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1. Cerebral Pharmacology
and Anesthesia
for Supratentorial Craniotomy
Mani K.C Vindhya M.D
Asst Prof of Anesthesiology
Nova Southeastern University

2.  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

3. Qualities of an Ideal Neuroanesthetic
 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)

4. Maintenance of Mean Arterial Pressure and
Cerebral Perfusion Pressure
CPP = MAP - ICP (or CVP, whichever is greater)
Change in MAP Inhaled Anesthetics Intravenous Anesthetics
Increase N2O
Little change Etomidate
Opioids
Decrease Halothane Thiopental
Isoflurane Propofol
Desflurane
Sevoflurane
Large Decrease Enflurane

5.  Decrease in ICP and Cerebral Blood Flow
 All inhaled anesthetics (in high concentrations) increase
CBF.
 All IV anesthetics (except ketamine) decrease CBF.

6.  The volatile agents have a biphasic effect on CBF in
normal subjects

7.  Effects of volatile agents on CBF and CMR in normal
subjects (coupling intact):
CBF
CMR

8.  Effects of volatile agents on CBF if coupling is
impaired or if CMR is already suppressed:
CMR
CBF

9.  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)

10.  Effects of Dexmedetomidine on CBF and CMR
 Dexmedetomidine decreases CBF and CBF velocity in
humans.
 Dexmedetomidine did not reduce CMR in an animal
model.
 A 2008 study showed that dexmedetomidine decreases
both
 CBF velocity and CMR in humans

11. • Decrease in CSF Production Relative to
Reabsorption.
– A decrease in CSF volume would tend to decrease
intracranial volume and ICP.
– 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

12.  No Inhibition of Cerebral Autoregulation
 Autoregulation is intact with IV agents (i.e. thiopental,
propofol, fentanyl)
 In high concentrations, all volatile inhaled anesthetics
impair autoregulation

13.  No Expansion of Closed Air Spaces
 N2O = the only anesthetic that expands closed air spaces
 Intracranial air pockets
 Pneumocephalus
 Air emboli (venous or arterial)
 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).

14. . 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

15. Anticonvulsant Activity = desirable property
Anesthetic Type Only Both pro- and Only
proconvulsant anticonvulsant anticonvulsant
activity activity activity
Intravenous Methohexital Etomidate* Thiopental
Narcotics Diazepam Midazolam
Ketamine
Propofol*
Methohexital
Inhalational Nitrous oxide Enflurane* Isoflurane (?)
Halothane Desflurane (?)
Sevoflurane*
Isoflurane (?)
Desflurane (?)

16.  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.

17.  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)
 Many anesthetics are associated with potential organ toxicity:
 Sevoflurane – renal toxicity might be caused by: compound A
from CO2 absorbents
 fluoride ion from hepatic metabolism
 Halothane > enflurane > isoflurane > desflurane
 Hepatotoxicity in proportion to hepatic metabolism
 Nitrous oxide – bone marrow toxicity
 Etomidate
 Adrenocortical suppression
 Propylene glycol toxicity caused by diluent

18.  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)

19. Three kinds of evoked potentials:
Evoked Potential Latency Anesthetic Interaction
Brainstem auditory evoked response 2 msec Barely affected
(BAER)
Somatosensory evoked potentials, 20 msec Somewhat affected
SSEPs (median nerve)
Somatosensory evoked potentials, 40 msec Somewhat affected
SSEPs (posterior tibial nerve)
Visual evoked response (VER) 70-100 msec Very variable under
anesthesia

20.  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

21.  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”

22. 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)

23. 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).

24.  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

25.  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

26. Maintenance of Anesthesia: How do the anesthetics stack up?
 Some agents we just don’t use:
 Ketamine
 Only cerebrovasodilating IV agent
 Increases CSF volume
 May cause neuronal damage due to its action on
glutamate (N-methyl-D-aspartate, NMDA) receptors
 Halothane
 Most cerebrovasodilating inhaled agent (cortical CBF)
 Hepatotoxicity limits use in adults
 Enflurane – no longer in our O.R.
 Second most cerebrovasodilating inhaled agent, after
halothane
 Increases CSF volume
 Epileptogenic (esp. with hypocarbia)

27.  Isoflurane, Sevoflurane, & Desflurane
 Bad Points:
 Decrease MAP (high concentrations)
 Increase CBF and ICP (high conc’s)
 Decrease CPP (high concentrations)
 Inhibit autoregulation (> 1% isoflurane)
 Good Points:
 Decrease CMRO2
 No expansion of closed air spaces
 Easily titratable
 Desflurane
 Bad Points:
 Decreases MAP (so former PDR’s prohibited its use in
intracranial neurosurgery)
 Maximum of 0.8 MAC recommended in current PDR
 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.
 Coughing and bucking on emergence
 Very Good Point:
 Rapid emergence (allows for rapid wake-up at end of case)

28.  Sevoflurane
 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)
 Good Points:
 Rapid emergence (perhaps use at end of case)
 Pleasant odor (less coughing and bucking?)
 Favorable regarding CBF and autoregulation

29.  Nitrous Oxide
 Bad points:
 Increases CBF more than isoflurane on a MAC to MAC
basis
 Increases CMRO2 (only I.A. that does)
 Expands closed air spaces (only I.A. that does)
 Tends to cause nausea and vomiting
 May cause neuronal damage due to its action on
glutamate (N-methyl-D-aspartate, NMDA) receptors
 Good Points:
 MAP is maintained.
 Rapid emergence
 Easily titratable
 Many neuroanesthesiologists routinely used it in the past
 ! No difference in outcome of elective supratentorial
craniotomy

30.  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

31.  Anesthetic Opioids (Fentanyl, sufentanil, alfentanyl, remifentanyl)
 Good Points:
 Little change in CBF
 Less decrease in MAP
 Little change in CBF
 Autoregulation is preserved.
 Bad Points:
 Nausea and vomiting = a frequent S.E.
 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

32.  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

33.  Anesthetic Management of Intracranial Neurosurgical Cases
 Reasonable Maintenance Regimens for Intracranial
Neuroanesthesia
 (going from routine to desperate).
 N2O + isoflurane (½%) + fentanyl
 N2O = the first agent to go if there’s brain swelling or venous
air emboli or ischemia danger (i.e. aneurysm or head trauma)
 MAC equivalents of sevoflurane or desflurane might also be
substituted for isoflurane.
 Sufentanil could be substituted for fentanyl.
 Isoflurane (1%) + fentanyl
 Isoflurane (½%) + propofol + fentanyl
 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

34.  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

35. Special Cases in Neuroanesthesia
• The ways to decrease intracranial volume and
pressure apply in typical intracranial neuroanesthetic
cases (i.e., supratentorial craniotomies).
Three components “Bad” Things that Ways to Decrease
inside the skull Increase ICV and ICP ICV and ICP
Brain (80% of ICV) Surgical excision
! Neurons, glia, Tumor Evacuation of hematoma
extravasated cells Hemorrhage Temporal lobe
Head injury decompression
! Interstitial fluid Edema Mannitol
Hypertonic saline
Furosemide
Dexamethasone
CSF (8% of ICV) Obstructive Spinal drain
hydrocephalus Ventriculostomy
Blood volume (12% of
ICV) Increase CBF: Decrease CBF:
! Arterial side Hypoventilation/ Hyperventilation/
hypercarbia mild hypocarbia
Hypoxia Avoid hypoxia
Heavy pre-medication Anesthetic choice
Hyperthermia Avoid hyperthermia
Inhibit cerebral venous Improve cerebral venous
! Venous side drainage drainage

36.  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

37.  Quirk of Anesthesia after Recent Craniotomy
 Avoid N2O if air is inside skull on CT scan
 Quirks of Head Trauma (ABC’s of TBI)
 Airway. Safely get control.
 Blood pressure. Avoid hypotension (SBP < 90 mm Hg) if
possible, or correct it immediately.
 CO2. Don’t routinely hyperventilate, only if necessary
for “swollen” brain.
 Diuretics or Dexamethasone?
 Usually do give diuretics, particularly mannitol
 Usually don’t give dexamethasone or steroids
 Early decompressive craniectomy or temporal lobe
decompression might be necessary in dire circumstances.
 Fluids. Avoid hypovolemia.
 Glucose. Treat hyperglycemia.
 Hypothermia was “hot,” but now it’s not. Avoid
hyperthermia.
 IV and Inhaled Anesthetics

38.  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.
 Infratentorial (posterior fossa) surgery is unique in that
it can be done in different positions – sitting, lateral
decubitus, or prone.

39. Thank you