Brain Protection 12-03-2013 A.N.Hamdy
Download
Report
Transcript Brain Protection 12-03-2013 A.N.Hamdy
Brain Protection
Ahmad N. Hamdy, MD
Objectives (IOLs)
1
Cerebral physiology
2 Explain cerebral ischemia
Strategies to protect the brain from
3 cerebral ischemia
4
Algorithm for brain protection
Cerebral Physiology
BRAIN 1350 gm- 2% of total adult body
wt
Receives 12 to 15 % of cardiac output
Global cerebral blood flow 45-55ml/100
gm / min
Cortical
75-80ml /100gm/min
Subcortical
20ml /100gm/min
Cerebral Physiology
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)
Factors Influencing CBF
Chemical/Metabolic /Humoral
Cerebral metabolic rate
Anaesthetics
Temperature
PaCO2 (20-80 mmHg)
PaO2
Vasoactive drugs - Anaesthetics,Vasodilators,
Vasopressors
Myogenic / Autoregulation
Blood viscosity
Neurogenic
Company Logo
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
Cerebral Ischemia
GLOBAL
• Cardiac arrest
• Resp. Failure
• Shock
• Hypoglycemia
• Asphyxia
FOCAL
• Head injury
• Vascular
Stenosis
• Occlusion
• Spasm
Biochemical & Pathophysiological
changes
Inadequate blood flow
↓↓O2 delivery
Ischaemia
Excitotoxic
cell death
Apoptotic
cell death
Inflammation
Strategies for Brain Protection
CMRO2
Oxygen
Glucose
Specific
Strategies
CBF&CPP
Future concepts
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
Ischaemic Injury
Hypo
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 postischemic 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
Company Logo
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
↑ of EPO in CNS
↓glial markers
of cerebral
injury
(S 100)
↓ infarct
size &
improved
recovery
Astrocytes in ischaemic penumbra produces
EPO in mammalian brain
Stimulates protein
of repair
↓↓neural
excitotoxicity
Stimulates
neurogenesis &
angiogenesis
↓neural
apoptosis
↓inflammatoin
Magnesium
Membrane stabilizer
Suggested 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
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
Specific
• CCBs
• Na CBs
• NMDA
antagonist
Future
• NO
• Cerebral
preconditioning
• Apoptosis
Add your company slogan