This document discusses mechanisms of cerebral injury and cerebral protection. It provides details on cerebral physiology including metabolism, blood flow, regulation of blood flow, and factors that influence blood flow such as perfusion pressure, autoregulation, respiratory gas tensions, temperature, viscosity, and autonomic influences. It also discusses intracranial pressure, signs of increased ICP, assessment of injury severity, and strategies and principles for cerebral protection including maintaining oxygen supply and reducing increases in ICP, cerebral metabolic rate, and cell damage. The effects of various anesthetic drugs on cerebral blood flow, metabolism, and injury are also summarized.

1. Presentor : Dr . Kumar
Moderator :
Dr.Prabhavathy
Mechanism
s of
cerebral
injury
&
Cerebral
protection

2.  “ PHINEAS GAGE “
 first reported case
of personality
change after brain
injury

3. Definition
 “damage to the brain resulting from external
mechanical force, such as rapid acceleration
or deceleration, impact, blast waves, or
penetration by a projectile”

4. Cerebral physiology
 CEREBRAL METABOLISM:
1. brain is normally responsible for consumption of
20% of total body oxygen.
2. Most of cerebral oxygen consumption (60%) is
used in generating adenosine triphosphate (ATP)
to support neuronal electrical activity
3. The cerebral metabolic rate (CMR) is usually
expressed in terms of oxygen consumption
(CMRO2), which averages 3–3.8 mL/100 g/min
(50 mL/min) in adults

5.  high oxygen consumption and the absence of
significant oxygen reserves, interruption of cerebral
perfusion usually results in unconsciousness.
 The hippocampus and cerebellum appear to be
most sensitive to hypoxic injury.

6.  CEREBRAL BLOOD FLOW:
1. CBF varies with metabolic activity.
2. It is most commonly measured with a -emitting
isotope such as xenon (133Xe).
3. total CBF averages 50 mL/100 g/min,
4. flow in gray matter is about 80 mL/100 g/min,
5. white matter is estimated to be 20 mL/100
g/min.
6. Total CBF in adults averages 750 mL/min (15–
20% of cardiac output

7. If CBF is altered
 20–25 mL/100 g/min - cerebral impairment
 15 and 20 mL/100 g/min - flat (isoelectric) EEG
 10 mL/100 g/min - irreversible brain damage.

8. REGULATION OF CBF
 Intrinsic mechanisms
a) Cerebral perfusion pressure
b) Auto regualtion
 Extrinsic mechanisms
a) Respiratory Gas tensions
b) Temperature
c) Viscosity
d) Autonomic influences

9. Cerebral perfusion pressure
 It is the difference between mean arterial pressure
(MAP) and intracranial pressure (ICP) (or central
venous pressure [CVP], whichever is greater).
MAP – ICP (or CVP) = CPP.
 CPP is normally 80–100 mm Hg
 Moderate to severe increases in ICP (> 30 mm Hg)
can significantly compromise CPP and CBF even in
the presence of a normal MAP

10.  CPP values
1. less than 50 mm Hg - slowing on the EEG,
2. 25 and 40 mm Hg - flat EEG.
3. less than 25 mm Hg - irreversible brain damage.

11. Autoregulation
 the brain normally tolerates wide swings in blood
pressure with little change in blood flow.
 changes in MAP will lead to transient changes in
CBF
 Normal MAP - 60 and 160 mm Hg
 Beyond these limits, blood flow becomes pressure
dependent
 Pressures above 150–160 mm Hg can disrupt the
blood–brain barrier and may result in cerebral
edema and hemorrhage

12.  Beyond these limits, blood flow becomes pressure
dependent
 .Pressures above 150–160 mm Hg can disrupt the
blood–brain barrier and may result in cerebral
edema and hemorrhage

13. Myogenic and Metabolic mechanisms
 Myogenic mechanisms involve an intrinsic response
of smooth muscle cells in cerebral arterioles to
changes in MAP
 Metabolic mechanisms indicate that cerebral
metabolic demands determine arteriolar tone.
 when tissue demand exceeds blood flow, the release
of tissue metabolites causes vasodilation and
increases flow

14. Respiratory Gas Tensions
 PaCO2 and PO2
 CBF is directly proportionate
to PaCO2 between tensions of
20 and 80 mm Hg
 Blood flow changes 1–2
mL/100 g/min per mm Hg
change in PaCO2.
 effect is almost immediate
and is due to secondary to
changes in the pH of CSF and
cerebral tissue.

15.  Only marked changes in PaO2 alter CBF.
 hyperoxia may be associated with only minimal
decreases (–10%) in CBF
 severe hypoxemia (PaO2 < 50 mm Hg) profoundly
increases CBF

16. Temperature
 CBF changes 5–7% per 1°C change in temperature.
 Hypothermia decreases both CMR and CBF,
whereas pyrexia has the reverse effect.
 for every 10° increase in temperature, the CMR
doubles.
 the CMR decreases by 50% if the temperature of the
brain falls by 10°C,

17.  At 20°C, the EEG is isoelectric, but further decreases
in temperature continue to reduce CMR throughout
the brain.
 Above 42°C, oxygen activity begins to decrease and
may reflect cell damage

18. Viscosity
 Normally, changes in blood viscosity do not
appreciably alter CBF.
 The most important determinant of blood viscosity
is hematocrit.
 A decrease in hematocrit decreases viscosity and
can improve CBF.
 a reduction in hematocrit also decreases the
oxygen-carrying capacity and thus can potentially
impair oxygen delivery.

19.  Elevated hematocrits with marked polycythemia,
increase blood viscosity and can reduce CBF.
 Some studies suggest that optimal cerebral oxygen
delivery may occur at hematocrits of approximately
30%.

20. Autonomic Influences
 Intracranial vessels are innervated by sympathetic
(vasoconstrictive), parasympathetic (vasodilatory),
and noncholinergic nonadrenergic fibers
 serotonin and vasoactive intestinal peptide appear
to be the neurotransmitters .
 Innervation of large cerebral vessels by
sympathetic fibers originating in the superior
cervical sympathetic ganglia.

21.  Intense sympathetic stimulation induces marked
vasoconstriction in these vessels, which can limit
CBF.
 Autonomic innervation play an important role in
cerebral vasospasm following brain injury and
stroke.

22. Pathophysiology of Brain
Injury
 Two types of brain injuries
 Primary Brain Damage :
Irriversible damage
2 types;
-Focal-Direct impact of skull
into brain causing contusion,
laceration, or hemorrage.
-Diffuse-Difused axonal injury
due to internal shearing,
streaching tearing forces

23.  Secondary Brain Damage
 Factors that causing ischaemia and further brain
damage.
Potentially reversible-role of cerebral protect
-Hypoxia
-Hypotension
-Hypercarbia
-Cerebral edema-cytotoxic/vasogenic
-Herniation

26. INTRACRANIAL PRESSURE
 The cranial vault - fixed total
volume
 brain (80%), blood (12%), and
CSF (8%)
 increase in one component
must be offset by an equivalent
decrease in another to prevent
a rise in ICP

27. compensatory mechanisms
 (1) an initial displacement of CSF from the cranial
to the spinal compartment,
 (2) an increase in CSF absorption,
 (3) a decrease in CSF production, and
 (4) a decrease in total cerebral blood volume
(primarily venous

28. Monro- Kelly Doctrine
 The intracranial Volume is fixed apart from some
minimal ‘give’ due to meninges and foremina
60% fliuds; 40% solid
 All the structures are incompressible for practical
purpose
Increase in the volume one of the compartment must
be buffered by others( spartial compensation)
 Later-Increase in volume within cranium lead to rapid
increase in pressure(elastance)
Raise ICP---reduce CPP
Reduce CPP---Cerebral ischaemia---Infraction ---
Brain death

29. Signs of ICP
 CUSHINGS’S TRIAD
a slow heart rate with high blood
pressure and respiratory
depression is a classic
manifestation of significantly
raised ICP.
 Anisocoria, unequal pupil
size, is another sign of serious
TBI
 Abnormal posturing, a
characteristic positioning of the
limbs caused by severe diffuse
injury or high ICP, is an

30. Assessment of Severity

31. Cerebral Protection
 Methods attempt to reduce the effects of Cerebral
Ischaemia and damage, in order to improve
neurological out comes
 Protective measures before the second insults.
 Possible neuronal recovery after period of
ischaemia Brain must be ‘protected’ from such
insult

32. Strategies :
1.Maintained adequate O2 supply-CPP & PaO2
2.Reduce/prevent raise in ICP
3.Reduce CMRO2
4.Reducing cell damage

33. Indications…
1.Post successful CPR
2.Post carotid Cerebral Protection artery surgery
3.Head injury
4.Compression - Tumour,hematoma
eg : Subdural Hematoma/Intraparenchymal.
5.Inflammatory – Meningitis.
6.Metabolic encephalopathies eg : Reyes Syndrome.
7.CVA / Cerebral haemorrhage

34. Principles Of Management
1. Position
- neutral position
- head elevate to 30°c to 45°c.
2. Observation
- vital sign, GCS and pupillary changes.
3. Maintaining O2 / Ventilation
- hyperventilate ~ keep PCO2 30 – 35mmHg
- maintain PaO2 100mmHg with low PEEP

35. 4. Control Blood Pressure
- maintain MAP ~ 70 – 100mmHg
- maintain adequate cerebral perfusion pressure
(CPP)
CPP = MAP – ICP
5. Diuretics
- osmotic diuretic ( Mannitol 20% )
- loop diuretic ( Frusemide )
6. Fluid Therapy
- control fluid therapy ~ avoid hypovolemia
- use Normal Saline or Hartmann

36. 7. Prevent Isometric Exercise
- eg: give IV Fentanyl before suctioning or any
procedure
8. Steroids
eg. Dexamethasone
- for brain tumour
- reduce cerebral oedema
9. Treatment Of Epilepsy
eg. Diazepam or Phenytoin
- control seizures to reduce cerebral metabolic rate

37. 10. Temperature Control
- maintain normothermia and avoid hyperpyrexia
11. Calcium Antagonist ( Nimodipime )
- for subarachnoid haemorrhage to reduce
cerebral spasm
12. Surgery
- to remove mass or lession
eg. Craniotomy,evacuation of clot,CSF drainage.

38. 13. Nutrition
- early enteral feeding ~ high nutrient and protein
( to prevent infection )
14. Electrolytes
- regular monitoring of
electrolytes,urea,creatinine,blood sugar,
osmolality are important to determine fluid and
electrolyte
therapy.

39. Maintain CPP & O2 supply
Subject to CPP=MAP-ICP and O2 Content
1. Maintain normotension,
2. Keep CVP 5-10 cm H2O
3. Reduce ICP-Head up 15-30 deg. with neutral
position
Consider inotropes
4. No PEEP
5. Hypotension & hypoxia significantly increase
mortality and morbidity
6. Hypotension profoundly increase mortality up to
150%

40. Reduce @ preventing Rise in
ICP
 -Reduce cerebral edema/ICF
1. Mannitol, frusemide
2. Fluid restriction -2/3 maintenance
3. IPPV /hyperventilation;Aim To maintain pCO2
between 30-35mmHg to prevent
hypercapnia(Cereb.Steal Synd)
4. ICP reduces by 30% per 10mmHg reduction in
CO2
5. Prevention hypoxia-cytotoxic cerebral edema
6. Acute change in hyperventilation return to normal
value after 48H, normalise CSF pH and

41. 7. Surgical decompression - craniotomy
8. Normothemia/hypothermia at 35 C Reduce
CMRO2
9. CSF Drainage-via ventriculostomy catheter
10. Encourage venous drainage-head at 15-30 deg
& neutral position
11. Steroids
12. hyperglycaemia- to start insulin

42. Reduce CMRO2
1. Normothermia@Hypothermia
2. Barbiturate/sedation
3. Anticonvulsants phenytoin , Diazepam
4. Muscle relaxants-avoid pancuronium, succinyl
choline
5. Adequate Analgesia

43. Reduce cell damage
1. Avoidance of hyperglycaemia
2. Ca2+ channel blocker-nimodipine
3. Free radical scavanger ie barbiturate,Vit C,E
4. Glutamate and NMDA receptor antagonist

44. Effect of Anaesthetic Drugs
 Barbiturates :
 Barbiturates have four major actions on the CNS:
(1) hypnosis,
(2) depression of CMR,
(3) reduction of CBF due to increased cerebral vascular
resistance, and
(4) anticonvulsant activity

45. o principally to suppression of CMR
o Barbiturate-induced EEG suppression
o effects of CBF redistribution and free radical
scavenging have been suggested to contribute,
and there is evidence that CMR suppression is
not the sole mechanism
o various barbiturates (thiopental, thiamylal,
methohexital, pentobarbital) have similar effects
on CMR and have generally been assumed to
have equal protective efficacy

46.  Benzodiazepines:
o Benzodiazepines cause parallel reductions in
CBF and CMR
o CBF and CMRO2 decreased by 25% when 15 mg
of diazepam was given to head-injured patients
o effects of midazolam on CBF (but not CMR)
o Increase in CSF absorption , Decreases CBV &
ICP

47.  VOLATILE ANESTHETICS:
o Isoflurane - a potent suppressant of CMR in the
cerebral cortex, and EEG evidence suggestive of a
protective effect in humans
o More recent data have shown that long-term
neuroprotection with isoflurane is achievable under
conditions in which the severity of ischemia is limited
and restoration of blood flow after ischemia is
complete
o Sevoflurane reduces ischemic injury
o Desflurane also reduces neuronal injury to the same
extent that isoflurane

48.  Isoflurane, on the other hand, facilitates absorption and is therefore
the only volatile agent with favorable effects on CSF dynamics
 circulatory steal phenomenon :
“Volatile agents can increase blood flow in normal areas of the brain but
not in ischemic areas, where arterioles are already maximally
vasodilated. The end result may be a redistribution of blood flow away
from ischemic to normal areas.”
 net effect of volatile anesthetics on ICP is the result of immediate
changes in cerebral blood volume, delayed alterations on CSF
dynamics, and arterial CO2 tension

49.  Propofol :
o EEG suppression can also be achieved with
clinically feasible doses of propofol
o Durable protection with propofol is achievable if the
severity of the ischemic insult is mild
o cerebral infarction was significantly reduced in
propofol-anesthetized
o propofol reduce ischemic cerebral injury

50.  ETOMIDATE
o It too produces CMR suppression to an extent
equivalent to barbiturates.
o administration of etomidate results in greater tissue
hypoxia and acidosis
o aggravation of injury produced by etomidate (an
imidazole) may be related to direct binding of NO as a
consequence of etomidate-induced hemolysis .
o combined with direct inhibition of the NO synthase
enzyme by etomidate.
o no scientific support for the current use of
etomidate for “cerebral protection”

51.  OPIOIDS :
o opioids generally have minimal effects on CBF, CMR, and
ICP, unless PaCO2 rises secondary to respiratory
depression
o hypotension Significant decreases in blood pressure
adversely affect CPP regardless of the opioid selected
o Normeperidine, a metabolite of meperidine, can induce
seizures, cardiac depression

52.  Ketamine:
o dilates the cerebral vasculature and increases CBF (50–
60%)
o Ketamine may also impede absorption of CSF without
affecting formation
o Seizure activity in thalamic and limbic areas is also
described
o Increases in CBF, cerebral blood volume, and CSF volume
can potentially increase ICP markedly in patients with
decreased intracranial compliance

53.  CALCIUM CHANNEL BLOCKERS
o administer nimodipine orally beginning as soon
as possible after subarachnoid hemorrhage.
o it has not yet become standard practice to
administer nimodipine or any other calcium
channel blocker routinely after neurologic stroke
o stroke victims have confirmed the benefits of
nimodipine

54.  XENON:
o inert gas xenon exerts its anesthetic action by
noncompetitive blockade of NMDA receptors
o neuroprotection against excitotoxic injury
o simultaneous administration of subanesthetic doses
of xenon in combination with either hypothermia or
isoflurane significantly reduces neuronal injury and
improves neurologic function
o specific use of xenon for the purpose of
neuroprotection awaits results from outcome studies

55.  LIDOCAINE:
o Intravenous lidocaine decreases CMR, CBF, and ICP but
to a lesser degree than other agents.
o decreases CBF (by increasing cerebral vascular
resistance) without causing other significant
hemodynamic effects.
o The risks of systemic toxicity and seizures, however,
limit the usefulness of repeated dosing

56.  VASOPRESSORS:
o normal autoregulation
- vasopressors increase CBF only when MAP is below
50–60 mm Hg or above 150–160 mm Hg.
o absence of autoregulation:
-vasopressors increase CBF by their effect on CPP. Changes
in CMR generally parallel those in blood flow
o Adrenergic agents have a greater effect on the brain when
the blood–brain barrier is disrupted.
o central B1-receptor stimulation increases CMR and blood
flow.

57.  Neuromuscular Blocking Agents:
o lack direct action on the brain but can have important
secondary effects
o Hypertension and histamine-mediated cerebral vasodilation
increase ICP, while systemic hypotension (from histamine
release or ganglionic blockade) lowers CPP.
o Succinylcholine can increase ICP, result of cerebral
activation associated with enhanced muscle spindle activity
o increases in ICP following administration of an NMBA are the
result of a hypertensive response due to light anesthesia
during laryngoscopy and tracheal intubation

58.  OSMOTIC DIURETICS:
 First line treatment to decrease high ICP
 Induce plasma expansion
i. Reduced hematocrit
ii. Reduced plasma viscosity
iii. Reduced CBV
iv. Mobilization of ECF
 Early high does of mannitol shown to improve long
term outcomes

59.  MAGNESIUM:
o Membrane stabilizer
o Suggested protective mechanism:
 Reduction of presynaptic release of glutamate
 Blockade of NMDA receptors
 Smooth muscle relaxation
 Improved mitochondrial Ca2+ buffering
 Blockage of Ca2+ entry
o Protection depends on:
 Time of treatment initiation
 Type of cerebral ischemia

60.  STEROIDS:
o Suggested protective mechanisms:
1. Increase lipid bilayer
2. Free radical scavenging
3. Reduces cerebral edema
4. Anti-inflammatory effects
5. Prevents FFA accumulation
6. Inhibits lipid peroxidation
o Not shown to decrease morbidity of mortality in
acute cerebral ischemia
o Not recommended for head trauma
o Methylprednisolone: mild benefits in acute spinal
cord injury

61. EFFECTS OF TEMPERATURE
 Hypothermia
o Reduce CMR in a temperature-dependent fashion
o Mild hypothermia(32-35℃) ; negliable effect on CMR
o But, in several studies mild hypothermia produce major
protection ; meaningful neuroprotection
o Deep hypothermia(18-22℃) ; highly neuroprotective
o In normothermic brain ; only a few minutes of
complete global ischemia cause neuronal death
o In deep hypothermia before circulatory arrest ; brain
can tolerate over 40 min and completely or near-
completely recover

62. To be Monitored..
 Haemodynamic; CVP,MAP, CPP
 Haematological ; PCV 35-40
 Oxygenation; Above 60mmHg
 Ventilation ; CO2 30-35mmHg
 Temperature;
 -BUSE
 I/O chart
 ICP; keep less than 20mmHg
 EEG-2 parietal electrodes
 Other organ function