Neuro Protective Anesthesia During Cerebral Aneurysm Repair

Jon Jordan CRNA, MSNA
Staff CRNA Providence Anesthesia
 Identify mechanisms of
brain injury during
intracranial aneurysm
 Compare and contrast
current therapeutic
modalities used to reduce
brain injury
 Select an anesthetic plan
utilizing medications and
or therapies designed to
reduce brain injury during
cerebral aneurysm repair.
Neuronal injury and death
 Early ischemic neuronal
death is primarily caused
by excitotoxicity.
 Mitochondrial function
 Delayed death is
caused by apoptosis
Cottrell, J. & Young, W. Neuroanesthesia (5th ed.).
Brain Ischemia
 Global ischemia, cessation of blood flow for greater
than 8 minutes.
 Focal ischemia, contains three regions.
1st region receives no blood flow.
2nd Penumbra, receives collateral flow and is
partially ischemic.
3rd Area surrounding penumbra that receives normal
Ischemia Induced Changes
Vascular changes
Neuronal changes
 ATP reduction
 Red cell sludging
 Na+ influx, K+ efflux
 Intracellular acidosis
 Hypoperfusion
 High cellular Ca++
 Vasospasm
Ca++ activated proteases
Caspase activation
Free radical production
Excitatory amino acid release
Goals of Neuro protective
 Maintain cerebral perfusion.
 Utilize an anesthetic plan that prevents cerebral
ischemia, limits excitotoxicity process
Reduce the risk of pre and intra operative rupture.
Facilitate surgical exposure ( relax the brain).
Minimize reperfusion injury.
Plan for prompt awakening to facilitate neurological
exam (good grade SAH only)
Cerebral Blood flow
 20%-25% of cardiac output goes to the brain
 Circle of Willis is primary collateral blow flow
 Complete circle with well developed collaterals present
in only 18%-20% of population.
 Deliberate hypertension , 30%-40% above baseline is
indicated in acute arterial occlusion or vasospasm.
 Szabo and Colleagues concluded increases in BP upon
induction of up to 37% above baseline did not cause
AVM rupture, (MAP 118 + 7mmHg)
Common Aneurysm Locations
SAH Grading Assessments
 Hunt and Hess, a
modification of Botterells
original grading system.
 Grading of SAH
 Most commonly used
 Evaluates LOC
comparatively to degree of
SAH and operative risk
Unruptured aneurysm
Asymptomatic or slight HA or
slight nuchal rigidty
Moderate to severe HA, nuchal
rigidity. No neuro deficit other
than cranial nerve palsy.
Drowsiness, conusion, or mild
focal deficits.
Stupor, mild or severe
hemiparesis, possible early
decerebrate rigidity, vegetative
Deep coma, decerebrate rigidity,
moribund appearance
Pong,R. Lam, A. Cottrell and Young’s Neuroanesthesia 2010
57 yo Female
A 57 yo female presents to the ED with a c/o of recent
onset of headache along with visual changes. An angio
CT performed demonstrates no embolic or hemorrhagic
stroke ; yet displays a 5mm cerebral aneurysm in the
anterior circulation, Hunt Hess grade o.
The question now becomes do we prepare to coil or clip,
and what are the differences?
Coiling or Clipping
 Clipping
 Coiling
Coiling means a trip to INR
 Can we safely administer general anesthesia outside of
the operating room.
 Need for invasive monitoring remains the same.
 Now were going to introduce medications that can
definitely effect neuro protection.
a. Systemic heparinization / reverasal.
b. Contrast media (anaphylactoid reaction)
c. Need for neuro muscular blockade
d. Need for rapid reversal and emergence for
detailed exam .
Communication with the Surgeon
Unruptured Aneurysm
Ruptured Aneurysm with SAH
 Baseline Neuro exam
 Baseline Neuro exam.
 Where is the aneurysm
 Onset time of injury?
 How large is it?
 Difficulty of surgical
 Will temporary clips be used,
if so how long is anticipated
clip time?
 Clinical grading of SAH.
 Size and location of
 Stability of the patient for
 Assessment of other
confounding co-morbidities
What not to Do
Its not that obvious
Maintaining Autoregulation
 Aneurysm with SAH presents an impairment in
autoregulation and a rightward shift in the lower
limit of autoregulation.
 Grade of SAH correlates directly with degree of
autoregulatory impairment.
 Degree of autoregulation impairment closely
correlates with incidence of vasospasm.
 May result in delayed ischemic injury and deficits.
 MAP of 50-60/150-160
 Negated by hypercapnia,
arterial hypoxemia and
the use of volatile
anesthetic gases.
 Also attenuated in the
area surrounding an
acute cerebral infarction
as vessels are typically
maximally vasodilated
Timing of Surgery
 International Cooperative study on the timing of
aneurysm surgery (1990)
 Same day as SAH found 50% of brains to be tight.
 Only 20% found to be tight after 10 days.
 North American results showed outcomes were
best when surgery performed within 3 days,
differing for overall results which showed no
difference between early or late surgery.
Reperfusion Injury
 Occurs when perfusion is restored to previously
ischemic tissue areas.
Reduced perfusion to area due to neutrophil adhesion
on vascular endothelium.
Free oxygen radicals are formed which react with
polyunsaturated fatty acid disrupting cell membranes
Formation of free radicals is associated with both
apoptosis and necrotic cell death.
May be mitigated by NMDA antagonists as well as
NOS inhibitors.
Perioperative Monitoring
 Standard anesthetic monitoring including twitch
Intra arterial pressure monitoring. Level transducer to
base of skull.
Two large bore 14ga – 16ga IV catheters
Consider triple lumen or Cordis placement.
Uses of jugular bulb oxygen saturation remains
Trans cranial doppler use currently remains
Patient Positioning
 Anterior circulation aneurysms, patient supine for a
frontal temporal incision.
 Basilar tip aneurysms, lateral position for a
subtemporal incision.
 Vertebral or Basilar aneurysm, seated or park bench
position for suboccipital incision.
Patient Positioning
 Ensure alignment of the neck
to promote adequate venous
 Once positioned palpate the
neck to ensure no venous
 Venous outflow obstruction
will cause the brain to remain
 Induction is a critical time period.
 7% incidence of rupture during induction of
 Potential unstable hemodynamics.
 Blunting sympathetic responses to laryngoscopy or
other painful stimulation is essential.
 Goal is to maintain current hemodynamics if they are
Pharmacology of Cerebral
Induction / Maintenance
Adjunctive neuro protectants
 Thiopental
 Magnesium sulfate
 Propofol
 Methylene Blue
 Fentanyl, Sufentanil,
 Anti epileptic drugs
 Etomidate
 Ativan vs. Midazolam
 Rocuronium, vecuronium, vs
atracurium, cisatracurium
 Mannitol
 Steroids
 Free radical scavengers
 Antioxidants
Decrease CMRO2, CBF and minimal change in ICP.
Preserved autoregulation.
Potent anticonvulsants.
May cause respiratory depression leading to
hypercapnia and elevated ICP
 Diazepam; t 1/2 21 – 37 hrs. To long for quick wakeup.
 Lorazepam; t ½ 10 – 20 hrs. Again to long for quick
wakeup and exam
 Midazolam; t ½ 1 – 4 hrs. May have similar protective
effects against hypoxia or cerebral ischemia similar to
 One of few drugs shown to be protective against
ischemic damage in humans
Cerebral vasoconstrictor, reduces CMRO2 and CBF.
Reduced CMRO2 ( 55% - 60%) is primary mechanism
of protection.
Blocks Na+, K+ and Ca++ fluxes, free radical scavenger,
decreases ICP
May cause inverse steal.
National shortage.
 Cerebrovascular profile much like barbiturates
 Decreases CMRO2, CBF and ICP. Autoregulation
remains intact.
Chemically similar to phenol based free radical
Potent antioxidant properties
Prevents lipid peroxidation
Protective against oxidative stress, hypo energy
metabolism and free radical mediated injury
 Cerebral vasoconstrictor, reduces CBF, ICP and
CMRO2 35% -45%.
Autoregulation is preserved.
May activate seizure foci.
Can cause cerebral desaturation with induction doses.
Burst suppression with High doses.
 Dose related reduction in CMRO2 and CBF
 Low dose possess anticonvulsant activities.
 Dose with induction augments the sedative effects of
 May further reduce incidence of ischema related
damage when given at clinical doses (1.5mg/kg)
following burst suppressive doses of barbiturates or
propofol. (reduces CMRO2 by 15% -20%)
 High doses result in seizure activity
 Fentanyl. Decreases ICP and cerebral blood volume
with no effect on perfusion pressure. No histamine
 Sufentanil. May cause vasodilitation which will
increase cerebral blood volume and ICP. Not the best
 Remifentanil. Ultra short acting, much like fentanyl
in its ability to decrease ICP and CBV with no effect on
CPP. May be best when quick wake up is needed for
neuro exam
 Produces decrease in sympathetic activity by
inhibiting norepinephrine release.
 Excess catecholamine levels correlate with increased
ischemic neuronal damage.
 Decreases CBF with little or no change in CMRO2.
 Can be used in conjunction with volatile agents or as
part of TIVA.
Neurmuscular Blockaide
Vecuronium, Little to no
change in CBF, ICP or
CMRO2. No histamine
Atracurium. No
significant effect on CBF,
CMRO2 or ICP. High doses
may cayse histamine
Rocuronium. Much like
Cisatracurium. Near
vecuronium. Rapid onset at similar or weaker effects
higher doses make it more
than atracurium with less
preferable to succinylcholine histamine release
for rapid sequence
Relaxation of the Brain
 CBF has near linear relationship with
arterial PaCO2 when between 20-80 mmHg.
 CBF is altered 2-3% for every 1 mmHg
change in PaCO2 or 1-2ml/100g/min.
 CBV will change approximately 1% for every
1 mmHg change in PaCO2
 Reducing PaCO2 causing cerebral
vasoconstriction, reducing brain volume.
 Excessive hyperventilation may lead to
excessive vasoconstriction causing further
brain ischemia.
 Vasoconstriction resulting in reduced brain
tension may cause an unruptured aneurysm
to rupture.
 Hyperventilation should be limited to a
paCO2 of 25 – 35 while the dura is open.
 A slow return to normal CO2
 Osmotic diuretic, dose of 0.25 – 1 gram/kg.
 Should be administered once the bone flap is removed
over 15 minutes.
 Biphasic effect as initial increase in plasma osmolality
will cause cerebral vasodilitation.
 May cause transient shift in serum electrolytes as
intravascular volume increase. (increase in serum K+,
decrease in Na+).
 Free radical scavenger.
Choice of Volatile Agents
 Isoflurane (0.5% - 1%).
Minimal increase in CBF.
Dose dependent loss of
 Desflurane (4% - 6%).
Much like Isoflurane. Low
blood gas solubility, high
concentration may cause
undesirable sympathetic
Unique property over
other volatile agents in
that autoregulation
remains preserved at
all concentrations.
IV Fluid and Blood Viscosity
 0.9 normal saline
 Lactated Ringers
 Component of triple H
 Reduced blood viscosity
reduces cerebral vascular
 Initial goals of 33% Hct due to
 5% Albumin. SAFE
concern for reduced oxygen
trial revealed
carrying capacity.
increased mortality in
patients resuscitated  Due to increased morbidity
mortality associated with
with albumin.
transfusion an Hct of 27 –
30% could be tolerated.
Interfering with Excitotoxicity
and Free Radical Formation
Magnesium Sulfate
 Essential element in over 300 enzyme systems
 Long known vasodilatory properties make peri-
operative use in neuro surgery questionable.
 Post operative use indicated for treatment of
reperfusion injury associated with vasoconstriction.
 Meta-analysis by Wong et al in 2011 on use of
Magnesium sulfate in patients with Subarachnoid
hemorrhage and delayed cerebral infarction (DCI).
 Six studies, 875 patients, Result was no beneficial
effect of magnesium sulfate infusion on DCI
Wong et al. Critical Care 2011
Methylene Blue
 Autoxidizable phenothiazine with potent antioxidant
 Easily crosses the blood brain barrier.
 Animal models have demonstrated the
neuroprotective effects of MB not only as an
antioxidant but also by triggering functional network
changes in brain metabolism.
 A potential valuable tool for reducing oxidative stress
and energy hypometabolism
(Rojas, J. Simola, N. Kermath, B. et al. Journal of Neuroscience. 2009
 Mild hypothermia, temp 33c to 35
 Reduces CMRO2 by 7% for each degree of change
 Nasopharyngeal temperature may best correlate to
actual brain temperature.
 Deep hypothermia (13c – 21c) in conjunction with
circulatory arrest may be indicated for clipping of
basilar or giant aneurysms
 Mild Intraoperative Hypothermia during Surgery for
Intracranial Aneurysm Trial(IHAST) 2005.
30 participating centers with 2856 surgeries for SAH.
1001 patients with good grade (WFNS) score of I II or
III and SAH no more than 14 days prior to surgery.
Intraoperative (hypothermia target temp of 33c) or
normothermia (target temp of 36.5c).
Pt’s evaluated at POD 90 using Glasgow Outcome
scale, Rankin Scale, Barthel Index and NIH Stroke
IHAST Results
 No significant difference in ICU Length of stay,
hospitalization, death rates 6% or discharge
Hypothermia 66% compared to Normothermia 63%
had a Glasgow Outcome score of 1. odds ratio 1.14;
95%CI P=0.32.
Hypothermia showed no improvement in outcomes in
patients undergoing craniotomy for good grade SAH.
Increased incidence of Bacteremia in hypothermia
Results further validated in Cochran Reviews meta
analysis published in 2012.
Prior to Clip Placement
 Check BP, ETCO2 and twitch monitor.
 The dura is open, hyperventilation and ETCO2 should
be optimal.
 Normotension should be the absolute lower limit
unless otherwise indicated (acute rupture).
 Patient coughing or movement could catastrophic. Re
paralyze prior to manipulation.
 Plan for disaster i.e. acute rupture. Need to lower MAP
ASAP. Be prepared to reduce cardiac output, nitrate
based vasodilators are not the best choice.
Cerebral Vasospasm
 Structural and pathological changes within the vessel
 Swelling and necrosis of smooth muscle.
 Hypothesized that vasoactive substances found in the
blood in the cisterns induce changes.
 Currently thought to be oxyhemoglobin,
deoxyhemoglobin in conjunction with endothelium
derived relaxing factor or nitric oxide.
Cerebral Vasospasm
 Accounts for 13.5% of major morbidity and mortality.
 Incidence and severity correlate to amount of blood found
in basal cisterns
40-60% occurrence rate by cerebral angiography.
Clinically significant vasospasms occur in only 20-30% of
Angiographically detectable vasospasm is usually not
detected until at least 72 hours after SAH, peaks at 7 days
and usually not seen after two weeks
50% of patients who develop significant vasospasm will die
or develop serious neurological deficits.
Putting it all together
 No definitive solution.
 Know what you have to work with before you start.
 Work to preserve autoregulation.
 Antioxidant therapy
 Tight control of BP.
 Avoid histamine releasing drugs or therapies
 Prepare for the worst case scenario
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Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and metaanalysis. Critical Care (2011), 15: RS2
Rojas, J. Simola, N. Kermath, B. Kane, J. Scallert, T. & Gonzalez-Lima, F. Striatal Neuroprotection with Methylene Blue.
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Alderson, P. Lefebvre, C. Li, WP. Roberts, I. & Schierhout, G. (2004) Human albumin for resuscitation and volume
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