Effects of anesthetics on cerebral blood flow

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

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

Intracranial compliance
• increase in volume are initially well
compensated.
• Later a point is eventually reached, at
which precipitous rises in ICP occurs.

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.

Features of raised ICP
• Headache
• Vomiting
• Visual disturbance
• Decreased cognition
• Bradycardia
• Hypertension
• Irregular respiration
• unconsciousness
• Coma

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

FACTORS EFFECTING CBF:
1. Chemical/ metabolic/ humoral:
1. CMR – depends on :anesthetic agents
temperature & seizures
2. PaCO₂
3. PaO₂
4. Vasoactive drugs: vasopressors & vasodilators
2. Myogenic :
1. Autoregulation/ MAP
3. Rheologic: blood viscosity
4. Neurogenic

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

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

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

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.

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

EFFECT OF ANESTHETIC AGENTS
ON CEREBRAL PHYSIOLOGY

 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.

 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.

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

 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

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

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

 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

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

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

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

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

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

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

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

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…..

REMIFENTANYL:
 Low sedative doses cause minor increase in
CBF
 Along with other anesthetics / higher doses 
modest reduction or no change in CBF

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

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

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.

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

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

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

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

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

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

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

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.

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

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

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

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%

 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

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

DESFLURANE:
 Reduce CBF
 Decrease CMRO2 by 22% @ 1 MAC
 In general:
the effect of Isoflurane , Desflurane and Sevoflurane
on CBF are modest

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

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

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

NITROUS OXIDE:
 CBF response to CO2 preserved
 No uniform agreement reached on its
effect on CMR

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

NON DEPOLARIZING RELAXANTS-
HISTAMINE RELEASE
Cisatracurium:
Least
Also :metocurine
atracurium
mivacurium
D-tubocurarine

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”

MESSAGE…. NDMR USE:
 All are reasonable in I.C. hypertension
 Avoid hypotension:
Metocurine/Atracurium/Mivacurium
 Anticonvulsant drug decrease the effect of NDMR

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

 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:

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

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.

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

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.

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

REFERENCES
MILLER’S ANESTHESIA,6/e
ANESTHESIA &COEXISTING
DISEASE,4e
WYLIE & CHURCHILL DAVIDSONS’
APRACTICE OF ANESTHESIA
TEXTBOOK OF NEUROANESTHESIA
AND CRITICAL CARE Basil F. Matta,
David K. Menon, John M. Turner

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