Brain Protection

Ahmad N. Hamdy, MD

Objectives (IOLs)

Cerebral physiology1

Explain cerebral ischemia2

3

Algorithm for brain protection4

Strategies to protect the brain from cerebral ischemia

Cerebral Physiology

BRAIN 1350 gm- 2% of total adult body wtReceives 12 to 15 % of cardiac output Global cerebral blood flow 45-55ml/100

gm / min

Cortical Subcortical 75-80ml /100gm/min 20ml /100gm/min

CMRO2 3 to 3.5 ml/100gm/min

Whole brain O2 consumption 50ml/min

(20% of total body O2 consumption)

Cerebral glucose utilization 5.5 gm/100gm of brain tissue (1ry energy source)

ICP ( supine) 5 to 15 mm Hg

CPP= MAP- ICP or (CVP), whichever is greater (90-100 mm Hg)

Cerebral Physiology

Factors Influencing CBF

Chemical/Metabolic /Humoral Cerebral metabolic rate Anaesthetics Temperature PaCO2 (20-80 mmHg) PaO2 Vasoactive drugs - Anaesthetics,Vasodilators,

Vasopressors Myogenic / Autoregulation Blood viscosityNeurogenic

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Cerebral Ischemia

It is the potentially reversible altered state of brain physiology and biochemistry that occurs when substrate delivery is cut off or substantially reduced by vascular stenosis or occlusion

Metabolic demands > substrate delivery

Pathophysiology

GLOBAL• Cardiac arrest• Resp. Failure• Shock• Hypoglycemia• Asphyxia

Cerebral Ischemia

FOCAL• Head injury• Vascular

Stenosis• Occlusion• Spasm

Biochemical & Pathophysiological changes

Inadequate blood flow

↓↓O2 delivery

Ischaemia

Excitotoxic Apoptotic Inflammationcell death cell death

Strategies for Brain Protection

Strategies

CMRO2Oxygen

CBF&CPP

Future concepts

Glucose

Specific

Oxygen & Glucose

In the absence of oxygen, glucose undergoes anaerobic glycolysis resulting in intracellular acidosis Patients with higher blood glucose concentrations have

worse outcomes from stroke, TBI, etc. More rapid expansion of ischemic lesion in

hyperglycemic, compared with normoglycemic patients

For all of this reasons, it is rational to maintain normoglycemia in all patients at risk for ,or recovering from acute brain injury

CMRO2

Hypothermia

Anesthetics

Body Temperature

Hyper HypoIschaemic Injury

Temperature

Hypothermia Reduce CMR in a temperature-dependent fashion Mild hypothermia(32-35 ) ; negliable effect on CMR℃

• But, in several studies mild hypothermia produce major protection ; provides scientific basis of using off-bypass hypothermia to provide meaningful neuroprotection

Deep hypothermia(18-22 ) ; highly neuroprotective℃• In normothermic brain ; only a few minutes of complete

global ischemia cause neuronal death• In deep hypothermia before circulatory arrest ; brain can

tolerate over 40 min and completely or near-completely recover

Temperature

Hyperthermia In animal studies, spontaneous post-

ischemic hyperthermia is common and intra-ischemic or even delayed post-ischemic hyperthermia dramatically worsen outcome

Advocate frequent temperature monitoring in patients with cerebral injuy

Aggressive treatment of hyperthermia should be considered

Anesthetics

Volatile anesthetics Protect against both focal and global ischemia

• Transient improvement in global ischemia• Persistent improvement in focal ischemia

Suppression of energy requirements• Inhibition of excitatory neurotransmission• Potentiation of inhibitory receptors• Regulation of intracellular calcium response during ischemia

Isoflurane, sevoflurane ; Desflurane ; insufficiently studied

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Anesthetics

Barbiturates have major actions on CNS: • hypnosis• depression of CMR • anticonvulsant activity.

These properties make barbiturates, particularly thiopental, the most commonly used induction agents in neuroanesthesia.

Anesthetics Propofol

Suppression of CMR Free radical scavenging Anti-inflammatory properties Appears efficacy similar to barbiturates

Etomidate Paradoxically exacerbate ischemic injury Cannot use for neuroprotection

Lidocaine Suppress CMR Inhibition of apoptosis No long-term outcome studies

Ketamine Inhibition of glutamate at NMDA receptor Little or no protection against global insult Substantial protection against focal insult However, no human data

CPP

More than 65-70mmHg

Elevation of MAP

Decrease ICP

Decrease blood viscosity

Specific

CCBs as nimodipine (SAH)

Na CBs as lamotrigine (SDH)

NMDA antagonist

Steroids (Brain tumors)

Preconditioning

Ischaemic Preconditioning

Homeothermic mammal

Elicits “an evolutionary conserved endogenous response to decreased blood flow and oxygen limitation such as seen during hibernation”

Clinical methods of preconditioning

Pre - op hyperbaric oxygen

Normobaric 100 % oxygen

Electroconvulsive shock

K+ channel opener→ Diazoxide

Erythropoietin (EPO)

Erythropoietin

Cytokine growth hormone-↓ apoptosis-↑ erythrocyte production

↑↑ haematocrit

Deleterious effect on ischaemia

Intravenous recombinant erythropoietin

Once daily for 3 days

60 -100 fold ↓glial markers ↓ infarct

↑ of EPO in CNS of cerebral size & injury

improved (S 100)recovery

Astrocytes in ischaemic penumbra produces EPO in mammalian brain

Stimulates protein Stimulates of repair

neurogenesis & angiogenesis

↓neural apoptosis

↓↓neural ↓inflammatoin excitotoxicity

Magnesium

Membrane stabilizerSuggested protective mechanism:

• Reduction of presynaptic release of glutamate• Blockade of NMDA receptors• Smooth muscle relaxation• Improved mitochondrial Ca2+ buffering• Blockage of Ca2+ entry

Protection depends on:• Time of treatment initiation• Type of cerebral ischemia

Benefit in neocortical stroke

Algorithm for Neuroprotection

Risk for IntraoperativeBrain ischemia?

No Standard Anesthesia CareReduce risk factors(HTN, smoking, recent MI, Afib)

yes

Embolic Risk(CPB, valve replacement)

HypothermiaGlucose controlHct ~32Maintain CPP when warmAlphastat pHArterial filters

neurologic Sx?

noyes

PCO2 30-35

Head positionMaintain CPPGlucose control

PCO2 30-35

MannitolLidocaineHead positionThiopentalCPP controlGlucose control

Aneurysm ClippingIntracranial Vessel BypassTemp. occlusion

RetractorPressure, etc.

Mild hypothermiaMannitolThiopental burst supp.EEG monitoringHct about 32%Treat vasospasmMaintain CPPPCO2 30-35 mmHg

Glucose control

Mild hypothermiaMannitolHct 32Maintain CPPPCO2 30-35 mmHg

Glucose control

Consider Specific Neuroprotection:

High TransientIschemia Risk

Elevated ICP/ persistentfocal ischemia (hematoma,mass)

Strategies for Brain Protection

O2

• HCT: 30-34 %

• PaO2 Levels

GL.

• 100- 150 mg/dl

CMRO2

• Hypothermia• Anesthetics

Strategies of Brain Protection (Cont.)

CBF

• CPP: ≥ 70 mmhg• MBP: Elevated• Viscosity:

Decresed• ICP: Decrease

Future

• NO• Cerebral

preconditioning• Apoptosis

Specific

• CCBs• Na CBs• NMDA

antagonist

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