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Effect of anesthetic drugs and techniques on CBF and CMR . Dr Prashant Kumar. University College of Medical Sciences & GTB Hospital, Delhi. Rationale . Why should we know the effect of anesthetic agents on CBF & CMRO2? CBF - Continuous delivery of energy substrates is dependent on CBF. ↓

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effect of anesthetic drugs and techniques on cbf and cmr

Effect of anesthetic drugs and techniques on CBF and CMR

Dr Prashant Kumar

University College of Medical Sciences & GTB Hospital, Delhi


Why should we know the effect of anesthetic agents on CBF & CMRO2?

  • CBF

- Continuous delivery of energy substrates is dependent on CBF.

can influence neuronal outcome (particularly during ischemia).

- CBF & CMR : important etiology of cerebral ischemia

  • CBF ≈ICP
intravenous anesthetic drugs
Intravenous anesthetic drugs

All IV Induction Agents (except ketamine)

GABAA receptor agonist

Opening of Cl- channel

Inhibition neuronal transmission

  • Ketamine acts as antagonist on excitatory NMDA receptor
Globally all IV Induction Agents (except ketamine)
  • reduction in CBF & CMR
  • Slowing of surface EEG

► Deep Level: Burst suppression pattern

► Extremely deep level: Isoelectric pattern

Ideal IV anesthetic drugsfor use in neuro anaesthesia
  • Rapid recovery of consciousness
  • Easily & rapidly titrable
  • Minimal effects on other organ systems
  • Analgesia
  • Non-epileptogenic (or even anti-epileptogenic)
Advantageous effects on cerebral hemodynamics:

►Reduction of CMR coupled with a decrease in CBF

►no increase in ICP (or even reduction in ICP)

► prevention of increase in CBV

►maintenance of cerebrovascular auto regulation

►maintenance of vasoreactivity to CO2

  • Antagonist at NMDA receptor
  • Limited use
  • In neuroanesthesia: -

► Increase in CBF (but not when used with other sedatives or in a brain injured pts)

► Increase in ICP (but not when used with other sedatives or in a brain injured pts)

► Increase in CMR (particularly in Limbic structures)

► Cerebral protection via NMDA antagonism in animals

Commercially available ketamine

►(S) enantiomer → ↑ in CMR

►(R) enantiomer → ↓in CMR, particularly in temporomedial cortex & in cerebellum

Anesthetic drugs (diazepam, midazolam, propofol, isoflurane) have been shown to blunt or eliminate ↑ in ICP effect of ketamine.

  • Uses in neuroanesthesia:-

► Premedication

►Limited use as induction agent

► Sedation in ICU (Head injury patients in whom hypothermia is being used)

Effects in neuroanesthesia:-

► Modest decrease in CBF

► modest decrease in CMRO2

► modest decrease in ICP

► maintains autoregulation

► Preserves vasoreactivity to CO2

► Increases seizure threshold – used as antiepileptic

► Antidote (flumazenil) is available

  • Highly specific, competitive benzodiazepine antagonist
  • Reverses the CBF, CMR, ICP lowering effects of BZD.
  • Analgesia

Potentiates the cardiovascular effects of hypnotics (so, with moderate dose of opioids, reduce the dose of hypnotics)

Stable haemodynamics during induction

  • Increased parasympathetic tone (large dose: Bradycardia)
Attenuation of pressure response because of ET intubation, suction, skull pin application.
  • Improved intra-op hemodynamics with rapid emergence.
  • Profound synergism b/w resp depressant action of opioid & hypnotics
Cerebral hemodynamics

► Modest reduction in CBF & CMRO2

► No effect on ICP (if MAP is maintained)

► Autoregulation : maintained

► Cerebral vasoreactivity to CO2 maintained

► EEG changes depends on dose (small dose: minimal change)

Other concerns with regard to neuro anaesthesia: -
  • Opioids underused in peri-op period

► fear of sedation, pupillary changes, nausea, cough suppression

Inspite of studies showing that morphine does not ↑S/E

  • Nausea & vomiting: rare after propofol-remifentanyl anesthesia
Impaired gastric emptying
    • constipation
    • Ileus
  • Large intra-op dose: delayed emergence
  • Modest reduction in CBF
  • Reduction in CMR
  • CBV: ↑ (histamine release)
  • ICP:

►No Change if MAP is maintained

►↑ 2º to autoregulatory vasodilatation after reduction in MAP

  • Moderate to large global reduction in CBF & CMR


  • No change in CBF, CMR, CBV, ICP.


  • No change or slight reduction in CBF & CMR (depending on doses)
  • ICP ↑ if MAP decreases
  • In low dose: minor ↑in CBF
  • Higher doses or with other anesthetic adjuvant

CBF unaltered or modest reduction

  • No change in ICP
  • Used in TIVA
  • Dose related reduction in CMR & CBF
  • Membrane stabilizing effect: ↓ CMR
  • In bolus dose (1.5-2mg/kg): adjunct to the prevention or treatment of ↑ICP.
  • Lidocaine (1.5mg/kg) Vs thiopentone (3mg/kg)→ equal reduction in ICP [more ↓in MAP with thiopentone ]
total intravenous anesthesia
Total intravenous anesthesia
  • Use of IV inducing agents with opioids for maintenance of anesthesia: popular
  • Propofol @3-12mg/kg/hr - suited for prolonged infusion
  • Blood target level of propofol

4-6μg/ml for induction

2-4μg/ml for maintenance

  • Ideal for use in addition to propofol for maintenance of anesthesia.
  • Maintenance dose 0.05 to 0.5μg/kg/min


  • Administered by TCI (for both induction & maintenance)
    • Improved hemodynamics, especially during induction- beneficial in neurosurgery
muscle relaxants
Muscle relaxants


  • Recent studies: SCh causes drug induced↑ICP (independent of other events)
  • Modest ↑in ICP (5mmHg) in lightly anesthetized humans
    • In deep anesthesia: no ↑ in ICP
  • Mechanism of ↑ ICP
    • Due to cerebral activation
    • Afferent activity from the muscle spindle apparatus

Although poor correlation between the occurrence of visible muscle fasciculation & ↑ in ICP is seen

Prevention of SCh induced ↑ ICP:-
  • Deep plane of anesthesia
  • Precurarization
    • Vecuronium (0.01-0.014mg/kg)
    • metocurine (0.03mg/kg)
    • Effect of other defasciculating drugs has not been studies in human
Does that mean SCh is C/I In Neurosurgery?
  • Probably NOT
    • Change in ICP is modest & transient
    • ↑ in ICP: not seen in head injured pts

Little reason to avoid SCh when rapid paralysis is required

  • Extra-ordinary benign effect on CBF & ICP [except large dose of d-TC ]:
    • ↑ed CBF & ICP through release of histamine
  • Interaction with phenytoin & other anti-convulsant:
    • ↑ dose required
    • ↓ duration of action
In presence of neurological deficit
    • Resistance to NDMR.
    • So, overdose & difficulty with reversal of anaesthesia.
  • Effect of histamine on intact BBB is not clear

►direct cerebral vasodilation

►2̊ (autoregulation) response to a reduction in MAP

D—TC is most potent histamine releaser: ↑ ICP
  • Metocurine, atracurium & mivacurium: lesser histamine release.
  • Cis-atracurium: least histamine releasing effect. No histamine release @ dose 0.15mg/kg (3 times ED95 for twitch suppression)
  • Vecuronium @ 0.1-0.14mg/kg: no significant effect on cerebral physiology
Pipecuronium & rocuronium: No human study but should be similar.
  • Pancuronium
    • In large doses, ↑in BP
    • ↑in ICP in Pts with impaired intracranial compliance & defective autoregulation
  • Laudanosine - crosses BBB, & is epileptogenic in animals


    • But highly unlikely in Humans
volatile anesthetics
Volatile anesthetics

Common Effects:-

  • All ↓ MAP
    • ↓ in CPP [ dose dependent manner ]
  • CBF & CMRO2
    • Direct vasodilation
    • ↓ cerebral activity

↓CMR (reduced need for substrate)

associated vasoconstriction (which balances vasodilation)

At > 0.6 MAC, vasodilatory effects predominate:- ↑ CBF
    • ↑ CBF in face of ↓in CMR : UNCOUPLING
  • Autoregulation
    • >0.5 MAC: Impaired autoregulation
        • Blood flow passively follow BP
        • Making ischemia or luxury perfusion with edema or hemorrhage more likely
Cerebrovascular response to PaCO2: Maintained
  • Slowing of EEG

Halothane > enflurane > desflurane= isoflurane > sevoflurane

nitrous oxide
Nitrous Oxide
  • Alone: stimulatory effect
    • ↑ CBF, CMR & ICP
    • Sympatho-adrenal stimulating effects

So, CMR may ↑ or ↓ or no change

  • N2O with IV anesthetics or hypocapnia:
    • No change in CBF (vasodilatory effects of N2O is attenuated/even completely inhibited)
N2O with volatile anesthetics:
    • Synergism b/w N2O & other volatile anesthetics
    • ↑in CBF: ↑ ICP
    • Ideally should not be used in pts with ↑↑ ICP.
  • Autoregulation: Maintained
  • Should be avoided in pneumocephalus
  • Inert gas
  • MAC: 63-71%, females lower MAC: 51%
  • At MAC 1:
    • CBF: cortex ↓ 15%, cerebellum ↓35%, white matter ↓22%
    • CMR ↓26%
ICP is maintained.
  • Cerebral autoregulation: Intact
  • CO2 reactivity: maintained
  • Diffusion of xenon into air containing spaces occur (less than N2O)
  • Use of xenon in NS: not evaluated,

but data suggests a favorable profile for neuroanesthesia

other drugs used in neuro surgical patients
  • Diuretics
  • Steroids
  • Antihypertensive


  • Mainstay of hyperosmolar therapy
  • Free radical scavenging property
  • Lack of toxicity
  • Very low irritant property
How does it reduces ICP?
    • Osmotic diuretics effect: ↓ in ICP
    • Rheological effect :↓ Blood viscosity→↑ CBF→autoregulatory vasoconstriction →↓ ICP
  • Dose: 0.25-1gm/kg (slow iv. over 10-15 minutes)
  • Neurotrauma guidelines
    • 20% mannitol
    • @ 2ml/kg
    • Pts with clinical signs of brain herniation & neurological deteoration
Combined with loop diuretics: maintains osmotic gradient

Fluid from brain parenchyma


Blood vessel


Renal excretion of fluid

  • Side effects :
    • Mild hyponatremia & hypokalemia
    • Rapid IV→ extreme hyperosmolarity→ cerebral vasodilation→ ↑ICP
  • Beneficial in primary & secondary brain tumor
    • Stabilize BBB
    • ↑ CSF absorption

↓ICP (onset 48-72 hours)

  • No role in traumatic brain injury
use of antihypertensive drugs in neurosurgery
Use of antihypertensive drugs in neurosurgery

- Obtundation of vasopressor response during laryngoscopy, incision or during extubation

Why optimization of BP is must before neurosurgery?

Sudden hypertensive episode

↓(Disturbed cerebral autoregulation)


Intra-cranial hemorrhage

Direct acting vasodilators
  • Drugs: SNP, GTN, hydralazine
  • MOA - Smooth muscle relaxation
    • Vasodilation
        • ↑CBF & ↑ICP
        • ↓ CPP
    • Steal phenomenon
  • Clinical Implication:
    • Caution with the use of these drugs
    • Drugs withdrawn cautiously (reduce risk of rebound HTN)
Adrenergic antagonist
  • Labetalol
    • Commonly used
    • α:β = 1:7
    • Advantages:
      • ↓in MAP without any ↑ ICP
      • CPP is better maintained
    • Agent of choice for obtundation of vasopressor response in NS
  • Esmolol
    • Ultra-short acting
    • Rapid onset & offset
    • Short half life
Calcium channel blocker
  • Little use in hypertensive emergency
    • Because of long duration of action
    • Potential to cause cerebral vasodilation
Effect of techniques on

cerebral physiology

factors influencing cbf during ga
Factors influencing CBF during GA
  • PaO2
  • PaCO2
  • CMR

- arousal/pain

- seizure

- temperature

- anesthetics

Use of Vasoactive drugs

- anesthetics

- vasodilators

- vasopressors

  • BP & state of Autoregulation
  • Rheogenic/ Blood viscosity
general anesthesia technique
General anesthesia technique
  • Premedication
    • Heavy premedn: inappropriate (pt already drowsy)
    • Apprehensive pts: small dose BZP
    • Spinal surgery (painful): analgesia
    • Hypoxia & hypercarbia Hypertension

cerebral vasodilation



- Hypotension → ↓ CPP

- Introduction of laryngoscope & traction

compression of neck veins

↓ed cerebral venous drainage


  • To avoid cerebral vasodilation induced by hypoxia & hypercarbia
  • Obtundation of vasopressor response due to ET Intubation, suctioning , skull pin application (fentanyl, lignocaine).
  • Use of hypnotic sparing effect of narcotics
  • Extremes of head position should be avoided

( reduces venous return from head)

  • IV induction of anesthesia is preferred.
  • NS lasts for several hours
  • Airway, venous access & monitors must be secured
  • Pin fixation, initial part of craniotomy & other painful procedures→ ↑BP → ↑ICP
  • Excessive retraction to brain tissue is avoided
  • Maintenance of BP (fluctuation not >10% of baseline)
  • Aim: full and smooth recovery without coughing & straining (↑ICP)
  • Reversal of muscle relaxation- only after head dressing or bandages have been applied
  • Hemodynamics should be maintained (IV lignocaine to avoid ↑ BP)
  • Post operative pain (spinal surgery) should be taken care
  • Indication
    • ↑ICP
    • Improve the surgical field
  • Consideration for use of hyperventilation

1. Hyperventilation Hypocapnia


Retraction of brain tissue ↓ CBF

Ischemia (more in pathological condition)

2. CBF & ICP lowering effect is not sustained (return to baseline in 6-18 hours)
  • Clinical implication
    • Hyperventilation as an adjunct to brain relaxation
    • No prolonged or unnecessary hyperventilation should be done.
effect of regional techniques on cerebral hemodynamics
Effect of regional techniques on cerebral hemodynamics
  • Hypotension induced by regional techniques can impair CPP (more with impaired autoregulation)
  • Raised ICP -Absolute c/I for SAB - as dural puncture may ppt. coning of brainstem.
  • Neurological deficit- worsening of disease in post op period may be erroroneosly blamed on RA- Documentation is must.

Case reports on immediate loss of hearing in the immediate post op are available.

key points
Key points
  • All IV anesthetic agents except ketamine cause decrease in CMR, CBF, ICP & maintain autoregulation & cerebral vascular response to CO2
  • Ketamine causes increase in CMR, CBF & ICP (only in absence of other sedation)
  • BZP has minimal effect on CBF, CMR & ICP
  • Opioids has minimal effects on CBF, CMR & ICP provided normocapnia & normotension is maintained
Hypnotic sparing effect of opioid should be used for stable hemodynamics during induction
  • Naloxone is best avoided in NS
  • SCh causes mild & transient increase in ICP but is not contraindicated when rapid airway control is required
  • Vecuronium, rocuronium & cis- atracurium causes no histamine release thus has no significant effect on cerebral physiology
All IAA are vasodilators at different concentration
    • Vasodilation is associated with increase in CBF & ICP, thus impairs autoregulation
    • Sevoflurane causes least vasodilation with no effect on CSF dynamics
  • Vasodilatory effect of N2O is attenuated when used with other IV anesthetic agents
  • For control of I/O & P/O HTN, labetalol is preferred over direct vasodilators
  • Steroids have role only in 1̊ & 2̊ brain tumors
  • Hypoxia, hypercarbia and hypertension should be avoided at induction of anesthesia.
  • Hyperventilation should be only used as brain relaxation technique.
  • Miller’s Anesthesia- Ronald D. Miller 7th edition
  • Clinical Anesthesia- Paul G. Barash 5th edition
  • Essentials of Neuroanesthesia and Neurointensive Care- Arun K. Gupta 1st edition
  • Wylie and Churchill-davidson’s A Practice of Anesthesia- 7th edition