CNS PHYSIOLOGY ANESTHETIC CONSIDERATION

1. ANATOMY AND
PHYSIOLOGY OF
CNS
MODERATOR: DR. SHALINDRA PAREEK
PRESENTER: DR.ANUPAMA NAGAR
1

2. Organization of the Nervous System
• Central nervous system (CNS)
–Brain and spinal cord
–Integration and command center
• Peripheral nervous system
(PNS)
–Paired spinal and cranial nerves
–Carries messages to and from the
spinal cord and brain
2

3. alamus
Brain stem
Cerebral cortex
Thalamus
(medial)
Basal nuclei
(lateral to thalamus)
Cerebellum
Spinal cord
Midbrain
Pons
Medulla
Brain component
Cerebral cortex
Basal nuclei
Thalamus
Hypothalamus
Cerebellum
Brain stem
(midbrain, pons,
and medulla)
3

4. Neurophysiology
•High metabolic rate
•No Oxygen stores
•Unable to maintain integrity through anaerobic
metabolism
•Insulin not required for transport of glucose
across cell membrane.
•CNS protection by means of meninges, CSF and
BLOOD BRAIN BARRIER.
4

5. CSF
•CSF found in cerebral ventricles and cisterns and in
subarachnoid space surrounding brain and spinal cord
•Major functions of CSF:
–Provides support (Mechanical protection)
–Regulates ionic composition
–Removes metabolites
•Clear colorless fluid
•Specific gravity of 1.007 & pH of 7.33-7.35
•Produced at the rate of 0.3-0.5ml/min or 450-500ml/day
•In an adult, CSF turn over rate is approx. 3 times a day
•Rate of formation is independent of the intracranial pressure
5

6. CSF FORMATION
CSF formed primarily by the choroid plexuses of the cerebral
ventricles (80%).
Smaller quantities from fluid leaking into perivascular spaces
surrounding cerebral vessels(10-15%)
Smaller amounts formed directly by ventricular ependymal cell
linings (3-5%)
CSF Absorption-
Primarily by arachnoid villi granulation extending into the dural
venous sinuses and Lymphatics of cranial and spinal nerves.
The rate of absorption is pressure dependent.
6

7. CSF flows from the lateral
ventricle→foramina of
monro →3rd ventricle
→cerebral aqueduct of
sylvius →4th ventricle→F.
Magendie and F. Luschka
→cerebellomedullary
cistern→subarachnoid
space circulating around
the brain and spinal cord
⇢ get absorbed in
arachnoid granules over
the cerebral hemispheres

8. BLOOD BRAIN BARRIER
• Fenestration between endothelial cells of cerebral blood
vessels are nearly fused.
• The movement of given substance depands upon -its size,
charge lipid solubility and degree of protein binding in blood.
• Water moves freely.
• Acute hypertonicity of plasma→net movement of water out of
brain
• Acute hypotonicity of plasma→water in the brain
8

9. Blood Brain Barrier
• May be disrupted by -
»Severe hypertension
»Tumours
»Trauma
»Stroke
»Infection
»Marked hypercapnia
»Hypoxia
»Sustained seizures
9

10. Blood supply of the brain- CIRCLE OF WILLIS
Derived from
2 INTERENAL CAROTID ARTERY-
anterior circulation
2 VERTEBRAL ARTERY- posterior
circulation forms basilar artery
ICA and basilar artery- vascular loop -c/a
circle of willis
ICA →3 paired anterior, middle cerebral &
posterior communicating arteries.
ACA: supplies superior & medial portions
of cerebral hemispheres
MCA: most of the lateral side of the
hemispheres & internal capsule
Posterior communicating artery: joins
ACA,MCA with PCA on both sides;
supplies base of the brain.
Anterior communicating artery- joins both
ACA

11. 11

12. Function as a collateral :
If one part of the circle becomes blocked or
narrowed (stenosed) or one of the arteries
supplying the circle is blocked or narrowed,
blood flow from the other blood vessels can
preserve the cerebral perfusion well enough to
avoid the symptoms of ischemia.
A significant proportion of individuals may have
an incomplete circular loop.
12

13. 13

14. VENOUS DRAINAGE
Venous drainage: 1) Superficial
2) deep cerebral veins
Superficial cortical veins
cortical surface
Deep cortical veins White
matter, brainstem, cerebellum,
basal ganglia, diencephalon
Deep veins Great cerebral
vein of Galen Inferior sagittal
S. Straight S. Sigmoid S.
Superficial veinssigmoid
sinusinternal jugular vein
SVC.
All blood eventually IJV.
Emissary veins connect venous
sinuses veins on external
surface of the skull.

15. CEREBRAL BLOOD FLOW
• Avg. CBF 50ml/100 gm of brain tissue/min.
• For an adult this is ~750ml/min total CBF ~15% of resting CO
(for an organ that represents 2% of body mass!!)
• Grey matter CBF(80ml/min/100gm) >>White matter
CBF(20ml/min/100gm).
• CBF very critical; If CBF falls to
➢ 20ml/100g/minslow EEG
➢15ml/100g/minflat EEG
➢10ml/100g/minirreversible ischemic damage
15

16. 16

17. Mechanisms for CBF
regulation:
➢Metabolic,Chemical,Humoral-
➢CMR-
➢ Anesthetics
➢ Temperature
➢ Arousal,seizures
➢Respiratory gas -PaCO2 and PaO2
➢Vasoactive drugs-
➢ Anesthetics
➢ Vasodilators
➢ Vasopressors
➢Myogenic
➢Autoregulation; MAP
➢Rheologic
➢Hematocrit or viscosity
➢Neurogenic
➢Extraaxial sympathetic and parasymapthetic pathways
17

18. • Changes in CMR, PaO2 & PaCO2 cause alteration in
cerebral biochemical environment  adjustment of
cerebral blood flow.
Cerebral metabolism rate
• Flow-metabolism coupling: Increased neuronal
activityincrease in local brain metabolism CMR
increases proportional increase in blood flow.
• Mechanism: Increased neuronal activityincrease
glutamate increased synthesis & release of
NO(potent vasodilator) increased CBF.
• Flow-metabolism coupling is mediated by a
combination of glial, neural & vascular factors.
18

19. CMR is influenced by
Functional state:Decreases during sleep/coma
Increases during sensory stimulation/injury/seizure
Anaesthetic drugs: Both inhalationals & IV in general decrease CMR
except Ketamine & N2O.
Administration of various anesthetics results in dose-related reduction
in CMRO2 and CBF. the max. reduction occurs with the dose that
results in electrophysiologic silence. At this point, the energy
utilisation a/w electrophysiologic activity has been reduced to zero,
but the energy utilisation for cellular homeostasis persists
unchanged.additional increase in dose cause no further decrease in
CBF and CMRO2 c/a “House keeping effect”.
Temperature: CMR decreases by 6-7 % per degree celsius fall in
temperature.
19

20. •
20

21. • The normal contents of cranium are:
1.Brain~neural tissue+ interstitial fluid~1500g.
2.Blood~75ml.
3.CSF~75ml; 7-18cm H2O (5-15 mm Hg)
• Intracranial pressure is pressure within the cranial
cavity exerted by the intracranial contents( viz 1,2 & 3).
•Munro Kellie Doctrine: Because each of these
components is relatively incompressible the combined
volume at any given time must be constant
21

22. • Intracranial elastance- is
determined by
measuring the changes
in ICP in response to a
change in intracranial
volume
• Normally small ↑ in one
component are initially
well maintained.
• A point is eventually
reached, at which
further rise produce
precipitous rise in ICP

23. Myogenic autoregulation
• Ability of cerebral circulation to maintain CBF constant over a wide
range; MAP~70-150 mm Hg.
• Above & below CBF pressure dependant; varies linearly with CPP.
• Changes in CPPdirect change in tone of vasular smooth muscles.
• ↑ MAP Cerebral vasoconstriction
• ↓ MAP Cerebral vasodilatation
• Reductions in cerebral blood flow  vasoactive substance
release(H+, K+, O2, adenosine) from the brain arterial dilatation.
• Abolished by hypercapnia /arterial hypoxemia/ volatile anaesthetics
/area surrounding acute infarction.
• Pressures above 160mmHg Disrupts BBB, cause Cerebral edema
and Haemorrhage.
23

24. Changes in cerebral blood flow (CBF) caused by independent alterations in
PaCO2, PaO2, and mean arterial pressure (MAP
24

25. • Absent ( Vasomotor paralysis )
– brain trauma/ acute ischemia
– surgical retraction
– Mass lesions
– Inflammation
– Prematurity
– Neonatal asphyxia
– high ICP
– Seizures
– Diabetes Mellitus
• Shift to right
– Systemic hypertension : In Hypertensive persons autoregulatory range
shifts to higher pressure levels : 180 – 200mm Hg
– States of sympathetic activation
– May suffer cerebral ishemia during hemorrhahypotension or shock.
• Shift to left
– Volatile anesthetic agents
25

26. NEUROGENIC
• The extracranil sympathetic fibers arise mainly from the superior
cervical ganglion
• The extra cranial parasympathetic from the sphenopalatine and otic
ganglia
• Sensory fibers from the trigeminal ganglion.
• SYMPATHETIC
• Large & Medium sized arteries normally overridden by autoregulation.
• Historically thought to have no role in cerebral circulation
• Comes into play in states of excessive circulatory activity / pathologic
states.
• Role in prevention of cerebral h’ge – cerebral vasospasm
26

27. 27

28. • CBF varies directly with Paco2.
• CBFchanges 1-2ml/100gm/min for each 1mmhg change in paco2 around normal values.
• This response is attenuated a paco2 less than 25mmhg.
• The sensitivity of CBF to changes in paco2 is positively correlated with resting levels of CBF.
• Changes in CBF apparently depandent on pH alterations in the ECF of the brain.
• Neuronal origin, NO and prostaglandins play the role of mediator in hypercapnia induced
vasodilation.
• A patient who has had sustained period of hyperventilation or hypoventilation deserves special
consideration. Acute restoration of a normal paco2 will result in significant CSF acidosis(after
hypocapnia) or alkalosis (after hypercapnia).
• CBF returns to normal in 6-8 hrs (as a result of extrusion of HCO3).
Paco2
28

29. 29

30. 30

31. 31

32. PaO2
• Changes in PaO2 from 60 to more than 300 mmHg have little
influences on CBF.
• Less than a PaO2 of 60 mmHg rapidly increases CBF,
mechanisms mediating cerebral vasodilation include
neurogenic effects initiated by peripheral and neuraxial
chemoreceptors and humoral influences.
• Hemoglobin saturation falls from ~100% at PO2 >70 mmHg to
~50% at PO2 <50 mmHg.
• Hypoxia drop in ATPKATP channels on smooth muscle
open hyperpolarization & vasodilation.
32

33. •Hypoxia more nitric oxide & adenosine
production locally promoting vasodilation.
Chronic hypoxia increases cerebral blood flow
through an effect on capillary density.
Unlike response to PaCO2, response to PaO2 is a
threshold phenomenon(CBF starts to increase
once PaO2 falls below 50 mm Hg and at PaO2 30
mmHg it doubles)
33

34. HAEMATOCRIT
Fall in haematocrit fall in
viscosity  Rise in CBF
Increased haematocrit
Increased viscosityFall
in CBF
In patients with focal
cerebral ischemia -
>Optimal haematocrit –
30% to 34%

35. TEMPERATURE
• CBF changes 5- 7%
per OC change in
temp.
• Hypothermia ↓ CBF
& CMR
• Pyrexia has reverse
effect

36. Effect of catecholamines
agonsits/antagonists on CBF and
CMR
36

37. 37

38. Effects of anesthetic
agents on CBF
38

39. 39

40. IV Induction agents
• Intravenous anesthetics reduce CBF in a dose dependent
fashion
• coupled to the reduction in metabolism
• Once maximal suppression of metabolism occurs, no
further reduction in CBF occurs
40

41. 41

42. BARBITURATES
• Barbiturates cause maximal 50% reduction in CBF and
metabolism; additional doses does not further ↓CMR.
• CO2 reactivity is maintained but is quantitatively
reduced compared to the awake response.
42

43. Barbiturates
• ‘Gold standard’ protectant among anesthetics.
• As it decreases the CMRO2 > CBF .so that increasing ratio of O2 supply to demand
.
• Selectively decrease the energy requirements for synaptic transmission only.
• Barbiturates induced vasoconstriction occurs only in normal areas⇢Redistribution
of regional cerebral blood flow and shunt blood from normal areas to ischemic
areas(Robin Hood or Reverse Steel Phenomenon -the cerebral vasculature in
ischemic areas maximally dilated and is less affected by barbiturates because of
ischemic vasomotor paralysis)
• Decrease in ICP, cerebral edema and CSF secretion
• It prolongs the brain tolerance for injury or prevent infarction altogether.
• Suppression of seizures

44. Propofol
• Propofol produces a coupled dose dependent
reduction in CMRO2 and CBF
• High doses vasodilator effect overcomes the coupling
& CBF increases
• Both CO2 responses and auto regulation are
maintained intact in the normal brain
• In head injury patients static auto regulation may be
impaired by high propofol infusion rates
44

45. Etomidate
• Reduces CMRO2 (50%)
• ↓CBF and ICP and CBV
• Maintains cardiovascular stability and CPP
• Drawbacks- myoclonus movements and suppression of
adrenal cortical activity

46. ketamine
• Dilates the cerebral vasculature and increases CBF ( 50 –
60%)
• Increases in CBF, CBV, CSF volume can increase ICP
markedly in patients with decreased IC compliance.
46

47. Effects of anesthetic drugs on CBF
VOLATILE AGENTS
• Volatile agents – dose dependent dilatation of cerebral vessels
• Impair auto regulation
• Response to CO2 retained
• May increase cerebral blood volume
• May result in elevated ICP
• Altered coupling of CMR and CBF but do not uncouple i.e. ↓ in CMR
>↑CBF c/a ‘luxury perfusion’ -beneficial in global ischemia but detrimental
in focal (circulatory steal phenomenon -volatile can ↑blood flow in normal
areas of the brain, not in ischemic areas, where arterioles maximally
dilated →redistribution of blood away from ischemic to normal areas)
47

48. • Volatile aesthetics
posses intrinsic
vasodilator property.
• At 0.5 MAC →CMR
suppression action
>>vasodilate
effect→CBF ↓.
• At 1 MAC→CBF
remains unchanged.
• At beyond 1 MAC →
Vasodilatory effect
predominates.

49. 49

50. 50

51. Halothane
• Has greatest effect on CBF
• Conc.> 1% - abolishes auto regulation
• Generalized increase in CBF
• At equivalent MAC, CBF increase up to 200%
• Prior hyperventilation to be initiated
Isoflurane
• CBF is ↑ by 19% and CMR ↓by 45% at 1.1 MAC
• ↑ CSF absorption.
• Better than all other volatile anesthetics.
Sevoflurane and Desflurane
• Almost similar to isoflurane ↑ in CBF by 38% and
22% and ↓ CMR by 39% and 35% respectively.

52. Nitrous oxide
• When administered on its own- increases both CBF and
metabolism.
• when added to a background of another anesthetic, it
increases CBF without changing metabolism
• It is a direct acting and potent cerebral vasodilator
52

53. CSF dynamics
• Halothane ↓ secretion of CSF ↓absorbation
• Isoflurane has no effect on secretion and ↑ absorption
• Enflurane and ↑ secretion ↓ absorption
• Desflurane ↑ secretion and no effect on absorption
• Etomidate ↓secretion and ↑absorbtion
53

54. Cerebral ischemia
Ischemic Penumbra
• Electrically silent but physiologically active
• Potentially salvageable

57. Cerebral protection
• Methods to reduce the effect of cerebral ischemia
and damage, in order to improve neurological
outcome.
• It can be achieved by -
1. pretreatment/prevention
2. Treatment- during or after ischemia to minimize
neuronal damage
3. resuscitation-
57

58. Strategies for protection
1. Maintain adequate O2 supply and CPP
2. Prevent/Rise in ICP
3. Reduce CMRO2
4. Reducing cell damage

63. maintain CPP and O2 supply
1. Maintain normotension
2. Keep CVP 5-10cm H2O
3. Reduce ICP with head elevation 15-30 degree
4. Consider inotrpoes
5. Hypotension and hypoxia s/b avoided.
6. Surgical decompression- craniotomy, or csf drainage by ventriculostomy
catheter
7. Steroids
8. Maintain euglycemia

64. Reduce /preventing rise in
ICP
1. mannitol/ frusemide
2. Fluid restriction
3. IPPV/ Hyperventilation- aim to maintain Paco2 between 30-35
mmhg to prevent hypercapnia
4. ICP reduces by 30% per mmhg reaction in co2
5. Prevent hypoxia- cytotoxic cell edema
6. Acute restoration of normal Paco2 value will result in significant
CSF acidosis after prolonged hypocapnia/hyperventilation →↑CBF
→↑ICP .

65. Reduce CMRO2
1. Hypothermia
2. Barbiturates
3. Anticonvulsants- phenytoin or diazepam
4. Muscle relaxants- avoid pancuronium and sucinylcholine
5. Adequate analgesia

66. Reduce cell damage
1. Avoidance of hyperglycaemia
2. Calcium channel blocker- nimodipine
3. Free radical scavanger e.g..barbiturates ,vita C and vita E
4. Glutamate and NMDA receptor antagonist

67. Other modalities under
evolution
• Xenon -Inert gas xenon exerts its anesthetic action by noncompetitive
blockade of NMDA receptors.Neuroprotection against exitotoxic injury.
• Free radical scavenger
• Preconditioning - Erythropoietin
• Nitric oxide
• Heat shock protein
• Oestrogen
• Bile acid

68. Thank you