Principles of Cardiopulmonary

Bypass

Seoul National University Hospital

Department of Thoracic & Cardiovascular Surgery
 Cardiac Surgery History
Pre-heart-lung machine era
• 1938. Gross. First successful PDA ligation
• 1944. Crafoord. Resection of coarctation of aorta
• 1945. Blalock. Blalock-Taussig operation
• 1946. Gross. Surgical closure of AP
window
• 1958. Glenn. Glenn shunt
 First Blalock-Taussig Shunt

“ Most powerful stimulus to the development of cardiac surgery ”

 Cardiac Surgery History

Era of cardiopulmonary bypass

• 1953. Gibbon. ASD closure
• 1953. Lillehei. VSD closure
• 1954. Lillehei. TOF correction
• 1956. Kirklin. TAPVR correction
• 1957. Kirkin. DORV correction
 Cardiac Surgery History
Era of cardiopulmonary bypass
• 1959. Senning. Atrial switch operation for TGA
• 1966. Ross. Ross procedure for TOF with PA
• 1971. Fontan. Fontan operation for TA
• 1975. Jatene. Arterial switch operation for
TGA
• 1983. Norwood. Norwood procedure for HLHS
• 1985. Bailey. Pediatric heart transplantation
 Cardiopulmonary Bypass
Development
• 1951. Dodrill. Mitral valve surgery under left heart
bypass
• 1952. Dodrill. Relief of PS under right heart bypass
• 1953. Lewis. ASD closure under surface cooling
• 1953. Gibbon. ASD closure by heart-lung machine
• 1954. Lillihei. VSD closure under controlled cross-
circulation
• 1954. Kirklin. Establishment of CPB with
oxygenator in cardiac surgery
 Cardiopulmonary Bypass
 Controlled Cross-circulation
• 1954. Lillehei
1st surgical closure of
VSD under controlled
cross-circulation
• Used in 45 patients
between 1954 to 1955
• VSD
TOF
AVSD
Dr.Lillehei
 Cardiopulmonary Bypass
J. Gibbon and heart-lung machine
 Single Ventricle Physiology

Francis Fontan
• Fontan operation for tricuspid atresia in 1971
Cardiopulmonary Bypass Circuit
 Scheme of CPB Circuit
• Pump
• Oxygenator
• Heat exchanger
• Reservoir
• Filter
• Sucker & vent
• Cardioplegic solution
delivery system
Cardiopulmonary Bypass
Heart-Lung Machine
 Development of CPB

Prerequisite
– Understanding of physiology of circulation
– Preventing the blood form clotting
– Pumping blood to pump
– Ventilating the blood
 Development of Pump
• Sigmamotor pump
This device had occlusive fingers that rhythmically
compressed the tubing to propel the blood in a
forward direction
• Roller pump
• Centrifugal pump
1. Cone shaped impellers encased in a cone-
shaped housing using principle of a constrained
vortex to generate pressure & flow
2. Delplim pump has impeller blades that rotate
and generate flow & pressure within the head
Development of Oxygenator
• Solid disc oxygenator
• Screen oxygenator
• Solid disc with rotation screens
• Bubble oxygenator
• Membrane oxygenator
1. Silicone elastomers
2. Microporous polypropylene
a. Sheet-type oxygenator
b. Hollow-fiber type oxygenator
 Development of Filtration
• Screen-type filters have pores in the medium that
are of a particular size.
For its better design and lesser trauma,
screen-type filter became more popular.
• The depth filters contain a medium through
which the blood flows.
This large wet surface blocks many particles
and thus prevents them from being carried in the
fluid stream; they are retained on the internal
medium surface by adsorptive forces.
 Size of Arterial Cannula
Arterial Cannula for Various Weights and BSA
Maximal Flow Rate

Weight kg BSA( ㎡ ) Cannula Size (Fr) cc/min

1.5-4.0 0.13-0.26 8 800
4.1-9.0 0.26-0.48 10 1200
9.1-14.0 0.48-0.56 12 1800
14.1-20.0 0.56-0.71 14 2800
20.1-26.0 0.71-0.84 16 3500
26.1-34.0 0.84-1.00 18 5000
34.1-50.0 1.00-1.40 20 5000
50.1-66.0 1.40-1.63 22 8000
over 66.1 over 1.63 24 8500
 Size of Venous Cannula
Venous Cannula for Various Weights and BSA
Weight kg BSA ㎡ Single Cannula Size (Fr) Flow
＞6 0.3 24 1200cc
6-8 0.3-0.45 26 1400cc
8-10 0.45-050 28-30 1600cc
10-40 0.50-1.10 40 or (32-40 two 1800cc
＞ 40 ＞ 1.1 stage cannula) 2600cc
Double Cannula Size(fr)
Weight kg BSA ㎡ SVC IVC Flow
＜5 0.28 12 16 12: 350cc

5-10 0.28-0.50 16 20 14: 450cc

11-15 0.51-0.57 20 24 16: 600cc
16-25 0.58-0.83 24 28 20: 900cc
25-50 0.83-1.40 28 32
＞ 50 ＞ 1.4 36 40
 Cannulation & Flow Rate
Estimated
Patient Maximum Estimated Blood Flow Double Single
Weight Flow BSA 2.4L/Min/M² Venous Venous Arterial

1-2kg 350mL/min 0.16m² 380mL/min 12-14 Fr 1/4˝ 14 Fr1/4˝ 8 Fr 1/4˝

2-4kg 800mL/min 0.26m² 625mL/min 12-14 Fr 1/4˝ 18 Fr1/4˝ 8 Fr 1/4˝
4-8kg 1200mL/min 0.44m² 1056mL/min 16-18 Fr 1/4˝ 24 Fr1/4˝ 10 Fr 1/4˝
10-14kg 1800mL/min 0.56m² 1500mL/min 20-22 Fr 3/8˝ 32 Fr3/8˝ 12Fr 1/4˝
30-70kg 5000mL/min 2.2m² 5000mL/min 32-36 Fr 3/8˝ 36 Fr3/8˝ 16 Fr 3/8˝
15-30kg 3000mL/min 0.97m² 2500mL/min 30-32 Fr 3/8˝ 36 Fr3/8˝ 14 Fr 3/8˝
 Prime Estimation for ECC
Patient blood volume: cc
+ (weight × BV) +
Pump Prime Volume: (PPV)
= =
Total Circulating Volume: TCV cc
Required Red Cells:RRC cc
(TCV × desired % HT)
- -
Patient Red Cells: PRC
(PBV × patient % HT) cc
= =
Total Red Cells needed : TRC cc
Note: 1. Desired % HT : 0.26 for hypothemia
0.22 for profound hypothermia
2. HT of packed cells: 0.65-0.70 volume 300mL/bag
HT of whole blood: 0.35-0.40 volume 500mL/bag
Blood Volume Estimation
Weight ㎏ Blood Volume
cc/ ㎏
Newborn to 10 ㎏ s 85 cc/ ㎏
11 to 10 ㎏ 80 cc/ ㎏
21 to 30 75 cc/ ㎏
31 to 40 70 cc/ ㎏
41 to ㎏ over 65 cc/ ㎏
 Pulsatile Bypass Flow
Advantages
• Increased urine volume
• Less metabolic acidosis
• Decreased stress hormone
• Decreased peripheral vascular R
• Increased oxygen consumption
• Improved myocardial perfusion
• Improve cerebral circulation
• Smaller transfusion volume
 Cardiopulmonary Bypass

Determination of body perfusion

• Externally controlled variables
• Patient response to CPB
• Damaging effect of CPB
 Cardiopulmonary Bypass
Externally Controlled Variables
• Systemic blood flow
• Temperature of perfusate & patient
• Arterial input pressure wave form
• Systemic venous pressure
• Pulmonary venous pressure
• Hemoglobin
• Albumin concentration
• Glucose concentration
• Ionic composition
• Arterial O2 & CO2 level
 Cardiopulmonary Bypass
 Differences between pediatric & adult
1. Exposed to biologic extremes.
1) Deep hypothermia
2) Hemodilution
3) Low perfusion pressure
4) Wide variation in pump flow rates
2. Variations in glucose supplementation
3. Cannula placement
4. Presence of aortopulmonary collaterals
5. Patient age and brain mass
 Cardiopulmonary Bypass
 Differences between infants & adults
• Smaller circulating blood volume
• Higher oxygen consumption rate
• Reactive pulmonary vascular bed
• Presence of intra- & extracardiac shunt
• Immature organ system
• Altered thermoregulation
• Poor tolerance to microemboli
 Cardiopulmonary Bypass
Patient’s response
• Change of systemic vascular resistance
• Increased venous tone
• Decreased oxygen consumption
• Mixed venous oxygen level
• Depression of cell mediated immune response
• Metabolic acidosis
• Catecholamine response
• Change of water body composition
• Thermal balance with hypothermic bypass
Cardiopulmonary Bypass
 Factors of fluid shift during CPB
1. Temperature
2. Flow rate
3. Hemodilution
4. Plasma colloid oncotic pressure
5. Interstitial fluid pressure
6. Capillary permeability
7. Urinary output
 Cardiopulmonary Bypass
Fluid balance
• General effect
• Preoperative factors
Whether heart failure or not
• Hemodilution & diminished colloidal oncotic pressure
Main cause of fluid retention
• Hypothermia
Less potent cause of tissue edema
• Oxygenator
• Interstitial fluid pressure
• Capillary permeability
• Osmotically active components
• Myocardial edema
 Cardiopulmonary Bypass
Body water change
• In oxygenator, denaturation of protein & destabilization
of soluble fat may affect colloidal property of blood & also
damage of platelet & WBC cause vasoactive substance
and microemboli may contribute to edema.
• Increase of Hct due to plasma volume shifted to the
interstitial space or excreted as urine and plasma volume
decrease in 24 hours after CPB, especially in 2nd day and
regain ECF or total body water from 2-5 days
postoperatively in usual patients.
• Interstitial fluid pressure is different due to compliance of
tissue, noncompliant in subcutaneous tissue & muscle, less
in myocardium, compliant in stomach.
Cardiopulmonary Bypass
Damaging effects
• Exposure of blood to abnormal events
Damage, activation & depletion of blood elements

• Exposure to nonendothelial surface

• Shear stress
• Incorporation of abnormal substance
• Altered arterial blood flow pattern
Cardiopulmonary Bypass
Systemic responses
• Injury to blood elements
• Emboli
• Initial events-blood contact
• Platelet activation
• Coagulation cascade
• Contact system
• Fibrinolysis
• Vasoactive substance
 Cardiopulmonary Bypass
Injury to blood elements
• Contact with synthetic non-endothelial cell surfaces,
turbulence, cavitation, osmotic forces and shear stresses
activate but also injure blood elements.
• Plasma proteins and lipoproteins are progressively
denatured during CPB
• Protein denaturation increases plasma viscosity,
decreases the solubility of plasma proteins, produces
macromolecules that aggregate, increase polarity and
the number of reactive side groups, and alters the
electrophoretic pattern of plasma proteins.
• Denatured proteins are probably removed from plasma
by the reticuloendothelial system
 Cardiopulmonary Bypass
Embolization
• The CPB system produce a variety of gaseous, blood-
derived and foreign emboli
• The CPB circuits can not prevent generation of emboli
but are designed to prevent or remove macroemboli,
defined as emboli greater than 40um.
• The architecture of the vascular system dictates that
macroemboli(40-400um) cause more ischemic organ
damage than microemboli
• Massive air embolism, macrogaseous emboli, nitrogen
emboli, fat, platelet aggregates, spallation of tubing and
exogenous emboli must be prevented and filtered
Cardiopulmonary Bypass
 Inflammatory response
1. Contact of blood component
with artificial surface
2. Ischemia-reperfusion injury
3. Endotoxemia
4. Operative trauma
 Cardiopulmonary Bypass
Whole body inflammation
1. Material-independent factor
1) Hypooncotic pressure by priming
Endotoxin translocation
Cytokine release
2) Retransfusion of shed blood
Highly activated by tissue contact
High concentration of plasminogen activator
2. Material-dependent factor
1) Surface characteristics activate complement system
2) Blood pumps
Shear forces causing hemolysis, lipid membrane
ghosts, spoliation from the tubing cause impaired
microcirculation
Foreign Surface Activation
 Deleterious effects of interaction
• Protein denaturation
• Activation of clotting factors
• Platelet aggregation
• Lipid peroxidation
• Activation of complement cascade
 Postoperative pathophysiologic effects
• Impairment of alveolar gas exchange
• Renal insufficiency
• Coagulopathy
• Cerebral dysfunction
• Vague systemic toxicity reaction
 Cardiopulmonary Bypass
Complement Activation

• Complement system is composed of more than 20 plasma proteins

( integral part of humoral immune system and are in a concerted
fashion to promote host defense mechanisms )
 Inflammatory Mediators
• C3a and C5a are potent inflammatory mediators known as
anaphylatoxins.
• These anaphylatoxins are smooth muscle spasmogens and result in
tissue changes including vasoconstriction, increased vascular
permeability, induction of histamine release and modulation of
host immune responses.
• Overall levels of C3a are directly dependent on the duration of
CPB, younger age at operation.
• C5a is unique in that it is rapidly bound to circulating neutrophils
that are sequestered in the pulmonary circulation.
• The C5a stimulated cell release superoxides, lysosomal enzymes
and proteases. A rise of this magnitude implies extensive
degranulation or destruction neutrophils circulating in the course
of CPB.
 Organ Preservation

Optimal conditions
1. Prevention of ischemia-reperfusion injury

2. Minimization of cell swelling and edema

3. Prevention of intracellular acidosis

4. Provision of substrate for regeneration of

high-energy phosphate on reperfusion
 Cardiopulmonary Bypass
 Vasomotor activity
• Minimal perfusion pressure : 35 – 45 mmHg mean
• Bypass flow in normothermia : 2.2-2.4 L/min/BSA
• Relative vascular resistance to blood flow
1. Arterial system (93%)
Aorta 4%, large artery 5%, main branch 10%,

terminal branch 6%, arteriole 41%,

capillary 27%
2. Venous system (7%)
Venule 4%, terminal vein 0.3%, main branch
0.7%, large vein 0.5%, vena cava 1.5%
 Cardiopulmonary Bypass
Vasomotor activity
• Phenomenon A
* Initial severe drop in peripheral circulatory vascular resistance at
the beginning of CPB, commonly occurs and lasts 5-10 minutes
* Dilution of catacholamine
* Homologous blood syndrome (incompatibility reaction of blood)
* Trauma state evokes release of histamine.
* Cold crystalloid priming affect smooth muscle tone.
• Phenomenon B
* Gradual recovery & progressive increase in peripheral resistance
* Diuresis & shift of fluid from vascular to cell & intercellular space
* Viscosity change with velocity gradient
* Hypothermia itself
 Cardiopulmonary Bypass
Venous compliance
• Effect of CPB on venous tone
Low venous pressure, low temperature during CPB cause
vasoconstriction, but before CPB, anesthesia, drugs, surgical
manipulation also decrease venous tone.
• Vasomotor state before & after surgery
Compensatory venous constriction is masked following cardiac
surgery with 75-80% reduction of venous capacitance in early
postoperative period.
• Vasodilator on venous tone after CPB
Nitroglycerin : primary on venous capacitance, effective vasodilation
and return of venous capacitance to normal
Nitroprusside & N-G : equivalent effect on reducing arterial resistance,
sometimes N-P reduce coronary perfusion
 Venous Vasomotor Dynamics
• Neural effects
* Mainly determined by norepinephrine
* Sympathetic innervation & smooth muscles are plentiful in
cutaneous and splanchnic veins, while little in skeletal veins
(but not insignificant due to big muscle mass)
• Smooth muscle
* Activity tone by norepinephrine
* Low BT – active vasoconstriction in cutaneous veins
• Passive effects
* As a result of distensible and compliant nature of elastin and
collagen fiber
• Resistance in veins
 Cardiopulmonary Bypass
Hypothermia
1. Aim
Protect the tissue from ischemia secondary to inadequate
perfusion and oxygenation during CPB

2. Pitfalls
1) Alterations in microcirculation associated with reduced
microcirculatory flow rates and tissue perfusion
2) More or less production of some cytokines than
normothermic CPB
3) More pronounced alterations of platelet aggregation
and endothelial related coagulation than normothermic
CPB (steep relation between PT, aPTT and temperature)
 Cardiopulmonary Bypass
Hypothermia
• Oxygen consumption
• Phenomena during hypothermia & arrest
1. No-reflow phenomena
2. Change in plasma volume
• Damaging effect of circulatory arrest
1. Brain function
2. Renal function
3. Liver function
4. Cardiac function : increase intracellular ionized calcium by
hypothermia– aggravated injury
• Hematologic effect of hypothermia
 Cardiopulmonary Bypass
 Hypothermic adverse effects
1. Activates kallikrein which increase circulating kinin
(vasoactive peptides that produce vasodilatation &
increase vascular permeability).
2. Produces platelet dysfunction ;
temperature dependent morphologic alterations in
membrane and function
3. Fibrinolytic activity is altered by hypothermia alone.
 Systemic Hypothermia

Hematologic effect
• Platelet membrane dysfunction
• Fibrinolysis
• Depression of clotting factor
Disadvantages of Hypothermia
• Attenuation of coagulation system
• Attenuation of glucose regulation
• Attenuation of endocrine system
• Attenuation of immune system
• Damaging effects associated with rapid
perfusion cooling in the kidney, liver, lung,
myocardium
• Longer duration of CPB
 Systemic Hypothermia

Adverse effects
1. Cardiac arrhythmia
2. Myocardial ischemia
3. Coagulopathy
4. Decreased myocardial contractility
5. Left shift of oxyhemoglobin dissociation
6. Impaired function of immune system
 Prebypass Hypothermia
Potential benefits
1. Modest reduction benefit (2-5 degree)
1) Inhibition of neurotransmitter release
(eg ; glutamate)
2) Reduction of calcium-mediated cell injury
3) Reduction of free radical formation
4) Attenuation of inflammatory responses
2. Adverse consequence
1) Bleeding
2) Infection
3) Cardiovascular events
 Postoperative Hypothermia
Adverse Effects
1. Respiratory
Diaphragmatic function is impaired.
2. Coagulation
Hypothermia reduces platelet aggregation and endothelial-associated
coagulation with increases in postoperative bleeding.
3. Hemodynamics
Increases in the incidence of atrial fibrillation
Temperature-dependent release of cytokines (TNF, interleukin-1,
beta & 6)
4. Splanchnic
Splanchnic hypoperfusion was common after CPB and associated
with postoperative complication.
5. Neurologic
Cerebral metabolism is reduced 5% to 7% for each degree centigrade
reduction in temperature.
 Myocardial Protection
 Adverse effects of cooling
1. Impairs the Na-K adenosine triphosphate (ATPase)
2. Impairs the mitochondrial adenosine triphosphate
(ATP) translocase
3. Impairs sarcoplasmic reticular Ca ATPase
4. Impairs oxygen–hemoglobin dissociation
 Thus hindering cell volume control, energy metabolism,
Ca sequestration, and oxygen delivery
 Myocardial Protection

Disadvantages of hypothermia
1. Effects on membrane stability
2. Effects on enzyme function
3. Effects on tissue calcium accumulation
4. Effects on cellular volume regulation
 Cardiopulmonary Bypass

Endocrine Response
• Increase catecholamine secretion
• Increase vasopressin or ADH secretion
• Paradoxical rise of atrial natriuretic hormone
• Altered response of cortisol secretion
• Hyperglycemia
• Lipid metabolism is dominant due to abnormal
glucose metabolism (increase free fatty acid)
Cardiopulmonary Bypass
Mechanisms of hyperglycemia
1. Reduction in GFR or increased tubular reabsorption
1) Alterations in glucose transport mechanism
2) Nonpulsatile flow on organ function
3) Decreased hematocrit and albumin level as a
decrease in ECF volume
2. Input of glucose from exogenous sources, and
glycogenolysis or gluconeogenesis
3. Hormonal and metabolic factors provide the basis
to develop hyperglycemia.
 Cardiopulmonary Bypass
 Causes of hyperglycemia
* Usually returns to normal within 12 hours
1. Increased glycogenolysis secondary to
epinephrine increase during CPB
2. Abnormal pancreatic insulin response due to
hypothermia
3. Impaired glucose transport & utilization
4. Binding of endogenous insulin to artificial surface
during CPB
Hyperglycemia after CPB

Pitfalls
• Osmotic diuresis
• Dehydration
• Glycosylation of protein
• Increased cerebral hemorrhage
 Cardiopulmonary Bypass
Effects on cerebral function
• Normally, cerebral blood flow is independent of cerebral perfusion
pressure over a range of 50-150mmHg, with the primary determinant
of flow being cerebral metabolic rate.
Outside of this range of autoregulation, CBF is directly
related to CPP.
• Variables such as the methods of acid-base management, mean arterial
pressure, flow rate, and type of perfusion, and their effect on cerebral
circulation remain controversial.
• Global increase in CBF due to elevation of PaCO2, and associated
cerebral vasodilation may critically reduce perfusion pressure and
jeopardize of areas of brain dependent on flow through stenosed vessels.
• Cerebral hyperperfusion may potentially deliver more gaseous and
particulate microemboli into cerebral circulation.
• Cerebral blood flow is also affected by anesthetic agents.
 Cardiopulmonary Bypass
Hematologic effect
• Platelet dysfunction & thrombocytopenia
Foreign surface
Blood –gas interface
Hypothermia
• Reduction of coagulation factors, fibrinogen,
and plasminogen
• Reduction & damage of RBC
 Cardiopulmonary Bypass
General renal effect
• Ischemia as a major factor in renal dysfunction with prolonged
bypass
• Early recognition of renal failure correlated with decreased renal
perfusion
• Vascular effect due to dilution of circulatory catacholamine
• Microemboli & hemolysis cause renal dysfunction.
• Hemodilution protect renal damage due to increased renal plasma
flow.
• Hypothermia decrease renal glomerular filtration due to cortical
vasoconstriction.
• Osmolar & oncotic agents : neutral effect for hemodilution
• Endocrine action : increase ADH due to low LA pressure &
hypotension, nonpulsatile flow
 Cardiopulmonary Bypass
Edema after CPB in neonate
1. Capillary permeability is naturally higher in younger
people
2. Greater exposure to bypass prosthetic surface area
relative to neonate’s endothelial surface area
3. Larger ratio of prime volume to blood volume than in
older
4. Exposure to greater extremes of temperature as well as
low-flow or circulatory arrest, thereby increasesing the
risk of ischemia-reperfusion injury
 Cardiopulmonary Bypass
 Pulmonary effects
1. Lung fluid exchange : excessive pulmonary capillary fluid
filtration due to capillary damage induced by complement release
and/or activation of coagulation cascade
2. Hemodilution reduce complications of intravascular
coagulopathy, coagulation and increase pulmonary lymph flow
and decrease blood use.
3. Pulmonary capillary hydrostatic pressure : effective left ventricle
venting
4. Interacting causes of alveolar collapse
5. Pleural cavity : opening the pleura lower lung volume and
increase the amount of alveolar collapse
6. Decrease in lung volume due to chest wall pain & increase in
interstitial fluid in the lung
Ideal Perfusion Flow Rate
Normothermia (whole blood)

Body Weight(kg) Flow(ml/kg/min)

5 under 200
5-10 170
10-20 135
20-30 100
30-60 85
60 over 60-70
 Cardiopulmonary Bypass
 Difference between infants & adult
• Smaller circulating blood volume
• High oxygen consumption rate
• Reactive pulmonary vascular bed
• Presence of intra- & extracardiac shunt
• Immature organ system
• Altered thermoregulation
• Poor tolerance to microemboli
Recommended Pump Flow Rate

Normothermic Cardiopulmonary Bypass

Patient weight (kg) Pump flow rate (ml/kg/min)
<3 150-200
3-10 125-175
10-15 120-150
15-30 100-120
30-50 75-120
>50 50-75
 Minimal Pump Flow Rate
Temperature CMRO2 Predicted MPFR
(c) (ml/100g/min) (ml/kg/min)
37 1.48 100
32 0.823 56
30 0.654 44
28 0.513 34
25 0.362 24
20 0.201 14
18 0.159 11
15 0.112 8
 Optimal Flow during CPB
• Normal flow & value , total body perfusion supplied by
left ventricle, an extracorporeal pump, or both

Normal value; Flow 3.2L/BSA/min

Oxygen uptake(VO2) 100-130ml/BSA/min
Hemoglobin value 15gm%
Hematocrit 45%
Normal systemic transport(SOT)
20 vol.% x 3.2L/BSA/min or (640ml/O2/min)
 Optimal Flow during CPB
Organ Blood Flow Rates During Profoundly Hypothermia(20 ℃),
Nonpulsatile, Hemodiluted Cardiopulmonary Bypass.

Organ Blood Flow Rate (mL.minc ­¹. 100 gm-¹)

Organ 1.5* 1.0* 0.5*

Whole body 10.29± 0.080 6.86±0.053 3.44±0.026

Brain 45±6.3(5.4%) 41±7.9(7.1%) 23±2.8(8.2%)
Heart 280±84 170±48 52±9.3
Lung 3.8±0.96 2.8±0.75 1.0±0.28
Liver 70±36 36±8.4 12±2.5
Kindney Medulla 55±14.2 18±5.7 8.4±1.52
Cortex 580±112 410±63 220±22
 Optimal Flow during CPB
Safe Duration of Circulatory Arrest
Temperature C˚ Oxygen Consumption Circulatory Arrest

37 100% 4-5

29 50% 8-10

22 25% 16-20

16 12% 32-40

10 6% 64-80
 Cardiac Venting
• Effects
1. Myocardial effect
Decrease intraventricular pressure
2. Pulmonary effect
Decrease pulmonary venous pressure
3. Evaluate valve function
• Complications
1. Myocardial injury at apex
2. Air embolism
3. Bleeding
4. Arrhythmia
 Coronary Blood Flow
 Regulating factors
1. Hydrostatic pressures
2. Anatomic factors
3. Metabolic control
4. Autoregulation
* well correlates with myocardial oxygen consumption
a) Myocardial tension development
b) External work
c) Heart rate
d) Contractility
Coronary Vasomotor Dysfunction

• Endothelial dependant cyclic guanosine

monophosphate – mediated vasorelaxation
(response to acetylcholine)
• Endothelial independant cyclic GMP-mediated
vasorelaxation
(response to Na-nitroprusside, nitroglycerin)
• Beta-adrenergic cyclic adenosine
monophosphate – mediated vasorelaxation
(response to isuprel)
 Cardiopulmonary Bypass

Factors influencing blood pressure

• Alteration in vascular response
• Anesthetic agents
• Operative trauma
• Perfusion flow rate
• Priming hemodilutional factor
• Perfusate colloidal osmotic pressure
• Temperature
• Anatomic factors, such as PDA, collaterals
 Cardiopulmonary Bypass
Vasodilatory hypotension
1. Etiology
1) Endothelial injury
2) Release of cytokines
3) Other inflammatory mediator
2. Treatment
1) Pressor catecholamines
2) Arginine vasopressin (pitressin)
Presence of arginine vasopressin deficiency
Predisposing factors
1) Hyponatremia
2) Atrial stretch receptor activation (ANP increase)
3) Autonomic dysfunction
 Multiorgan Failure
 Definition
* Laboratory indices of cellular death in every
tissue and with intractable loss of peripheral
vascular response similar to sepsis.
* This situation, in general, is accompanied by
excessive whole body edema, so-called,
capillary leak syndrome, organ recovery
cannot be achieved.
 Cardiopulmonary Bypass
 Abdominal complications
• Incidence
About 1%, frequent in valve surgery
Gastrointestinal ulceration associated with bleeding
Acute gastric dilation, Cholecystitis, Acute appendicitis
Acute pancreatitis
• G-I bleeding
Ulcer history in 50%, frequent in old age, men, valvular disease
• Acute pancreatitis
0.03% of CPB, mortality 30%, not related amylase level
hypercalcemia, embolism, low perfusion
• Intestinal ischemia & infarction
Very rare, due to embolism, cardiac failure, splanchnic pooling
(CPB effect), digitalis
 Cardiopulmonary Bypass
Potassium kinetics
• Urinary loss
Not related to urine volume, not equilibrium to interstitial space
• Hemodilution
Move to interstitial space
• Acid-base balance
• Glucose metabolism
• Catecholamine
Intrinsic catecholamine decrease serum potassium level
• Propranolol (beta-adrenergic blocking agents)
Inhibit the decrease in serum potassium
 Assisted Circulation
Control blood activation
1. Surface modifications
1) Physical modification
2) Chemical modification by grafting a hydrophilic component
3) Surface modification by inclusion of bioactive components
4) Biomembrane mimicry
5) Cellular seeding and lining
2. Inhibition of initial events leading to blood activation
1) Platelet anesthesia
2) Contact phase inhibition
3) Complement inhibition
4) Monocyte inhibition
3. End point inhibition of biologic cascades
1) Antifibrinolytic drugs
2) Modulation of neutrophil-mediated injury
 Coagulation Function Test

• Coagulation time, whole blood coagulation time

(WBCT), Activated clotting time (ACT)
Assess the integrity of the coagulation system
• Partial thromboplastin time
Identify the abnormality existing in the intrinsic system
• Prothrombin time (Quick test)
Measure the integrity of the extrinsic system (factor VII)
• Thromboplastin generation time
Measure intrinsic system (factor VIII, IX)
• Thrombin time
Identify qualitative or quantitative fibrinogen defect
 Protein C System
Action
1. Plasma factors protein C and S
2. Endothelium-bound thrombomodulin
1) Thrombomodulim binds circulating thrombin to form a
complex that catalyzes the conversion of protein C to
activated protein C.
2) Activated protein C together with its cofactor protein S,
inhibits further thrombin generation by inactivating
factor Va & VIIIa.
3) Activated protein C neutralize plasmogen activator inhibitor
PAI-1, PAI-3, & enhance fibrinolysis.
3. Congenital deficiency of protein C
Resistance of factor Va ---> hypercoagulable state
4. Aprotinin is an inhibitor of activated protein C.
 Nature of Aprotinin
1. Nature
Aprotinin, a polybasic polypetide, naturally occurring
serine protease inhibitor derived from bovine lung

2. Action
1) Decrease fibrinolytic action
2) Decrease platelet activation
3) Inhibit kallikrein activation
4) Inhibit neutrophil activation
5) Reduce cellular & immune inflammatory reaction
 Nafamostat Mesilate
• Nafamostat mesilate is a synthetic, specific, and reversible
serine protease inhibitor
• Nafamostat mesilate has a potent inhibitory activity on thrombin,
XIIa, Xa, kallikrein, plasmin, C1r and C1s subcomponent proteins
of complement system, and trypsin, all classified as trypsin-like
serine proteases, which are known to have a substrate specificity
for arginyl and lysyl residue–containing substrates.
• Hydrolysis of NM occurs mainly in the blood and liver, followed
by glucuronic acid conjugation, with a half-life of 8 minutes in
human plasma.
• Nafamostat mesilate almost completely inhibits either the
formation or activity of XIIa and kallikrein, two of the key
enzymes of the contact system, and is thought to interact directly
with platelets to reduce aggregability.
 Use of Desmopressin
Actions
* Desmopressin acetate is a synthetic vasopressin
analogue that lacks vasoconstrictor abilities
* This reduces bleeding time and surgical blood
loss by inducing release of circulating level of
coagulation factor VIII & Von Willebrand
factor
* It improves hemostasis in patients with certain
congenital or acquired disorder of platelet
function
 Actions of Adrenomedulin
• Adrenomodulin is potent vasodilator peptide initially
isolated from adrenal medulla,but in the vascular beds
of organs such as heart,lungs, and kidneys
• Synthesized & secreted by the endothelial cells and
smooth muscle cells of the pulmonary vasculature
• Impaired ability to synthesize or secrete ADM in
pulmonary circulation contribute development of
pulmonary hypertension
• Multiple biologic effects involved in cardiovascular
homeostasis
 Issues for Heparin Use
• Dose of heparin
• Evaluation to assess anticoagulation
• Heparin titration during CPB
• Protamine dose for reversal
• Assessment of adequate reversal
• Heparin resistance
• Heparin rebound
• Complications of heparin therapy
 Properties of Heparin
• Heparin consists of a group of glycosaminoglycans with molecular
weights from 3000 to 30000 daltons and is prepared from beef lung
or porcine intestinal mucosa and is a heterogenous mixture of
polysaccharides with molecular weights upto 100000 daltons
• Heparin inhibits both Factor Xa and thrombin. The active site is a
pentasaccharide which binds to antithrombin III, a serine protease
inhibitor in plasma. Additional saccharide units are needed for
heparin to bind factor Xa and thrombin.
• Intravenous bolus injection 100, 400, or 800u/kg will produce
anticoagulant activity half-lives of 1, 2.5, and 5 hours respectively.
• Extravascular depots, hemodilution, and hypothermia all affect the
anticoagulant effect of heparin
• Heparin is removed primarily by reticuloendothelial system, and
inactivated in the liver by heparinase and excreted in the urine
 Actions of Heparin
Anticoagulation properties
• Heparin exerts its anticoagulant effect by enhancing the action of
antithrombin III, the major naturally circulating inhibitor of
coagulation
• Heparin binds antithrombin III causing a conformational change
that exposes additional binding sites on the antithrombin III
molecule
• This increases the ability of antithrombin III to bind with factors
XIIa, XIa, IXa, and Xa thus accelerating their inhibition and
preventing the formation of fibrin
• The ACT is a gross test of coagulation and as such is affected by
all aspects of the coagulation cascade, except factor XIII.
• In addition to residual heparin, destruction of serine proteases,
hypofibrinogenemia, fibrinolysis, and platelet abnormalities, both
qualitative and quantitative , can all influence the ACT.
 Action of Heparin
Additional properties
• Modulate the inflammatory response by inhibiting
activation of polymorphonuclear leucocytes as well
as components of complement cascade
• Production & release of several endothelial vasoactive
mediators including endothelin and nitric oxide
• Protecting effect in the setting of myocardial ischemia
and reperfusion injury
• Heparin activates lipoprotein lipase which releases free
fatty acids from plasma triglyceride
 Alternatives of Heparin
• Some low molecular weight heparins may lack some
side-effects of commercial heparin
• Framin, a low molecular weight heparin, attenuates
both platelet activation and complement activation.
Low molecular weight heparins tend to inhibit Factor
Xa more than thrombin and also require anti-thrombin
III as a co-factor
• Hirudin, the natural anticoagulant found in leeches,
reversibly inhibits thrombin with very high affinity and
produced by recombinant DNA technology
• Other thrombin inhibitors include boroarginines and
chloromethyketones
 Adverse Effects of Heparin
• Heparin increases the sensitivity of platelets
to platelet agonists; ADP, epinephrine and
collagen
• Heparin may also affect complement activation
and neutrophil release
• Heparin contributes to activation of platelets,
complements, neutrophils and plasminogen
during CPB
• Therefore heparin directly contributes to the
whole body inflammatory response