Cerebral circulation

and anaesthetic implications

Modreator-Dr Manoj Bharadwaj

Speaker-Dr Amlan Swain
www.anaesthesia.co.in

anaesthesia.co.in@gmail.com

Overview of cerebral circulation

Overview of cerebral circulation

Arterial supply

Posterior
Cerebral
artery
Anterior
Cerebral
artery
Middle
Cerebral
artery
Internal
Carotid
artery
(70% of CBF)

Basilar
artery
Vertebral
artery

30%
of
CBF

Overview of cerebral circulation

Circle of Willis

Anterior CA
Internal CA
Middle CA
Posterior CA
Basilar A

Vertebral A

Overview of cerebral circulation

Venous drainage

Cerebral Artery Areas

1. anterior cerebral

2. Middle cerebral

54

3. Penetrating branches
of middle cerebral
4. anterior choroidal

5. Posterior cerebral

Cerebral physiology
2% of BW
20% of Total body oxy consumption
(60% used for ATP formation)
CMR O2 3-3.8mL /100 gm/min
(50 ml /min in Adult)
15% 0f CO
Glucose consumption 5 mg/100gm/min
(25% of total body consumption/min)

.contd

High oxygen consumption but no reserve

Grey matter of cerebral cortex consumes more
Directly proportional to electrical activity
(Hippocampus & cerebellum most sensitive to
hypoxic injury)

NORMAL PHYSIOLOGIC VALUES

CBF
GLOBAL
CORTICAL
SUBCORTICAL
CMRO2

45-55ml/100g/min
75-80ml/100g/min
20ml/100g/min
3-3.5ml/100g/min

CVR
Cerebral venous Po2

2.1mmHg/100ml/min/ml
32-44mmhg

Cerebral venous So2

55%-70%

ICP(supine)

8-12mm Hg

Approximately 60 % of the brain's energy

consumption is used to support
electrophysiological function.
Remaining 40%-?

 Local CBF (l-CBF) and local CMR (lCMR) within the brain are very
heterogeneous, and both are
approximately four times greater in gray
matter than in white matter.

The brain's substantial demand for

substrate must be met by adequate
delivery of O2 and glucose.
However, the space constraints imposed
by the noncompliant cranium and
meninges require that blood flow not be
excessive.
Not surprisingly, there are elaborate
mechanisms for the regulation of CBF.

Cerebral perfusion pressure

MAPICP( or CVP whichever is greater)
Normally 80 to 100mm Hg
ICP is <10 mmHg so CPP primarily dependent
on MAP
Increase in ICP>30 =CPP & CBF compromise
CPP<50 slowing of EEG

25-40 Flat EEG

CPP <25 result in Irreversible brain death

Factors influencing CBF

CHEMICAL/METABOLIC
MYOGENIC
RHEOLOGIC
NEUROLOGIC

CHEMICAL/METABOLIC
CERBRAL METABOLIC RATE
Arousal/seizures
mental tasks
Anesthetics
Temperature
Paco2
Pao2
Vasoactive drugs
Anesthetics
Vasodilators
Vasopressors

Cerebral Metabolic Rate

Increased neuronal activity results in
increased local brain metabolism
Although it is clear that local metabolic
factors play a major role in these
adjustments in CBF, the complete
mechanism of flowmetabolism coupling
remains undefined.

 CMR is influenced by several

phenomena in the neurosurgical
environment
functional state of the nervous system
anesthetic agents, and
temperature

Functional State.
CMR decreases during sleep and
increases during sensory stimulation,
mental tasks, or arousal of any cause.
During epileptoid activity, CMR increases
may be extreme, whereas CMR may be
substantially reduced in coma.

Anesthetics.
In general, anesthetic agents suppress CMR
Ketamine and nitrous oxide the notable
exceptions.
It appears that the component of CMR on which
they act is that associated with
electrophysiologic function.
However, increasing the plasma level beyond
that required first to achieve suppression of the
EEG results in no further depression of CMR..

The interdependencyof cerebral

electrophysiologic function and CMR

Temperature.
CMR decreases by 6 to 7 percent per
Celsius degree of temperature reduction.
However, in contrast to anesthetic agents,
temperature reduction beyond that at
which EEG suppression first occurs does
produce a further decrease in CMR

The effect of temperature reduction on

the cerebral metabolic rate of oxygen

Temperature on CBF
6-7 % decrease /0C FALL IN TEMP.
37-42 0C >42 0C 20 0C

CBF & CMRO2

CMRO2

- ISOELECTRICITY

Partial Pressure of Carbon Dioxide

CBF varies directly with PaCO2
The effect is greatest within the range of
physiologic PaCO2 variation.
CBF changes 1 to 2 mL/100 g/min for
each 1 mm Hg of change in PaCO2around
normal PaCO2 values.
This response is attenuated below a Pa
CO2 of 25 mm Hg.

 The changes in CBF caused by PaCO 2 are

apparently dependent on pH alterations in
the extra cellular fluid of the brain
Note that in contrast to respiratory
acidosis, acute systemic metabolic
acidosis has little immediate effect on CBF
because the blood-brain barrier (BBB)
excludes the hydrogen ion from the
perivascular space.

 Although the CBF changes in response to

Pa CO2 alteration occur rapidly, they are
not sustained.
In spite of the maintenance of an elevated
arterial pH, CBF returns to normal over 6 to
8 hours because cerebrospinal fluid (CSF)
pH gradually normalizes as a result of the
extrusion of bicarbonate.

 Although the CBF changes in response to

Pa CO2 alteration occur rapidly, they are
not sustained.
In spite of the maintenance of an elevated
arterial pH, CBF returns to normal over 6
to 8 hours because cerebrospinal fluid
(CSF) pH gradually normalizes as a result
of the extrusion of bicarbonate.

. Acute normalization of PaCO 2 results in a

significant CSF acidosis (after hypocapnia)
or alkalosis (after hypercapnia).
The former results in increased CBF with a
concomitant intracranial pressure (ICP)
increase that will depend on the prevailing
intracranial compliance. The latter conveys
the theoretic risk of ischemia.

Steal Phenomenon
If local autoregulation is impaired and
PaCO2 increases, vessels in surrounding
normal brain will dilate.
Vessels in the abnormal area are already
maximally dilated due to loss of
autoregulation.

Vascular resistance will be decreased in

surrounding normal brain; blood will be
shunted away from abnormal areas,
resulting in further hypoxia

Inverse Steal or Robin Hood

Phenomenon
Opposite may occur as PaCO2 is
decreased by hyperventilation.
Vessels in surrounding normal brain will
vasoconstrict; vessels in the damaged or
abnormal area of brain are already
maximally dilated and are unable to
constrict.

Because of the vasoconstriction in normal

brain, vascular resistance increases,
shunting blood into the abnormal area

Partial Pressure of Oxygen

Changes in PaO2from 60 to more than
300 mm Hg have little influence on CBF.
When the PaO2is less than 60 mm Hg,
CBF increases rapidly .
At high PaO2values, CBF decreases
modestly.

The mechanisms mediating the cerebral

vasodilation during hypoxia are not fully
understood, but they may include
neurogenic effects initiated by peripheral
and/or neuraxial chemoreceptors as well
as local humoral influences
At 1 atm O2,CBF is reduced by 12
percent.

Myogenic Regulation (Autoregulation)

Autoregulation refers to the capacity of
the cerebral circulation to adjust its
resistance in order to maintain CBF
constant over a wide range of mean
arterial pressure (MAP).

In normal human subjects, the limits of

autoregulation occur at MAPs of
approximately 70 and 150 mm Hg
Above and below the autoregulatory
plateau, CBF is pressure dependent
(pressure passive) and varies linearly with
CPP.

Autoregulation Curve shift to Rt in

Chronic hypertensive
Decreased CPP Leads to vasodilation
Increased CPP leads to vasoconstriction

The precise mechanism by which

autoregulation is accomplished is not
known.
NO may participate in the vasodilation
associated with hypotension in some
species, but not, according to a single
study, in primates

Neurogenic Regulation
There is considerable evidence of
extensive innervation of the cerebral
vasculature.
The density of innervation declines with
vessel size, and the greatest neurogenic
influence appears to be exerted on larger
cerebral arteries.

This innervation includes autonomic,

serotonergic, and vasoactive intestinal
peptide-ergic (VIPergic) systems of extraaxial and intra-axial origin.

Viscosity Effects
Blood viscosity can influence CBF.
Hematocrit is the single most important
determinant of blood viscosity.
In healthy subjects, hematocrit variation
within the normal range (33-45%) probably
results in only trivial alteration of CBF.
Beyond this range, changes are more
substantial.

EFFECTS OF ANESTHETIC AGENTS

ON CBF AND CEREBRAL METABOLIC
RATE
In neuroanesthesia, considerable
emphasis is placed on the manner in
which anesthetic agents and techniques
influence CBF.
The rationale is 2-fold.

First, the delivery of energy substrates is

dependent on CBF, and, in the setting of
ischemia, modest alterations in CBF can
substantially influence neuronal outcome.

 Second, the control and manipulation of

CBF are central to the management of
ICP because, as CBF varies in response
to vasoconstrictor-vasodilator influences,
such as Pa CO2 and volatile anesthetics,
CBV varies linearly with it
Autoregulation normally serves to prevent
MAP-related increases in CBV

 In healthy subjects, the initial increases in

CBV do not result in significant ICP
elevation because there is latitude for
compensatory adjustments by other
intracranial compartments
When intracranial compliance is reduced,
a CBV increase can cause herniation or
may reduce CPP sufficiently to cause
ischemia.

There have been several investigations of the

effects of anesthetic agents on CBV in normal
brain.
In general, the observed effects confirm a
parallel relationship between CBF and CBV.
However, the relationship is not consistently one
to one, and CBF-independent influences on
CBV may occur.

Anesthetic agents may influence the

venous side of the cerebral circulation.
At present, there is no evidence that these
direct effects have clinical significance.

Nonetheless, the importance of blood

volume on the venous side of the cerebral
circulation should not be overlooked.
Passive engorgement of these vessels as
a result of the head-down posture,
compression of the jugular venous
system, or high intrathoracic pressure can
have dramatic effects on ICP

Intravenous Anesthetic Agents

The general pattern of the effect of
intravenous anesthetic agents is one of
parallel alterations in CMR and CBF.
Most intravenous agents cause a
reduction of both.
Ketamine, which causes an increase in
CMR and CBF, is the exception.

Barbiturates
A dose-dependent reduction in CBF and CMR
occurs with barbiturates.
With the onset of anesthesia, CBF and CMR are
reduced by about 30 percent.
When large doses of thiopental cause complete
EEG suppression, CBF and CMR are reduced
by about 50 percent.
Further increases in the dose of barbiturate have
no additional effect on CMR

Propofol
The effects of propofol (2,6-di-isopropylphenol)
on CBF and CMR appear to be quite similar to
those of the barbiturates.
Three investigations in humans have revealed
substantial reductions in both CBF and CMR
after propofol administration.
Both CO2 responsiveness and autoregulation
appear to be preserved during the administration
of propofol in humans

Narcotics
There are inconsistencies in the available
information, but it is likely that narcotics
have relatively little effect on CBF and
CMR in the normal, unstimulated nervous
system.
When changes occur, the general pattern
is one of modest reductions in both CBF
and CMR.

Morphine.
When morphine (1 mg/kg) was
administered as the sole agent in human
patients, Moyer et al observed no effect
on global CBF and a 41 percent decrease
in CMRO2 .
There have been no other such
investigations of morphine alone in
humans.

Fentanyl.
Limited human data are available
Several investigations in lightly anesthetized
animals demonstrated much larger fentanylinduced reductions in CBF and/or CMR than
those observed in humans.
These data taken together suggest that fentanyl
causes a moderate global reduction in CBF and
CMR in the normal quiescent brain and, like
morphine, causes larger reductions when
administered during arousal.

Benzodiazepines
.The extent of the maximal CBF and CMR
reductions produced by benzodiazepines is
probably intermediate between the decreases
caused by narcotics (modest) and barbiturates
(substantial).
It appears that benzodiazepines should be safe
to administer to patients with intracranial
hypertension provided respiratory depression
and an associated increase in Pa CO2 do not
occur.

Ketamine
Among the intravenous agents, ketamine
is unique in its ability to cause increases in
both CBF and CMR
In the only investigation of CMR effects in
humans, Takeshita et al observed a 62
percent increase in CBF and no change in
CMR, and the explanation for this
discrepancy is unclear.

The anticipated ICP correlate of the CBF

increase has been confirmed to occur in
humans.
However, anesthetic agents (diazepam,
midazolam, isoflurane/N2 O) have been
shown to blunt or to eliminate the ICP or
CBF increases associated with ketamine

Accordingly, although ketamine is

probably best avoided as the sole
anesthetic agent in patients with impaired
intracranial compliance, it may be
reasonable to use it cautiously in patients
who are simultaneously receiving the
other agents mentioned earlier.

Lidocaine
Lidocaine produces a dose-related
reduction of CMRO2 in experimental
animals.
In unanesthetized human volunteers,
Lam et al observed CBF and CMR
reductions of 24 and 20 percent,
respectively

Changes in (CBF) and the (CMRO2 )

caused by I V agents

Volatile Anesthetics
The pattern of volatile agent effects on
cerebral physiology is a striking departure
from that observed with the intravenous
agents, which cause generally parallel
changes in CMR and CBF.
All the volatile agents produce a doserelated reduction in CMR while
simultaneously causing no change or an
increase in CBF.

effect of increasing concentrations of a

typical volatile anesthetic on
autoregulation of cerebral blood flow

It has been said that volatile agents cause

"uncoupling" of flow and metabolism.
It is probably more accurate to say that
the CBF/CMR ratio is altered (increased)
by volatile anesthetics.

The important clinical consequences of

volatile agent administration are derived
from the increases in CBF and CBV, and
consequently ICP, that can occur.
Of the commonly employed volatile
agents, the order of vasodilating potency
is approximately halothane >> enflurane >
isoflurane = sevoflurane = desflurane.

CMR Effects
All the volatile agents cause reductions in
CMR.
The degree of CMR reduction that occurs
at a given MAC level is less with
halothane than with the other four agents

With isoflurane (and almost certainly

desflurane and sevoflurane as well),
maximal reduction is attained
simultaneously with the occurrence of
EEG suppression.
This occurs at clinically relevant
concentrations, that is, 1.5 to 2.0 MAC in
humans

Estimated changes in (CBF) and the

(CMRO2 )caused by volatile
anesthetics.

Distribution of CBF/CMR Changes.

The regional distribution in anestheticinduced changes in CBF and CMR differs
markedly with halothane and isoflurane.
Halothane produces relatively
homogeneous changes throughout the
brain.
CBF is globally increased, and CMR is
globally depressed.

 The changes caused by isoflurane are

more heterogeneous.
CBF increases are greater in subcortical
areas and hindbrain structures than in the
neocortex
For CMR, the converse is true, with
greater reduction in the neocortex than in
the subcortex.

Cerebral Vasodilation by Volatile

Agents: Clinical Implications.
Isoflurane and, probably, desflurane and
sevoflurane may have little cerebral
vasodilating effect in cortex, they
nonetheless probably cause net cerebral
vasodilation in a dose-dependent fashion.
Are isoflurane and desflurane and
sevoflurane therefore contraindicated in
the face of abnormal intracranial
compliance? No

Instances of ICP increases in response to

the administration of isoflurane observed
in the studies of Adams et al and Campkin
et al were usually readily prevented or
reversed by the induction of hypocapnia.

This indicates that, particularly in the subMAC concentrations typical of balanced

anesthesia, the use of these drugs is
reasonable when there is proper attention
to the other important determinants of ICP,
in particular CO2 tension.

CO2 Responsiveness and

Autoregulation
CO2 responsiveness is well maintained during
anesthesia with all the volatile anesthetic agents.
By contrast, autoregulation of CBF in response
to rising arterial pressure is impaired.
This impairment appears to be most apparent
with the agents that cause the greatest cerebral
vasodilation, and it is dose related

Nitrous Oxide
The available data indicate unequivocaly
that N2O can cause increases in CBF,
CMR, and ICP.
When N2O is administered alone, very
substantial increases in CBF and ICP can
occur
.

The addition of N2 O to an established

anesthetic with a volatile agent results in
moderate CBF increases.
in combination with intravenous agents,
including barbiturates, benzodiazepines,
narcotics, and propofol, its cerebral
vasodilating effect is attenuated or even
completely inhibited.

Clinical Implications.
The data indicate that the vasodilatory
action of N2O can be clinically significant
in neurosurgical patients with reduced
intracranial compliance.
However, it appears that N2O induced
cerebral vasodilation can be considerably
blunted by the simultaneous
administration of intravenous agents

 Nonetheless, when ICP is persistently

elevated or the surgical field is persistently
"tight," N2O should be viewed as a
potential contributing factor.
In addition, the ability of N2O to enter a
closed gas space rapidly should be
recalled, and this drug should be avoided
or omitted when a closed intracranial gas
space may exist.

Effect of volatile anesthetics on

cerebral blood flow

Effect of volatile anesthetics on the

cerebral metabolic rate of oxygen

Nondepolarizing Relaxants
The only recognized effect of
nondepolarizing relaxants on the cerebral
vasculature occurs via the release of
histamine.
Histamine can result in a reduction in CPP
because of the simultaneous increase in
ICP (caused by cerebral vasodilation) and
decrease in MAP

d-Tubocurarine is the most potent

histamine releaser among available
muscle relaxants.
Metocurine, atracurium, and mivacurium
also release histamine in lesser quantities.
Vecuronium, in relatively large doses 0.1
to 0.14 mg/kg, had no significant effect on
cerebral physiology

Succinylcholine
Succinylcholine can produce an increase
of ICP in lightly anesthetized human
patients.
?

Effect appears to be the result of cerebral

activation (as evidenced by EEG changes
and CBF increases) caused by afferent
activity from the muscle spindle apparatus.
Note, however, that there is a poor
correlation between the occurrence of
visible muscle fasciculations and an
increase in ICP. .

Although succinylcholine can produce ICP

increases, it need not be viewed as
contraindicated when its use for rapid
attainment of paralysis is otherwise seen
as appropriate

Critical CBF Levels and the Ischemic

Penumbra Concept
In the face of a declining O2 supply,
neuronal function deteriorates
progressively
It is not until CBF has fallen to
approximately 22 mL/100 g/min that EEG
evidence of ischemia begins to appear.

At a CBF level of approximately 15

mL/100 g/min, the cortical EEG is
isoelectric.
CBF is reduced to about 6 mL/100 g/min indications of potentially irreversible
membrane failure (elevated extracellular
potassium ) and loss of the direct cortical
response rapidly evident.

 As CBF decreases in the flow range between

15 and 6 mL/100 g/min, a progressive
deterioration of energy supply occurs, leading
eventually, to membrane failure and neuronal
death.
The brain regions falling within this CBF range
(6-15 mL/100 g/min) are referred to as the
"ischemic penumbra"--a region within which the
neuronal dysfunction is temporarily reversible
but within which neuronal death will occur if flow
is not restored

Relationships between cerebral

perfusion, (CBF), (EEG)&viability of
neurons.

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