CPB & Neurological Impairment

Age

• Elderly patients have an increased risk & incidence of stroke and neuropsychological deficits

Sex

• Cardiovascular mortality & morbidity and neuropsychiatric impairment are higher for women, however, women are generally older when operated on [due to protective effect of sex hormones]

Cardiac Disease

• Increased incidence of neurological sequelae associated with: open heart surgery (valves), presence of left ventricular thrombus, severity of valvular calcification, extent of atherosclerosis in ascending aorta

Cerebrovascular Disease

• Preoperative symptomatic cerebrovascular disease appears to increase stroke risk in CABG
• An asymptomatic carotid bruit per se may not alter risk

Hypertension

• Neither chronic hypertension nor the use of antihypertensives affects the incidence of stroke post surgery

During CPB:

· CNS damage may be caused by decrease perfusion of the brain secondary to low blood flows or embolic occlusion or vessels or to adequate perfusion with hypoxic perfusate

Risk Factors for CNS injury

• Patient related:
1. 70 years
2. Overt cerebrovascular dx
3. Extensive aortic atherosclerosis
4. Diabetes mellitus
• Procedure-related
1. Open-chambered procedures
2. 90 min CPB duration
3. Perioperative haemodynamic instability
4. Multiple aortic clampings; cannulations

• Equipment related
1. Use of bubble oxygenators
2. Lack of arterial filters
3. Use of Nitrous oxide

Mechanism of neural damage during CPB

A) Embolism

1) Microembolism

i) Gas

ii) Fat

iii) Cellular aggregates

vi) CPB circuit material

2) Macroembolism

i) Air

ii) Particulate matter

a) Atheroma

b) Calcific debris

c) Thrombus

B) Cerebral Hypoperfusion

1) Systemic hypoperfusion

2) Low pump flow

3) Nonpulsatile flow

4) Incorrect cannula placement

• Cardiac surgical patients develop more frequent, more severe brain injury than patients with comparable preoperative risk factors undergoing noncardiac surgery
• Frank neurological disturbances such as stroke may reflect a mechanism such as macroembolization
• Subtle changes detected by neuropsychological testing may be due to microembolization or anaesthetic effects
• There is continuing debate about whether the fate of the brain is predominantly determined by blood flow & pressure or by embolization; and if perfusion methods do have an effect, is this due to the effect on global cerebral perfusion or on total embolic load delivered to brain

Etiology of CNS Damage during CPB

A.Focal ischaemia

· Most often due to isolated cerebral arteriolar obstruction by a particulate or gaseous embolus

· Emboli vary in size, natue (gaseous versus particular), and origin (patient versus equipment)

· Open-chamber procedures entail a greater risk of embolic debris than do closed-chamber procedures

Sources of emboli:

a) Patient related:

i) Aortic atheroma: 2° aortic clamping & cannulation; dislodgement of atheroma due to jetting from arterial cannula

ii) Intraventricular thrombi: recent mural thrombi

iii) Valvular calcifications: embolisation of intracavitary valve debris

b) Procedure related:

i) Open chambered procedures; entraiment of air via vents

ii) Aortic cannulation & clamping

iii) Long durations of CPB

c) Equipment related

i) Filters on arterial line & cardiotomy reservoir

ii) Membrane versus bubble oxygenators

iii) use of NO2

B. Global Ischaemia

Watershed areas

Boundary areas or watershed zone infarcts in the brain are situated between the territories of major cerebral or cerebellar arteries

Cerebral perfusion pressure

i) 28-30°C & alpha stat: autoregulation preserved over CPP range from 20 - 100 mmHg

ii) 15-20°C: hypothermia-induced vasoparesis —> loss of autoregulation

iii) Diabetic patient may have impired autoregulation at moderate hypothermia

iv) Raised CVP: decrease CPP

Circulatory Arrest

i) 16-18°C (profound circulatory arrest) used to decrease CMRO2 and increase tolerance for ischaemia

Types /aspects of surgical procedures likely to produce/be associated with neurological damage

• Open heart procedures (valvular repairs & replacement, ventricular aneurysmectomy) have been associated with a two- to threefold higher incidence of neurological sequelae than CABG ; 80 — 100% of cases have intravascular air at termination of CPB [by US over carotid artery]
• Cerebral emboli resulting from manipulation of diseased ascending aorta is thought to be a major cause of neurological morbidity after CABG
• Even gentle palpation of a severely diseased aorta may be hazardous
• Severe disease in ascending aorta may require modification of surgery: retrograde plegia; proximal anastomosis whilst X-clamped to obviate use of side-clamping; femoral cannulation
• There is a correlation between the duration of CPB and incidences of neurological impairment; this may reflect the deleterious effect of bypass per se, or an increase in risk due to patient factors such as severity of atherosclerosis, valvular calcification, etc
• Air may be introduced into the systemic circulation at the time of left ventricular venting, or by dislodgment of air which is trapped beneath the edge of the side-clamp once resumption of cardiac activity has occurred
• Air emboli can be introduced into the patient’s arterial blood when the cardiac chambers are open for valvular, or septal repairs — air is often entrained on the luminal surfaces of the heart or trapped within the muscular trabeculae [cardiac ejection should be avoided until complete blood filling occurs]
• Embolization of particulate matter may occur from calcific debris dislodged at the time of aortic cannulation or when the proximal aortic clamp is released
• Platelet-fibrin deposition at the aortic suture line may be a cause of early or late embolization
• The greatest risk of macroembolization from the surgical field occurs with aortic manipulation and resumption of left ventricular ejection
• Microembolization occur during stable extracorporeal perfusion, but are most frequently observed associated with aortic manipulation, onset of bypass, and separation from bypass
• “Surgical air”: enters arterial circulation during:

i) cannulation of heart & aorta

ii) aortic cannula insertion

iii) caval

iv) right atrial

v) left ventricular vent

vi) following removal of aortic clamp

vii) air entrapment at site of venous cannulation

viii) after restoration of cardiac function

Role of CPB management in the genesis of neural damage

Oxygenator Type

• See improved neuropsychological outcome using membrane versus bubble oxygenator
• No data on stroke rates

Arterial Filters

• Arterial filtration can reduce neuropsychological dysfunction after cardiac surgery; however controversy exists

Hypothermia

• Cerebral protection by hypothermia:

i) reduced cerebral oxygen consumption

ii) increased cerebral intracellular pH [intracellular acidosis contributes to cellular damage]

Acid-Base Management

• studies show no difference in alpha-stat vs pH-stat in terms of neurological outcome!
• However, in alpha-stat some patients may be vulnerable to cerebral hypoperfusion; in pH-stat some patients may be exposed to an excess microembolic load [“luxury perfusion syndrome”]

Mean Arterial Pressure

• Bulk of recent studies (retrospective) show that no association exists between mean BP & neurological outcomes
• However, recent prospective study with randomisation of patients [Gold] shows reduced neurological morbidity with high pressure (80—100 mmHg) versus low (50—60 mmHg)

Pump Flow

• No prospective controlled studies
• Relevant studies conclude that patients with post op deficits had similar flows and pressures compared to patients with no deficit

BSL

• Preexisting hyperglycaemia exacerbates ischaemic brain injury
• Extent of cerebral damage correlates with blood glucose and brain glucose concentrations
• Lack of prospective controlled studies; unclear whether blood glucose may affect post op morbidity {worthwhile issue to study?}

Barbiturates

• A prospective controlled study randomising thiopental administration for CABG showed no difference in neurological outcomes between the two groups —> no role in routine CABG

Calcium Channel Antagonists

• Nimodipine may protect the brain by cerebral vasodilation: one small study showed benefits after CPB

Prostacyclin

• Prostacyclin may protect the brain by reducing platelet microembolization, but no difference seen in a prospective controlled study

Conduct of Perfusion

• Use of emboli detectors on CPB circuitry; vigilance on venous reservoir

Reduction of “Surgical Air”

• Air emboli can be introduced into the patient’s arterial blood when the cardiac chambers are open for valvular, or septal repairs — air is often entrained on the luminal surfaces of the heart or trapped within the muscular trabeculae [cardiac ejection should be avoided until complete blood filling occurs]
• Methods to reduce air embolism at operative site:
1. needle aspiration of chambers and pulmonary veins
2. left ventricular vent
3. flooding surgical site with CO2
4. closure of left atrium under blood
5. lung expansion to clear pulmonary venous blood
6. Trendelenburg position