Transcript Systemic Inflammatory Response Syndrome in Cardiopulmonary

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.
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1952. Dodrill.
1953. Lewis.
1953. Gibbon.
1954. Lillihei.
• 1954. Kirklin.
Mitral valve surgery under left heart
bypass
Relief of PS under right heart bypass
ASD closure under surface cooling
ASD closure by heart-lung machine
VSD closure under controlled crosscirculation
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
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Pump
Oxygenator
Heat exchanger
Reservoir
Filter
Sucker & vent
Cardioplegic solution
delivery system
Cardiopulmonary Bypass
Heart-Lung Machine
Development of CPB
Prerequisite
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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 coneshaped 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
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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, screentype 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
1.5-4.0
4.1-9.0
9.1-14.0
14.1-20.0
20.1-26.0
26.1-34.0
34.1-50.0
50.1-66.0
over 66.1
BSA(㎡)
0.13-0.26
0.26-0.48
0.48-0.56
0.56-0.71
0.71-0.84
0.84-1.00
1.00-1.40
1.40-1.63
over 1.63
Cannula Size (Fr)
8
10
12
14
16
18
20
22
24
cc/min
800
1200
1800
2800
3500
5000
5000
8000
8500
Size of Venous Cannula
Venous Cannula for Various Weights and BSA
Weight kg
＞6
6-8
8-10
10-40
＞40
BSA ㎡
0.3
0.3-0.45
0.45-050
0.50-1.10
＞1.1
Weight kg
＜5
5-10
11-15
16-25
25-50
＞50
BSA㎡
0.28
0.28-0.50
0.51-0.57
0.58-0.83
0.83-1.40
＞1.4
Single Cannula Size (Fr)
24
26
28-30
40 or (32-40 two
stage cannula)
Double Cannula Size(fr)
SVC
IVC
12
16
16
20
20
24
24
28
28
32
36
40
Flow
1200cc
1400cc
1600cc
1800cc
2600cc
Flow
12: 350cc
14: 450cc
16: 600cc
20: 900cc
Cannulation & Flow Rate
Estimated
Patient Maximum
Weight
Flow
Estimated Blood Flow
BSA
2.4L/Min/M²
Double
Single
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:
+ (weight × BV) +
Pump Prime Volume: (PPV)
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Total Circulating Volume: TCV
Required Red Cells:RRC
(TCV × desired % HT)
Patient Red Cells: PRC
(PBV × patient % HT)
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=
Total Red Cells needed : TRC
Note:
cc
cc
cc
cc
cc
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
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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
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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
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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
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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
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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
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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, bloodderived 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
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Protein denaturation
Activation of clotting factors
Platelet aggregation
Lipid peroxidation
Activation of complement cascade
 Postoperative pathophysiologic effects
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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
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5.
6.
Cardiac arrhythmia
Myocardial ischemia
Coagulopathy
Decreased myocardial contractility
Left shift of oxyhemoglobin dissociation
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.
2.
3.
4.
Effects on membrane stability
Effects on enzyme function
Effects on tissue calcium accumulation
Effects on cellular volume regulation
Cardiopulmonary Bypass
Endocrine Response
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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
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6.
Lung fluid exchange : excessive pulmonary capillary fluid
filtration due to capillary damage induced by complement release
and/or activation of coagulation cascade
Hemodilution reduce complications of intravascular coagulopathy,
coagulation and increase pulmonary lymph flow and decrease
blood use.
Pulmonary capillary hydrostatic pressure : effective left ventricle
venting
Interacting causes of alveolar collapse
Pleural cavity : opening the pleura lower lung volume and
increase the amount of alveolar collapse
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)
5 under
5-10
10-20
20-30
30-60
60 over
Flow(ml/kg/min)
200
170
135
100
85
60-70
Cardiopulmonary Bypass
Difference between infants & adult
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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)
<3
3-10
10-15
15-30
30-50
>50
Pump flow rate (ml/kg/min)
150-200
125-175
120-150
100-120
75-120
50-75
Minimal Pump Flow Rate
Temperature
CMRO2
(c)
(ml/100g/min)
37
1.48
32
0.823
30
0.654
28
0.513
25
0.362
20
0.201
18
0.159
15
0.112
Predicted MPFR
(ml/kg/min)
100
56
44
34
24
14
11
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
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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
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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