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
r
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
•
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
.
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
.
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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