Effect of pH

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Pediatric Perfusion
Gerald Mikesell, CCP
Childrens National Medical Center
Washington DC
Fundamental Goals of CPB
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To facilitate a surgical intervention
Provide a motionless field
Provide a bloodless field
Supply adequate substrate for the metabolism of
all tissues
Remove unwanted byproducts of metabolism
Minimize the deleterious effects of bypass
The Cardiovascular Perfusionist
The perfusionist
controls the patients
blood flow, blood
pressure, and gas
exchange as well as
monitoring and
delivering
anticoagulation and
protective heart
medications
Differences Between Adult and
Pediatric Cardiopulmonary Bypass
Major differences exist between adult and
pediatric cardiopulmonary bypass (CPB),
stemming from anatomic, metabolic, and
physiologic differences in these 2 groups of
patients.
Cardiopulmonary Bypass
Generalized inflammatory reaction
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Capillary Leak
Cardiac dysfunction
Organ dysfunction/MSOF
Mortality
CPB Deleterious Effects
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Coagulopathy
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Platelet dysfunction/ consumption
Coagulation factor consumption
Cellular destruction/Hemolysis
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Systemic heparinization
Hemodilution of factors
Mechanical stress
Inflammatory Activation
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Mechanical stress
Non-endothelial exposure
Complement activation
Cytokine and leukocyte activation
White cell activation
Effects of CPB
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All the discussed effects of bypass are related to
exposure to our circuits and the mechanical devices
used to allow bypass to procede
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Total bypass time continually emerges as a risk factor for
morbidity and mortality
Optimal outcome is benefited by surgeons operating
accurately and rapidly, using efficient sequencing of repair
Bypass Management
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No perfect means to measure level of support
Normal monitoring: EKG, NIRS, Saturations
and Pressures are designed for non-bypass
monitoring
With bypass, loss of normal physiologic
homeostatic control, loss of pulsatility, change
of oxygen supply, hemodilution
Venous Saturation Measurement
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Though looked to as a standard of perfusion adequacy,
there are limitations
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Cooling causes left shift of oxyhemoglobin dissociation curve
Cooling causes increase of pH
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Fetal Hemoglobin in neonates
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Alkaline blood also causes left shift of oxyhemoglobin curve
Left shift of curve
Lower levels of 2,3DPG in bank blood also cause left shift
Therefore, as temperature of blood drops, venous
saturation will rise but brain and tissues are still warm
and not receiving the O2 needed to meet metabolic
demand
Venous Saturation Measurements
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Left Heart Return and collateral steal
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Dangerous to assume all flow pumped into patient is going
where planned. Colleteral development with some lesions
can steal up to 50% of flow and return directly to venous
return
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Collaterals to pulmonary veins to LA across unrepaired ASD,VSD to
venous cannula
Differental return flow from SVC vs IVC
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Warm brain uses lots of O2 and SVC with low sat but
Systemic blood colder, IVC with higher sat, blood mixes in
venous line and sat monitor reading appears fine
Bypass Management
We do things to exert control of the patient on
CPB and work to maintain a margin of safety for
the patient even if all parameters aren’t perfectly
controlled.
The important decisions that we can control:
Temperature
pH
Hematocrit
Perfusion flow
Temperature
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Advantage:

Reduce Metabolic Rate
Tissue preservation
 Myocardial preservation
 Allows flow variation to improve surgical access
 Flexibility in cannulation
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Decreased inflammatory response to CPB
Decreases Complement activation and release of vasoactive substance
 Decreases white cell activation
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Temperature
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Disadvantages:
Prolongs bypass
 Increases probability of post-operative bleeding
 Possible prolonged post-operative recovery
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Especially in adults
Use of Hypothermia
Effect on Central Nervous System
 The effect of hypothermia on the nervous system is
multifactorial. In addition to decreasing the metabolic
rate, hypothermia has been demonstrated to decrease
the release of glutamate, which is involved in CNS
injury during CPB.
 A negative effect of hypothermia on brain function is
the loss of autoregulation at extreme temperatures,
which makes the blood flow highly dependent on
extracorporal perfusion.
Techniques of Hypothermia
Currently, two surgical techniques
commonly used in congenital heart
surgery, namely,
 Deep hypothermic circulatory arrest
(DHCA)
 Hypothermic low-flow bypass (HLFB)
Deep Hypothermic Circulatory Arrest
DHCA provides excellent surgical exposure by
eliminating the need for multiple cannulas within the
surgical field. Normally use arterial cannula and a single
venous cannula in the right atrium.
Surgical technique
 Initiate the cooling phase prior to institution of CPB by
simple cooling of the operating room environment and
begin surface cooling the patient
 After systemic heparinization and cannulation, initiate
CPB.
 Monitor body temperature via esophageal, tympanic,
and rectal routes.
 Have also seen less edema.
Deep Hypothermic Circulatory Arrest
Disadvantages:
Time constraints on the surgical team. Must be
highly organized with the repair and efficient with
technique. Precise and accurate repairs must be
completed in limited time.
Deep Hypothermic Circulatory Arrest
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Late 1980’s study out of Boston Childrens looking at
DHCA vs low flow in arterial switch patients
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Both groups with deep hypothermia and hematocrit of 20%
One group had circulatory arrest, the other group a low flow
of 50 mL/kg/min
Patients have now been followed for 20+ years
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CA patients had lower verbal and development scores until age 4.
Caught up with developmental scores by age 4 and by age 8 caught
up with verbal.
Both groups were below mean controls.
If longer periods of arrest are anticipated, may be
advantageous to apply ancillary procedures such as
intermittent reperfusion.
Deep Hypothermic Circulatory
Arrest
Mechanical Problems
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Arterial cannula misplacement can occur. If the cannula inadvertently
slips beyond the takeoff of the right innominate artery, preferential
perfusion to the left side of the brain can be observed.
Presence of any anomalous systemic-to-pulmonary shunts can lead to
shunting of blood away from the systemic circulation, through the
pulmonary circuit, and then through the venous cannula returning to
the CPB circuit.
Thus, the systemic perfusion is shunted away from the body in a futile
circuit back to the CPB circuit. Anatomic lesions where such shunting
can occur include an unrecognized patent ductus arteriosus and large
aortopulmonary collaterals as found in pulmonary atresia.
Effect of pH
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pH and pCO2 have strong systemic and cerebral
vasodilatory effects
Effects are opposite with pulmonary circulation
Shift in pH or pCO2 can cause a marked shift in
blood flow between pulmonary and systemic beds
 A-P collaterals or systemic to pulmonary shunts
(B-T shunt for example) need to be considered
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Effect of pH
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Perfusionist important to acid-base control
during CPB
Flow rate
 Dilution
 Hypothermia
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As temperature drops, pH of H2O increases
Effect of pH
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Alpha Stat vs pH Stat: First studies in the 1980s
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Alpha Stat
 Maintains optimal intracellular enzyme activity
 Maintains cerebral auto-regulation and the coupling of
flow and metabolism at low temperatures
 In adults, showed improved cognitive outcome
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Possibly related to reduced number of micro-emboli
pH Stat:
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Loss of cerebral auto-regulation as temperature drops
Cerebral flow is pressure dependent, could cause “luxuriant”
flow with the potential for increased micro-emboli
Effects of pH
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Boston Childrens Hospital did multiple studies, both
clinical and animal, in the late 1980’s
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Alpha stat patients had worse developmental outcome
during cooling than pH stat. There was strong
correlation during cooling of pCO2 and developmental
outcome
The circulatory attest time of 35-60 minutes had no
impact
With alpha stat patients, there were 19 cases of
choreoathetosis in 4 years/ With pH stat, there were
none
In lab studies with piglets, found that cerebral microcirculation was better in pH stat piglets vs alpha stat
Effect of pH
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In 1990’s Boston Childrens completed two randomized
clinical studies which both showed better outcomes
with pH stat
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pH stat had lower mortality (p=0.058)
pH stat, with continuous EEG monitoring during surgery
and 48 hours post bypass, show lower rate of post-op
seizures
pH stat: First EEG activity returned faster after circulatory
arrest
pH stat: Decreased post-op acidosis (p=0.02)
pH stat: Decreased post-op hypotension (p=0.05)
Effect of pH
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Boston pH vs Alpha stat clinical studies (Cont)
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pH stat: Shorter mechanical ventilation time and ICU stay
(p=0.01)
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pH stat: in d-TGA sub-group, higher cardiac index with
lower inotrope requirement
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pH stat: A trend to better developmental scores at 1 yr of age
Effect of pH
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Boston study:
Conclusion was pH stat:
 Suppresses cerebral metabolism and lengthens safe
duration of DHCA for a given temperature and
hematocrit
 Improves oxygen availability by counteracting the
oxy-hemoglobin curve’s leftward shift with
dropping temperature
 Very important in early cooling period when
blood is cold but brain still warm
 Improved developmental outcome
pO2 and Bypass
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Historically feeling that hyperoxia was responsible for
microemboli associated mobidity post CPB
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A problem with bubble oxygenators, especially without
arterial filters
Two studies in piglets at Boston Childrens in 1999
looked at this issue
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Compared bubble oxygenator vs membrane oxygenator with
arterial filter
Compared normoxia with hyperoxia and DHCA
Compared free radical production
Compared histological injury of normoxic vs hyperoxic
pO2 and Bypass
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Study Results:
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At cold temperatures there was increased microemboli with
bubble oxygenator vs membrane oxygenator with filter
As temperature was dropping, there were more microemboli
with normoxia vs hyperoxia
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Reasoned that nitrogen was less soluble in the blood than oxygen as
the temperature dropped
Looking at histological injury, there was significantly more
injury in the brains of normoxic animals vs hyperoxic animals
after 120 minutes of arrest at 15 deg C
An interesting observation was that temperture gradient both
cooling and warming had no effect on microemboi
Bypass and Optimal Flow
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The standard bypass flow target has always been 2.4
L/min/m²
Must weigh all the options:
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Normal may be as much as 3.5-4 L/min/m²
Hemodilution can add up to 3-4 times greater flow demand
to meet O2 demand
Add aorto-pulmonary collaterals with 50% of pump flow
returning directly to the pump. Leaves an effective flow of
1.2 L/min/m²
Potential for hypoxic injury
Bypass and Optimal Flow
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Flow considerations for bypass: What is the metabloic
demand for different temperatures
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Normal thermia
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Mild hypothermia: temperature greater than 30ºC
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Moderate hypothermia: temperature 25-28º C
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Deep hypothermia: temperature less than 18ºC
CPB Flows
• 2.4 -3.0
at
• 1.6 l/ m2 at 28o
• 1.2 – 1.6 l/m2 at 25o
• 1.0 – 1.6 l/m2 at 20o
2
o
• 0.5 – 1.0 l/m at 15
2
l/m
o
37
Hemodilution
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Decreased concentration of cells & solids in
the blood
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RBC’s, WBC’s, Platelets, Plasma Proteins,
Clotting factors, Lytes (Ca,Mg)
Is hemodilution bad?
May allow better perfusion as temperature drops
 Causes a drop in O2 delivery
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Prime Volumes
Adult
30% of blood volume
blood volume
prime volume
23% of total volume
Hct 35%  27%
Pediatric
50% of blood volume
blood volume
prime volume
33% of total volume
Hct 35%  23%
Infant
176% of blood volume
blood volume
prime volume
63% of total volume
Hct 40%  14%
Hemodilution
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On bypass and before cooling, O2 demand still high
flow not compensated
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Thought to be related to drop in perfusion pressure
Perfusion pressure change in direct proportion to change of
viscosity with hemodilution
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If hemodilution not on bypass, body compensates by increasing
cardiac output
Hemodilution vs Cerebral Protection
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1996 study by Shinoka et al, in JTCVS. Working with
piglets looked at 3 levels of hematocrit, 10,20 and 30%;
went on bypass and cooled to 15ºC and arrested for 60
minutes.
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Low hematocrit piglets had worse neurological outcome,
both physiologically and histologically.
Lowest hematocrit piglets showed hypoxic stress during
cooling and before arrest
Hemodilution vs Cerebral Protection
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2001 Study by Sakamoto et al looked at the interaction
of hematocrit (20 and 30%), pH (alpha stat vs pH stat)
and temperature on the neurological impact of piglets
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Lower hematocrit, more alkaline pH and longer circulatory
arrest were predictive of neurological damage
Hematocrit: 30% showed distinct advantage to
neuroprotection vs 20%
pH stat was more neuro-protective with lower histological
injury vs alpha stat
A temperature of 15ºC was more neuro-protective than a
temperature of 25ºC
Study looked at circulatory arrest times of 60, 80 and 100 min
Hemodilution vs Cerebral Protection
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2001 a companion study by Duebener et al looked at
microcirculation (capillary blood flow) and at tissue
oxygenation with hematocrits of 30% vs 10%.
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30% was associated with improved re-perfusion (functional
capillary density) vs 10%
There was no evidence of capillary plugging or white cell
activation with the higher viscosity level of the 30%
hematocrit
Hemodilution vs Cerebral Protection
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2002 Study by Jonas et al, JTCVS. The Influence of
Hemodilution on Outcome After Hypothermic CPB:
Results of a Randomized Trial in Infants
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147 patients randomized to a hematocrit of 21 (74) or 27 (73)
Hematocrit 21: post-operative serum lactate was higher, cardiac
index was lower and had greater total body water at POD1.
Blood product usage was the same for both groups
Baley Scales of Infant Development: at 1 year the high
hematocrit group had higher Psycomotor Development Index
(low hct group was 2 SD below normal populations) , there was
no difference in Mental Development Index
Showed that a hemodilution practice thought to be safe
was associated with adverse perioperative and
developmental outcomes in infants
Hemodilution and Bypass
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Hemoconcentration
 During bypass
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Conventional
 Modified
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MUF
Ultrafiltration
Hemodilution and Hemoconcentration
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Conventional
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Removes free water, dissolved ion and small molecules
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Remove byproducts of bypass and excess volume, i.e. cardioplegia
after delivery
Maximize hematocrit before termination of bypass
We like to come off with hct of 30-35 or even 35-40 with single
ventricle repairs
Modified Ultra-Filtration (MUF)
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Hemoconcentration of patients circulating blood volume
along with remaining volume in circuit
Improvement with CO and blood pressure
Disadvantages are the need to maintain heparinization and
cannulation for extended time and…
Complexity of circuit and risk of air around arterial cannula
Myocardial Protection Strategies
Myocardial Protection
The term "myocardial protection" refers to strategies and
methodologies used either to attenuate or to prevent
postischemic myocardial dysfunction that occurs during and
after heart surgery.
Principles of Myocardial Protection
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The main principles of myocardial protection are
the reduction of metabolic activity by hypothermia
the therapeutic arrest of the contractile apparatus
and all
electrical activity of the myocytes by administering cardioplegic
solution (e.g. depolarizing of the membrane potential by high
potassium crystalloid or blood cardioplegia)
CARDIOPLEGIC TECHNIQUES
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Cardioplegic solutions contain a variety of chemical
agents that are designed to
arrest the heart rapidly in diastole,
create a quiescent operating field, and
provide reliable protection against ischemia/reperfusion injury.
There are two types of cardioplegic solutions:
crystalloid cardioplegia
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extracellular
intracellular
blood cardioplegia.
These solutions are administered most frequently under
hypothermic conditions.
CARDIOPLEGIA DELIVERY SYSTEM
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Purpose = arrest and preservation
Two types of delivery
crystalloid cardioplegia: no blood
added
 blood cardioplegia: blood is mixed
with crystalloid)
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proposed advantages: oxygen, buffers,
proteins
Cardioplegia Delivery
Antegrade
Retrograde
Directly to coronary
Cases CNMC
Cardioplegia Delivery
2-3o C
Conducer Recirculation System
 Plegisol
(Oxygenated)
 First dose
20 ml/kg
 Following doses 10 ml/kg
 Above 50 kg
1000 ml
With 500 ml second dose
Blood Cardioplegia at CNMC
Use a modified Plegisol
recipe. Potassium is
added with a high K and
low K formulation.
Cardioplegia is delivered
4:1 blood:crystalloid.
High K: 20 mEq/L
Low K: 10 mEq/L
First dose is high K
then switch to low K for
redosing
Hemodilution and Prime
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1985 study by Haneda et al, compared crystalloid prime
vs blood and plasma prime in pediatrics
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Crystalloid prime patients had a +63 mL/kg fluid balance vs
+ 16 mL/kg with blood/plasma
Blood/plasma prime group had a lower mortality and 50%
reduction in ICU time compared with the crystalloid group
There is a general consensus that prime for children
should not include lactate or dextrose. Hyperglycemia is
associated with a worse neurological outcome.
Prime used at Childrens National Medical
Center
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Circuit primed with Plasma-lyte A, excess drained off
Packed Cells between 3-7 da old
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Try to maximize 2,3-DPG and have lower K+
Units are leuco-depleted in the blood bank
Primary unit of RBC is divided, half for perfusion for prime
and half for anesthesia to use post bypass so donor exposure
can be reduced
FFP: Same donor as RBC when possible
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We use some of the unit in the prime, add some to the circuit
while rewarming and any remaining goes to anesthesia post
CPB.
If using clear prime, will add 100-300 mL 25% Albumin
CNMC Prime
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Cefazolin: 25 mg/kg, (1 gm maximum dose)
Lasix: 0.25 mg/kg
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Mannitol 25%: 0.5 gm/kg (12.5 gm maximum dose)
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Feel a loop diuretic is helpful to maintain renal function
Potent osmotic diuretic with free radical scavenger properties
Add to prime, some also give a second dose on release of
cross clamp
Heparin
Sodium Bicarbonate 84%
Solumedrol: 30 mg/kg

Patients ˂ 1 week and DHCA patients
CNMC Bypass

Magnesium Sulfate: 50 mg/kg (1 gm maximum)
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Given immediately after cross clamp release
Has significantly reduced incidence of junctional ectopic
tachycardia ( JET)
Calcium Gluconate: 500 mg-1 gm
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Given 5 minutes after release of cross clamp
Current Primes
CNMC
250-300 Neonates
300-400Infants
400-600 Toddlers
Blood product use for CPB
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Hemodilution from pump
prime
Volume expansion
Treatment of iatrogenic or
concomitant coagulopathies
Surgical blood loss
Descending order
of incidence
PRBC Transfusion

Hematocrit
On CPB < 27%
 Post CPB < 27%
 This is patient dependent: size and lesion
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Oxygenation
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SVO2 < 65% at maximal flow on bypass
Hemodynamics

Acute blood loss
FFP Transfusion

Coagulopathies

Obvious non surgical bleeding
Long pump runs
 Hemodilution
 Preexisting conditions
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Heparin resistance
Inadequate ACT despite 2X normal Heparin
Dose
 “Fast” easy source of ATIII

Platelet Transfusion Triggers
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Coagulopathies

Obvious non surgical bleeding
Long pump runs
 Hemodilution
 Preexisting conditions
 DHCA patients
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Low platelet count
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< 70,000
How do we achieve low
prime circuits
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Get mind set
Look at circuit as separate components
Be willing to use different venders
Must modify perfusion techniques
Must be adaptable
 Constantly update equipment & techniques

Our goal with bypass is reduce the surface
area of exposure of the patient’s blood to
our circuits. We can accomplish this goal
through our selection of circuit
components and cannulae and the use of
techniques such as bio-passive circuit
coatings to attenuate the response of our
patients to bypass
Tubing
2/32" I.D.
0.6ml/ft.
3/32" I.D.
1.8ml/ft.
1/8" I.D.
3.5ml/revolution(2.5 ml/ft.)
5/32" I.D.
5ml/revolution(3.7 ml/ft.)
3/16" I.D.
7ml/revolution(5 ml/ft.)
1/4" I.D.
13ml/revolution(9.65 ml/ft.)
5/16" I.D.
18ml/revolution(13.5 ml/ft.)
3/8" I.D.
27ml/revolution(21.71 ml/ft.)
7/16" I.D.
38ml/revolution(28.5 ml/ft.)
1/2" I.D.
45ml/revolution(38.61 ml/ft.)
5/8" I.D.
65ml/revolution(55.77 ml/ft.)
Arterial Lines
3/16”
1200 ml/min
1/4”
2500 ml/min
3/8”
7000 ml/min
Venous Lines
3/16”
600 ml/min
1/4”
1500 ml/min
5/16”
2200 ml/min
3/8”
4000 ml/min
1/2”
>7000 ml/min
A-V LOOPS
CNMC
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Flows 0-1 L/min
 3/16 x 1/4
Flows 1 – 1.5 L/min
 1/4 x 1/4
Flows 1.5 – 2.5 L/min
 1/4 x 3/8
Flows 2.5 – 4.0 L/min
 3/8 x 3/8
Flows > 4.0 L/min
 3/8 x 1/2
Oxygenators

New Oxygenators specific for infants and pediatrics

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Reduced volume
Arterial flilters incorporated in design

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Improved flow dynamics

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Reduces prime of circuit (??)
Reduced pressure drop
Improved reservoir design with improved drainage and
volume handling

VAVD capable
Most common
Maquet
Terumo
Medtronic
Sorin
Medos
VENOUS RESERVOIR

Two types of venous reservoirs

hardshell venous reservoir


“open” system
collapsible bag venous reservoir

“closed” system
VENOUS RESERVOIRS
HARDSHELL VS. BAG
Arterial Blood Gas Control
 Blender
and Gas Flowmeter
 Carbon Dioxide
 Anesthesia - Forane
Arterial Blood Gas Control
Anesthesia: Forane
CDI500
On-line arterial blood gas,
hemoglobin/hematocrit,
K+ and venous saturation
Cannula Selection

Arterial
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Important component of the circuit as it’s a point of
narrowing in the pressurized limb of the bypass circuit
A point of increased flow velocity and potential high sheer
stress and increased hemolysis
Want largest cannula possible for expected flow but not large
enough to obstruct vessel lumen preventing retrograde flow
around the cannula
Other factors include: thin wall, tolerate temperature
variations without kinking or stressing aorta when cold
Ease of insertion
VENOUS CANNULA

Two types of venous cannulation procedures

right atrial cannulation
single RA cannula: through the RA appendage; tip in body
of the RA
 cavo-atrial cannula (or two-stage cannula): through the
RA appendage; tip in the IVC and “basket” in the body of
the RA
 used when the heart IS NOT going to be opened

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vena caval cannulation
one cannula through the RA appendage into the IVC
 a second cannula through the RA wall into the SVC
 used when the heart IS going to be opened

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a tie encircling the IVC and SVC is secured
Cannula Selection

Venous
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Essential for surgeon to have a cannulation plan based on the
defect to allow for optimal venous return and perfusion of
the entire body throughout the procedure
Cannulation must not interfere with appropriate sequencing
of operative steps
A balance of a size large enough to meet flow demands and
small enough to be accommodated with a particular defect
Right angle vs straight
Develop flow tables for cannulas ( and for each surgeon)
Cannulas

Venous

Drain blood from the
body
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2 stage
Bicaval
Femoral
Arterial

Return blood to the
body

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Aortic
Femoral
THE SUCTION SYSTEM

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
Purpose = evacuate shed blood
Usually ¼” I.D. tubing
Requires an occluded roller pump
This blood directed to the cardiotomy reservoir
filters any fluid to 19-35 microns
 open system: cardiotomy integral with venous
reservoir
 closed system: cardiotomy is separate from venous
reservoir
 blood, priming fluids, blood components

VENT (or sump) SYSTEM

Purpose = evacuate LV blood

sources of LV blood
right atrium escaping the venous cannula
 bronchial venous blood
 non-coronary collateral blood



Usually ¼” I.D. tubing
Usually requires an occluded roller pump


requires a negative pressure relief valve
This blood directed to the cardiotomy
reservoir
SAFETY SYSTEMS



Reservoir level detection
Air bubble detection (arterial line)
Arterial line pressure
Safety Systems
Flow Meter: Distal
to all shunts to give
more accurate flow
delivery to the
patient
Safety Systems
Level and air
sensors
Safety Systems
Pressure Monitoring
Cardioplegia delivery
pressure
Arterial line pressure
Cardiopulmonary bypass…

Do you ever
wonder….How does it
affect your patient?
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