Cerebral Pharmacology
and Anesthesia
for Supratentorial Craniotomy
Mani K.C Vindhya M.D
Asst Prof of Anesthesiology
Nova Southeastern University
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Introduction to Cerebral Pharmacology. In addition to anesthetic
agents and neuromuscular junction blockers, don’t forget:
 Drugs to decrease brain interstitial fluid
 Dexamethasone (edema around solid brain tumors)
 Mannitol and hypertonic saline (osmotic diuretics)
 Furosemide (loop diuretic)
 Antibiotics – usually two for intracranial neuroanesthesia
 Nafcillin or oxacillin (or vancomycin, if penicillin allergic)
 Gentamicin
Qualities of an Ideal Neuroanesthetic
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Maintenance of mean arterial pressure and cerebral
perfusion pressure
Decrease in intracranial pressure (ICP)
Decrease in cerebral metabolic rate coupled with decrease in
cerebral blood flow
Decrease in CSF volume (production < reabsorption)
No inhibition of cerebral autoregulation
No expansion of closed air spaces
Rapid emergence
Anticonvulsant
Lack of toxicity to major organ systems
Cerebroprotective (or at least not harmful)
Compatibility with neuromonitoring (such as SSEP’s)
Maintenance of Mean Arterial Pressure and
Cerebral Perfusion Pressure
CPP = MAP - ICP (or CVP, whichever is greater)
Change in MAP
Inhaled Anesthetics
Increase
N2O
Little change
Intravenous Anesthetics
Etomidate
Opioids
Decrease
Halothane
Isoflurane
Desflurane
Sevoflurane
Large Decrease
Enflurane
Thiopental
Propofol
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Decrease in ICP and Cerebral Blood Flow
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All inhaled anesthetics (in high concentrations) increase
CBF.
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All IV anesthetics (except ketamine) decrease CBF.
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The volatile agents have a biphasic effect on CBF in
normal subjects
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Effects of volatile agents on CBF and CMR in normal
subjects (coupling intact):
CMR
CBF
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Effects of volatile agents on CBF if coupling is
impaired or if CMR is already suppressed:
CBF
CMR
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Decrease in Cerebral Metabolic Rate (CMRO2) coupled with
decrease in Cerebral Blood Flow (CBF)
Decrease in Cerebral Metabolic Rate (CMRO2)
 IV anesthetics – coupled with decreased CBF (metabolic effect)
 Volatile inhaled anesthetics - “uncoupling” of CBF from
CMRO2 in high concentrations
Only 2 anesthetics increase CMRO2 (coupled with an increase in
CBF):
Ketamine
Nitrous oxide (N2O)
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Effects of Dexmedetomidine on CBF and CMR
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Dexmedetomidine decreases CBF and CBF velocity in
humans.
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Dexmedetomidine did not reduce CMR in an animal
model.
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A 2008 study showed that dexmedetomidine decreases
both
CBF velocity and CMR in humans
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Decrease in CSF Production Relative to
Reabsorption.
– A decrease in CSF volume would tend to decrease
intracranial volume and ICP.
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Effects of anesthetics on CSF secretion and
absorption
ANESTHETIC
SECRETION
ABSORPTION
Halothane
Decrease
Decrease
Enflurane
Increase
Decrease
Isoflurane
---
Increase
Desflurane
Increase (hypocapnia only)
---
Fentanyl
---
Increase
Etomidate
Decrease
Increase
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No Inhibition of Cerebral Autoregulation
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Autoregulation is intact with IV agents (i.e. thiopental,
propofol, fentanyl)
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In high concentrations, all volatile inhaled anesthetics
impair autoregulation
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No Expansion of Closed Air Spaces
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N2O = the only anesthetic that expands closed air spaces
 Intracranial air pockets
 Pneumocephalus
 Air emboli (venous or arterial)
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Teaching Points:
 Don’t turn on N2O at the end of case
(but perhaps O.K. to leave it on during case).
Don’t use in patients after recent craniotomy (i.e., air
pockets on CT scan).
. Rapid Emergence from Anesthesia
(Lower Blood:Gas Solubility)
Inhaled Agent
B:G Solubility
Halothane
2.4
Enflurane
1.9 (cf. MAC = 1.7)
Isoflurane
1.4 (cf. MAC = 1.2)
Sevoflurane
0.68
Nitrous oxide
0.47
Desflurane
0.42
Anticonvulsant Activity = desirable property
Anesthetic Type
Only
proconvulsant
activity
Both pro- and
anticonvulsant
activity
Only
anticonvulsant
activity
Intravenous
Methohexital
Narcotics
Etomidate*
Diazepam
Ketamine
Propofol*
Methohexital
Thiopental
Midazolam
Inhalational
Nitrous oxide
Enflurane*
Halothane
Sevoflurane*
Isoflurane (?)
Desflurane (?)
Isoflurane (?)
Desflurane (?)
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Numerous case reports of convulsion-like muscle activity
during induction and emergence from anesthesia with:
 Sevoflurane
 Enflurane
 Etomidate
 Propofol
To prevent peri-operative drug-induced seizures in epileptic
patients
 Continue anticonvulsant therapy.
 Consult with the patient’s neurologist to discuss
management.
 Avoid etomidate.
 Do not use sevoflurane routinely in epileptic patients.
 Limit maximum concentration to < 1.5 MAC.
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Lack of toxicity to major organ systems
1. All of the volatile inhaled anesthetics can form toxic metabolites in
CO2 absorbents (baralime > soda lime).
A = compound A (vinyl compound produced by sevoflurane)
B = BCDFE (vinyl compound produced by halothane)
C = carbon monoxide (formed by pungent volatile anesthetics in the
following rank order)
D = desflurane > E = enflurane >F = Forane R (isoflurane)
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Many anesthetics are associated with potential organ toxicity:
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Sevoflurane – renal toxicity might be caused by: compound A
from CO2 absorbents
fluoride ion from hepatic metabolism
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Halothane > enflurane > isoflurane > desflurane
Hepatotoxicity in proportion to hepatic metabolism
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Nitrous oxide – bone marrow toxicity
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Etomidate
Adrenocortical suppression
Propylene glycol toxicity caused by diluent
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Cerebroprotective (or at least not harmful)
 Thiopental = the “gold standard” for cerebral
protection at the present time (i.e., during
clipping of an intracranial aneurysm)
Three agents may be harmful so far as cerebral
protection is concerned:
Ketamine
Nitrous oxide
Etomidate
Compatibility with Neuromonitoring (such as
somatosensory evoked potentials)
Three kinds of evoked potentials:
Evoked Potential
Latency
Anesthetic Interaction
Brainstem auditory evoked response
(BAER)
2 msec
Barely affected
Somatosensory evoked potentials,
SSEPs (median nerve)
20 msec
Somewhat affected
Somatosensory evoked potentials,
SSEPs (posterior tibial nerve)
40 msec
Somewhat affected
Visual evoked response (VER)
70-100 msec
Very variable under
anesthesia
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Effect of isoflurane on upper extremity SSEPs
Summary of effects of anesthetics on SSEPs:
Inhaled anesthetics – dose-related decrease in amplitude and
increase in latency
Less than 1 MAC volatile agent
Nitrous oxide – profound depressant effect on SSEPs,
especially when used in combination with volatile agent
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Intravenous agents:
Propofol and thiopental – small decrease in amplitude
and increase in latency. Propofol is commonly used for
TIVA (total IV anesthetic) technique.
Opioids – negligible effect on SSEP’s
Ketamine and etomidate – increase SSEP amplitude.
(Etomidate is exceptional. It increases SSEP amplitude but
decreases BAEP amplitude).
Summary. Six I’s that inhibit SSEP’s:
Inhaled anesthetics (isoflurane and nitrous oxide)
IV anesthetics (to a lesser extent than inhaled anesthetics).
Ketamine and etomidate are the exceptions; they increase
amplitude.
Ischemia or hypoxia – anywhere from limb to cortex
Injury – anywhere from limb to cortex
Ice cold temperatures – < 34.5 oC “Incompetence”
I.V. Induction of Anesthesia for Intracranial Neurosurgery
Typical induction agents
 Thiopental, propofol, or etomidate =suitable I.V.
induction agents
Fentanyl or sufentanil
– as narcotic analgesics to supplement
Lidocaine IV – to blunt hypertensive and ICP response to
intubation
Neuromuscular junction blockers –
rocuronium, vecuronium, or succinylcholine (with prior
defasciculating dose of a competitive NMJB)
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Succinylcholine for intracranial neurosurgery
 1. Increased CBF and ICP in dogs
 2. Succinylcholine has been postulated to increase ICP by
causing muscle afferent activity and stimulation of muscle
spindle fibers (innervated by A-gamma fibers).
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A more recent study in patients with neurologic injury
showed that succinylcholine did not change ICP, CBF
velocity, or EEG activity.
The increase in ICP induced by succinylcholine can be
blocked with a defasciculating dose of NMJ blocker
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Teaching points:
Don’t use succinylcholine if it’s contraindicated
(i.e., hemiplegia).
If OK, use succinylcholine if you’re at all worried
about the airway.
Use a defasciculating dose of a competitive
neuromuscular junction blocker if you plan to use
succinylcholine
Maintenance of Anesthesia: How do the anesthetics stack up?
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Some agents we just don’t use:
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Ketamine
 Only cerebrovasodilating IV agent
 Increases CSF volume
 May cause neuronal damage due to its action on
glutamate (N-methyl-D-aspartate, NMDA) receptors
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Halothane
 Most cerebrovasodilating inhaled agent (cortical CBF)
 Hepatotoxicity limits use in adults
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Enflurane – no longer in our O.R.
 Second most cerebrovasodilating inhaled agent, after
halothane
 Increases CSF volume
 Epileptogenic (esp. with hypocarbia)
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Isoflurane, Sevoflurane, & Desflurane
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Bad Points:
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Decrease MAP (high concentrations)
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Increase CBF and ICP (high conc’s)
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Decrease CPP (high concentrations)
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Inhibit autoregulation (> 1% isoflurane)
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Good Points:
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Decrease CMRO2
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No expansion of closed air spaces
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Easily titratable
Desflurane
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Bad Points:
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Decreases MAP (so former PDR’s prohibited its use in
intracranial neurosurgery)
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Maximum of 0.8 MAC recommended in current PDR
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Increased lumbar CSF pressure in one study but not in
another more recent study in the setting of hyperventilation.
! Carbon monoxide (CO) production in CO2 absorbent is a concern.
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Coughing and bucking on emergence
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Very Good Point:
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Rapid emergence (allows for rapid wake-up at end of case)
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Sevoflurane
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Bad Points:
EEG seizure activity has led to recommendation that
sevoflurane not be used routinely in epileptics
Possible nephrotoxicity is a concern:
 Fluoride ion production from hepatic metabolism
 Compound A production from CO2 absorbent
 Should not use for > 10 MAC hours (i.e., long neuro
cases)
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Good Points:
 Rapid emergence (perhaps use at end of case)
 Pleasant odor (less coughing and bucking?)
 Favorable regarding CBF and autoregulation
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Nitrous Oxide
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Bad points:
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Increases CBF more than isoflurane on a MAC to MAC
basis
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Increases CMRO2 (only I.A. that does)
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Expands closed air spaces (only I.A. that does)
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Tends to cause nausea and vomiting
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May cause neuronal damage due to its action on
glutamate (N-methyl-D-aspartate, NMDA) receptors
Good Points:
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MAP is maintained.
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Rapid emergence
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Easily titratable
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Many neuroanesthesiologists routinely used it in the past
! No difference in outcome of elective supratentorial
craniotomy
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Propofol
 Good Points:
 Decreases CBF
 Decreases CMRO2
 Autoregulation is preserved.
 Apparent antiemetic action
 Bad Points:
 Decreases MAP
May have delayed emergence relative to
inhalational techniques
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Anesthetic Opioids (Fentanyl, sufentanil, alfentanyl, remifentanyl)
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Good Points:
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Little change in CBF
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Less decrease in MAP
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Little change in CBF
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Autoregulation is preserved.
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Bad Points:
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Nausea and vomiting = a frequent S.E.
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Fentanyl was thought to be better than sufentanil or alfentanyl, based on their
effects on MAP and CPP
Sufentanil does not increase ICP in patients with brain injury so long as MAP is
maintained
Remifentanyl
 Good Point: A logical choice for rapid emergence
 Bad Points:
 Severe hypertension on emergence
(recommended to give MSO4 prior to DC’ing
remifentanyl)
? High incidence of post-op nausea and vomiting
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Anesthetic Management of Intracranial Neurosurgical Cases
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Reasonable Maintenance Regimens for Intracranial
Neuroanesthesia
(going from routine to desperate).
 N2O + isoflurane (½%) + fentanyl
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N2O = the first agent to go if there’s brain swelling or venous
air emboli or ischemia danger (i.e. aneurysm or head trauma)
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MAC equivalents of sevoflurane or desflurane might also be
substituted for isoflurane.
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Sufentanil could be substituted for fentanyl.
Isoflurane (1%) + fentanyl
Isoflurane (½%) + propofol + fentanyl
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Volatile agents are next to go if intractable ICP or brain
swelling
Total IV anesthetic: Propofol + fentanyl
Barbiturate coma -- for intractible brain swelling or cerebral
protection during aneurysm clipping (titrated to EEG burst
suppression):
 Thiopental
 Pentobarbital
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Reasonable Muscle Relaxants for Maintenance
of NM Blockade
 Vecuronium
 Rocuronium
 Pancuronium – increases HR
 Cis-atracurium:
No histamine release (different from atracurium)
An epileptogenic metabolite, laudanosine
Special Cases in Neuroanesthesia
• The ways to decrease intracranial volume and
pressure apply in typical intracranial neuroanesthetic
cases (i.e., supratentorial craniotomies).
Three components
inside the skull
Brain (80% of ICV)
! Neurons, glia,
extravasated cells
! Interstitial fluid
CSF (8% of ICV)
Blood volume (12% of
ICV)
! Arterial side
! Venous side
“Bad” Things that
Increase ICV and ICP
Ways to Decrease
ICV and ICP
Tumor
Hemorrhage
Head injury
Surgical excision
Evacuation of hematoma
Temporal lobe
decompression
Edema
Mannitol
Hypertonic saline
Furosemide
Dexamethasone
Obstructive
hydrocephalus
Spinal drain
Ventriculostomy
Increase CBF:
Hypoventilation/
hypercarbia
Hypoxia
Heavy pre-medication
Hyperthermia
Inhibit cerebral venous
drainage
Decrease CBF:
Hyperventilation/
mild hypocarbia
Avoid hypoxia
Anesthetic choice
Avoid hyperthermia
Improve cerebral venous
drainage
Transphenoidal Hypophysectomy = an exception.
For resection of tumor confined to pituitary:
 No furosemide or mannitol
 Dexamethasone (solid brain tumor)
 Spinal drain (to put air or NSS in, not to take CSF out)
 No hyperventilation
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Quirk of Anesthesia after Recent Craniotomy
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Avoid N2O if air is inside skull on CT scan
Quirks of Head Trauma (ABC’s of TBI)
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Airway. Safely get control.
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Blood pressure. Avoid hypotension (SBP < 90 mm Hg) if
possible, or correct it immediately.
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CO2. Don’t routinely hyperventilate, only if necessary
for “swollen” brain.
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Diuretics or Dexamethasone?
 Usually do give diuretics, particularly mannitol
 Usually don’t give dexamethasone or steroids
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Early decompressive craniectomy or temporal lobe
decompression might be necessary in dire circumstances.
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Fluids. Avoid hypovolemia.
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Glucose. Treat hyperglycemia.
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Hypothermia was “hot,” but now it’s not. Avoid
hyperthermia.
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IV and Inhaled Anesthetics
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Ruptured intracranial aneurysm or arteriovenous
malformation (AVM)
 Prevent sudden increases or decreases in MAP that
predispose the aneurysm to rupture
Hyperventilation may depend on Hunt-Hess Grade:
 Grade 0 – hyperventilation O.K.
 Grades 1-2 – normocarbia or modest hypocarbia (paCO2 =
35) to prevent vasospasm
 Grades 3-5 – hyperventilation may be necessary anyway
EEG monitoring if barbiturate coma is needed during
temporary clipping.
 Moderate induced hypothermia? The results of the
completed IHAST trial indicate no better outcome with
hypothermia (33.5 oC) than normothermia (36.5 oC)
Induced hypotension might be requested if aneurysm
ruptures.
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Infratentorial (posterior fossa) surgery is unique in that
it can be done in different positions – sitting, lateral
decubitus, or prone.
Thank you