1. Effects of Cardiopulmonary Bypass
Ns. Ida Simanjuntak, S.Kep
Perfusionist Staff
National Cardiovascular Center Harapan Kita
Jakarta

2. Effects of Cardiopulmonary
Bypass
Glucose metabolism
 Hyperglycemia usually accompanies the stress response
associated with CPB.
 A more common complication of paediatric CPB is
hypoglycemia. This is largely because of the decreased
glycogen stores and reduced hepatic potential for
gluconeogenesis.
 In patients with CHD, hepatic perfusion may be impaired further,
which leads to compromised liver function. Neurologic
consequences of hypoglycemia are aggravated by hypothermia
and other factors that may modify cerebral perfusion. Glucose
monitoring during CPB and rapid correction with dextrose is
essential for decreasing morbidity resulting from paediatric heart
surgery.

3. Effects of Cardiopulmonary
Bypass
Haematologic effects
 Paediatric patients develop a more exaggerated response to
CPB. The inflammatory response is inversely proportional to the
patient’s age. Interleukin (IL)–8 and IL-6 production have been
linked to this inflammatory reaction, with their expression linked
to the duration of CPB.
 The synthetic surfaces of the bypass circuit have been
associated with activation of inflammatory mediators. These
include activation of the complement system, including plasma-
activated complement 3 (C3a). A potent stimulator of platelet
aggregation, C3a causes histamine release from mast cells and
basophils, increases vascular permeability, and stimulates
WBCs to release oxygen free radicals and lysosomal enzymes.
Elevated levels of C3a have been linked to the duration of CPB.

4. Effects of Cardiopulmonary
Bypass
Haematologic effects
 Contact of blood with the bypass machine surface
activates platelets and causes an increase in thrombus
formation. If not corrected, activation of coagulation and
fibrinolytic pathways can lead to excessive bleeding.
Expression of binding proteins on endothelial surfaces
leads to extravascular migration of neutrophils and
subsequent tissue injury.
 Activated neutrophils obstruct the capillaries, thus limiting
reperfusion of ischemic tissue (i.e. no-reflow
phenomenon).

5. Effects of Cardiopulmonary
Bypass
Stress response
 Low perfusion, hypothermia, and exposure of the blood
to the tubing and surface of the pump cause release of
hormones and other substances, including
catecholamines, cortisol, growth hormone,
prostaglandins, complement, glucose, insulin, and
endorphins.
 Other factors involved in secreting these substances
include the type of anesthetic used and decreased renal
and hepatic function leading to decreased clearance from
the kidneys and liver.
 The lung normally is responsible for metabolizing and
clearing many of these hormones, particularly
catecholamines.

6. Effects of Cardiopulmonary
Bypass
Cardiac effects
 Studies on immature animal hearts have demonstrated
conflicting data with regard to the relative sensitivity of
the neonatal heart to ischemia compared to the adult
heart.
 Reasons for better tolerance to ischemia in the neonatal heart
include
 the increased glycolytic capability of the immature myocardium and
 better preservation of high-energy phosphates because of decreased
levels of 5'-nucleotidase, which catalyzes the breakdown of adenosine
monophosphate (AMP) to adenosine.
 Conversely, accumulation of lactic acid as a result of
anaerobic metabolism has been hypothesized as a cause
of ischemic intolerance in the neonatal heart.

7. Effects of Cardiopulmonary
Bypass
Central nervous system effects
 Neurologic injury after routine CPB is uncommon in
neonates, but the risk is increased when deep
hypothermic circulatory arrest (DHCA) is required.
Although permanent injury is less common, evidence of
some neurologic injury is observed in as many as 25% of
infants who have undergone DHCA.
 Neurologic morbidity includes seizures, strokes,
changes in tone and mental status, motor disorders,
abnormal cognitive functioning, and postpump
choreoathetosis. Areas most vulnerable for ischemic
injury include the neocortex, hippocampus, and striatum.

8. Effects of Cardiopulmonary
Bypass
Central nervous system effects
 Another potential mechanism of brain injury involves
binding of glutamate to the N-methyl-D-aspartate
receptor (NMDAR). This binding increases the amount of
intracellular calcium and subsequently activates
proteases, phospholipases, and deoxyribonucleases
(DNAases) and promotes generation of free radicals. The
net result of these processes is cell injury, cell death, or
both.
 Microemboli can be detected in patients on CPB. The
long-term effect of these emboli is not well defined.

9. Effects of Cardiopulmonary
Bypass
Pulmonary effects
 Lung injury is mediated in one of two ways. Leukocyte
and complement activation cause an inflammatory
response, or a mechanical effect leads to surfactant loss
and atelectasis. These types of dysfunction cause a
reduction in static and dynamic compliance, reduced
functional residual capacity, and an increased alveolar-
arterial (A-a) gradient.
 Hemodilution reduces oncotic pressure and causes
extravasation of fluid into the lung parenchyma.
 CPB activates complement and leukocyte degranulation,
causing capillary membrane injury and platelet activation,
both of which eventually lead to increased pulmonary
vascular resistance.

10. Effects of Cardiopulmonary
Bypass
Renal effects
 CPB leads to production of renin, angiotensin,
catecholamines, and antidiuretic hormone. In turn, these
substances cause renal vasoconstriction and reduced
renal blood flow.
 Risk factors for postoperative renal dysfunction include
preoperative renal disease, contrast-related renal injury,
and profound post-CPB reduction in cardiac output.
 In the period following CPB, 8% of patients have acute
renal insufficiency as indicated by oliguria and increased
creatinine levels.
 After spontaneous urine output, diuretics are effective at
inducing diuresis and reversing renal cortical ischemia
associated with CPB, but their use does not alter the time
to recovery of renal function.

11. Use of Hypothermia
Effect on Metabolic Rate
 In a patient undergoing CPB, hypothermia helps protect
against injury caused by the compromised substrate supply
to tissues resulting from reduced flow.
 This protection occurs because of a reduction in metabolic
rate and decreased oxygen consumption.
 The metabolic rate is determined by enzymatic activity, which
in turn depends on temperature.
 The decrease in metabolic rate is not the only factor involved
in hypothermic protection. The actual safe period of
hypothermic CPB is longer than the period predicted by a
sole reduction in metabolic activity.

12. Use of Hypothermia
Effect on pH
 The effect of hypothermia on pH is mediated by its effect
on the ionization constant of water and, therefore, its
effect on the ionized-to-nonionized ratio of metabolic
substrates.
 In ischemia, the intracellular pH decreases because of
the accumulation of hydrogen ions. In turn, the
accumulation of hydrogen ions causes a decrease in the
ratio of ionized-to-nonionized metabolic substrates.
Nonionized substrates can cross the cellular membrane
and are lost. Hypothermia affects this by decreasing the
metabolic rate, then by increasing the ionized-to-
nonionized ratio.
 In addition, the transformation of a semiliquid cellular
membrane to a semisolid membrane is postulated to
decrease calcium influx.

13. 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.

14. Techniques of Hypothermia
Currently, two surgical techniques are
used in congenital heart surgery,
namely,
 Deep hypothermic circulatory arrest
(DHCA)
 Hypothermic low-flow bypass (HLFB)

15. Deep Hypothermic
Circulatory Arrest
DHCA provides excellent surgical exposure by
eliminating the need for multiple cannulas within
the surgical field and by providing a motionless
and bloodless field.
Surgical technique
 Initiate the cooling phase prior to institution of
CPB by simple cooling of the operating room
environment.
 After systemic heparinization and cannulation,
initiate CPB.
 Monitor body temperature via esophageal,
tympanic, and rectal routes.

16. Deep Hypothermic
Circulatory Arrest
Mechanical Problems
 Obstruction of the inferior vena cava (IVC) by a
misplaced IVC cannula can lead to increased venous
pressure, which causes ascites and decreased perfusion
pressure in mesenteric, hepatic, and vascular beds.
Monitor infants with ascites for GI tract, renal, and hepatic
functioning.
 Misplacement of the cannula in the superior vena cava
(SVC) can result in increased venous pressure in the
cerebral venous system. Subsequent cerebral edema
results from inadequate venous drainage and a
consequent reduction in cerebral blood flow, potentially
resulting in ischemia.

17. Deep Hypothermic
Circulatory Arrest
Mechanical Problems
 Arterial cannula misplacement also 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 to the CPB machine.
 Thus, the systemic perfusion is shunted away from the
body in a futile circuit back to the CPB machine. Anatomic
lesions where such shunting can occur include an
unrecognized patent ductus arteriosus and large
aortopulmonary collaterals as found in pulmonary atresia.

18. Deep Hypothermic
Circulatory Arrest
Inflammatory response
 Activation of the inflammatory pathway leads to serious
complications, morbidity, and mortality. Several
strategies have been used to modify the inflammatory
response. These include:
 Use of heparin-coated CPB circuit to reduce the
inflammatory response
 Modifying the blood cardioplegia solution has been
investigated as a means of reducing inflammatory-
mediated myocardial injury after intracardiac repair.
 Since neutrophils may mediate the local inflammatory
response in the heart, a leukocyte-depleted blood
cardioplegia (LDBC) has been postulated as a means for
improving myocardial protection during CPB.
 Modified ultrafiltration.

19. Anticoagulation for
Cardiopulmonary Bypass
Anticoagulation and heparin reversal
 Paediatric and neonatal patients undergoing CPB for
cardiac surgery are prone to coagulopathy in the early
postoperative period.
 Contributing factors include
 hemodilution,
 immaturity of the coagulation system,
 depletion of platelets and other hemostatic proteins, and
 the complex nature of the operations performed, which
often include multiple suture sites and, therefore, an
increased number of potential bleeding sites.

20. Anticoagulation for
Cardiopulmonary Bypass
Anticoagulation
 To avoid forming thrombi in the CPB machine, heparin is
administered prior to cannulation. Heparin is chosen
because it is a fast-acting anticoagulant and its action
can be inhibited rapidly by protamine.
 Heparin activates antithrombin III, which inhibits thrombin
activity.
 Heparin can be stored in the vascular endothelium and
smooth muscle, contributing to heparin rebound, which is
observed after discontinuation of CPB and heparin
reversal.
 Clearance of heparin also is determined by hepatic and
renal function.

21. Anticoagulation for
Cardiopulmonary Bypass
Anticoagulation
 Typically, a loading dose of 200-300 U/kg of heparin is
given and then heparin activity is monitored by
measuring activated clotting time (ACT) and heparin
levels.
 Physicians at some centers administer 300 U/kg, check
to see if this leads to an ACT of 450-480 seconds, then
administer supplemental heparin based on subsequent
ACT levels.
 The use of only one of these monitoring methods may
not reflect the full degree of anticoagulation.
 ACT levels can be affected by factors unrelated to
heparin concentration, including the patient's hematocrit
and temperature.

22. Anticoagulation for
Cardiopulmonary Bypass
Heparin reversal
 Protamine binds to heparin and releases antithrombin III.
 One method of administering protamine is to administer
1-1.3 mg for each 100 U of heparin administered. This
method does not take into account the half-life of heparin
or its clearance from circulation.
 Other methods include ACT-heparin dose-response
curves, direct measurement of heparin levels, and use of
the heparin-protamine titration.

23. Anticoagulation for
Cardiopulmonary Bypass
Adverse effects of protamine
 Release of histamine, which can lead to a decrease in
systemic vascular resistance
 True anaphylaxis, which is mediated by antiprotamine
immunoglobulin E (IgE) and observed primarily in
patients with prior exposure to protamine (e.g. neutral
protamine Hagedorn [NPH] insulin) and in patients with
fish allergy
 Thromboxane release, which leads to pulmonary
vasoconstriction and bronchoconstriction

24. Anticoagulation for
Cardiopulmonary Bypass
Strategy to counteract post-CPB bleeding
 Bleeding after CPB is not unusual.
 Identify any sources of obvious surgical bleeding since
this is the most common cause of post-CPB bleeding.
 Assess the adequacy of the protamine dose.
 If the dose appears to be sufficient, the next most common
cause of bleeding is platelet dysfunction, and platelet
infusion is warranted, even if the platelet count is within
reference range. Often, platelets are dysfunctional after
CPB in infants and children.
 Administration of aprotinin can decrease blood transfusion
requirements in patients undergoing repeat surgeries and
in patients who are cyanotic.
 Desmopressin has antifibrinolytic activity and acts as a
kallikrein inhibitor. Mild hypersensitivity reactions and
anaphylactic reactions are reported.

25. Hypothermic Low-Flow
Cardiopulmonary Bypass
 The finding that DHCA was associated with neurologic
morbidity has led researchers to investigate the use of
HLFB.
 This technique allows continuous low-flow perfusion to
the organs during the operation, which may lead to an
increase in oxygen supply, better nutrient supply, and
better achievement of homogeneous hypothermia during
bypass.
 Recent trials comparing the 2 methods have reported
lower rates of neural dysfunction in the group of patients
undergoing HLFB.