perfusion students should know about the CPB effects on Central Nervous System while performing CPB

1. CPB on CNS
NAHAS N
CLINICAL PERFUSIONIST
NIMS Medicity

2. INTRODUCTION
• Provide an overview of the neurologic effects of cardiac surgery and
cardiopulmonary bypass.
• Basic cerebral physiology during CPB will be reviewed
• Interventions having the potential to reduce neurologic morbidity will
be considered
• Applicability of neurologic monitoring techniques for CPB

3. Factors Increasing Risk of Neurologic
Dysfunction Following Cardiac Surgery
• Preoperative or Patient Predictors
• Advanced age
• History of prior neurologic events
• Diabetes
• Systemic Hypertension
• Cerebrovascular Disease

4. • Intraoperative Predictors
• Cardiac Disease: Open vs Closed Procedures
• Aortic Disease
• Hypotension
• Pump Flow
• Equipment (Oxygenators, Arterial Filters)
• Temperature Management
• Glucose Management
• Blood Gas Management
• Duration of Bypass

5. Neurologic Complications in Cardiac Surgery
cerebral deaths
nonfatal strokes
aortic atherosclerosis or thrombus
Seizures
• predictors of outcomes are aortic atherosclerosis or thrombus
new intellectual deterioration at discharge or new seizures
• predictors of outcomes are aortic atherosclerosis, a history of endocarditis,
postoperative low cardiac output state, a history of alcohol abuse, perioperative
arrhythmias, and elevated systolic blood pressure on admission.

6. Etiology of Cerebral Ischemia During CPB
and Cardiac Surgery
• Factors contribution to Neurologic risk
• Atheroembolic risk,
• Hypo- and hypertension,
• Anemia,
• Arrhythmias,
• Dehydration,
• Disorders of coagulation

7. Embolization
Primary cause of serious brain injury during cardiac surgery
These embolic events are related to
• Atheromatous debris
• Platelet–fibrin and leukocyte aggregates
• Bubbles generated in the CPB circuit or in the surgically exposed
left-sided circulation.

8. Hypoperfusion
• Alterations in blood flow and distribution during the CPB (pump flow)
may adversely affect global and regional cerebral perfusion.
• Perioperative MAP is a primary determinant of neurologic outcome.
• Regional hypoperfusion (either as a direct result of vascular disease, or
as the inability to compensate for the regional ischemia associated with
microembolization) for understanding perioperative cerebral ischemia
• Regional cerebral hypoperfusion probably occurs during CPB secondary
to hypertensive, diabetic, or senile atherosclerotic disease.
• The increased neurologic risk associated with hypertension and diabetes
may result from either increased embolization or regional hypoperfusion.

9. Inflammation
• CPB is associated with ischemia and reperfusion injury (both are
potent triggers for activation of leukocytes, and for leukocyte–
endothelial or leukocyte–platelet–endothelial binding) to the heart
and lung as well as a generalized inflammatory response.
• Pathophysiologic mechanisms may impact the vascular lining and
these events may contribute to post-CPB encephalopathy
• CPB-related inflammation is sufficient to alter CNS endothelial
function in the absence of an ischemic substrate.

10. Cerebral Physiology
Autoregulation of Cerebral Blood Flow
CBF is maintained at approximately 50 mL/lOO g/min over a
range of mean arterial pressure (MAP) from 50 to 150 mm Hg,
described as the autoregulatory plateau.
factors that tend to decrease CMR02 will tend to lower the
autoregulatory plateau.
Factors that tend to produce cerebral vasodilatation, however,
including certain anesthetic agents and direct-acting smooth-muscle
relaxants – of which CO2 is probably the most potent - will alter
cerebral autoregulation.

11. Determinants of Cerebral Blood Flow
Cerebral oxygen demand [cerebral metabolic rate for oxygen (CMRO2)] during
CPB varies primarily in inverse proportion to brain temperature. CBF is strongly
influenced by CMRO2, PaCO2,Hct, and MAP.
1. Threshold cerebral blood flow at normothermia
under 30ml/100g/min ; brain acidosis occurs
less than 20 ml/g/min ; loses electrical activity
less than 10ml/g/min ; loses further cellular membrane integrity
Brain average 2% of total body weight,
14% of cardiac output,
20% of oxygen consumption

12. Factors Affecting CBF During CPB
• Acid-Base Management
• Temperature
• Carbon Dioxide and oxygen
• Mean Arterial Pressure
• Hematocrit
• Pulsatility
• Cardiopulmonary Bypass Flow and Brain Perfusion

13. Acid-Base Management
The mode of pH management during moderate hypothermia has
been shown to profoundly influence cerebral vasodilation and flow-
metabolism coupling.
During hypothermic CPB with alpha-stat pH management CBF is
unaltered despite increases in MAP.
With pH-stat management observed that CBF varies and is directly
proportional to MAP.
During pH-stat management, the relative hypercarbia causes
cerebral vasodilation and a concomitant increase in CBF and loss of
cerebral autoregulation

16. Temperature management
• Temperature is the primary determinant of CBF
flow-metabolism coupling
The brain regulates its flow in response to its oxygen demand
such that increases or decreases in CMRO2 are associated with
proportional changes in CBF.
• As temperature decreases, the effects of hypothermia on CBF become
more complex.
• The Q10, or CNS respiratory quotient, describes the increase in
CMRO2 per 10◦C increase in temperature

17. Protective effect mechanism
• Preservation of high energy
phosphate store
• Preventing excitatory
neurotransmitter release
(glutamate, dopamine)
• Restricting membrane
permeability
• Preventing calcium entry into the
cell

18. Determinants of changes
1. Cerebral blood flow
2. State of metabolic rate
3. Heat exchange with environment

19. Hypothermia effect on blood gas
• Hypothermia increases the solubility of blood gases into the
blood
• As temperature is lowered, oxyhemoglobin dissosciation curve
shifts to left, so that for a given partial pressure of oxygen in
the tissues, less of the gas is unloaded from the hemoglobin.
• Decreasing temperature increase the carrying power of blood
for carbon dioxide through an increased activity of the blood
buffers.

20. Profound Hypothermia
• Produces impaired cerebral autoregulation.
• Induce a form of cerebral vasoparesis that impairs cerebral
autoregulation, although cerebral responsiveness
Deep Hypothermic Circulatory Arrest
• DHTCA appears to produce a persisting decrease in CBF, the
mechanism for which is unclear.

21. Carbon Dioxide and hypoxia
• Carbon dioxide is one of the most potent determinants of CBF.
• Changes in PaCO2 alter CBF largely independent of CMRO2;
changes in PaCO2 may alter the ratio of CBF to CMRO2 without
indicating
• During bypass an elevated PaCO2 (upper curve) is associated with
a higher CBF for any given MAP.
• Autoregulation is preserved with an α-stat strategy between MAPs
of 55 and 95 mm Hg.

22. • The arterial partial pressure of oxygen also contributes to CBF
autoregulation.
• Cerebral vascular resistance is reduced and CBF is increased with
arterial hypoxemia, even when Paco2 is decreased.
• Hyperoxia will cause a decrease in CBF seconcfury to an increase in
cerebral vascular resistance.
• CBF is reduced by 15% when the Pao2 is increased from 125 to
300 mm Hg during bypass with alpha-stat acid-base management.

23. Mean Arterial Pressure
• Under non-CPB conditions, the healthy brain maintains CBF to an MAP of
approximately 50 to 55 mm Hg.
• large part of CPB is now conducted with mild hypothermia.
• Where multiple cerebral physiologic measurements can be made at
differing MAPs with extremely tight physiologic control
• The relation between MAP, CBF, CDO2, and CMRO2 was described as
consisting of two parts, a pressure-independent portion and a pressure-
dependent portion.
• CBF and CDO2 were preserved at MAPs of 60 mm Hg and higher, whereas
at 50 mm Hg or less, CBF, and more importantly CDO2, became pressure
dependent.
• Significant autoregulatory capacity may also be preserved during CPB, but
this depends in large part upon how other CPB variables are managed

24. Hematocrit
• CPB hemodilution typically reduces hemoglobin (Hgb)
concentration (and hence Hct) by a third.
• Hemodilution reduces blood viscosity and vascular resistance and
increases CBF.
• During hypothermic CPB, the increase in CBF occurring with
hemodilution may be offset by the decrease in CBF associated
with the reduction in CMRO2
• Hemodilution increases tolerance for hypotension because it
increases organ blood flow

25. Cardiopulmonary Bypass Flow and Brain Perfusion
• The effect of pump flow on cerebral perfusion is indirect.
• Pump flow did not alter CBF until the MAP decreased below 50
mm Hg.
• CPB flow is important to cerebral perfusion in so far as it
generates an MAP and that maintenance of CPB flow is not
sufficient to guarantee cerebral perfusion if MAP is reduced.

26. Pulsatility
• Like the acute changes in temperature and Hct, which may occur
during CPB, the loss of pulsatile flow is a physiologic condition unique
to CPB.
• Non-pulsatile perfusion has been reported to result in arteriolar
closure and a disturbance in the coupling of blood flow and
metabolism.
• Pulsatile flow has been reported to improve CBF, microcirculatory
perfusion, and tissue oxygen consumption, and to facilitate the
recovery of CBF following ischemia, low-flow CPB, and circulatory
arrest

27. Pump Flow
• The "perfect" pump flow would be that which provides adequate
oxygen delivery without excess cerebral perfusion and the attendant
increased embolic load.
• Factors affecting blood flow are changes CBF
• Hemodilusion
• Hypothermia
• Anaesthetic agents
• pH-stat management
• ECC device

28. INTRAOPERATIVE MANAGEMENT AND
NEUROLOGIC OUTCOME

29. Temperature management
Cooling:
• A slow rate of cooling or rewarming and a high blood flow are the
two factors ensuring homogenous changes of the body
temperature.
• Occlussive vascular disease and altered vascular reactivity may
reduce cerebral perfusion and delay temperature equilibrium.
• Oxygen availability is reduced during hypothermia and parallel
decrease in metabolic rate is likely to preserve a balance between
availability and requirement of oxygen.
• Increased HCT could compensate for decreased O2 availability
related to hypothermia, so cooling should be performed slowly
and with an adequate HCT.

30. Rewarming:
• Restart perfusion slowly after circulatory arrest, ensuring optimal
hemodynamic conditions, and avoiding cerebral hyperactivity.
• Initial cold blood flow with sufficient HCT, washes out metabolites,
buffers free radicals, and provides substrates before cerebral
electrical activity.
• Hyperglycemia stimulated by release of endogenous
catecholamines, increases intracellular acidosis and prevent
metabolic homeostasis .
• During rewarming, cerebral vascular resistance and energetic
metabolism are impaired in proportion to ischemia, glucose is in
part diverted to less efficient anaerobic pathway, and oxidative
phosphorylation is disturbed.

31. Glucose Management
• Elevations in blood glucose aggravate neurologic ischemic injury.
• Blood glucose concentrations during CPB ranged from 103 to 379
mg/dL, and glucose concentrations greater than 250 mg/ dL were
treated with insulin.
• Reflects the phenomeno of anaerobic conversion of glucose to
lactate, resulting in a decrease in intracellular pH, and subsequent
impairment of cellular metabolic processes.
• This metabolic impairment leads to a decreased cellular tolerance for
ischemic insult
• Moderate hypothermia (30 ° C) attenuates the disruptive effect of
hyperglycemia on blood-brain barrier integrity.

32. Cerebral ischemia

33. Blood Gas Management
• The type of acid-base management during CPB (alpha-stat or pH-stat)
greatly affects CBF during extracorporeal circulation.
• During pH-stat management, the relative hypercarbia causes cerebral
vasodilation and a concomitant increase in CBF and loss of cerebral
autoregulation.
• pH-stat management causes a mismatch of CBF and CMR02, a so-
called luxury perfusion(potentially advantageous during bypass).
• It may be disadvantageous, because it increases the embolic load to
the brain.

34. INTERVENTIONS
• Surgical and technical changes
• Pharmacologic interventions
• Physiologic management strategies.

35. Surgical and Technical
• To reduce the problem of Atheroembolism ( to reduce embolic
risk).
• Aortic embolization has also been addressed by devices designed
to deflect or trap emboli liberated from the root.
• CPB circuit management, such as hollow fiber oxygenators, arterial
inflow ‘‘line’’ filters, and minimizing transfusion of mediastinal
shed blood, may also impact neurologic morbidity.
• Biocompatibility (glycoprotein surfaces) of the CPB circuit
constitutes another technical factor that has the potential to
impact outcomes

36. Pharmacologic
At least three forms of pharmacologic neuroprotection can be
considered:
Metabolic depressants:
• Thiopental
• Propofol
Agents that inhibit different steps in the cellular ischemic
pathway:
• Calcium Antagonists
Antiadhesive agents:
• Leukocyte Inhibition and Endothelial Protection

37. • Calcium Antagonists :
- Intracellular accumulation of calcium is one of the key factors
leading to cell death in cerebral ischemia. nimodipine treatment to
bleeding complications and speculate that this might have resulted
from a combination of vasodilatation and the antiplatelet effects of the
drug

38. • Leukocyte Inhibition and Endothelial Protection: Antiadhesion Therapies:
Multiple inflammatory mediators contribute to the progression of ischemic
injury.
Neutrophils aggregate in the capillary beds of ischemic tissues and may
contribute to plugging, endothelial dysfunction, and tissue damage.
Characterization of the receptors responsible for neutrophil–endothelium
binding is leading to the development of specific monoclonal antibodies
against these receptors as well as nonspecific inhibitors of neutrophil–
endothelium binding.
Glycoproteins representing the selectin binding sites for leukocytes have
also been shown to decrease ischemic injury and increase CBF after
transient focal ischemia.
The inhibitory oligosaccharide fragments are structurally related to, and can
be generated from, multiple fractionations of heparin and there is some
evidence that heparin itself may reduce cerebral ischemic injury by acting as
an antiadhesion molecule

39. Physiologic Interventions
Temperature:
Hypothermia provides flexibility in surgical and perfusion practice.
Cerebral hypothermia attenuates the physiologic impact of reductions
in perfusion pressure and Hct and extends the ‘‘safe’’ period of low-
flow CPB and circulatory arrest.
Even small temperature differences have important effects on
neurochemical, neuropathologic, and neurophysiologic outcomes
after ischemia.
Mild hypothermia attenuates the depletion of cerebral adenosine
triphosphate (ATP) following ischemia and decreases the production
of the excitatory neurotransmitter, glutamate infarct volume is
reduced, particularly in the neocortex, and neurologic outcome may
be improved

40. • Physiologic Interventions to Reduce Embolization: Carbon Dioxide,
Temperature, and Cardiopulmonary Bypass Flow
Surgical attention to embolic risk and technical changes in the CPB
circuit decrease cerebral embolization.
Increases in CBF, as would occur with pH-stat management or
normothermic CPB, may result in a higher incidence of cerebral
embolization. Acute reductions in CBF during periods of embolic
risk might reduce cerebral embolization.
Hypocarbia, hypothermia, and a high flow rate were all effective in
reducing cerebral embolization.

41. NEUROLOGIC MONITORING
• Measurement of venous oxyhemoglobin saturation at the jugular
bulb oxyhemoglobin saturation (SjvO2)
• Near-infrared optical spectroscopy (NIRS)
• TCD (Transcranial Doppler)
• Electrophysiologic monitors
• Eg., EEG, and evoked potentials.

42. • Jugular Bulb Oxyhemoglobin Saturation (SjvO2):
An index of the adequacy of global cerebral oxygenation and
normal values are established.
Can provide useful trends in cerebral oxygenation, the technique
is limited by the fact that it is a measure of global oxygenation, so
focal events may be undetected.
The effect of CO2 management had a greater effect on SjvO2 than
patient temperature.

43. • Near-Infrared Spectroscopy (NIRS):
Hemoglobin undergoes a characteristic near-infrared absorption
shift with O2 binding
so NIRS has the potential to provide a continuous, noninvasive
transcutaneous assessment of regional brain oxygenation.
NIRS is sensitive to changes in temperature, PaCO2, and Hct, as
well as the cessation and reestablishment of CPB flow.

44. • Transcranial Doppler (TCD):
TCD measurements of blood flow velocity in the middle cerebral
artery may show good correlation with measured CBF. Evaluated as
a monitor of cerebral perfusion during CPB.
The technique is noninvasive and provides continuous
measurements, Greater application in pediatric CPB.
TCD monitoring may be useful to determine whether these reduced
CPB flows and MAPs are sufficient to maintain cerebral perfusion.
TCD has found much greater use in emboli detection than
assessment of cerebral perfusion.
Blood flow velocity may be sensitive to temperature change, MAP
and pump flow, as well as to PaCO2 and Hct,

45. • Electroencephalogram and Evoked Potentials:
• Electrophysiologic monitors should provide one of the best means for
determining adequacy of cerebral oxygenation.
• Evoked potentials provide another means of assessing functional
neurologic integrity during CPB. Somatosensory evoked potentias
(SSEP), in which a stimulus is delivered peripherally and the integrity
of its transmission from the peripheral nerve thorough the spinal cord
and to the sensory cortex is recorded, have been most commonly
used.
• A decrease in signal amplitude may represent ischemia, as can an
increase in signal latency. evoked potential amplitude and latency are
sensitive to hypothermia