Neuro I

Question 1

Describe the function of the circle of willis, as well as the major vasculature that supplies and creates the circle of willis.

What is the venous drainage system of the brain?

Answer 1

• Functions as a shunt, providing collateral flow when there is a regional disruption of blood flow
  
  • Limited because there’s lots of variation in anatomy
• Miller emphasizes that a lot of people have complete CoW but lots of variation (figure B)
  
  • Consider that CoW is not complete in everyone
• 4 major arteries supply CoW
  
  • L Internal carotid & R internal carotid⇒ anterior portion CoW
  • L and R vertebral artery ⇒ basilar artery (posterior portion) ⇒allows for nice circle of flow with intact CoW
    
    • If blockage at any point (ie internal carotid) there’s some hope of collateral flow to that region of the brain
• Venous drainage is predictable
  
  • Superficial cortical veins ⇒supply pia mater, superficial cortical layer
  • Deeper cortical veins⇒ drain deeper structures of brain
    
    • Ultimately drain into major sinuses (superior sagittal sinus, inferior sinus, vein of galan)
      
      • All drain into jugular vein

Question 2

Describe the spinal cord blood supply.

Answer 2

• Not as well collateralized as brain
• Anterior spinal artery comes off of vertebral arteries
  
  • Lots of flow from radicular arteries
    
    • 6-8 other radicular arteries that help supply SC (including Artery of Adamkiewicz)
  • Some regions of SC are well perfused (cervical/thoracolumbar area) other areas are more tenuous
    
    • Artery of Adamkiewicz (T11/T12) really important for 2/3 of blood flow to inferior SC (supplies T8 to conus medullaris)
      
      • Interruption of artery can cause major ischemic damage
• Anterior 2/3 cord by anterior spinal artery with very little collateralization
  
  • Interrupted= big trouble
  • Primarily motor function
  • Anterior side also covers lateral so can see combo of sensory/motor issues when
• Posterior 1/3 SC has 2 arteries provides more opportunities for collateral flow
  
  • Slightly less at risk for ischemic damage
  • Primarily sensory

Question 3

Why is cerebral blood flow important? When can it be harmful?

Answer 3

• Important to provide the brain with energy
  
  • Oxygen
  • Glucose
• Too much flow can be harmful though…..
  
  • Cranial space constraints
• Brain encased rigid cranial vault. Too much flow can have issues with increased intracranial pressure

Question 4

Whe is the relationship between cerebral blood flow and cerebral blood volume?

Answer 4

• Parallel but not 1:1 relationship
• We care about flow because it influences total cerebral blood volume
  
  • CBV = 5ml/100 gm of brain tissue
  • VA increase CBF even if cerebral blood volume doesn’t increase
  • Think of arterial and venous drainage/tone
• Consider not only arterial flow (and tone) but also venous drainage (and tone)
  
  • Obstruction to outflow (position, PP vent with high PIP)
  • Positioning makes big impact on ICP and impacts CBV significantly

Question 5

What is ICP? What determines ICP?

Answer 5

• Normal pressure 8-12 mmHg (B8th= 7-15 mmHg)
• ICP by convention means supratentorial CSF pressure measured in the lateral ventricles or over the cerebral cortex and is usually 10mmHg or less. Rigid cranial vault fixed volume
  
  • In lateral recumbent position lumbar CSF approximates supratentorial pressure
• 2 problems with increased ICP
  
  • 1) decreased CPP to the point that the brain becomes ischemic
  • 2)herniation across the meninges, down the spinal canal, or through an opening in the skull
• ICP components are:
  
  • Brain (cellular and ICF) (80%= 1400ml)
    
    • Cells impacted by sugeon, anesthesia world we don’t control cell size
    • Can control ICF with diuretics, steroids
    • The cellular compartment (neurons, glia and ICF).
      
      • compartment is in the hands of the surgeon.
      • However, when the brain is bulging into the surgical field at the conclusion of evacuation of an extradural hematoma, the clinician should ask whether a subdural or extradural hematoma is present on the contralateral side that warrants either immediate bur holes or immediate postprocedure radiologic evaluation.
    • The fluid compartment. This compartment can be addressed with steroids and diuretics.
  • Blood (arterial and venous)(12% 150ml)
    
    • Limitation to how much we can impact this because it’s only 12% of volume
    • Decrease cerebral blood flow or improve venous drainage
    • This is the compartment is the most amenable to rapid alteration. The blood compartment should be considered two separate components: venous and arterial.
  • CSF (8%= 150ml)
    
    • 8% in someone with no hydrocephalus
    • Can control with venticulostomy/lumbar drain
    • Remove CSF and augment control
    • There is no pharmacologic manipulation of the size of the CSF space
      
      • The only relevant means for manipulating the size of this compartment is by drainage
        
        • A tight surgical field can sometimes be improved by passage of a brain into a lateral ventricle to drain CSF.
          
          • relevant in both supratentorial and infratentorial procedures when poor conditions in the posterior fossa are thought to be the result of downward pressure by the contents of the supratentorial space
      • Lumbar CSF drainage can be used to improve surgical exposure in situations with no substantial hazard of uncal or transforamen magnum herniation.

Question 6

What is intracranial elastance? What determines intracranial elastance? Compensatory mechanisms?

Answer 6

Determined by the change in ICP after a change in intracranial volume – compensatory mechanisms include:

1. Initial displacement of CSF from cranial to spinal compartment
2. Increased CSF absorption
3. Decreased CSF production
4. Decreased CBV (primarily venous)

• Healthy patients can tolerate change on ICP curve well. (Bottom left of curve normally)
  
  • Intracranial pressure-volume relationship.
  • The horizontal portion of the curve indicates that initially there is some compensation with expanding intracranial lesion
    
    • is accomplished largely by displacement of cerebrospinal fluid (CSF) and venous blood from the intracranial to the extracranial spaces
    • once compensation exhausted, small changes causes large increase in ICP with r/f herniation or decreased CPP resulting in ischemia
• Someone with swelling, edema, hematoma, can reach point where small change in volume makes a big change in ICP.
  
  • Think of where do we think pt is on curve
    
    • Avoid hypoventilation, maintain CPP, mannitol, CSF diversion, cerebral vasoconstricting anesthetics, decompressive craniectomy
  • Completely awake, no signs increase ICP, no nausea A&OX3 no pupillary changes⇒ may be able to tolerate
  • If patient confused, throwing up, cushing triad, ICP issues,⇒ avoid ANY increase in volume, be very conservative with which anesthetics are chosen
• If ICP gets close to MAP⇒too much resistant to perfusion and CPP will drop to unacceptable levels and won’t get glucose/O2 to brain and then you start to worry about herniation
• Elastance is change pressure/change volume. Compliance is change in volume/change in pressure.
  
  • Used interchangeably in texts
  • Compliance varies locally in diff areas of brain
    
    • Affected by arterial BP and PCO2
      
      • Autoregulation kicks in with hypotension (vasodilation- increase CBV) or hypertension (vasoconstriction- decrease CBV)
      • CBV increases 0.05mL/100g of brain per every 1 mmHg increase PaCO2

Question 7

What are the various type of ICP waveforms and their significance?

Answer 7

• A waves (plateau waves)
  
  • ominous…. Compensation exhausted reflect intense vasodilation and severe ischemia
  • ICP >50 mmHg
    
    • Situation where you want to be incredibly aggressive to get it lower
• B waves
  
  • ICP 30-40 mmHg
  • CCP at lower limit of autoregulation
• C waves
  
  • ICP normal
  • Not significant
• Most commonly via ventriculostomy/external vascular drain. Also microtransducer and fiberoptic interparenchymal options available.

Question 8

What is CPP?

Answer 8

• MAP – ICP (or CVP whichever is greater)
• Normal is 80-100mmHg
  
  • When ICPs are higher, augment (increase) MAP to help CPP
• Cardiac output also appears to influence CBF (appears to be linear relationship)
  
  • particularly in hypovolemia
    
    • when patient hypovolemicà get huge impact in CBF (19:26)
  • Decrease in CO by 30% resulted in a 10% decrease in CBF in several recent Doppler studies
    
    • Improvement in CBF with increase CO observed in acute storke, SAH induced vasospasm, and sepsis
    • However, not a uniform relationship b/w CO-CBF. Depends on pathophys at hand. No improvement in CBF with increase in CO with traumatic head injury, neuro surgery, cardiac surgery
    • Does appear CO influences CBF when circulating volume is reduced and in shock states.
• Normal ICP is 10mmhg so CPP usually determined by MAP MM615
• Miller 9^th 302The conventional view of cerebral hemodynamics is that perfusion pressure (MAP or CPP) is the primary determinant of CBF and that the influence of cardiac output is lim- ited.

Question 9

What is cerebral blood flow? Normal? Important factors impacting CBF during anesthesia?

Answer 9

• Normal Adult 45-55ml/100g/min =750ml/mi
  
  • Global blood Flow
  • Gray matter(cortical) has lots of electrophys activity (80mL/100g/min)
  • White matter (subcortical- myelinated) 20mL/100g/min
  • Infants 40ml/100g/min
  • Children 95ml/kg/min
  • Spinal cord gray matter (60ml/100g/min) and white matter (20ml/kg/min)
• Blood flow closely linked with metabolism
  
  • Making fist, motor cortex will get more blood flow
  • Reading, occipital blood flow will increase
  • Wherever you have activity going in brain, will see more blood flow
    
    • Regional CBF parallels metabolic activity and can vary from 10-300ml/100g/min (MM615).

Important factors impacting CBF during anesthesia

1. Anesthetic Agents
2. Level of arousal (stimulation & pain)
3. Metabolic by-products
4. Blood Viscosity
5. Temperature
6. Concentration of CO₂ and H⁺ ions
7. O₂

Question 10

Describe how neuronal activity (metabolism) influences local CBF?

Answer 10

• “Flow-metabolism coupling”
  
  • Metabolic by-products (glial, neuronal, vascular)
    
    • H ions, adenosine, prostaglandin, lactate, glutamate can influence local blood flow
    • Ie glutamate stimulates NMDA receptor (on neurons), Ca enters cell, Ca stimulates NO production, NO is major vasodilator.
      
      • Ca can also create arachidonic acid⇒ PG ⇒major vasodilator
    • Different substances couple metabolism with vascular tone and blood flow
  • Multiple signaling pathways involved
• CBF to localized brain regions change up to 100-150% within seconds in response to local neuronal activity changes (sensory input/arousal)
• Barash 8^th
  
  • vasoconstrictive forces= catecholamines, ionic calcium, endothelin, and thromboxane.
  • Dilators= B2 agonists, nitric oxide, adenosine, prostaglandins, .
  • Other mediators – acetylcholine, bradykinin, serotonin, substance P, dopamine.

pic:

• Figure 11-4.. From Miller 9^th description below:
• Cerebral flow-metabolism coupling. Synaptic activity leads to glutamate release, activation of glutamatergic receptors, and calcium entry in neurons. This results in a release of arachidonic acid (AA), prostaglandins (PGs), and nitric oxide (NO). Adenosine and lactate are generated from metabolic activity. These factors all lead to vascular dilation. Glutamate also activates metabotropic glutamate receptors (mGluR) in astrocytes, causing intracellular calcium entry, phospholipase A ₂ (PLA ₂ ) activation, release of AA and epoxyeicosatrienoic (EET) acid and prostaglandin E ₂ (PGE ₂ ). The latter two AA metabolites contribute to dilation. By contrast, AA can also be metabolized to 20-hydroxyl-eicosatetraenoic acid (20-HETE) in vascular smooth muscle. 20-HETE is a potent vascular constrictor. cGMP, Cyclic guanosine monophosphate; eNOS, endothelial nitric oxide synthase; NMDAR, N-methyl d -aspartate glutamate receptor; nNOS, neuronal nitric oxide synthase.

Question 11

What happens to cerebral blood flow with increase PaCO2 and H ions?

Answer 11

• CO₂ + H₂0 = carbonic acid
  
  • More aerobic metabolism⇒ more CO2⇒ more H ions from dissociation
• Carbonic acid disassociates into H⁺
  
  • H⁺ ions cause “almost” proportional vasodilation of cerebral vessels
    
    • Thought that vasodilation increases blood flow to carry away H, reduce chance for CO2 narcosis
• Other acidic metabolic substances can also increase CBF (lactic acid, pyruvic acid, etc.)
• Each 1 mmHg change in PaCO₂ between 20-80mmHg
  
  • CBF changes approximately 1-2ml/100g/min
    
    • Double CO2 20⇒ 40 then will double CBF
    • Hyperventilate 50⇒ 25, ½ CBF
      
      • Use in short term in anesthesia when we turn on VA since we expect increase CBF with VA
  • Below 20mmg- tissue hypoxia reflexive dilation
    
    • Don’t want to go below 20 mmHg⇒ extreme tissue hypoxia
    • Typically don’t go below 30 mmHg when hypoventilating. Don’t want extreme value. Causes more harm than good
• Effect lasts ~ 6-8 hrs and then in will return to normal despite maintenance of altered CO₂ levels (bicarb transport)

1. Effect useful in anesthesia for short periods with VA
2. Critical to recognize if a patient with ICP alterations has been hyperventilated for extended period - why?
   - need to maintain same level of ventilation/don’t’ make major change quickly because it can cause some major problems
   * The benefit of increased CBF with increased H ion is a compensatory mechanism to prevent CO2 narcosis - that increased H ion concentration greatly depresses neuronal activity and increased CBF carries away the increased CO2 ( H ions) and therefore helps maintain a constant H ion conc. and a normal constant level of neuronal activity

Question 12

What is normal brain metabolism?

Answer 12

• Only 2% of total body mass, 15% of total body metabolism and cardiac output
  
  • Gets huge percent CBF based on size
• Cerebral Metabolic Rate (CMRO_<u>2</u>)
  
  • 3.5ml/100g/min = 50ml/min of O₂
• Pediatric patients higher CMRO₂ = 5.2ml/100g/min (mean age 6 yr)
  
  • One of the reasons why kids desaturate so quickly on induction
• Metabolism used to maintain normal K/Na to pump against gradient after AP
  
  • 60% of O2 used to maintain normal EP activity, 40% used to maintain healthy cell membrane
• Brain not capable of much anaerobic metabolism (high metabolism coupled with low local glycogen and oxygen stores)
• Brain glucose consumption 5 mg/100g/min
  
  • 25% of total body glucose consumption
• Use barbituates, propofol etc to get EP activity down to suppression levels and drop metabolic need
  
  • Anesthetics can’t reduce into basal cerebral maintenance metabolism (last 40% of CMRO2- mainly accounts for Na-K ATPase pump to restore intracellular gradients)
  • Anesthetics only help reduce CRMO2 to a certain point
• Reason for this is because brain does not work well on only anaerobic metabolism. Anaerobic can’t keep up with needs for brain
  
  • Only 2 minutes of glucose in brain at time, why LOC occurs with 5-10 seconds loss of blood flow
    
    • In absence of O2, brain resorts to anaerobic metabolism where only 2 units ATP produced for each molecule of glucose
  • Glucose utilization not dependent on insulin

Question 13

What is the relationship between CBF and O2 concentration?

Answer 13

• Except for cases of intense brain activity, O₂ utilization by brain tissue remains within narrow range ( a few % points around 3.5mlO₂/100gm brain tissue)
• If PO₂ of brain tissue drops below 30mmHg (35-45mm Hg normal) or PaO₂ drops below 50-60mmHg CBF increases dramatically
  
  • PaO2 doesn’t really have significant impact until in ischmic territory (Pao2 <50) then will see dramatic increase in CBF
  • See hail mary with cerebral blood vessels dilating to get as much O2 delivered as possible
  • CBF not really changed until you fall below 60mmHg that is the same level where there is a rapid reduction in oxyhemoglobin saturation. See an inverse linear relationship with O2 sat and CBF. Deoxyhemoglobin plays a central role here by causing the release of NO and its metabolites as well as ATP.
• Slight vasoconstriction >350 mmHg

Slide notes:

• Thus, the oxygen mechanism for local regulation of cerebral blood flow is a very important protective response against diminished cerebral neuronalactivity and therefore, against derangement of mental capability.
• At 3-8 minutes ATP stores are depleted and irreversible cellular injury begins to occur. The Hippocampus and cerebellum appear most sensitive to hypoxic injury MM616.
• Neurons have a very high metabolic rate using more energy than other cells – 2% body mass, 20% total body O2 consumption. N10
• Hypoxia induced K+ATP channel opening= hyperpolarization and vasodilation. The response to hypoxia is synergistic with the hyperemia produced by hypercapnia and acidosis. This hypoxic driven increase in CBF appears to be controlled at least in part by the rostral ventrolateral medulla - O2 sensor within the brain.

Question 14

What is cerebral autoregulation of CBF and arterial BP?

Answer 14

• CBF auto-regulated between MAP of 60-150mmHG
  
  • Barash8th 60-160 mmHg; some individuals lower limit <60mmHg others >80 mmHg
    
    • New edition of miller challenges this.
    • For purposes of boards/OR still assume autoregulation 6-150
  • Miller 9^th emphasizes this is an oversimplification of “complex regulation”
• Cerebral vasculature adjusts to changes in CPP/MAP after 1-3 minutes
• Varies between individuals: HTN will shift auto-regulatory range to higher minimum values and maximums of 180-200mmHg
• Above the upper limit = BBB disruption, cerebral edema, cerebral hemorrhage
  
  • Pressure dependent situation
  • Can burst smaller vessels and end up with hemorrhage
• Below the upper limit= ischemia
• Mechanism of reflex still controversial. Thought to be myogenic in nature (more stretch ⇒ dilation, less stretch ⇒ constriction) probably a little simplistic

Question 15

Describe the relationship between BP, hypercapnia, and CBF autoregulation?

Answer 15

• Point of 2 graphs, CO2 responsiveness can be influenced by blood pressure
• Red⇒ linear relationship with CO2 and CBF is true with normotension
  
  • Patients that are hypotensive, will see curve for CO2 flattening.
    
    • Not as much influence of CO2 with hypotension
  • In extreme hypotension, CO2 doesn’t have any impact on CBF and not much CBF to begin with
• If flip the other way, if patient has normal CO2 autoreg in typical range (60-150)
  
  • When hypercapnic, will see loss of autoregulation and be impaired
  • CO2 on lower end, will see plateau of autoregulation extended.
    
    • More consistent CBF across larger range of MAPs with hypocapnia
      
      • Why we like to hyperventilate too, get more cerebral autoregulation

Pic:

A, Relationship between cerebral blood flow (CBF) and partial pressure of carbon dioxide (Paco2).

• CBF increases linearly with increases in arterial Paco2.
  
  • Below a Paco2 of 25 mm Hg, further reduction in CBF is limited.
  • Similarly, the increase in CBF above a Paco2 of approximately 75 to 80 mm Hg is also attenuated.
• The cerebrovascular responsiveness to Paco2 is influenced significantly by blood pressure.
  
  • With moderate hypotension (mean arterial pressure [MAP] reduction of <33%), the cerebrovascular responsiveness to changes in Paco2 is attenuated sig- nificantly.
  • With severe hypotension (MAP reduction of approximately 66%), CO2 responsiveness is abolished.
• B, The effect of Paco2 variation on cerebral autoregulation.
  
  • Hypercarbia induces cerebral vasodilation and, consequently, the autoregulatory response to hypertension is less effective.
  • By contrast, hypocapnia results in greater CBF autoregulation over a wider MAP variation.

Question 16

How does the SNS impact CBF?

Answer 16

• Cerebral circulation strong SNS innervation (vasoconstricive)
  
  • Especially larger vessels
    
    • SNS important with sudden extreme rise in blood pressure to vasoconstrict and protect smaller vessels from higher pressure and protect against edema/hemorrhage
    • Not primary mediator in autoregulations because when transect, still see autoregulation
• Neither transection of these nerves or mild to moderate stimulation causes much change - the auto-regulation mechanism overrides
• May shift the auto-regulation curve to the right
  
  • SNS minor role in autoregulation unless sudden extreme BP rise (stroke prevention) or hemorrhagic shock

Question 17

What is the impact of temperature on CBF?

Answer 17

• CBF changes 6-7% per 1 degree C change
• Hypothermia decreasesCBF and CMRO2
  
  • Why people can drown in cold temperatures and come back neurologically intact
• Hyperthermia opposite effect
• Clinical evidence does NOT currently support the use of hypothermia <35 degrees C without CP bypass
  
  • It is beneficial following cardiac arrest
  • It might be beneficial in high risk patients with temporary focal ischemia (need more research)
    
    • Research saw increase in infection, influence coagulation, and decreased cardiac function
    • For now, keep above 35 Celsius and avoid hyperthermia
• Temperature can influence basal metabolic rate of brain (unlike anesthetics, which only influence EP activity)
• At 37 C, CRMO2 is 3.3mL/100g/min function and 2.2 integrity. With decrease to 27 celsius, see function decrease to 1.4 mL/100gm/min AND integrity decrease to 0.9mL/100gm/min

Question 18

Relationship between blood viscosity and CBF?

Answer 18

• Decrease in HCT will increase CBF but decrease O2 carrying capacity of the blood
• Severe polycythemia can reduce CBF
  
  • Might consider intervention ~ Hct of 55%
• Hct 33-45% probably no significant change in CBF
• By optimal Hct – best CBF with maintenance of adequate O2 carrying capacity.
• In theory probably most useful to have decreased viscosity with focal ischemia where max vasodilation already has occurred. Early studies have not shown this optimal hct to really improve outcome with acute ischemic stroke however- probably only true clinical relevance is to avoid polycythemia.

Question 19

What factors influence cerebral blood flow?

Answer 19

• Autoregulations 50-150 not reliable in every clinical situation. Very complex
• ABP,⇒ myogenic autoregulation
• CO ⇒ impacts CV function
• Neurogenic control can influence autoregulation
• Metabolic activity⇒neurovascular coupling
  
  • Increase H, PG, adenosine, will see enhanved CBF
• CO2 levels, parallel relationship in vascular reactivity AND Extreme hypoxia will see change in CBF⇒ vascular reactivity
• In healthy patients, autoregulatory range was pretty narrow and other factors impacted CBF
  
  • One study with 48 patients
  • In future, autoregulation pressure may be redefined. For now, 50-150

Question 20

What leads to secondary injury in cerebral pathology?

Answer 20

• Cerebral Ischemia Leads to Secondary Injury

1. Hypoxia
2. Hypotension
   
   1. Limit hypoxia/hypotension to prevent secondary injury

• Elevated ICP Leads to Secondary Injury

1. Cerebral edema
2. Hemorrhage
3. Herniation

Question 21

What are the regions of focal ischemia? What is global versus focal ischemia?

Answer 21

Focal ischemia there are three regions

1. No blood flow – same as global ischemia
2. Penumbra – receives collateral flow only partially ischemic, marginal blood flow may be <15ml/100g/min)
   
   1. CBF 6-15 mL/100g/min
   2. With someone with focal ischemia, think of what can you do to save penumbra
   3. Optimize blood flow to penumbra
3. Normal perfusion

• Global – total circulatory or respiratory arrest (cardiac arrest, drowning, asphyxia, etc.)
• Focal – embolic, hemorrhagic and atherosclerotic strokes, or trauma. In the penumbra if further injury can be limited and normal flow is rapidly restored these areas may recover completely. MM623
  
  • Impacts specific region of brain
  • Withinfocal, have 3 areas
• If the insult is maintained for a prolonged period the neurons in the penumbra will die. More neurons in the penumbra will survive if collateral blood flow is increased with such mechanisms as inverse steal (why TPL is useful in focal not global ischemia). Preventing secondary ischemia is the key following focal brain injury. Intracranial blood can cause free radical formation using the iron from Hgb.

Question 22

What are various key occurences that happen when CPP or CBF is reduced?

Answer 22

CPP

• less than 50 mmHg slowing seen EEG
• between 25-40mmHg flat EEG
• < 25mmHg sustained = irreversible brain damage

CBF

• Normal is 50ml/100g/min
• 20ml start to see slowing
  
  • When 12-15 mL/100gm/min will see neurons at risk (ischemic penumbra) lose EP activity and see cellular integrity take hit
• between 6-12ml you have the ischemic pneumbra
  
  • ​​<6 mL/100gm/min or CPP of 10mmHg⇒ see cellular integrity fail and rapid cell death

Question 23

What the cerebral pathophysology of ischemia?

Answer 23

• Oxidative phosphorylation is blocked – ATP production falls 95%
  
  • Needed to maintain ionic gradients
    
    • Can’t reestablish Na/K levels
  • Needed to maintain cellular integrity
• ATP-dependent pumps fail – intracellular Ca and Na increase, K decreases – neurons depolarize excessively
  
  • Water rushes into the cell down osmotic gradient leading to neuronal edema (necrotic death)
• Glutamate is released as cells die– more Ca enters
  
  • Apoptotic death
  • Positive feedback cascade ensues
  • Glutamate stimulates AMPA, NMDA, metabatropic glutamate increases intracelular Na and Ca.
    
    • Increased intracelular Ca is what signals apoptosis/cell death
    • With cell damage, release more glutamate, which impacts other cells locally
• Intracellular Ca increases because ATP-dependent pumps fail, increased intracellular Na and release of the excitatory neurotransmitter glutamate.
• High Ca levels increases damage via proteases and phospholipases (free fatty acids and free radicals damage the cell membranes, DNA, mitochondria, etc. )
• Lactate and Hydrogen build up (pH drops)
• No ATP available to repair damaged DNA proteins/lipids
• Arachidonic acid is produced in excess is converted to thromboxane (intense vasoconstriction), prostaglandins, and leukotrienes (edema)
• Reperfusion of previously ischemic regions can increase damage secondary to free radical generation and inflammatory mediator infiltration
  
  • Can cause lesions to expand
  • Interest on research side to stop process of excitotoxicity (too much glutamate, Ca, activity etc)

Question 24

What are the various types of herniation?

Answer 24

• 4 common types

1. Subfalcine (cingulate gyrus)- asymmetric expansion of cerebral hemisphere displaces the cingulate gyrus under the falx cerebri
   
   1. Compressions of anterior cerebral artery (supplies primary motor/sensory cortex)
   2. Subfalcine (cingulate gyrus) – asymmetric expansion of cerebral hemisphere displaces the cingulate gyrus under the falx cerebri (strong process which descends vertically in the longitudinal fissure between the cerebral hemispheres). Pts at risk for compression of anterior cerebral artery with ischemia of primary motor and/or sensory cortex with weakness and sensory deficits in the leg.
2. Transtentorial (uncal)- medial temporal lobe compressed against tentorium cerebelli
   
   1. Compress posterior cerebral artery leading to pupillary dilation, ocular paralysis, visual deficits
   2. Transtentorial- medial temporal lobe compressed against tentorium cerebelli. With progressive temporal lobe displacement 3^rd cranial nerve and PSNS fibers compressed = pupillary dilation and occular paralysis on the side of the lesion. Also posterior cerebral artery is often compressed resulting in ischemia of the visual cortex which is supplied by this vessel.
3. Tonsillar - displacement of cerebellar tonsils through the foramen magnum
   
   1. Compression of vasoactive/respiratory centers, not compatible with life
   2. Tonsillar – displacement of cerebellar tonsils through the foramen magnum. Life threatening – causes brain stem compression with disruption of vital respiratory centers in the medulla oblongata. Often the patient gets secondary hemorrhages in the midbrain and pons most likely a result of kinking of penetrating branches of basilar artery with resultant necrosis and hemorrhage during displacement of the brainstem.
4. Transcalvarial -through a skull defect
   
   1. Fracture in skull with herniation through defect
   2. Also happens in surgery with skull/dura mater open. Make sure patient completely relaxd and no Valsalva in surgery

Question 25

What is CSF?

Answer 25

• CNS “lymphatic system”/shock absorber
  
  • Glymphatic pathway
  • Protect brain from trauma
• Subarachnoid space enclosing the brain & spinal cord has a capacity of ~ 1650 ml
  
  • Of that…~150ml = CSF
• CSF formed by choroid plexuses in ventricles (lateral specifically, some in 3^rd/4^th but less significant) (⅔ form in choroid plexus, remaining from ependymal surfaces of ventricles, brain itself)
  
  • 0.3ml/min
  • 21mL/hr
  • Total turnover 3-4 times/day
    
    • total CSF space 150 mL and total daily production 450mL
• CSF is reabsorbed by arachnoid villi – function like one way valves fluid flows when CSF pressure is 1.5mmHg > than venous pressure
  
  • Absorb arachnoid villi⇒cerebral sinuses
  • If venous pressure is really high (high PIP, pt laying funny) then will decrease CSF reabsorption
  • Need venous pressure lower than CSF in order for CSF to drain properly
    
    • Since continuously producing, need to continuously absorb

CSF has an osmotic pressure and Na concentration equal to plasma (isotonic), chloride ion 15% greater than plasma, K 40% less, and glucose 30% less. G712. Also less Bicarb, protein content limited to small amount that leaks into perivascular fluid.

Question 26

What is the flow of CSF?

Answer 26

• Fluid from lateral ventricles passes through intraventricular foramina (of Munro) to the third ventricle additional fluid is added
• then it flows downward along the aqueduct of Sylvius into the fourth ventricle, more fluid is added and then it passes out of the fourth ventricle through three small openings
• two lateral foramina of Luschka, and a midline foramen of Magendie entering the cisterna magna ( a large fluid space that lies behind the medulla and beneath the cerebellum) which is continuous with the subarachnoid space
• lateral ventricle-→ Intraventricular foramina of Munro⇒ third ventricle⇒ aqueduct of sylvius⇒ fourth ventricle⇒ two lateral foramina of lushcka or midline foramen of Magendie
• Each ventricle adds more CSF to the flow

Question 27

What decreases CSF production?

Answer 27

1. Carbonic anhydrase inhibitors (acetazolamide)*
   
   1. Prescribed in PICU for neuro patients
2. Corticosteroids
3. Spironolactone
4. Furosemide*
5. Vasoconstrictors

*=Clinically relevant

• 2 clinically useful: furosemide (inhibits the combined transport of NA and Cl) and acetazolamide which reduces bicarb transport by inhibiting carbonic anhydrase.

Question 28

Anesthetic impact on CSF production?

Answer 28

• Increased during sleep (and during anesthesia)
• Increased by desflurane and enflurane
  
  • Could make theoretical case against des in hydrocephalus
• Decreased by halothane and etomidate
• No change isoflurane and fentanyl

* Info derived from animal data- may or may not be true in humans

Question 29

What factos affect absorption of CSF?

Answer 29

• Decreased by halothane and enflurane
  
  • Enflurane definitely worse choice in someone with hydrocephalus (get increased production of CSF and decreased absorption)
• No change desflurane
• Increased by isoflurane, fentanyl, and etomidate

* Info derived from animal data

• So enflurane is clearly the less desirable agent compared to the others from a CSF dynamics perspective.

Question 30

What is the blood brain barrier? What can cross the BBB?

Answer 30

• Fenestrations between endothelial cells in brain 1/8th size of fenestrations in other areas
  
  • Protect brain from foreign substances
• Exists in tissue capillary membranes in all areas of the brain parenchyma excepthypothalamus, pituitary, and area postrema
  
  • Need hypothalamus/pituitary to be exposed to osm, electrolyte, etc
  • Area postrema important in N/V important for body to recognize poison
• Movement across BBB depends on size, charge, lipid solubility, and degree of protein binding in the blood
  
  • Small size, no charge, lipid soluble, low protein binding gets across BBB
  • Permeable: H20, C20, O2, lipid soluble substances (anesthetics, ETOH)
  • Slightly permeable: Na, Cl, K, Ca, Mg
    
    • Take longer to get accross
  • Impermeable: polar molecules, plasma proteins, glucose (facilitated diffusion only), non-lipid soluble large organic molecules (mannitol)
• Substances needed by brain that do not cross BBB are transported across capillary endothelial cells by carrier mediated process – active or passive (facilitated diffusion). Glucose is example of facilitated diffusion can only move molecules of glucose in if concentration in blood is higher than in the brain

Question 31

What causes disruption in BBB?

Answer 31

• Anesthetics might/might not directly breech BBB. However…
  
  • They may produce conditions that lead to a breech
    
    • Ie extremes in BP
    • They may have different effect in a brain with disrupted BBB
• Disruptions:
  
  • severe HTN
  • tumors
  • CHI (closed head injury)
  • stroke
  • nfection
  • marked hypercapnia
  • hypoxia
  • prolonged seizures
  • osmotic shock
  • irradiation
• BBB disruption: movement dependent on hydrostatic rather than osmotic pressure
  
  • May cause anesthetics to have more access/different effect on brain
  • Patient with disrupted BBB can be more sensitive to HTN causing edema

Question 32

What are types of cerebral edema?

Answer 32

• Cytotoxic
  
  • Intracellular/failure of ionic pumps in ischemia
• Vasogenic
  
  • Reduced BBB integrity
  • Seens with brain tumors
    
    • Corticosteroids are effective at improving vasogenic edema
• Interstitial
  
  • Hydrocephalus or acute hyponatremia
• Corticosteroids are particularly effective in reducing vasogenic edema presumably because of upregulation of proteins that enhance the tight junction integrity between endothelial cells in the brain.

Question 33

What effect do volatile anesthetics have on cerebral hemodynamics?

Answer 33

• Dose related, reversible alterations in CBF, CMR & electro-physiologic activity
  
  • Decreases CMR
  • Direct vasodilatory effect of cerebral vascular smooth muscle
    
    • If have tight cerebral vault, then this increase in blood flow can be detrimental
• Effect on ICP depends on
  
  • CSF dynamics,
  • CBV,
  • PaCO₂,
  • surgical stimulation,
  • other drugs administered &
  • baseline compliance
• Dose dependent impairment of auto-regulation
  
  • Sevoflurane appears to impair autoregulation the least
• Typically in normal physiology, CBF and CMRO directly related
• Carbohydrate metabolism decreases while energy stores (ATP, adenosine diphosphate,and phosphocreatine) increase. Effects of specific agents are complicated by other factors such as other drugs, surgical stimulation, intracranial compliance, BP, PaCO2. (ex. Hypocapnia or TPL blunts increased CBF, ICP seen with ketamine and VA). MM619-20.
• When producing an isoelectric EEG Isoflurane and sevoflurane the relative reductions in the CMR and CBF are more intense in the neocortex than in other areas of the cerebrum.

Question 34

Relationship between volatile anesthetics, CBF and CRMO?

Answer 34

• Direct vascular smooth muscle dilation (↑ CBF)
• ↓ CMR (↓ CBF) (d/t flow metabolism coupling)
  
  • huge clarification in miller ch 11 pg 311. this is due to the naturally occur flow-metabolism relationship,. because CMR decreases, you will get a decrease in CBF until higher doses of VA are administered
• “Luxury Perfusion” Dose related
  
  • 0.5 MAC CMR reduction is predominate ↓ ; not much change CBF (miller says may be small decrease c/t awake state)
  • 1.0 MAC CMR decrease & vasodilation in balance no change CBF (3:38)
    
    • Sevo and Des may actually still decrease CBF at 1.0 MAC depending on which study you look at
  • >1.0 MAC vasodilation dominate ↑ CBF
• Decouple is older terminology because amount of uncoupling depends on dose of VA
• All studies in healthy volunteers. Never comfortable running 1 MAC VA. Generally stick to 0.5 MAC or less
• If assessment of patient makes you think they won’t tolerate any increase in CBF, then stick to 0.5 MAC or less
• Uncoupling probably too strong a term if you are talking about a lower dose VA as the drop in CMR can have a favorable impact on CBF and CBV – in addition the two still seem to be coupled (although the ratio changes) even at larger doses. Difficult to interepret some of these results because most studies use normal brains and not diseased brains (I.e. our neuro patients).

Question 35

What is the effect of VA on CMR?

Answer 35

• All agents = dose dependent ↓ CMR (except nitrous oxide)
• Order of CMR ↓
  
  • Halothane< Enflurane< Desflurane < Isoflurane < Sevoflurane
    
    • With Sevo, Iso and Des max EEG reduction at 1.5-2.0 MAC = max CMR reduction
• i.e. sevo reduces CMR the most and is theoretically superior for reducing CMR.. Desflurane and Sevoflurane are about the same as Iso and Enflurane.
• Unlike hypothermia, there is no further decrease in CMR after the EEG goes isoelectric.
• VA CMR reduction is not uniform throughout the brain – isoflurane reduces mostly in the neocortex.
• Exception with enflurane – if enflurane precipitates sz then CMR will increase. MM619-21
• Table 27-5 is important pg B754. Isoflurane’s metabolic effect which reduces CBF competes with its direct vasodilatory action to limit the net increase in CBF with this agent. Enflurane causes sz type discharges especially with hypocapnia and auditory stim can increase CMR and CBF by 50%. Des advantage over iso faster onset and recovery. However, has shown to increase ICP more in patients with altered intracranial compliance and it causes sympathetic hyperactivity. Sevo has demonstrated cerebral protection during incomplete ischemia in rats. Thus, Sevo and Iso agents of choice in neuroanesthesia

Question 36

Relationship between VA and CBF/CBV?

Answer 36

• Order of vasodilating potency:
  
  • halothane >> enflurane > isoflurane = desflurane > sevoflurane
    
    • sevo is best choice in pt with impaired neuro hemodynamics
    • halothane vasodilates the most, sevo the least
• Agent and dose dependent ⇑
  
  • CBF 20% (isoflurane)-200%(halothane)
    
    • Desflurane & Sevoflurane may actually ⇓ CBF in some areas of the brain
• Studies difficult to interpret because CBF doesn’t ⇑ uniformly throughout different brain regions
• Would not want high dose prop and VA in someone with high ICP. Stick with just prop
• CBV⇑ 10-12% and this is the factor that is most important when considering ICP
• Effect depends on baseline CMR reduction
  
  • If CMR already reduced by another drug (propofol) the VA vasodilating potency will be more dramatic and could negatively impact ICP.
• Response of cerebral vasculature to CO2 retained (in normal brain)
  
  • Hyperventilation can blunt the increased CBF/ICP with isoflurane or sevoflurane even if initiated after the VA is started ( >1.5 MAC this effect is abolished)
• Volatile agents when used at anesthetic concentrations increase CBV (compared with propofol)
  
  • should be used with caution in patients with mass occupying lesions/elevated ICP
    
    • → any chance of ICP increase, stick to TIVA

Question 37

What is the impact of VA on autoregulation?

Answer 37

• All VA impair autoregulation → Dose dependent effect
  
  • Ex: Increasing dose → BP dependence on cerebral BF more narrow
    
    • **high dose= no autoregulation
    • Importance of MAP > 50-60 w/ VA to maintain CPP
• Note left shift= less protection with HTN (worry about cerebral edema, etc)

In preliminary studies it appears sevo preserves autoregulation the most of all the volatile agents.

Looking at the graph above - what is the clinical significance? HTN during DVL, emergence, etc. maybe less protection from HTN related BBB disruption and/or hemorrhage.

Question 38

What is circulatory steal phenomenon in neuro?

Answer 38

• Possible when anesthetics are used in patients with focal ischemia
  
  • Focal= stroke, tumor, brain injury
• VA increase CBF in normal areas, however ischemic areas are already maximally dilated
• Thus, blood is redistributed from ischemic to normal areas
• Also termed “uncoupling” of CMR and CBF. VA’s alter this relationship and increase CBF when CMR is decreasing also known as “luxury perfusion” . This might be a useful effect if you are using isoflurane for controlled hypotension for example.

Question 39

Effect of VA on seizures?

Answer 39

• 1.5-2.0 MAC Enflurane → precipitate seizure patterns on EEG (spike and wave activity)
• Effect enhanced by:
  
  • Hypocapnia
  • auditory stimuli
• Sevoflurane:
  
  • rarely a/w promotion of seizure activity - might consider avoiding in patients with epilepsy
• Isoflurane:
  
  • promote spike activity – does not progress to seizure
    
    • Has been used to control patients in status epilepticus

Question 40

N2O effect on CBF?

Answer 40

• N2O Alone = CBF effect is greatest
  
  • cerebral dilation occurs
  • CMR increases
  • ICP increases
    
    • All not desirable
• With VA = CBF effect intermediate
  
  • (although can see an additive effect)
• With IV agents (propofol) = minimal effects on CBF, CMR, ICP
• Risks:
  
  • Risk with VAE or pneumocephalus → N2O expands size of emboli/air pocket
• Use in neuro patients controversial
  
  • Interferes w/ myelination & neurotoxicity

Question 41

What is the effect of IV anesthetic agents on CMR or CBF?

Answer 41

• General trend → maintain coupling between metabolism and blood flow
• CMR decrease
• CBF decrease
  
  • Exception: Ketamine (both increase)
• Range of effects:
  
  • Dramatic:
    
    • Propofol
    • Etomidate
    • Thiopental
  • Intermediate:
    
    • Dexmedetomidine
    • Benzos
  • Mild:
    
    • Opioids
      *

Question 42

Effect of barbituates on neuro hemodynamics?

Answer 42

1. Hypnosis
2. Depression of CMR 30% induction dose
3. Reduction of CBF 30% induction dose (increased cerebral vascular resistance)
4. Anticonvulsant activity (one exception)
   
   1. Methohexital promotes seizure activity
5. Robin Hood/Reverse Steal Phenomenon
   
   1. Thiopental preserves blood flow to ischemic areas
      
      1. Vasoconstrict normal brain and maintain dilation ischemic
      2. Direct blood flow from healthy to diseased brain (robin hood/reverse steal)
6. Facilitate CSF absorption

Question 43

Effects of propofol on neurohemodynamics?

Answer 43

• ⇓ICP, CBF, CBV, CMR
  
  • Appears to have efficacy in reducing ischemic cerebral injury
  • CO₂ responsiveness and autoregulation are preserved
• Anticonvulsant activity
• Short E1/2t allows for immediate post-operative neuro assessment
• CPP is a concern with cardio-depression
  
  • Although autoregulation and CO2 responsiveness maintained

Question 44

Etomidate effect on neurohemodynamics?

Answer 44

• ⇓ CMR (not a global effect cortex>brainstem)
• ⇓CBF & ICP
  
  • Propofol better at decrease in CMR and CBF
• ⇓CSF production + enhances absorption
• CO2 responsiveness retained (?autoreg no studies)
  
  • Brainstem sparing effect, why we use it in hemodynamic compromise
• Limited long-term use (adrenal suppression)
  
  • Not helpful beyond induction dose like propofol
• Might increase local tissue hypoxia & acidosis
  
  • NOT PROTECTIVE DURING ISCHEMIC EVENTS
    
    • Unlike thiopental and propofol
    • Good in trauma if you don’t think they can handle decrease in SNS
      
      • Otherwise, propofol better choice
• Caution in epileptic patients (sz foci can be activated or myoclonus can look like sz)
  
  • During ECT promotes longer/more reliable seizure activity than methohexital & propofol
  • The brainstem “sparing” effect may be responsible for the increased hemodynamic stability seen with etomidate. Myoclonic movements seen are not associated with sz on EEG in patients with no pre-existing sz disorder

Question 45

Opioids effect on neurohemodynamics?

Answer 45

Opioids

• Minimal ⇓ in CBF, CMR, and ICP unless patient awake in which case the effect is larger
  
  • Not as effective as propofol, thiopental
• May indirectly ⇑ICP via :
  
  • respiratory depression
  • histamine release (morphine/meperidine)
    
    • Histamine release can vasodilate and increase ICP
  • activation of seizure foci in temporal lobe epilepsy patients (alfentanil),
  • chest wall rigidity
  • reflex cerebral vasodilation after sudden BP ⇓with sufentanil & alfentanil
• Small doses of remifentanil (sedative doses) can cause mild ⇑in CBF, larger doses CBF ⇓
• This reflex cerebral vasodilation can occur with any opioid although more likely with sufentanil> alfentanil. Morphine not a great idea in this population because of poor lipid solubility. Later results in slow CNS penetration and prolonged CNS effects. MM621
• If the patient is aroused or in pain they can cause a modest reduction in CMR, CBF, ICP. Alfentanil has the greatest effect on MAP and CPP. B754
• Opioids have not been conclusively proven to promote seizure activity – there is one report of fentanyl increasing EEG seizure activity in patients with partial complex seizures undergoing anterior temporal lobectomy.

Question 46

Benzodiazepine effect on neuro hemodyanmics?

Answer 46

• ⇓CBF & CMR (than opioids)
• Strong anticonvulsant properties
• CO₂ responsiveness maintained.
• Midazolam best choice: short ½ life
• Flumazenil will reverse beneficial effects & potentially dramatically ⇑ICP (“overshoot”)-avoid if possible
• CPP may be reduced if large doses of midazolam are given to elderly or unstable patients and emergence may be prolonged

MM560. As with barbs blood flow reduction by benzos is thought secondary to reduction in CMR.

Question 47

Ketamine effect on hemodynamics?

Answer 47

• Unique among the IV induction agents – dilates the cerebral vasculature ⇑CBF by 50-60%
• CMR no change (limbic and reticular activation offset by depression of somatosensory, cerebellum & auditory)
• Seizure activity (thalamic & limbic areas)
• ⇓CSF absorption
• Overall effect : ⇑ ICP (in theory- not conclusively shown in humans) but might be OK if co-administered w/other agents (propofol)
  
  • In animal studies saw increase in ICP
    
    • Latest edition of Miller emphasizes the lack of human studies to verify ketamine increases ICP, even in trauma patients
  • If ketamine given with prop, benzo, sedative, tend to see no change in ICP
    
    • May be ok to give ketamine in setting with increased ICP if giving other meds to attenuate ICP
  • Ketamine also increases MAP which may be beneficial for CPP maintenance and neuroprotective
  • Ketamine is NMDA antagonist:
    
    • NMDA receptor binds to glutamate normally
    • Blocking this receptor can block the glutamate cascade and have a neuroprotective property

Stay tuned…… The universal conclusion “avoid in neuro patients” is becoming controversial-

Question 48

Effect of lidocaine, droperidol, naloxone, flumazenil on cerebral hemodynamics?

Answer 48

• Lidocaine- good adjunct
  
  • ⇓ CMR, CBF, ICP
  • Keep dose 1.5-2mg/kg to reduce systemic toxicity d/t r/f seizure
• Droperidol
  
  • Little ICP effect
  • Delay emergence
• Naloxone – caution
  
  • Reverse beneficial effects → rebound effect
  • Severe HTN
  • Vomiting
  • Try to avoid, reverse the beneficial effect of opioids and get rebound increase in ICP
  • Also can wakeup vomiting if you reverse opioidsà don’t want valsava!
• Flumazenil- caution
  
  • Reverse beneficial effects → rebound effect

Question 49

What are the effects of various adrenergic agents on cerebral hemodynamics?

Answer 49

• Effect depends on
  
  • baseline BP,
  • amt. of change in BP,
  • integrity of BBB
  • autoregulation
• Alpha - 1 agonists - little direct influence on CBF (beyond increased CPP)
• B- adrenergic agonists increase CMR & CBF (increase cardiac output + central B-1 stimulation)
  
  • Enhanced effects with BBBdisruption
• B-antagonists no direct effect CMR, CBF
  
  • Depends on how they impact overall CO and BP
• Alpha-2 agonists decrease CBF and CMR in parallel
  
  • Dexmedetomidine decreases CBF 30%
  • no evidence it causes cerebral ischemia (but watch CPP)
    
    • don’t want BP getting too low!
• Esmolol shortens seizures indicating it might cross the BBB.

Question 50

Vasodilators effect on cerebrla hemodynamics?

Answer 50

• i.e. NTP, NTG, hydralazine, adenosine, calcium channel blockers
• Response to most is cerebral vasodilation and increased CBF (dose dependent)
  
  • Maintains CBF in face of decrease MAP
• Despite reductions in BP, CPP often remains the same or increases as does ICP
• when hypotension is induced with a cerebral vasodilator, CBF is maintained at lower MAP values than when induced by either hem- orrhage or a noncerebral vasodilator. In contrast to direct vasodilators, the ACE inhibitor enalapril does not have any significant effect on CBF. L-type calcium channels highly expressed on cerebral vessels. ACE and ARBs do not impact resting BF and autoregulation is maintained

Question 51

Effect of neuromuscular blockers on cerebral hemodynamics?

Answer 51

• No direct actions
• Side-effects may be problematic
• Avoid histamine releasing (cerebral vasodilation – ICP ↑and HoTN– CPP↓)
  
  • Atracurium
  • Mivacurium
• Succinylcholine:
  
  • ↑ ICP ~ 5mmHg
    
    • offset with other drugs (propofol) and baseline decreased LOC - not contraindicated in emergency
• Pancuronium:
  
  • tachycardia
  • HTN
• Avoid light anesthesia, hypercapnia, & hypoxemia
• *Sugammadex has not been evaluated

Question 52

What are some cerebral protective agents?

Answer 52

• Calcium Channel Blockers:
  
  • Nimodipine- reduces frequency of vasospasm subsequent to subarachnoid hemorrhage and may improve outcome.
    
    • Otherwise, unclear if beneficial (thought that reducing Ca would decrease cell death → not proven)
• Steroids:
  
  • reducing edema associated with tumors (not useful in most other neurosurgical contexts – potentially harmful)
• Diuretics: (Mannitol, Furosemide)
  
  • reduce volume of brain’s ICF and ECF compartments
• Anticonvulsants:
  
  • any acute irritation of the cortical surface, head injury, SAH, cortical incisions and irritation of the brain surface by retractors has the potential to result in seizures

Question 53

What are key considerations for anesthesia during/after a cerebral ischemic event?

Answer 53

• Adequate anesthesia (no agents conclusively protective)
• Prevent seizures
• Normocapnia and normoglycemia
  
  • Hypocapnia only beneficial short term and can cause reflexive vasodilation if <20
• Avoid hyperoxia
  
  • Not conclusive if it’s a problem, but some evidence it can increase production of oxygen free radicals and cause inflammatory damage
  • O2 doesn’t have huge impact on cerebral hemodynamics, so just better to avoid hyperoxia
• CPP at least 60mmHg; MAP 70-80mmhg or 30% of baseline
• Hypothermia (prevent hyperthermia!)
  
  • 32-34 degree C for 24 hours following global ischemia with cardiac arrest improves outcome
  • Lg. studies of hypothermic patients 1) undergoing aneurysm repair under anesthesia 2) trauma patients demonstrated no benefit
  • Studies on-going in stroke patients
  • Re-warm slowly….
    
    • Don’t want them to shiver and increase CMR
• Volatile agents, propofol, TPL all have been shown to be cerebral protective. Higher incidence of thrombocytopenia, bradycardia, ventricular ectopy, hypotension and infection are common
• Barash 8th mentions that long-term cooling after TBI up to 5 days shows promise while short term cooling 24-48 hours not helpful.

Question 54

What is an EEG?

Answer 54

• The EEG signal represents summations of excitatory and inhibitory postsynaptic potentials that create electrical potentials in dendrites of neurons; if this activity is large enough, this voltage is then detected on the scalp
  
  • Measures large, spontaneous signals
  • No stimuli/measurement of specific stimuli
• EEG records the electrical potentials produced by neurons in the cerebral cortex
• The specific cells are pyramidal cells of the granular cortex that create dipole fields. If a number of dipoles develop at once the summation can be detected by voltage on the scalp.

Question 55

How is EEG interpreted?

Answer 55

• Pattern recognition – morphology, spatial & temporal distribution, waveform reactivity
• Frequency (Hz) = the number of times per second the wave crosses the zero voltage line
• Amplitude (microvolts) = the electrical height of the wave
• EEG is a plot of voltage against time usually 16 channels are recorded (reflect different brain regions)
• Table 36-1 7^th edition Barash good reference for clinical significance of EEG changes NOT in 8^th edition
• Frequency Bands**** on boards

1. Delta (0-3 Hz) – deep sleep, deep anesthesia, pathology (brain tumor, hypoxia, metabolic encephalopathy)
2. Theta (4-7 Hz) – sleep and anesthesia in adults, hyperventilation in awake pt.
3. Alpha (8-13 Hz) – resting awake with eyes closed
4. Beta (>13 Hz) mental activity, light anesthesia

• EEG used less and less as we have more sophisticated monitoring like evoked potentials
• Usually induction produces a decrease in alpha activity and an increase in beta activity. As depth of anesthesia increases EEG frequency decreases until theta and delta predominate. By further increasing the dose of anesthesia burst suppression pattern occurs, with near maximal depression of cerebral metabolic activity.

Question 56

What are intraoperative uses of EEG?

Answer 56

• Detection of cerebral ischemia and/or functional assessment of the brain (carotid endarterectomy, aneurysm repair, cardiopulmonary bypass, deliberate hypotension)
• Detection of intraoperative seizures
  
  • Ie ECT
• Assessment of pharmacologic intervention – i.e. burst suppression with TPL, recall prevention with BIS
• Special application of EEG called electrocorticogrphy - localizes epileptic foci during surgery for intractable epilepsy. Crani under local and MAC. (avoid cortical depression – with heavy anesthesia will surpress sz)B753
• BIS – the monitor collects raw EEG data from a small electrode paced over the forehead and temporal area. The raw data undergo bispectral analysis (a proprietary process involving mathmatical models) and other processed EEG parameters. A number between 1-100 is displayed on the screen which should corresponds to the degree of sedation or hypnosis of the patient. Lower numbers indicate deeper hypnosiswhile higher numbers indicated a lightly sedated or awake patient.

Question 57

What are evoked potentials?

Answer 57

• Compared to the EEG which is a recording of spontaneous random electrical activity, nonspecific function and large signal (>50microvolts)…
• Evoked potentials are smaller amplitude responses (0.1- 20microvolts) specific stimulus – pathway specific.
• Peaks and troughs characterized in terms of amplitude and latency
• Background noise (EEG, ECG, muscle activity, extraneous electrical activity) must be removed by a process called signal averaging.

Question 58

What are types of sensory evoked potentials?

Answer 58

• Monitor the functional integrity of ascending sensory pathways (afferent/posterior lateral spinal cord) Three clinically used SEPS –

1. Somatosensory – SSEP
   
   1. Middle of the road resistance to anesthetics c/t BAEP and VEP
2. Auditory – BAEP
   
   1. Anesthetics interfere the least with auditory
3. Visual – VEP
   
   1. Very, very sensitive to anesthetics

Notes:

• VEP- eye, optic nerve, optic chiasm, and visual cortex of occipital lobe. Bright stimulus via googles and detected via scalp electrodes VERY very sensitive to anesthetics. The most sensitive of all the evoked potentials.
• Amplitude measured in microvolts in SSEP and BAEP and in millivolts with MEPs.
• Sensory stimulus (click, flash, shock, etc.) – afferent nerve impulse that is detected surface electrodes. Individual peaks in the waveform are described in terms of morphology/polarity (negative and positive) latency (msec), peak-to peak amplitude (in microvolts). Compromise or injury of a neurological pathway is manifested as an increase in the latency an or a decrease in the amplitude of evoked potential waveforms B754
• brain stem responses are considerably more resistant to anesthetic influences than are cortical responses, (BAEP subcortical SSEP less sensitive). B760
• SSEPs are elicited in a cyclical repetitive manner from a peripheral nerve (median, ulnar, posterior tibial) and are usually measured at subcortex (upper cervical spine) and cortex (scalp). Latency reflects transit time along neural pathway.

Question 59

What are SSEPs?

Answer 59

• Evaluate the ability of the dorsal spinal columns to conduct an electrical signal from the periphery (or from a cranial nerve) to the sensory cortex via specific neural pathways
• Median, ulnar, common peroneal, posterior tibial, tongue, trigeminal, pudendal stimulated
• Usually measured at subcortex (upper cervical spine) and contralatertal cortex (scalp)
• Very small signal
• Prevention of neurological damage during brachial plexus exploration, resection of spinal tumors, spinal instrumentation and fusion, tethered cord release, sensory cortex lesion resection, carotid endarterectomy and aortic surgery
• A 50% reduction in amplitude or latency > 10% from baseline in response to a surgical maneuver considered significant mechanical/vascular compromise

Question 60

What are the effects of anesthetic agents on SSEPs?

Answer 60

• All VA, TPL, and N₂O⇑ the latency and ⇓the amplitude = minimize % used
  
  • Limit to 0.5 MAC
  • Get level of aneshtesia established after induction to get baseline
    
    • Avoid large boluses of anything, slow, steady, consistent anesthesia
  • fyi- TPL induction dose 3-5 mg/kg
• Opioids and Benzodiazepines– slight ⇑in latency and slight ⇓in amplitude =
  
  • good choices/avoid boluses
• Propofol-
  
  • minimal alterations in latency and ⇓ amplitude = good choice
• Ketamine and Etomidate –
  
  • may improve signals = good choices
• Dexmedetomidine minor depressant effects
  
  • OK choice
• Muscle relaxants – decrease artifact (myogenic interference)

Question 61

What are other impacts on SSEPs?

Answer 61

• Temperature – including local temperature changes via irrigating fluid
  
  • Cool irrigating fluid can cause change
• Systemic blood pressure – especially hypotension beneath limits of auto-regulation
  
  • Decreased perfusion to regions can show drop in SSEP
• Alterations in PaCO2 and PaO2

Question 62

What should you do if SSEP signals change?

Answer 62

• Look to see if another factor is influencing it → temp, BP, CO2, O2 change?
• Ask surgeon if anything changed on field
  
  • Ex: Decrease VA- add IV agents, Increase BP, correct anemia, correct hypovolemia, improve PaO2, ask the surgeon to reduce retractor pressure, reduce surgical dissection in the affected area, decrease Harrington rod distraction.
• Overall: keep steady state and communicate clearly about meds administered

Question 63

What are motor evoked potentials?

Answer 63

• Test the functional integrity of descending motor pathways. (ventral)
• Stimulation can be direct – epidural or indirect – transcranial stimulation via scalp electrodes
  
  • A larger signal than SSEP so can use a single pulse or train of pulses
• Following transcranial stimulation signal descends through dorsolateral and ventral spinal cord (pyramidal tracts primarily)
• Electromyographic signal (compound muscle action potential) can be recorded from spinal cord, contralateral peripheral nerve and/or muscle

Useful in procedures where the motor system is at risk: (anterior spinal artery risk)

1. Intramedullary tumor resection
2. Scoliosis surgery (anterolateral spinal cord)
3. Cerebral tumors/cerebrovascular procedures near motor cortex/subcortical motor pathways
4. Aortic cross clamping

* Always place a bite block to avoid tongue injury

Notes:

• Adequacy of perfusion of the spinal cord during aortic surgery better assessed using MEP (as compared with SSEP). Again there is a lot of electrical interference so averaging techniques are used as are electromyographic techniques. MEPS primarily assess the pyramidal tracts. You can also use transcranial magnetic stim – although painless these are less popular cumbersome in OR environment. B763.
• Usually MEPs are monitored in conjunction with SSEPs to fully evaluate the functional integrity of both motor and sensory pathways.

Question 64

What is the impact of anesthetics on MEPs?

Answer 64

• Extremely sensitive!
• 60% N2O abolishes MEPS (50% little change)
• Volatile Anesthetics powerful inhibitors
• Benzos, barbiturates, and propofol produce marked dose dependent depression
• Muscle Relaxants block myoneural transmission –need 1-2 twitches
  
  • Ok to give ROC for induction, but no redose
• Fentanyl, Etomidate, and Ketamine little of no change – best agents to use.
• Like SEPS hypothermia, hypoxia, and hypotension will alter MEPs under anesthesia

Question 65

What is an electromyogram (EMG)

Answer 65

• Used to monitor cranial or peripheral nerves at risk during surgery (ex: acoustic neuroma)
• Very sensitive to muscle relaxants → monitoring level at muscle
• Passive or active- Electrode placed in innervated muscle
  
  • Active
    
    • Nerve electrically stimulated
    • Response measured in terms of intensity of stimulus needed and degree of response
  • Passive
    
    • Continuous measurement of all generated responses for innervated muscle groups
    • Detects “irritation” or “impending nerve damage” audible signal real time warns the surgeon
• No interference via our anesthetic agents.
  
  • Only anesthetic restriction is muscle relaxant – AP in muscle not possible with full NMB – usually need at least 2 twitches.
• EMG is sensitive to both thermal and mechanical injury. Not a monitor of ischemia.

Question 66

Positioning basics for neuro anesthesia?

Answer 66

• Neurosurgical procedures are lengthy
• Pressure points should be padded
• Avoid pressure and traction on nerves
• Thromboembolic precautions (support hose and sequential pneumatic compression devices)
• Head-up posturing
  
  • Ex: 15-20 degrees HOB up → ensures optimal venous drainage
• exceptions are chronic subdural hemorrhage patients are usually nursed flat to discourage reaccumulation. Patients are also often maintained flat after CSF shunting to avoid overly rapid collapse of the ventricles

Question 67

Key considerations with supine positoning in neuro anesthesia?

Answer 67

• Horizontal supine almost no perfusion gradient exists between the heart and arteries in the head
• Pressures change by 2 mmHg for each 2.5cm that a given point varies in vertical height above or below the heart
  
  • May keep transducer at external auditory meatus to measure pressure in brain
  • Head 25 cm higher than heart, then 20 mmHg diff in MAP
• Head neutral or rotated for frontal, temporal, or parietal access
• Extremes of head rotation can obstruct jugular venous drainage consider a shoulder roll
• The head is neutral for bifrontal craniotomies and transsphenoidal approaches to the pituitary
• Adjusting the operating table to a chaise lounge (lawn chair) position (flexion, pillows under the knees, slight reverse Trendelenburg) promotes cerebral venous drainage and decreases back strain

Question 68

Key positioning considerations ofr lateral decubitus for neuro anesthesia?

Answer 68

• Access to:
  
  • posterior parietal
  • occipital lobes
  • lateral posterior fossa
• Useful for tumors at the cerebellopontine angle and aneurysms of the vertebral and basilar arteries
• If the legs are maintained in the long axis of the body →
  
  • almost no pressure gradients exist from head to foot
• Small hydrostatic differences are detected between the values recorded simultaneously by BP cuffs on the two arms

Question 69

Positoning considerations for prone procedure for neuroanesthesia?

Answer 69

• Uses:
  
  • Spinal cord, occipital lobe, craniosynostosis, and posterior fossa procedures
• Cervical spine and posterior fossa procedures
  
  • require neck flexion
  • reverse Trendelenburg
  • elevation of the legs
• Head positioned in a pin head holder (applied before the turn), a horseshoe headrest, or a disposable foam headrest
• This orientation serves to bring the surgical field to a horizontal position. Awake tracheal intubation and prone positioning can be used in patients with an unstable cervical spine-unchanged neurologic status confirmed before anesthesia induction
• Important to place chest rolls to prevent:
  
  • abdominal compression
  • resultant decreased diaphragmatic excursion
  • obstruction of aorta and IVC
    
    • translate pressure in other areas and increase bleeding
• Head/neck neutral –
  
  • turning can obstruct arterial perfusion and venous drainage
    
    • → increased ICP decreased CPP
• Considerations:
  
  • Head below heart level → venous congestion of the face/neck/head occur
  • Head above heart level → air entrapment in open veins possible
  • No pressure on breast/genitals, arms < 90 deg, iliac crest, knees, heels, etc padded, ETT well secured

Question 70

Discuss the prone position and risk for blindness?

Answer 70

• Caused by occlusion of central retinal vessel as a result of orbital compression
• Considerations:
  
  • Confirm eye free of pressure q15 minutes and after any surgery-related movement
  • Ischemic optic neuropathy (ION) appears to be a more frequent cause
    
    • Low BP, Hct and lengthy surgical procedures with impaired venous drainage statistically associated
  • Increased risk: lower threshold for Aline
    
    • HTN
    • Diabetes
    • Smoking
    • hyperlipidemia
    • excessive fluid admin
• However, it should be understood that not all postoperative visual loss (POVL) is a result of direct orbital compression. Note that the notion that ION is merely a function of arterial hypotension is probably an inaccurate oversimplification of a phenomenon that almost certainly involves the interplay of numerous preoperative and intraoperative factors. poor collateralization or absence of auto-regulation of the vasculature of the optic nerve head (or both), a small and therefore

anatomically “crowded” optic nerve head (the “disk at risk“)

Question 71

Considerations for sitting position? Benefits?

Answer 71

• Semi Recumbent rather than sitting.
  
  • Legs kept high w/ pillow to promote venous return → enhance CV stability
  • Pin holder apparatus
    
    • A: correct → quickly lower head (in case of emergency, VAE etc)
    • B: incorrect → cannot lower HOB w/o causing severe damage or moving to diff location
• Access to posterior fossa - midline structures (the floor of the fourth ventricle, the pontomedullary junction, and the vermis)
• Multiple complications possible, often avoided
• Number of complications often related to experience level of team
• Benefits of Sitting position:
  
  • provides excellent surgical exposure
  • facilitates venous and CSF drainage.
  • Better ventilation and easier access to the chest airway ETT and extremities.
  • Facial and conjuctival edema is reduced.

Question 72

What are some hemodynamic impacts of sitting position

Answer 72

Sitting Position and Hemodynamics

• Measuring and maintaining perfusion pressure at level of the surgical field
  
  • Transducer placement: level of Circle of Willis (tragus of ear)
• NIBP - must correct for hydrostatic difference between the arm and the operative field
  
  • Ex: A column of water 32 cm high exerts a pressure of 25 mm Hg
• Consider PA catheter if CAD or valvular heart disease
  
  • Typically place central line in case of VAE in sitting position

Sitting Position and Circulatory Stability

• Changes r/t sitting position:
• Atrial filling pressures: decrease (left > right)
• Sympathetic tone: increases
  
  • SVR increase 30-60%
  • PVR increase 50-100%
• Parasympathetic tone: decreases
• RAAS activated
  
  • Fluid and electrolytes are retained by the kidneys
  • Intrathoracic blood volume: decrease 500ml
  • Renal BF: decrease 30-75%
• CO: decrease 20-40%
• SV: decrease 50%
• HR: increases 30%
• CBF: decrease 20%
• Treatment of HoTN:
  
  • pressor administration
  • aggressive pre-positioning hydration
  • elastic bandages to legs
  • slow movement
• Evaluate the patient’s ability to tolerate reduced cardiac index, increased SVR
• Healthy patients:
  
  • CPP minimum value= 60 mmHg
• Higher CPP
  
  • elderly, hypertensive, cerebral vascular disease , cervical spinal stenosis or sustained retractor pressure to brain or spinal cord

Question 73

What are some complications of the sitting position?

Answer 73

• Head flexion
  
  • limited to by placing 2 fingers between mandible and sternum
• Macroglossia - swelling of pharyngeal structures
  
  • including soft palate, posterior wall, pharynx, and base of the tongue, has been observed
  • Caution: AW swelling → AW compromise
    
    • Avoid foreign bodies (oral AW)
• Quadraplegia or Paraplegia
  
  • Head flexion causing cervical spine cord strain or compression of vertebral arteries
• Pneumocephalus
  
  • Caution w/ N2O
• Venous Air Embolism
  
  • Head above level of heart
• Paradoxical Air Embolism
  
  • Ex: PFO, right to left shunt

Question 74

What is the rate of occurence of VAE? High risk procedures? VAE sources?

Answer 74

• Rate of occurrence depends on:
  
  • Procedure
    
    • Higher risk: near venous sinuses
  • Patient position
    
    • Risk: Sx site above level of heart
      
      • May occur when operative field is elevated 5 cm or more above the right atrial level.
  • Method of detection used (sensitivity of monitor)
    
    • Ex: Posterior fossa sx
      
      • w/ doppler → 40% detection in sitting
      • transesophageal ECHO → 76% detection
• High risk of VAE: Posterior fossa, upper c-spine procedures, and supratentorial procedures
  
  • (ex. parasagittal or meningiomas near sagittal sinus, craniosynostosis procedures- premature fusion of head bones)
• VAE sources:
  
  • emissary and cervical epidural veins
  • major cerebral venous sinuses (transverse, sigmoid, posterior half of sagittal sinus)
    
    • Problem → non-collapsible bc of dural attachments (suck air in if left exposed)
  • Pins
    
    • Important to remove pins AFTER head lowered at end of case

Question 75

What is the pathophysiology behind VAE?

Answer 75

• intense vasoconstriction in pulmonary circulation (secondary to mechanical obstruction and hypoxic vasoconstriction) which results in:
  
  • VQ mismatch
  • interstitial pulmonary edema
  • reduced cardiac output as pulmonary vascular resistance increases.
• Air may also pass directly through the pulmonary circulation or through right to left cardiac shunts (PFO 20-30% population) to the coronary and cerebral circulation when right atrial pressure exceeds left atrial pressure.
  
  • In sitting position 50% of patients right atrial pressure exceeds left atrial pressure – risk PAE (paradoxical air embolism) is 5-10%. Avoid in patients with a known PFO.

Question 75

What are various means to monitor for VAEs? Most sensitive detector?

Answer 75

• Precordial Doppler and ETCO2 monitoring
  
  • current standard of care
• TEE
  
  • more sensitive to VAE than precordial Doppler
  • offers advantage of identifying right-to-left shunting of air
    
    • detects low volumes of air
    • Cons: risk of esophageal perforation
• Expired N2 concentrations
  
  • very small unless large VAE thus lack sensitivity

VAE sensitivity monitors

• T-ECHO- very sensitive
  
  • Detect before any compromise (ideal)
  • TEE is more sensitive to VAE than precordial Doppler) and offers the advantage of identifying right-to-left shunting of air. However, its safety during prolonged use (especially with pronounced neck flexion) is not well established.
• Doppler- standard of care
  
  • Detect before compromise
    
    • Technique: placed parasternal (R or L side- better R) between 4^th and 6^th intercostal spaces
      
      • Better R → more likely to have R atrial air
• ETCO2- see greatly dampened
  
  • Modest physiologic change by ETCO2 dampen
  • Use WITH doppler as standard of care
• CO/CVP
  
  • Clinically apparent changes

Question 76

Management of VAE?

Answer 76

• Prevent further air entry

1. Notify surgeon (flood or pack surgical field)     
2. Jugular compression    
3. Lower head
   
   1. Stop more air from entering

• Treat the intravascular air     

1. Aspirate via a right heart catheter
2. Discontinue N2O     
3. FIO2: 1.0 (max)   
4. Pressors/inotropes/CPR

Question 77

Placement of right heart catheter during neurosurgical procedures?

Answer 77

• All patients who undergo sitting posterior fossa procedures should have one
• Catheter location:
  
  • Multiorifice catheter → tip 2 cm below the superior vena cava (SVC)-atrial junction
• Single-orifice catheter→ tip 3 cm above the SVC-atrial junction
• After full evaluation may omit the right sided catheter for pt. in non-sitting position or lower risk sitting procedures (microvascular nerve decompression etc.)