EFFECTS OF EFFECTS OF ANESTHETICS ON ANESTHETICS ON CEREBRAL CEREBRAL BLOOD FLOW & BLOOD FLOW & CMRO2CMRO2

PRESENTERPRESENTERDr Unnikrishnan P Dr Unnikrishnan P

COORDINATORCOORDINATORDr Linnette MorrisDr Linnette Morris

MODERATORSMODERATORSDr UshakumariDr UshakumariDr ChitraDr Chitra

Why this session…?

What is the substance of this discussion?

How Physiology transforms into Anesthesiology….

What should be our ultimate aim in neuroanesthesia?

……………. is to give the patient the best possible brain

Keep the terms close to your heart….

CMRO2 how fast the brain eats its foodWhy it eats food?

1. electrical activity(signaling) 2. cellular homeostasisCBF the amount of the food supply to brain

If CBF increase brain swellsICP increaseWhat is coupling?Why it is so important in this discussion?

CBV-CBF

Cerebral perfusion= mean BP - ICP

CBF or CBV.. Which is more important in determining ICP?

Remember CBF and CBV may not always go parallel..So be cautious

CBV AND AUTOREGULATION

When MAP rises autoregulation CBV decrease

When MAP rise no autoregulation CBV increase

When MAP decreases vasodilation CBV increase

If intracranial compliance is poor reduce Cerebral Perfusion Pressure[CPP]

EpileptogenesisEpileptogenesis-concerns

Seizure increase CMRO2go unnoticed in anesthetizedCMRO2 exceed blood supply neuronal injury

Also can persist in post op period….

INTRAVENOUS ANESTHETICS

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I V ANESTHETICS Generally we suppress brains appetite {CMRO2 decrease}

So CBF decrease

Hence coupling

Ketamine is the rebel among us

We also have direct effects

BARBITURATES

Dose dependent reduction in CBF& CMR

Metabolism related with brain’s electrical activity is mainly suppressed

CMRO2 decreasevascular resistance increaseCBF decrease ICP decrease

CBF/CMRO2 ratio unchanged

Barbiturates….

Cerebral perfusion= mean BP - ICP MAP reduction +ICP reduction +++So cerebral perfusion pressure preserved

Thiopentone protect brain from incomplete ischemia:

Suppression of CMR

Free radical scavenging

CBF redistribution effects

Decrease ATP consumption

Barbiturates….

Tolerance…

Autoregulation maintained

CO2 responsiveness intact

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ABOUT METHOHEXITAL

Myoclonic activity

Patients with seizures of temporal lobe origin[psychomotor variety ]are specifically at risk

Used to activate seizure foci during cortical mapping

PROPOFOLPROPOFOL

Primarily reduce CMR vasoconstriction decrease CBF & ICPIn patients with high ICP, significant reduction in CPPFentanyl + propofol ablates increase in ICP at intubationCO2 responsiveness preservedAutoregulation preserved

Propofol and seizure incidence

π Though seizures,dystonic & choriform movements,opisthotonus etc have been reported with its use, SYSTEMATIC STUDIES SYSTEMATIC STUDIES HAVE FAILED TO CONFIRM THE NOTION HAVE FAILED TO CONFIRM THE NOTION THAT PROPOFOL IS PROCONVULSANTTHAT PROPOFOL IS PROCONVULSANT

π ECT induced seizures are shorter with Propofol

π Awake resection of seizure foci with propofol- no seizures

π Appears to be anticonvulsant in animals [Millers

anesthesia,6/e]

Propofol & brain protection

Etomidate

Parallel reductions in CBF and CMRRegionally variable; more in forebrainReactivity to CO2 preservedConcerns …………

ETOMIDATE continued

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

NARCOTICS

In general, little effects in normal brain

When occur, modest reduction in CBF& CMR

?reduction in arousal ?pain relief

MORPHINE

Modest depressive effect on CMR & CBF

Histamine release

Autoregulation preserved

FENTANYL & ALFENTANYL

FENTANYLFENTANYL modest reduction CBF & CMR in

quiescent brain Larger reduction during arousal

ALFENTANYLALFENTANYL No significant changes

Fentanyl

Grandmal seizures reported

No neuro excitatory activity

? exaggerated rigidity phenomenon

But alfentanyl augments temporal lobe spike activity

SUFENTANYL

Either reduction or no change in CMR&CBF

But sometimes…. Sudden decrease 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 between that caused by

narcotics(modest) barbiturates(substantial)

Remember they can produce respiratory depression increase in paCO2

If we avoid this… BENZODIAZEPINES appears safe

FLUMAZENIL # true or false #

It cant reverse the cerebral effects of benzodiazepinesOvershoot phenomenon may occurOvershoot may be a part of arousal phenomenonBetter avoided or used cautiously to reverse BZD sedation in patients with impaired I.C. compliance

DROPERIDOL

Tranquillizer[antidopaminergic] used in post operative refractory nausea & vomiting

Can cause abrupt fall in MAP vasodilation increase in ICP [occasional]

No action per se

KETAMINE

Increases CMR secondarily increase CBF increase ICPEffect is regionally variable[limbic system^]Racemic mixture: S increase , R decrease CMRDiazepam , Midazolam ,Isoflurane /N2O, Propofol …. They blunt this effectBetter to avoid as sole agent….Reasonable to use it along with the above drugs… cautiously

LIDOCAINE

Reduce CMRO2Large doses : reduction greater with

lignocaine than with high dose barbiturate!How? ? membrane stabilizing effect of

lignocaine also reduces energy needs for membrane integrityRx & prevention of a/c rise in ICP, also

during ETT suctioningTrials ..

INHALED ANAESTHETICSINHALED ANAESTHETICS

VOLATILE AGENTS….

EFFECTS @ DIFFERENT MACs

Beyond 1 MAC what happens?

Coupling persists…..(most probably)

Dose related increase in CBF/CMR occur

Greater luxury perfusion

Order of vasodilatory potency:

HALOTHANE >> ENFLURANE > DESFLURANE HALOTHANE >> ENFLURANE > DESFLURANE = ISOFLURANE > SEVOFLURANE= ISOFLURANE > SEVOFLURANE

Volatile agents Also……

The vasodilator effect usually appear rapidly than the effects on CMRO2. The CBF falls to near- prevolatile agent levels , 2.5 to 5 hrs later

If antecedent lowering of CMR by drugs/disease, then vasodilator effect may predominate

Continued (general properties) volatile agents

It can also reduce BP

CO2 responsiveness preserved

Autoregulation :rising BP(less imp) - impaired

falling BP(important) - preserved

HALOTHANEHALOTHANE

CBF dramatic increase in CBF with a simultaneous modest reduction in CMR

CMR suppression is less compared to other agents

Produces isoelectricity in EEG at MACs >4

MACs beyond this what happens?

Halothane….. continuedHalothane….. continued

Further reduces CMRO2….

Surprised or alarmed?

Means that these doses interfere with cell metabolism [?oxidative phosphorylation]

Means toxicity at higher concentrations [reversible]

ENFLURANEENFLURANE

CBF dramatic increase in CBF with a simultaneous modest reduction in CMRPotentially epileptogenic and hypocapnoea potentiates this effectSeizure activity elevate brain metabolism by as much as 400% Will you prefer?So avoid: if seizure predisposition/

h/o occlusive cerebrovascular disease/with hypocapnoea/ high doses

ISOFLURANEISOFLURANE

CBF increases CBF; but to a lesser extent^̂

CMR decreases CMRO2 and maximal reduction is attained simultaneously with EEG suppression at clinically relevant concentrations [1.5-2.0 MAC]

@ 1 MAC decrease CMRO2 by 25%** ^̂ Human studies @1.1 MAC halothane 191%

isoflurane 19%, Miller 6/e

**collation of data p:827 ,Miller 6/e

Isoflurane Isoflurane moremore

Distribution of CBF/CMR changes: CBFCBF CBF increases are greater in

subcortical and hindbrain areas than neocortex CMRCMR CMR suppression is greater in the neocortex than subcortex

The institution of hyperventilation , simultaneous with its introduction can prevent increase in ICP [ which may occur with normocarbia]

SEVOFLURANESEVOFLURANE

Reduce CBF Reduce CMRO2 by 38% @ 1 MAC

Max at EEG suppression At 1.5-2.0 MAC

DISTRIBUTION Reduction in CBF within cortex Increase in CBF within cerebellum

Has small potential to evoke epileptiform activity ; use with caution in patients with epilepsy ( Miller 6/e)

DESFLURANEDESFLURANE

Reduce CBFDecrease CMRO2 by 22% @ 1 MACOthers = sevoflurane

In general, the effect of Isoflurane , Desflurane and Sevoflurane on CBF are modest

Summary of volatile Summary of volatile agentsagents

MAJOR IMPACT ON CBF/CBV & ICP OCCURS WHEN WE EXCEED 1 MAC

BECOMES SIGNIFICANT IF INTRACRANIAL COMPLIANCE IS ABNORMAL

HERE, IT IS BETTER TO USE A PREDOMINANTLY INTRAVENOUS TECHNIQUE UNTIL THE POINT OF OPENING OF CRANIUM & DURA

NET VASODILATORY EFFECT OF ISO/DES & SEVO LESS THAN HALO;SO IF ONE IS TO BE USED, PREFER THE FORMER ONES

EFFECT OF HYPOCAPNOEA : HALOTHANE Vs ISO/DES/SEVO

ENFLURANE IS EPILEPTOGENIC; SLIGHT RISK WITH SEVOFLURANE

CO2 REACTIVITY AND AUTOREGULATION PRESERVED

NITROUS OXIDENITROUS OXIDE

Can cause significant increase in CBF,CMR & ICP [ sympathoadrenal stimulating effect]

Most extensive increase when used alone

With IV agents: CBF effect considerably reduced[thiopentone , Propofol ,benzodiazepines ,narcotics]

With Volatile Agents: CBF increase is exaggerated

Nitrous oxide…

Vasodilator effect clinically significant in those with abnormal i.c. compliance so add IV agents

Surgical field persistently “tight”? N2O may be a culprit

It should be avoided in cases, where a closed intracranial gas space may exist , since it can enter and expand it

N2ON2O continued

CBF response to CO2 preserved

No uniform agreement reached on its effect on CMR

MUSCLE RELAXANTSMUSCLE RELAXANTS

NON DEPOLARIZING NON DEPOLARIZING RELAXANTSRELAXANTS

Main effect is via Histamine release

Cerebral vasodilation increase ICP

Simultaneous decrease in BP

Reduction in cerebral perfusion pressure

Non depolarizing relaxants- Non depolarizing relaxants- histamine releasehistamine release

NDMR continued

Pancuronium- large bolus abrupt increase in BP if autoregulation defective increase ICP

A metabolite of atracurium, Laudanosine epileptogenic properties in trials

But” it appears highly unlikely that epileptogenesis will occur in humans with atracurium”*

*miller 6/e p:831

Message…. NDMR useMessage…. NDMR use

All are reasonable in I.C. hypertension

Avoid hypotension… Metocurine/Atracurium/Mivacurium

Dose and rate of administration adjusted

Curare die-hard fan? Small divided doses

SUCCINYL CHOLINESUCCINYL CHOLINE

Increase ICP in lightly anaesthetizedPrevented by

May be an arousal phenomenon , caused by increased afferent signals from muscle spindlesConsider rise in ICP Vs rapid attainment of paralysis… in a given caseControl of CO2 tension , BP , depth of anesthesia, Defasciculation etc should be taken care of

Deep anesthesia

Defasciculation with metocurine 0.03 mg/kg

“paralysis with Vecuronium”

Also knowAlso knowWorried about CSF dynamics?

Prolonged closed cranial procedure ?enflurane: increase secretion, decrease absorption

Blood Brain Barrier acute hypertension can breach

BBB; certain anesthetics may facilitate this

Textbook of neuroanesthesia & criticalcare/Basil F MattaSURGERY INDUCTION RELAXANT MAINTENANCE

SUPRATENTORIAL ICSOL

TPS/P’FOL ATRA/VEC/MIVA/ROC

P’FOL-FENT / FENT- LD ISO / N2O- HD ISO

VASCULAR Sx TPS/ETO/P’FOL VEC/ATRAC/PAN/? SCOLINE*

P’FOL-OPIOID +/- VOL AGENT* ?N2O

CAROTID Sx FENT/ETO/TPS/ P’FOL

VEC FENT/ISO/N2O

POST FOSSA OPIOID/TPS/ P’FOL

NDMR VARIES ?N2O-PC/VAE ?VOL-TRANS PUL,SSEP

NSx WITHOUT CRANIOTOMY

FENT/TPS/P’FOL NDMR ISO WITH HYPOCAPNOEA

Cx SPINE RSI-SCOLINE

PED TPS/P’FOL/SEVO SUXA/NDMR N2O+LD ISO/SEV OR P’FOL i/FEN OR AIR+HD VA

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Great Brain , Great Brain , Great anesthesia Great anesthesia First surgical operation carried out with a general anaesthetic at the Massachusetts Hospital in Boston on 16 October 1846. Dr Thomas Morton (1819-1868), administered the anaesthetic - sulphuric ether - and can be seen at the far end of the table holding a flask near the patient's face. Dr John Collins Warren successfully removed a tumour from the neck of the patient, Gilbert Abbot. A diorama, based on an original daguerreotype of the scene

THANK THANK YOUYOU

REFERENCES

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

BRAIN PROTECTIONBRAIN PROTECTION.

COMPLETE GLOBAL ISCHEMIA

CULPRITS: Hypotension and late phase intracranial hypertension

INDUCTION OF MILD HYPOTHERMIA IN THE RANGE OF 32-32 ^C X 24 HRSPASSIVE REWARMING OVER 8 HRS

CALCIUM CHANNEL BLOCKER NIMODIPINE

NORMALIZATION OF pH

Rx OF SEIZURES

NORMOTENSION

FOCAL [INCOMPLETE] ISCHEMIA

Anesthesia per se is protective

Thiopentone Thiopentone

Decrease ATP consumptionSuppress CMRFree radical scavengingCBF redistribution effectsPotentiate GABAergic actionInhibit glucose transfer across BBB

Also shown by Methohexital

Propofol Propofol

Attenuate changes in ATP,Ca++,Na & K caused by hypoxic injury

Antioxidant action by inhibiting lipid per oxidation

Used in aneurysm Sx & Carotid endarterectomy

ISOFLURANE/VOLATILE AGENTS

Potent suppressant of CMR in cortex

Similar among the group

Isoflurane’s effect not sustained

ETOMIDATE

Was proposed to have neuroprotection

NO synthase inhibition/ NO binding

?worsening of hypoxia,acidosis

Not used now

Others Others

Nimodipine

Nicardipine

Tissue plasminogen activator for thrombolysis

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Great Brain , Great Brain , Great anesthesia Great anesthesia First surgical operation carried out with a general anaesthetic at the Massachusetts Hospital in Boston on 16 October 1846. Dr Thomas Morton (1819-1868), administered the anaesthetic - sulphuric ether - and can be seen at the far end of the table holding a flask near the patient's face. Dr John Collins Warren successfully removed a tumour from the neck of the patient, Gilbert Abbot. A diorama, based on an original daguerreotype of the scene

THANK THANK YOUYOU

REFERENCES

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

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