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 33.8 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 2025 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 80100 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 150160 mm Hg can disrupt the bloodbrain barrier and
may result in cerebral edema and hemorrhage
12. Beyond these limits, blood flow becomes pressure dependent
.Pressures above 150160 mm Hg can disrupt the bloodbrain 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 12 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 57% per 1C 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 10C,
17. At 20C, the EEG is isoelectric, but further decreases in
temperature continue to reduce CMR throughout the brain. Above 42C,
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
24. 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
25. 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
26. 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
27. Signs of ICP CUSHINGSS 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
28. Assessment of Severity
29. 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. Principles Of Management 1. Position - neutral position -
head elevate to 30c to 45c. 2. Observation - vital sign, GCS and
pupillary changes. 3. Maintaining O2 / Ventilation - hyperventilate
~ keep PCO2 30 35mmHg - maintain PaO2 100mmHg with low PEEP
34. 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
35. 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.
36. 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.
37. 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%
38. 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
39. 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. 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
43. 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
44. 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
45. 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
46. 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
47. 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
48. 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
49. 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
50. 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
51. 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
52. 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
53. 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
54. VASOPRESSORS: o normal autoregulation - vasopressors
increase CBF only when MAP is below 5060 mm Hg or above 150160 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 bloodbrain barrier is disrupted. o central B1-receptor
stimulation increases CMR and blood flow.
55. 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
56. 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
57. 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
58. 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
59. 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
60. 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
