble oxygenators). Applying Fick’s law to the artificial lung,
Modern day oxygenators provide gas a higher partial pressure difference of oxygen
exchange to blood through a membrane (maximum pressure gradient of 760 mm Hg
(e.g. sheet and hollow-fibre oxygenators). minus oxygen tension in blood) and to some
Sheet membrane oxygenators can either be extent carbon dioxide (maximum gradient is
configured as a flat plate microporous equal to carbon dioxide tension in blood
polypropylene membrane or spiral wound phase) is required to compensate for an
silicone membrane. Microporous membranes increased diffusional distance and fixed,
consist of 0.05–0.3 mm pores that initially reduced surface area. Despite the pressure
create a direct blood gas interface until a thin gradient for carbon dioxide (CO2) being
protein film quickly forms, producing considerably lower than oxygen (O2), the
molecular membranes. Silicone membranes artificial lung material is more gas perme-
are considered ‘true membranes’ and prevent able to CO2 than (O2); silicone membranes
David Machin BSc ACP ‘plasma leakage’ into the gas phase, which is have a CO2 : O2 transmission ratio of about
Perfusionist characteristic of microporous membranes 5 : 1.2
Theatres
Glenfield Hospital after long periods of CPB. Plasma leakage is Oxygen transfer in modern blood oxy-
Groby Road thought to occur when the micropores lose genators is described by the advancing front
Leicester their hydrophobicity by the adsorption of theory. Demonstrated by studies of oxygen
LE3 9Q
UK protein, which leaks through the micropores transport through constantly moving
Tel: 0116 256 3604 and reduces gas exchange performance.1 blood films, the large binding capacity of
E-mail: machin_david36@[Link] Hollow-fibre oxygenators allow high surface haemoglobin for oxygen and rapid oxygen–
(for correspondence)
area-to-blood volume ratios and mainly con- haemoglobin kinetics are thought to create
Chris Allsager MB ChB FRCA sist of microporous polypropylene or poly- two distinct zones in the blood film. Oxygen
Consultant Anaesthetist methylpentene material. diffuses through a fully oxygen saturated
Glenfield Hospital
Leicester The physical process of convection, dif- zone to an unsaturated front where the
UK fusion and chemical reactions that occur oxygen binds with unsaturated haemoglobin.3

Advance Access publication August 24, 2006 doi:10.1093/bjaceaccp/mkl043

176 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 5 2006
ª The Board of Management and Trustees of the British Journal of Anaesthesia [2006].
All rights reserved. For Permissions, please email: [Link]@[Link]
 Principles of CPB

Aortic
Cross Clamp

Arterial
Filter
Cardioplegia
Solution

Gas
In
Gas
Exchanger
Gas
Out

Cardiotomy
Reservoir
Sucker Vent Cardioplegia Pump
Pump Pump Water
In
Heat Exchanger
Water
out
Venous Reservoir

Systemic Blood
Pump

Fig. 1 Diagrammatic representation of a ‘closed’ extracorporeal circuit for cardiopulmonary bypass.

Carbon dioxide transfer in modern oxygenators is more difficult haemolysis (plasma haemoglobin per 100 ml of pumped blood).
to predict, because of factors such as dissolved CO2, plasma Roller pumps (RPs) and centrifugal pumps (CPs) are routinely
bicarbonate ions and varying partial pressure of CO2 in the gas used and can accurately deliver blood over wide range of flow
phase. The latter can be decreased by increasing the ventilating rates against a variable resistance.
gas flow rate (sweep gas) entering the oxygenator gas phase. The RP comprises a length of PVC or silicone tubing situated
against a curved metal backing plate (raceway) which is com-
pressed by two rollers located on the ends of rotating arms at
Blood pumps 180
to each other. The direction of compression of the tubing
During CPB, constant blood flow is delivered to the patient by a by the rotating arm containing the roller permits forward blood
mechanical pump. The characteristics of an ideal blood pump flow. Hence, this type of pump is described as a positive dis-
should consider properties that effect blood flow, as described placement device, allowing constant delivery of blood volume
by the Hagen–Poiseuille equation: despite minor variations in the outlet afterload. Blood flow
depends upon the pump tubing internal diameter (see Hagen–
ðPressure gradientÞ · ðTube radiusÞ4 · p Poiseulle equation), rotation rate of the rollers and diameter of
Blood flow rate ¼
ðFluid viscosityÞ · ðTube lengthÞ · 8 the pump head.
Put simply, CPs consist of a vaned impeller or a nest of smooth plastic
cones within a plastic casing. These impellers or cones are
Pressure
Blood flow rate ¼ magnetically coupled (at the base) with an electric motor and,
Resistance
when rotated rapidly, generate a centrifugal force to the blood,
Thus, the pump should be able to generate blood flow and which is received by the pump body. Centrifugal force is
pressure against a degree of resistance. It should be made converted into kinetic energy, which gives flow, or potential
of biocompatible materials, create no areas of blood stasis or energy, which gives pressure. An object that produces centrifu-
turbulence and be able to adjust for different sizes of extra- gal force (CF) can be defined as
corporeal tubing. These mechanical pumps have low priming
volumes, are easily controlled and produce a low index of CF ¼ mass · radius · angular velocity

Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 5 2006 177
Principles of CPB

In a clinical setting, oxygen consumption. The potassium channel opener, nicorandil,

may offer advantages over potassium-based cardioplegia by
CF ¼ Mass of blood · radius of pump head
providing cardiac arrest near its resting membrane potential,
· speed of revolutions ðRPMÞ
allowing balanced trans-membrane ion gradients and minimal
Unlike RPs, CPs are totally non-occlusive and are afterload energy requirements.5
dependant. Any significant change in resistance/pressure at the Non-cardioplegic techniques include the use of moderate
outlet or inlet of the pump will alter blood flow rate. The non- systemic hypothermia (i.e. core temperature of 30–32
C) with
occlusive feature of the CP prevents generation of excessive short periods of aortic cross-clamping and ventricular fibril-
pressure in the extracorporeal circuit, thus preventing circuit lation (VF). A variation of this technique involves hypo-
rupture. thermic systemic perfusion combined with prolonged VF,
enabling continuous coronary perfusion. Unfortunately, this
Myocardial protection greatly increases myocardial oxygen consumption compared
with the empty beating heart; it also reduces subendocardial
To provide a dry, motionless, operative area, a cross-clamp is perfusion.6 Ischaemic preconditioning for myocardial protec-
placed across the ascending aorta above the coronary ostia tion is also practiced by introducing brief periods
and proximal to the aortic cannula, thus isolating the coronary of myocardial ischaemia to tolerate a longer ischaemic
circulation and preventing blood entering the chambers of challenge.
the heart. Therefore, techniques of myocardial protection are
used to preserve myocardial function and prevent cell death.
Cardioplegic techniques for myocardial protection involve the Temperature management during CPB
delivery of cardioplegic solution to the myocardium to provide CPB is performed under systemic hypothermia (typically a
diastolic electromechanical arrest. This is administered by an nasopharyngeal temperature of 25–32
C) or normothermic
anterograde approach via the aortic root or direct coronary conditions. More challenging operations may require deep
ostium access, or by a retrograde manner if severe coronary hypothermia (15–22
C) to allow periods of low blood flow or
artery occlusions exist. The latter may not provide adequate deep hypothermic circulatory arrest. Systemic hypothermia has
right-heart protection; thus, the delivery of both anterograde remained a cornerstone of cardiac surgical practice, with a great
and retrograde cardioplegia may ensure adequate distribution deal of evidence demonstrating that it decreases myocardial
and subsequent improved myocardial protect. Intermittent oxygen consumption. This ensures protection and increased
cardioplegia delivery (i.e. every 15–30 min) allows a relatively tolerance for ischaemia of vital organs and allows periods of low
bloodless surgical view during more challenging operative blood flow during CPB. At a biochemical level, temperature
periods. Continuous administration would improve for myocar- changes the reaction rates and metabolic processes by a factor
dial protection but this is not always practical. known as the Q10 effect, which defines the amount of increase or
Potassium is the main agent used to induce cardiac arrest; in decrease in these processes relative to a 10
C difference. Total
a concentration of approximately 20 mmol litre1 it causes a body oxygen consumption is said to have a Q10 factor of
reduction in myocardial membrane potential. Fast inward approximately 2.6 in adults and 3.65 in infants.7 However,
sodium channels are inactivated preventing the upstroke of because of many of the detrimental processes associated with
myocardial cell action potentials, causing the myocardium to hypothermia (e.g. impaired myocardial cell membrane function,
become unexcitable in diastolic arrest.4 Cardioplegia can be possible excessive postoperative bleeding), normothermic CPB is
administered as a cold crystalloid cardioplegia, cold blood practiced by some surgeons to provide a more physiological
cardioplegia or warm blood cardioplegia. Blood cardioplegia is state. It is also hypothesized that electromechanical work is the
thought to offer the advantage of delivering oxygen at the cellular main determinant of myocardial oxygen requirement rather
level via its haemoglobin content, but it may be less efficient than cooling of the heart.5 Hence, a chemically induced
during cold delivery because of the left shift of the oxygen- mechanical arrested heart, without added hypothermia, is
dissociation curve. Blood cardioplegia also provides other benefits expected to reduce myocardial metabolic requirements to such
including hydrogen ion buffering, free-radical scavenging, reduced a degree that it can be matched by regular doses of blood
myocardial oedema and improved micro-vascular flow. cardioplegia.
Various ratios of blood to cardioplegic solution can be
administered (e.g. 1 : 1, 2 : 1, 4 : 1) or even neat potassium (micro-
Acid–base management
plegia). The addition of glutamate and aspartate to cardioplegic
solutions may promote oxidative metabolism in energy-depleted Management of the acid–base status throughout the hypo-
hearts. The use of esmolol and nicorandil as cardiac electro- thermic CPB period remains controversial. Arterial blood gas
mechanical arrest agents has also been considered as possible parameters are either corrected for temperature and pH is kept
alternatives to potassium. The negative inotropic and chrono- constant (i.e. pH-stat) or blood gas levels are uncorrected
tropic effects of esmolol result in a reduction in myocardial (measured at 37
C) and alkalosis is permitted during cooling

178 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 5 2006
 Principles of CPB

(i.e. alpha-stat). pH-stat blood gas management increases CO2 blood flow requirements without excessive resistance or pressure
content during cooling and, as cerebral blood flow is dependent generation. The CPB circuit is typically primed with a
onPCO2 , cerebral blood vessels dilate. Autoregulation, which crystalloid solution with electrolyte composition and osmolarity
normally keeps cerebral blood flow constant at arterial pressures similar to plasma and a colloid solution to provide a degree
of 50–150 mm Hg, is lost during pH-stat and cerebral blood of plasma colloidal oncotic pressure, which is reduced as a
flow becomes pressure-dependent. Alpha-stat blood gas manage- repercussion of haemodilution in CPB. Other prime additives
ment seems more appropriate as it maintains autoregulation, may include mannitol (diuresis, oedema reduction, possibly free-
offers better control of cerebral blood flow and demand, radical scavenging); sodium bicarbonate (buffers the prime);
and limits cerebral microemboli load. However, the pressure- heparin; and blood, if required. CPB blood flow, estimated
dependent characteristics of pH-stat may improve cooling and haematocrit on CPB and the amount of blood required in the
oxygen delivery to the brain.8 prime are calculated:
CPB blood flow rate ¼ Body surface area ðBSAÞ · Cardiac index ðCIÞ‚
Filtration ðlitre min1 Þ ðm2 Þ ðlitre m2 min1 Þ
Recycling of suctioned blood from the surgical field is
where BSA is calculated by DuBois formula/DuBois BSA nomogram;
accomplished by a cardiotomy reservoir incorporating a screen
CI is 2.4–2.8 (dependant upon age) at 37
C, 2.1 at 32
C, 1.8 at 28
C, 1.2
and depth filter to reduce fat emboli, fibrin and surgical
at 25
C, 0.6 at 15
C.
contamination. Screen filters comprise a woven mesh material
such as polypropylene, with a defined pore size to determine its PBV · Hct
Estimated haematocrit on CPB ¼ ‚
filtration ability. Depth filters incorporate packing materials TCV
such as Dacron wool or polyurethane foam that have no definite where PBV is the patient blood volume; Hct is the patient
pore size; thus, filtration depends on the thickness, tightness and haematocrit; TCV is the total circulatory volume, that is PBV þ
tortuous nature of the packing. Generation of gaseous (e.g. drug circuit prime volume þ estimated cardioplegic solution volume.
injection and venous air) and particulate (e.g. circuit material
ðTarget Hct · TCVÞ  ðHct · PBVÞ
debris) emboli exiting the oxygenator is associated with vital Blood required in prime ¼ ‚
Hct of RBCs
organ injury, for example cognitive dysfunction. An arterial
screen filter is often used to limit sources of embolic load to the where Target Hct is the required haematocrit on initiation of CPB
patient. Air emboli retention within the wetted filter is (typically above 20% in adults and 28% in children); TCV is the
accomplished by surface-active forces, which maintains fluid in total circulatory volume; PBV is patient blood volume; Hct is
the pores and prevents displacement of fluid by gas through the patient haematocrit; Hct of RBCs is haematocrit of donor blood.
pores. However, excessive pressure across the filter medium can Before initiation of CPB, the patient is adequately antico-
allow the passage of air through the pores; this is termed the agulated with heparin (300–400 iu kg1) to achieve an activated
‘bubble point pressure’. Bacterial filtration of the gas flow line to clotting time (ACT) generally above 480 s (celite ACT above
the oxygenator and the use of pre-bypass filters to reduce 750 s when aprotinin is used) to maximize inhibition of thrombin
extracorporeal circuit debris are often practiced. There is a generation. The placement of arterial and venous cannulae to
current trend to utilize leucocyte depleting filters, as activated perform CPB is generally via a median sternotomy, to the
leucocytes are considered to have a pivotal role in the inflamm- ascending aorta and right atrium or directly/indirectly to the
atory response to CPB and post-ischaemic injury. The applica- superior and inferior venae cavae. Alternative cannulation sites
tion of this technique during all or part of CPB (i.e. before aortic include the femoral vessels, axillary artery, left ventricular apex
cross-clamp removal, during blood cardioplegia delivery or (e.g. redo procedures and aortic aneurysm), and both ascending
both) has demonstrated some clinical benefits.9 and descending aorta (e.g. interrupted arch). Venous cannula
Haemofilters (haemoconcentrators or ultrafilters) are utilized size is important, as blood flow is determined by the Hagen–
in CPB circuitry to remove excess fluid and electrolytes, attenuate Poiseuille equation. To achieve sufficient venous drainage for
inflammatory mediators and raise haematocrit. These devices effective CPB, the cannula radius is the predominant factor (a
mainly consist of a hollow-fibre semipermeable membrane to small change in dimension can have a drastic effect on venous
allow the passage of water and electrolytes from the blood to a drainage); fluid viscosity and tubing length remain relatively
filtrate compartment. Conventional ultrafiltration (haemoconcen- fixed. Arterial cannulae sizing is less significant as the blood can
tration) and zero balance ultrafiltration (filtrate replaced with be pumped at relatively high pressures oxygen (generally 160–
equal crystalloid volume) can be performed during CPB; modified 180 mm Hg). However, maintenance of blood flow at higher
ultrafiltration can be initiated at the termination of CPB. pressures with smaller diameter arterial cannulae may result in
turbulent flow, as predicted by the Reynolds number, which is
Conduct of CPB determined by the density, velocity and viscosity of blood for a
Components selected for the extracorporeal circuit are deter- given temperature. Correct positioning of the arterial cannula is
mined to minimize haemodilution, while being able to achieve verified by arterial line pressure measurement within the

Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 5 2006 179
Principles of CPB

extracorporeal circuit. After cannulae insertion, CPB is com- Table 1 Suggested target blood chemistry values for termination of CPB

menced by releasing the venous line clamp and increasing the pH 7.35–7.45
blood pump until calculated blood flow is achieved. Mainten- PaO2 20–30 kPa
ance of adequate venous drainage into the reservoir is essential PaCO2 4.6–5.5 kPa
to provide CPB support and prevent patient air embolism. The SvO2 >65%
Base excess (arterial) −2 to þ2
application of pulsatile blood flow during CPB may increase or Naþ (plasma) 135–144 mmol litre1
preserve arterial blood flow to organs such as the kidney, liver, gut Cl (plasma) 95–105 mmol litre1
and brain, and reduce systemic vascular resistance. However, the Caþþ (plasma) 2.1–2.6 mmol litre1 (adjusted for albumin)
Mgþ (plasma) 0.7–1.0 mmol litre1
generation of an arterial waveform to provide substantial Kþ (plasma) 3.3–5.3 mmol litre1
‘physiological’ blood flow is a significant a technical challenge. Glucose 3.3–6.0 mmol litre1
Adequacy of blood flow and oxygen requirements requires Haematocrit >25% (adults); >28% (children)

frequent, if not continuous (i.e. in-line monitoring) arterial and

venous blood gas monitoring, in addition to haematological and
biochemical analysis. Effective blood flow during CPB can be pressure and blood flow during hypothermia can facilitate in
monitored by whole body oxygen consumption (VO2), accord- reducing this problem.
ing to the Fick principle: Weaning from CPB is considered when surgical intervention
has been completed. The patient should be fully warm with
VO2 ¼ ðCaO2  CvO2 Þ · CO physiological biochemical and haematological values (Table 1)
and an appropriate ECG. After confirmation of mechanical
where VO2 ¼ oxygen consumption, (CaO2CvO2) ¼ arterio- ventilatory support, the venous line is clamped and volume is
venous oxygen content difference and CO¼cardiac output. infused from the CPB circuit until a desired filling pressure is
Thus, with the additional knowledge of the level of oxygen obtained. Patient heparinization can be reversed with protamine
extraction (arteriovenous oxygen content difference) and sulphate after stabilization and discontinuation of the extra-
haemodilution (total haemoglobin) during CPB, the patient’s corporeal circuit.
requirements can be accommodated. To enable VO2 to be a
reliable indicator of blood flow adequacy, the age, size and Reducing consequences of CPB
temperature of the patient need to be considered. VO2 to body
weight ratio in the infant is about twice that of the adult CPB and cardiac surgery induce a systemic inflammatory
(approximately 8 : 4 ml kg1 min1). The use of in-line mixed response and cause disturbances of the inflammatory and
venous oxygen saturation monitoring during CPB allows quick fibrinolytic system. Pharmacological agents are used to
assessment of sufficient oxygen delivery, but should be inter- reduce these consequences. Such agents include aprotinin;
preted with caution. Certain patient conditions, such as anti-fibrinolytics; corticosteroids; and novel approaches with
anatomical or physiological shunts, and abnormal haemoglobin angiotensin-converting enzyme inhibitors, exogenous anti-
types, may under or overestimate oxygen delivery and uptake. oxidants, monoclonal antibodies and phosphodiesterase inhib-
Other parameters assessed during CPB include oxygenation, itors. Surface coated and miniaturized extracorporeal circuits
arterial perfusion pressure, venous pressure, temperature, are being continually developed to potentially improve bio-
ECG, urine output and periodic assessment of the antico- compatibility.11 Isolation of cardiotomy suctioned blood and
agulant status (ACT > 480 s to prevent extracorporeal circuit utilization of cell salvage devices to reduce activated blood
thrombosis). components and particulate emboli are of recent interest.
During CPB with the aorta cross-clamped and the heart in an
arrested state, gradual distension and potentially irreversible Acknowledgement
damage to the heart can occur. This is because of bronchial and
The authors acknowledge the assistance of Miss Aimee Hurst in
coronary vessels (e.g. myocardial sinusoids, arterio-sinusoidal,
the preparation of the figure.
arterio-luminal vessels) draining into the heart, which can
contribute to 1–2% of the cardiac output.10 These circulations,
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Please see multiple choice questions 6–8.

Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 5 2006 181