Neuropharmacology of Anesthetic Agent

8/13/2019 Neuropharmacology of Anesthetic Agent

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Robert H. Sirait. dr., SpAn

Dept. Anesthesiology FK UKI

NEUROPHARMACOLOGY OF

ANESTHETIC AGENTS


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NEUROPHARMACOLOGY OF

ANESTHETIC AGENTS

I. BASIC UNDERSTANDING :

NEUROPHYSIOLOGY

1.CEREBRAL BLOOD FLOW (CBF)2.CEREBRAL METABOLIC RATE (CMR)

3.CEREBROSPINAL FLUID (CSF)

4.INTRACRANIAL PRESSURE (ICP)

5.BLOOD BRAIN BARRIER (BBB)


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1. CEREBRAL BLOOD FLOW (CBF)

Total CBF in adults 750 ml/min (15-20% CO)

- Gray matter 80 ml/100gr/min

- White matter 20 ml/100gr/min

- Averages 50ml/100gr/min

- < 20-25 ml/100gr/min slowing

electroencephalogram (EEG)

- 15-20 ml/100gr/min flat (isoelectric) EEG- < 10 ml/100gr/min irreversible brain damage


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Regulation Cerebral Blood Flow

1.1. Cerebral perfusion pressure (CPP)

- Normal : 80 - 100 mmHg

- CPP = MAPICP

- Normal ICP 5-15 mmHg- CPP < 50 mmHg slowing EEG

- CPP 25-40 mmHg flat EEG

- < 25 mmHg : irreversible brain damage- Decreases CPP: Cerebral vasodilatation

- Increases CPP: Cerebral vasoconstriction


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1.2. Autoregulation

- CBF constant between MAPs 60-160 mmHg- MAPs > 160 mmHg disrupt BBB

- MAPs shift to the right in patient with chronic

arterial hipertension- Cerebral autoregulation: miogenic and metabolic

mechanism arterial tone tissue

metabolitest ( H+, NO, adenosine,

prostaglandins,and ionic concentration gradients)vasodilatation and increases flow


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1.3. Extrinsic mechanism

a. PaCO2 (particularly)- CBF directly proportionate to PaCO220-80

mmHg- CBF changes 1-2 ml/100g/min per mmHg change

PaCO2- Hyperventilation (PaCO2 < 20 mmHg ): shift to the

left the oxygen Hb dissociation curve.- Cerebral blood volume (CBV) 0.05ml/100gr/min

of brain per 1 mmHg in PaCO2


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b. PaO2- Hiperoxia : associated minimal CBF (-10%)

- Severe hipoxemia PaO2< 50 mmHg : CBF

c. Temperature

- CBF changes 5 - 7% per 1C changetemperature

- Hypothermia CMR and CBF

- If the temperature the brain falls 10C the CMR

50%

- If the temperature the brain increases 10C the

CMR doubles


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d. Viscosity

- The most important determinant blood

viscosity is hematocrit

- The optimal cerebral oxygen delivery occur athematocrit 30%


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e. Autonomic Influences

- Intracranial vessels are innervated by sympathetic

(vasoconstrictive) , parasympathetic (vasodilatory),

and non-cholinergic non adrenergic fiber, serotoninand vasoactiv intestinal peptide


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2. CEREBRAL METABOLIC RATE (CMR)

- 20% of total body oxygen- 60% cerebral oxygen used to generating ATP to

support neuronal electrical activity

- CMR for oxygen consumption (CMR 02) 3 - 3,8

ml/100gr/min- CMR for glucoseconsumption is 5 mg/100gr/min,

> 90% is metabolized aerobically

- During starvation : ketone bodies become majorenergy substrates

- Acute hypoglicemia hypoxia

- Hyperglycemia global and focal hypoxic

cerebral acidosis & cellular injury


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3. CEREBROSPINAL FLUID (CSF)

- Production 21 ml/h (500 ml/d), total volume

150ml, formed :

a. >> choroid plexuses of the cerebral lateral

ventricles active secretion of Na+

b. smaller by the ventricle ependymal cell linings- isotonic fluid, lower : K+, HCO3-, glucose

concentration

- Decreases production: acetazolamide,

corticosteroids, spironolactone, furosemide,

isoflurane, and vasoconstrictors

- Absorption: translocation fluid from arachnoid

granulations cerebral venous sinuses


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4. INTRACRANIAL PRESSURE (ICP)

The cranial : rigid structure. fixed total volume : brain 80%, blood 12%,

and CSF 8% Normal pressure 10 mmHg

Major compensatory mechanism to rises ICP :a.Displacement CSF from cranial to the spinal

compartmentb. CSF absorpstion

c. CSF productiond. Cerebral blood volume (CBV)


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4. INTRACRANIAL PRESSURE (ICP)

Elevation ICP can lead to catastrophic herniation:

a.Gyrus falx cerebrib.Tentorium cerebelli

c.Foramen magnum

d.Defect in the skull (transcarvarial)

The initial management increases ICP.

Maintaining cerebral O2delivery with :

a. Supplemental O2

b. Elevation of headc. Intubation

d. Hyperventilation

e. Limitation excees free water and vol resusc.


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5. BLOOD BRAIN BARRIER (BBB)

Tight junctions vascular endhotelial cells

Freely enter : CO2, O2 and Lipid soluble

substances (such as most anesthetics)

Penetrates poorly: most ions, proteins, andlarge substances such as mannitol

Disrupted by : severe-hypertension, tumors,

trauma, strokes, infections, marked

hypercapnia, hypoxia, and sustained seizureactivity


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II. EFFECT OF ANESTHETIC AGENTS

Effect on CNS reducing electrical activity :- Decreases carbohydrate metabolism

- Increases energy stores (ATP, ADP, and

Phosphocreatine)

A.VOLATILE/INHALATION AGENTS

- Decreases CMR

- Dilate cerebral vessels dose dependent

- Impaired autoregulation


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Agent CMR CBFCSF

ProductionCSF

AbsorptionCBV ICP

Halothane

Isoflurane

Desflurane

Sevoflurane ? ?

Nitrous oxide

Barbiturates

Etomidate

Proprofol ? ?

Benzodiazepines

Ketamine

Opioids

Lidocaine ? ?

Comparative effects of anaesthetic agents on cerebral physiology


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b. Propofol- Similar to barbiturates : CBF and CMR

c. Benzodiazepin

- CBF and CMR but lesser extent thanbarbiturates and propofol

d. Ketamine- Dilates the cerebral vasculature and CBF


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e. Neuromuscular blocking agents (NMBAs)- Lack direct action secondary effect(histamin released cerebral vasodilatation

ICP)

f. Opioids- Minimal effect on CBF, CMR and ICP, unless

PCO2(respiratory depression)

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C. ANESTHETIC ADJUNCTS

- Lidocaine ( CMR, CBF and ICP )

- Vasopressors ( CBF : normal autoregulation and

intact BBB)

- Vasodilators ( Cerebral vasodilatation and CBF)- Mannitol (osmotic diuretic)


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Neuropharmacology of Anesthetic Agent