1. CEREBRAL BLOOD FLOW & ITS REGULATION
Dr. Shahnawaz.

2. INTRODUCTION
Cerebral circulation refers to the movement of blood through the network of blood vessels supplying the brain.
The amount of blood that the cerebral circulation carries is known as cerebral blood flow.

3. Blood supply of brain

4. WHY UNDERSTANDING OF CBF IMPORTANT?
Delivery of energy substrates is dependent on CBF, and in the setting of ischemia, modest alterations in CBF can substantially influence neuronal outcome
Control and manipulation of CBF are central to management of ICP because CBV and CBF usually vary almost in parallel fashion.
The magnitude of change in CBV is less than the magnitude of change in CBF ; for a given increase in CBF, the increase in CBV is considerably less.

5. CEREBRAL BLOOD FLOW: Varies with metabolic activity
CBF can vary from ml/100 g/min
Approx 15% of total cardiac output
Gray matter: 80ml/100g/min
White matter: 20ml/100g/min
Total CBF: on an average 50 ml/100g/min OR 750ml/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

6. FACTORS EFFECTING CBF:
Myogenic :
Autoregulation/ MAP (CPP)
Chemical/ Metabolic/ Humoral:
CMR – depends on : Anesthetic agents
Temperature & Seizures
PaCO₂
PaO₂
Vasoactive drugs: Vasopressors & vasodilators
Rheologic: Blood viscosity
Neurogenic : Extracranial sympathetic and parasympathetic pathways , Intra-axial pathways

7. 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 = mm Hg
ICP normally is ≤ 10 mm Hg, so , CPP depends primarily on MAP

8. 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 mm Hg – flat EEG
CPP ≤ 25 mm Hg – irreversible brain damage

9. 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 mm Hg
beyond these limits, CBF becomes pressure dependent
MAP ↑ mm Hg – disruption of BBB & cerebral edema

10. AUTOREGULATION:

11. AUTOREGULATION: Ex. H⁺, NO, adenosine, prostaglandins etc.
Autoregulation curve, in chronic hypertension – shifted to right
Flow more pressure dependent at low normal pressures
Long term antihypertensive Rx - restores cerebral autoregulation limits towards normal
Mechanism of autoregulation:
Myogenic- intrinsic response of smooth muscle cells in arterioles, to changes in MAP
Metabolic- tissue demand exceeds CBF → release of tissue metabolites determines arteriolar tone
Ex. H⁺, NO, adenosine, prostaglandins etc.

12. PaCO₂ : Most imp. extrinsic influences on CBF – PaCO₂
CBF directly proportional to PaCO₂ b/w tensions of mm Hg
Depends on pH changes in ECF of brain.
CBF changes 1-2 ml/100g/min/mmHg change in PaCO2.
Change is almost immediate
Results from CO₂ readily crossing BBB
The effect is not sustained
CBF normalises over 6 to 8 hrs
pH of CSF returns to normal due to adjustment in HCO3 .

13. PaCo2:
The CBF to changes in Paco2 appears to be positively correlated with resting levels of CBF.
Anesthetic drugs that alter resting CBF cause changes in the response of the CBF to CO2.
The magnitude of the reduction in CBF caused by hypocapnia is greater when resting CBF is high .
When resting CBF is low, the magnitude of the hypocapnia-induced reduction in CBF is decreased.

14. PaO₂ : Changes in PaO₂ B/W 60 – 300mm of Hg – Little influence on CBF.
Severe hypoxemia (PaO₂ < 60mm Hg) – profound ↑ in CBF
Hypoxia induced hyperpolarisation and
Neurogenic effects initiated by peripheral and central chemoreceptors.
Stimulation of the RVM by hypoxia results in an increase in CBF (but not CMR)
High PaO₂ values – ↓ CBF minimal.

15. Effect of chemical factor on CBF

16. TEMPERATURE: CBF changes 5-7% per 1° change in temp
Hypothermia decreases both CBF and CMR
Hyperthermia increases both CBF and CMR
EEG isoelectric at 20 °C
B/w 17°C - 37°C, Q10 for humans – approx 2
i;e for every 10 ° ↑ in temp – CMR doubles
Conversely, CMR ↓ by 50% , if temp of brain falls by 10
In contrast with anesthetic drugs, temperature reduction beyond that at which EEG suppression first occurs does produce a further decrease in CMR.

17. INTRACRANIAL PRESSURE: (ICP)
Monro-Kellie Doctrine:
“The Total Volume of Intracranial Contents Must Remain Stable”
↑ In one component - offset by equivalent ↓in another, to prevent rise in ICP

18. Increase in volume is initially well tolerated
Further increase cause precipitous ↑ ICP.
Major compensatory mechanisms include:
Displacement of CSF from cranium to spinal compartment
↓ CBV (primarily venous)
↑ CSF absorption
↓ CSF production

19. EFFECT OF ANESTHETIC AGENTS ON CEREBRAL PHYSIOLOGY

20. 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

21. 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

22. 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

23. PROPOFOL: Reduce CMR, CBF & ICP CO2 responsiveness preserved
Autoregulation preserved
Short elimination half life
Excessive hypotension & cardiac depression – in
elderly/ unstable pts can compromise CPP

24. 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

25. ADRENOCORTICAL SUPPRESSION
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

26. 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

27. 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

28. 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.

29. 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

30. LIDOCAINE: Reduce CMR, CBF & ICP, but to a lesser degree
Decreases CBF without other major hemodynamic effects
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

31. VOLATILE AGENTS….
Reduce CMR .
Cerebral vasodilation augment CBF

32. 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 areas & hindbrain (unlike halothane)
Qualitatively & quantitatively – des/sevoflurane closest to isoflurane

33. 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

34. EFFECTS @ DIFFERENT MACs:
CMR suppression predominates
So net CBF decreases
@ 1 MAC
CMR suppression = vasodilation
CBF unchanged
Dose beyond 1 MAC
CMR reduced; but vasodilatory effect predominates
CBF increases

35. 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

36. 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 administration of halothane
In contrast, simultaneous hyperventilation with iso/sevoflurane- can prevent ↑ in ICP

37. Altered Coupling of Cerebral Metabolic Rate & Blood Flow
Volatile agents alter but do not uncouple the normal relationship of CBF and CMR. The combination of a decrease in neuronal metabolic demand with an increase in CBF (metabolic supply) has been termed luxury perfusion.

38. In contrast to this potentially beneficial effect during global ischemia, a detrimental circulatory steal phenomenon is possible with volatile anesthetics in the setting of focal ischemia.
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.

39. NON DEPOLARIZING RELAXANTS:
Lack direct action, but have 2° effects
Main effect is via Histamine release
Cerebral vasodilation
increase ICP
d-Tubocurarine is the most potent histamine releaser among available muscle relaxants.
Metocurine, atracurium, and mivacurium also release histamine in lesser quantities.

40. 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”

41. SUCCINYLCHOLINE: Increases ICP in lightly anaesthetized
Possibly result of cerebral activation
Enhanced muscle spindle activity
Prevention by:
Adequate dose of inducing agent- deep plane
Institute hyperventilation at induction
Defasciculating dose of non depolarizing NMBA

42. VASOPRESSORS: With normal autoregulation & intact BBB
vasopressors ↑ CBF, only when MAP <50-60 mmHg or > mm Hg
In absence of autoregulation – vasopressors ↑ CPP → ↑ CBF.
β adrenergic agents → (+) central β-1 receptors → ↑ CMR and blood flow.
Show greater effect when BBB is disrupted.
β blockers have no effect on CMR or CBF
α2 agonists produce cerebral vasoconstriction.

43. VASODILATORS: In absence of hypotension:
cause cerebral vasodilation and ↑ CBF in a dose related fashion
When they ↓ systemic BP:
CBF either maintained or increases (d/t autoregulation)
Can significantly ↑ ICP in pt with ↓ intracranial compliance

44. VASODILATORS: Only trimethaphan has no or little effect on CBF
But it constricts pupils
May interfere with neurological examination
No longer available in USA

45. BLOOD VISCOSITY Hematocrit – most imp determinant of blood viscosity.
↑ Hct can reduce CBF.
↓ Hct → improve CBF in ischemic area
More obvious during focal cerebral ischemia
May ↓ the O2 carrying capacity of blood → impair O2 delivery (potentially)
A Hct of 30 – 34 % is optimal for patients with focal cerebral ischemia.

46. THANKYOU…