2. CEREBRAL PERFUSION PRESSURE: (CPP)
CPP = difference b/w mean arterial pressure
(MAP) and intracranial pressure (ICP) or central
venous pressure (CVP) , whichever is greater.
MAP – ICP (or CVP) = CPP
Normally CPP = 80- 100 mm Hg
ICP normally is ≤ 10 mm Hg, so , CPP depends
primarily on MAP
3. CEREBRAL PERFUSION PRESSURE: (CPP)
Moderate to severe ↑ ICP (≥ 30 mm Hg) - impairs
CPP and CBF even in presence of normal MAP.
CPP ≤ 50 mm Hg – slowing on EEG
CPP 25 - 40 mm Hg – flat EEG
CPP ≤ 25 mm Hg – irreversible brain damage
4. SOME FACTS…….
Adult human brain weighs approx : 1350 gm
about 2% of body weight
Cranial vault – rigid structure with a fixed total volume
Brain Tissue (80 %)
Blood (12%)
CSF (8%)
Receives 12-15% of cardiac output
Reflects brain’s high metabolic rate
5. Intracranial compliance
• increase in volume are initially well
compensated.
• Later a point is eventually reached, at
which precipitous rises in ICP occurs.
6.
7. Importance of the effect of anaesthetic
drugs on ICP
• Most of the neurosurgery cases have ↑ ICP.
• Various compensatory mechanisms are
exhausted.
• Small change in cerebral volume produces large
change in ICP.
8. Features of raised ICP
• Headache
• Vomiting
• Visual disturbance
• Decreased cognition
• Bradycardia
• Hypertension
• Irregular respiration
• unconsciousness
• Coma
9. CEREBRAL BLOOD FLOW:
Varies with metabolic activity
CBF can vary from 10 -300ml/100 g/min
Total CBF: on an average 50 ml/100g/min OR
750ml/min
Approx 15% of total cardiac output
Gray matter: 80ml/100g/min
White matter:20ml/100g/min
CBF < 20 – 25 ml/100 g/min - cognitive impairment
CBF < 15 – 20 ml/100 g/min - isoelectric EEG
CBF < 1o ml/100 g/min – irreversible brain damage
11. CEREBRAL METABOLISM:
Normally brain consumes- 20% of total body O₂
60% - to support neuronal activity
to generate ATP’S
Cerebral metabolic rate (CMR) measured in terms of
O₂ consumption (CMRO₂)
Approx 3- 3.8mL/100g/min OR 50mL/min
Greatest in gray matter of cerebral cotrex
12. CEREBRAL METABOLISM:
high O₂ consumption & absence of significant O₂ reserves
So, interrurption of perfusion → unconsciousness
within 10 sec (as O₂ tension falls below 30 mm hg)
Within 3-8 min: (if blood supply not re- established)
ATP stores deplete
Irreversible cellular injury begins to occur
HIPPOCAMPUS
CEREBELLUM most sensitive to hypoxic injury
13. AUTOREGULATION:
Normally, brain tolerates wide swings in BP
Cerebral vasculature adapts rapidly (10-60 sec) to change in
CPP.
But , abrupt changes in MAP, even with intact autoregulation,
lead to transient changes in CBF.
↓ CPP- cerebral vasodilation
↑ CPP- cerebral vasoconstriction
CBF nearly remains constant b/w MAP of about 60- 160 mm
Hg
beyond these limits, CBF becomes pressure dependent
MAP ↑ 150-160 mm Hg – disruption of BBB & cerebral
edema
15. RESPIRATORY GAS TENSIONS:
Most imp. extrinsic influences on CBF – esp. PaCO₂
CBF directly propotional to PaCO₂ b/w tensions of 20-80
mm Hg
CBF changes 1-2 ml/100g/min/mmHg change in PaCO2.
Change occurs very quickly – almost immediate
Results from CO₂ readily crossing BBB
Acute changes in PaCO₂, but not HCO3,⁻affect CBF
So, acute metabolic acidosis- little effect on CBF
Chronic Changes (24 – 48 hrs) offset by HCO3⁻ in CSF.
16.
17. CSF:
21ml/hr or 500 ml/day
Total volume 150ml
CSF turnover 4-5 hrs
CSF formation is independent of ICP
CSF absorbtion is directly proportional to ICP and
inversely proportional to venous pressure
19. Anesthetic drugs cause dose-related and reversible
alterations in many aspects of cerebral physiology,
including CBF, cerebral metabolic rate (CMR), and
electrophysiologic function.
The effects of anesthetic drugs and techniques
have the potential to adversely affect the diseased
brain and conduct of the neurosurgical procedure
and are thus of clinical importance in patients with
neurosurgical disease.
20. The effects of general anesthesia on CBF and CMR
can be manipulated to improve both the operative
course and the clinical outcome of patients with
neurologic disorders.
22. INTRAVENOUS ANESTHETICS:
Generally, CMRO₂ and CBF decrease
KETAMINE is an exception.
Changes in CBF generally parallel those in CMR
Cerebral autoregulation and CO₂ responsivenes-
preserved with all agents
23. Increasing plasma concentrations cause progressive
suppression of EEG activity and a concomitant reduction
in CMR.
Increasing the plasma level beyond what is required to
first achieve suppression of the EEG results in no further
depression of CMR.
The component of CMR required for maintenance of
cellular integrity, the “housekeeping” component, is
unaltered by intravenous anesthetic drugs
24.
25. BARBITURATES:
4 major actions on CNS:
Hypnosis
Depression of CMR
↓ CBF, due to ↑ cerebral vascular resistance
Anticonvulsant activity
make thiopental ‘the most commonly used’ induction
agent in neuroanesthesia
Dose dependent reduction in CBF& CMR, until EEG
becomes isoelectric
max. reduction of nearly 50% is observed
26. BARBITURATES:
CMR reduction is uniform – throughout the whole brain
CMR decreased more than CBF
So, supply exceeds demand
barbiturate induced cerebral vasoconstriction occurs
only in normal areas
Vasculature in ischemic areas remain maximally
dilated & unaffected by barbiturates
Net result is : redistribution of blood flow
From normal to ischemic areas
Called as – ROBIN HOOD or REVERSE STEAL
phenomenon
27. Facilitate CSF absorption
Highly effective in lowering ICP
Autoregulation is maintained
CO2 responsiveness also persists.
Other possible actions:
Blockade of sodium channels
↓ intracellular calcium influx
Decrease ATP consumption
Scavenging/ suppression of free radical formation
Retardation of cerebral edema
Acc. To studies:
Effective in preventing brain injury during focal ,
but not, global ischemia
28. ABOUT METHOHEXITAL…
Myoclonic activity
Pts with seizures of temporal lobe- specifically at risk
Small doses activate seizure foci
Higher doses- anticonvulsant like thiopental
Used to activate seizure foci during cortical mapping
Myoclonic activity
Pts with seizures of temporal lobe- specifically at risk
Small doses activate seizure foci
Higher doses- anticonvulsant like thiopental
Used to activate seizure foci during cortical mapping
29. PROPOFOL:
Effects on CBF and CMR are quite similar to those of
barbiturates.
Reduce CMR vasoconstriction decrease CBF & ICP
Fentanyl + propofol ablates increase in ICP at
intubation
CO2 responsiveness preserved
Autoregulation preserved
Short elimination half life
Excessive hypotension & cardiac depression – in
elderly/ unstable pts can compromise CPP
30. PROPOFOL AND SEIZURE INCIDENCE:
dystonic & choriform movements, opisthotonus etc have
been reported with its use,
SYSTEMATIC STUDIES FAILED TO CONFIRM THAT
PROPOFOL IS PROCONVULSANT
Appears to be anticonvulsant in animals
32. ETOMIDATE :
Parallel reductions in CBF, CMR & ICP
Effect on CMR variable: more in cortex than brainstem
May be responsible for greater hemodynamic stability
in unstable pts.
↓ CSF production & ↑ absorption
Concerns …………
ADRENOCORTICAL
SUPPRESSION
33. ETOMIDATE :
High incidence of myoclonic movements
May precipitate generalized epileptic EEG activity in
epileptic patients..avoided here
Activate seizure foci and low doses used for intra op EEG
localization
When used in ECT longer seizures compared to
Thiopentone and Propofol
But used in refractory status epilepticus
34. OPIOIDS:
In general, little effects in normal brain
When occur, modest reduction in CBF& CMR, unless
PaCO₂ ↑ 2° to respiratory depression
Morphine, generally not considered optimal, due to poor
lipid solubility and prolonged sedation
35. FENTANYL & ALFENTANYL:
FENTANYL
modest reduction CBF & CMR in
quiescent brain
Larger reduction during arousal
ALFENTANYL
No significant changes
Small doses <50 mg/kg) can activate
seizure foci in pts with epilepsy
36. SUFENTANYL :
Either reduction or no change in CMR&CBF
But sometimes in pts with intracranial tumors:
Sudden precipitous fall in MAP decrease
in CPP autoregulation small increase in
ICP
So be cautious…..
37. REMIFENTANYL:
Low sedative doses cause minor increase in
CBF
Along with other anesthetics / higher doses
modest reduction or no change in CBF
38. BENZODIAZEPINES:
Modest reduction in CBF
The reduction attained is intermediate b/w that
caused by
opioids (modest)
barbiturates (substantial)
Midazolam preferred- short half life
Useful as anticonvulsant also
Remember they can produce
respiratory depression increase in paCO2
If we avoid this… BENZODIAZEPINES
appear safe
39. DROPERIDOL:
Little or no effect on CMR
minimally reduces CBF
Can cause abrupt fall in MAP vasodilation increase in
ICP (occasional)
When used with opioids as part of neuroleptic technique-
may cause prolonged sedation – UNDESIRABLE
40. KETAMINE:
Only IV agent to cause VASODILATAION ↑CBF
(50-60%)
Effect is regionally variable
limbic system & reticular formation are activated
Somatosensory & auditory areas are depressed
Total CMR doesn’t change
Seizure activity in thalamus and limbic area.
41. KETAMINE:
May impede absorption of CSF
↑CBF, CBV & CSF volume : ↑ ICP (potentially)
Better to avoid as sole agent…
Diazepam , Midazolam ,Isoflurane /N2O, Propofol
…. They blunt its effects
Reasonable to use it along with the above drugs…
cautiously
42. LIDOCAINE:
Reduce CMR, CBF & ICP, but to a lesser degree
Decreses CBF without other major hemodynamic
effects
membrane stabilizing effect of lignocaine also
reduces energy needs for membrane integrity
Rx & prevention of acute rise in ICP, also during
laryngoscopy , intubation & ETT suctioning
Risk of systemic toxicity and seizures – limit the
usefulness of repeated dosing
46. VOLATILE AGENTS & CMR:
↓ CMR- dose dependent
Max depression – isoflurane (about 50%)
Least effect – halothane (less than 25%)
No further decrease in reduction in CMR is observed once
EEG is isoelectric. (Unlike hypothermia)
Reduction in CMR – not uniform
Mainly in neocortex
47. VOLATILE AGENTS & CBF:
Dilate blood vessels & impair auto regulation - in a dose
dependent manner
Greatest effect – halothane
Conc >1%- nearly abolishes auto regulation
Blood flow increase - generalized throughout brain
At equivalent MAC – halothane ↑ CBF 200%, compared
to 20% for isoflurane.
Isoflurane increases blood flow mainly in subcortical ares &
hindbrain (unlike halothane)
Qualitatively & quantitatively – des/sevoflurane closest to
isoflurane
48. EFFECTS @ DIFFERENT MACs:
D o s e b e y o n d 1 M A C
CMR reduced; but vasodilatory
effect predominates
CBF increases
@ 1 M A C
CMR suppression = vasodilation CBF unchanged
@ 0 . 5 M A C
CMR suppression predominates So net CBF decreases
49.
50. VOLATILE AGENTS:
The vasodilator effect usually appear rapidly than the
effects on CMR.
The CBF also appears to be time dependent
Returns to almost normal after continued admn (2-5
hrs)
If antecedent lowering of CMR by drugs/disease, then
vasodilator effect may predominate
↑ in CBV (10-12%) generally parallels CBF
But relation is not necessarily linear
51. VOLATILE AGENTS & PaCO₂:
CO2 responsiveness of vasculature - preserved
Hyperventilation can therfore abolish/blunt the effects on
CBF
Timing is important
Effect is observed only if hyperventilation is initiated prior
to admn of halothane
In contrast, simultaneous hyperventilation with
iso/sevoflurane- can prevent ↑ in ICP
Hypocapnia most effective during isoflurane admn.
52. HALOTHANE:
CBF dramatic increase in CBF with a
simultaneous modest reduction in CMR
CMR suppression is less compared to other agents
↓ CMR with ↑CBF- termed as luxury perfusion
may be desirable during induced hypotension
Beneficial during global ischemia
53. HALOTHANE:
Circulatory steal phenomenon:
In setting of focal ischemia, ↑CBF in normal
areas of but not in ischemic areas- where
arterioles are already maximally vasodilated
End result- redistribution of blood away from
ischemic areas
54. ENFLURANE
CBF dramatic increase in CBF with a simultaneous
modest reduction in CMR
Potentially epileptogenic
hypocapnea potentiates this effect
Seizure activity elevate brain metabolism by as much as
400%
Will you prefer?
So avoid: if seizure predisposition
55. ISOFLURANE:
CBF increases CBF; but to a lesser extent
20% (halothane increases by 200%)
CMR decreases CMRO₂
maximal reduction is attained simultaneously with EEG
suppression (at clinically relevant 1.5-2.0 MAC)
1 MAC decrease CMRO2 by 25%
Max depression upto 50%
56. Distribution of CBF/CMR changes:
CBF increases are greater in subcortical and hindbrain
areas than neocortex
CMR suppression is greater in the neocortex than
subcortex
Isoflurane facilitates absorption and is the only volatile
agent with favorable effects on CSF dynamics.
Institution of hyperventilation :
Simultaneous, with its introduction can prevent increase
in ICP
57. SEVOFLURANE:
Reduce CBF
Reduce CMRO2
by 38% at 1 MAC
Max at EEG suppression at 1.5-2.0 MAC
Distribution in CBF
Reduction in cortex
Increase in cerebellum
Has small potential to evoke epileptiform activity
use with caution in patients with epilepsy
58. DESFLURANE:
Reduce CBF
Decrease CMRO2 by 22% @ 1 MAC
In general:
the effect of Isoflurane , Desflurane and Sevoflurane
on CBF are modest
59. SUMMARY OF VOLATILE AGENTS:
MAJOR IMPACT ON CBF/CBV & ICP OCCURS WHEN > 1 MAC
BECOMES SIGNIFICANT IF - INTRACRANIAL COMPLIANCE IS
ABNORMAL
HERE, BETTER TO USE A MAINLY IV TECHNIQUE – UNTIL OPENING
OF CRANIUM & DURA
NET VASODILATORY EFFECT OF ISO/DES & SEVO <HALOTHANE- SO
PREFER THE FORMER
ENFLURANE IS EPILEPTOGENIC & SLIGHT RISK WITH
SEVOFLURANE
CO2 REACTIVITY PRESERVED
60. NITROUS OXIDE:
When given alone: increase in CBF,CMR & ICP
(sympathoadrenal stimulating effect)
Effects easily overcome by other agents or
CO2
With IV agents: effect on CBF considerably reduced
With Volatile Agents: CBF increase is exaggerated
61. NITROUS OXIDE:
Vasodilator effect clinically significant in those with abnormal
intracranial compliance
so add IV agents
Surgical field persistently “tight”?
N2O may be a culprit????
should be avoided in cases, where a closed intracranial gas
space may exist
it can enter and expand it
62. NITROUS OXIDE:
CBF response to CO2 preserved
No uniform agreement reached on its
effect on CMR
65. NON DEPOLARIZING RELAXANTS:
Lack direct action, but have 2° effects
Main effect is via Histamine release
Cerebral vasodilation
increase ICP
Simultaneous ↓in systemic BP
histamine/ganglion blockade
↓ CPP
67. NDMR:
Pancuronium- large bolus : abrupt increase in
BP
if autoregulation defective - increase ICP
metabolite of atracurium- Laudanosine:
epileptogenic properties in trials
But” it appears highly unlikely that
epileptogenesis will occur in humans with
atracurium”
68. MESSAGE…. NDMR USE:
All are reasonable in I.C. hypertension
Avoid hypotension:
Metocurine/Atracurium/Mivacurium
Anticonvulsant drug decrease the effect of NDMR
69. SUCCINYLCHOLINE:
Increases ICP in lightly anaesthetized- small and
transient.
Possibly result of cerebral activation
Enhanced muscle spindle activity- Increases
metabolic rate and thus CBF
Prevention by:
Adequate dose of inducing agent- deep plane
Institute hyperventilation at induction
Defasciculating dose of non depolarizing NMBA
70. With normal autoregulation & intact BBB
CBF↑, only when MAP <50-60 mmHg or >150-
160 mm Hg
CMR generally parallels changes in CBF
Excessive elevation in BP can disrupt BBB
VASOPRESSORS:
71. VASODILATORS:
In absence of hypotension:
cause cerebral vasodilation and ↑CBF in a dose
related fashion
When the ↓ syetemic BP:
CBF either maintained or increases
Can significantly raise ICP in pt with ↓ intracranial
compliance
72. VASODILATORS:
Sodium nitroprusside is a direct-acting smooth
muscle relaxant that produces arteriolar and
venous dilatation, acts as cerebral vasodilator
Cerebral blood volume is increased and ICP may
be elevated.
It is best avoided if ICP is high.
73. VASODILATORS:
Nitroglycerin is primarily a venodilator and coronary
vasodilator
It acts by relaxing smooth muscle and works on the
intracerebral venous capacitance vessels.
It increases cerebral blood volume and may
increase ICP
74. VASODILATORS:
Propofol, lidocaine or labetalol should be preferred
instead.
Labetalol, a mixed α- and β- blocker, lowers MAP
by lowering systemic vascular resistance and
depressing cardiac output.
It has no direct effect on cerebral blood vessels.
75. VASODILATORS:
Only trimethaphan has no or little effect on CBF
But it constricts pupils
May interfere with neurological examination
No longer available in USA