Cerebral Physiology and the Effects of Anesthetic Drugs

Question 1

The brain has a high metabolic rate and receives approximately …% of cardiac output.

Under normal circumstances, cerebral blood flow (CBF) is approximately …

Gray matter receives …% and white matter receives …% of this blood flow

Answer 1

12% to 15

50 mL/100 g/min

80

20

Question 2

CBF is autoregulated and remains constant over a mean arterial pressure (MAP) range estimated
at …, given normal venous pressure

Answer 2

65 to 150 mm Hg

Question 3

Vasopressors such as phenylephrine, norepinephrine, ephedrine, and dopamine cause significant cerebral vasoconstrition. Thus, they should be used with caution in patients with increased ICP

T or F

Answer 3

F

Vasopressors such as phenylephrine, norepinephrine, ephedrine, and dopamine do not have appreciable direct effects on the cerebral circulation. Their effect on CBF is via their effect on arterial blood pressure. When the MAP is less than the lower limit of autoregulation, vasopressors increase the
MAP and thereby increase CBF. If the MAP is within the limits of autoregulation, then vasopressor-induced increases in systemic pressure have little effect on CBF

Question 4

All volatile anesthetics suppress cerebral metabolic rate (CMR) and, with the exception of
…, can produce burst suppression of the electroencephalogram

Answer 4

halothane

Question 5

Brain stores of oxygen and substrates are limited, and the brain is extremely sensitive to
decreases in CBF. Severe decreases in CBF (< … mL/100 g/min) lead to rapid neuronal death.

Answer 5

6-10

Question 6

… [list of anesthetics] have neuroprotective efficacy and can reduce ischemic cerebral injury in experimental models.

This anesthetic neuroprotection is sustained only when the severity of the ischemic insult is mild; with moderate-to-severe injury, long-term neuroprotection is not achieved. The neuroprotective efficacy of anesthetics in humans is limited.

Administration of … can decrease regional blood flow, which can exacerbate ischemic brain injury

Answer 6

Barbiturates, propofol, ketamine, volatile anesthetics, and xenon

etomidate

Question 7

In general, anesthetic drugs suppress the CMR, with the exception of …

Answer 7

ketamine and nitrous oxide (N2O)

Question 8

The CMR decreases by …% per degree Celsius of temperature reduction

Answer 8

6% to 7

Question 9

Hypothermia can slow the EEG but can not cause it’s complete supression

T or F

Answer 9

F

Hypothermia can also cause complete suppression of the EEG (at approximately
18°C-20°C)

Question 10

Temperature reduction beyond that at which EEG suppression first occurs (18°C - 20°C) does produce a further decrease in the CMR

T or F

Answer 10

T

Question 11

CBF changes … for each 1 mm Hg change in Paco2 around normal Paco2 values. This response is attenuated at a Paco2 less than … mm/Hg or bigger than … mm/Hg

Answer 11

1 to 2 mL/100 g/min

25

75-80

Question 12

Why does respiratory acidosis have a bigger acute effect in the CBF than metabolik acidosis?

Answer 12

The changes in CBF caused by Paco2 are dependent on pH alterations in the extracellular fluid of the brain. NO, in particular NO of neuronal origin, is an important although
not exclusive mediator of CO2-induced vasodilation. The vasodilatory response to hypercapnia is also mediated in part by prostaglandins. The changes in extracellular pH
and CBF rapidly occur after Paco2 adjustments because CO2 freely diffuses across the cerebrovascular endothelium and the BBB. In contrast with respiratory acidosis, acute
systemic metabolic acidosis has little immediate effect on CBF because the BBB excludes H+ from the perivascular space

Question 13

The CBF changes in response to alterations in Paco2 rapidly occur, but they are not sustained. Despite the maintenance of an increased arterial pH, CBF returns toward normal over a period of … hours because the …

Answer 13

6 to 8

pH of CSF gradually returns to normal levels as a result of extrusion of bicarbonate

Question 14

Changes in Pao2 from … to more than … mm/Hg have little influence on CBF.

A reduction in Pao2 below … mm/Hg rapidly … CBF

Answer 14

60

300

60

increases

Question 15

Will the administration of α1-agonists (phenylephrine, norepinephrine) reduce CBF?

Answer 15

Studies in humans and nonhuman primates do not confirm this concern

Question 16

Alfa 2 agonists effects in the CBF

Answer 16

Dexmedetomidine reduces CBF.

The effects of dexmedetomidine on CBF are primarily mediated by its ability to suppress the CMR; the reduction in CBF is commensurate with the reduction in CMR, and there is no evidence that dexmedetomidine causes cerebral ischemia. However, the well-known effect of dexmedetomidine in decreasing arterial blood pressure merits careful consideration if used in patients who are critically dependent on collateral perfusion pressure, especially in the recovery phase of an anesthetic

Question 17

Calcium channel blockers effects in the CBF

Answer 17

The available data indicate that CCBs are moderate cerebral vasodilators. Their net impact on CBF is therefore dependent on the extent of systemic vasodilation and MAP. When MAP is maintained, increases in CBF should be expected.

Question 18

How do benzodiazepines affect the CBF? Compare with barbiturates and narcotics

Answer 18

The available data indicate that benzodiazepines cause a moderate reduction in CBF in humans, which is coupled to metabolism.

The extent of the maximal reductions of CBF and CMR produced by benzodiazepines is probably intermediate between the decreases caused by narcotics (modest) and barbiturates (substantial)

Question 19

Ketamine enantiomers and general effects in the CBF e and ICP

Answer 19

The (S)-ketamine enantiomer substantially increases CMR, whereas the (R) enantiomer tends to decrease the CMR, particularly in the temporomedial cortex and in the cerebellum

A recent metaanalysis concluded that, in humans, ketamine administration increases CBF, particularly in the anterior cingulate gyrus, medial prefrontal cortex, and occipital lobes. In aggregate, the available data indicate that ketamine does increase CBF, and the accompanying increase in CMR is at best modest. Ketamine does not increase CBV.
The anticipated increase in ICP with an increase in CBF has not been confirmed to occur in humans

In fact, decreases in ICP occur when relatively large anesthetic doses of ketamine (1.5-5 mg/kg) are administered to patients with head injuries who are sedated with propofol. However, it should be noted that, in most of the studies in which the ICP effects of ketamine have been evaluated, patients received sedative agents in addition to ketamine. It has been established that anesthetic drugs (diazepam, midazolam, isoflurane-N2O, propofol, opioids, methohexital) blunt or eliminate the increases in ICP or CBF associated with ketamine

Question 20

Of the commonly used volatile anesthetics, the order of vasodilating potency is approximately

Answer 20

halothane ≫ enflurane > desflurane ≈ isoflurane > sevoflurane

Question 21

Volatile anesthetics effects in the CBF

Answer 21

The net effect of volatile anesthetics on CBF is therefore a balance between a reduc-tion in CBF caused by CMR suppression and an augmen- tation of CBF caused by the direct cerebral vasodilation. When administered at a dose of 0.5 MAC, CMR suppression–induced reduction in CBF predominates, and net CBF decreases in comparison with the awake state. At 1 MAC, concentrations of isoflurane, sevoflurane, or desflurane, CBF remains unchanged; at this concentration, CMR suppression and vasodilatory effects are in balance. Beyond 1 MAC, the vasodilatory activity predominates, and CBF significantly increases, even though the CMR is substantially reduced

Question 22

Do volatile anesthetics cause loss of neurovascular coupling?

Answer 22

The increase in CBF produced by volatile anesthetics at doses larger than 1 MAC has been referred to as reflecting a loss of neurovascular coupling. However, coupling (CBF adjustments paralleling changes in the CMR) persists during anesthesia with volatile anesthetics. Accordingly, the conclusion should be that the CBF/CMR ratio is altered (increased) by volatile anesthetics. This alteration is dose related, and under steady-state conditions, increasing doses of volatile agents lead to greater CBF/CMRO2 ratios — that is, higher MAC levels cause greater luxury perfusion

Question 23

Cerebrovascular CO2 responsiveness is well maintained during anesthesia with all volatile anesthetics

T or F

Answer 23

T

Question 24

Do volatile anesthetics cause increase in the ICP?

Answer 24

Volatile anesthetics have modest effects on cerebral hemodynamics in patients with normal intracranial compliance.

However in patients with abnormal intracranial compliance, the potential for volatile anesthetic–induced increases in CBV and ICP exist. Accordingly, volatile anesthetics should be
used with caution in the setting of large or rapidly expanding mass lesions, unstable ICP, or other significant cerebral physiologic derangements in which CO2 responsiveness
and neurovascular coupling may be impaired

Question 25

N2O effects o CNS perfusion

Answer 25

N2O can cause increases in CBF and ICP

Question 26

Volatile anesthetics assocaiated with seizures

Answer 26

Enflurane is potentially epileptogenic in clinical setting. Of particular relevance to neuroanesthesia is the observation that hypocapnia potentiates seizure-type discharges during enflurane anesthesia

Seizures can occur during the induction of anesthesia with high concentrations of sevoflurane in children, including those without a recognized seizure diathesis. In two healthy humans, EEG burst suppression with 2 MAC sevoflurane was accompanied by epileptiform discharges that were observed during EEG monitoring

• Isoflurane can cause EEG spiking and myoclonus, but it has not been associated, in the experimental setting, with the frank epileptoid activity induced by enflurane.

Question 27

Does etomidate cause seizures?

Answer 27

Etomidate has been shown to precipitate generalized epileptic EEG activity in epileptic patients, and its use in this population should probably be avoided.

In subjects who are neurologically normal, no convincing reports indicate epileptogenesis and the use of etomidate need not be restricted on this basis. In fact, etomidate has been used to
control refractory status epilepticus

Question 28

Is benefical to induce mild hypothermia after cardiac arrest?

Answer 28

Induced mild hypothermia is effective in reducing mortality and morbidity in patients who sustain a cardiac arrest that is followed by altered mental status with a Glasgow Coma Scale score of 7 or less

• Induction of mild hypothermia in the range of 32°C to 34°C for a period of approximately 24 hours improved neurologic outcome and
  survival 6 months after cardiac arrest in comparison with a normothermic group. Mild hypothermia was induced without difficulty. Passive rewarming of patients was slowly
  accomplished over a period of 8 hours

Question 29

Barbiturates appear to promote neuroprotection in cases of focal cerebral ischemia. Does this neuroprotection occur with all barbiturates?

Answer 29

Recent data suggest that the neuroprotective efficacy of barbiturates is not similar. In a direct comparison of three clinically used barbiturates, methohexital and thiopental, but not pentobarbital, reduced injury in an animal model of focal ischemia.
These data suggest that mechanisms other than or at least in addition to metabolic suppression may contribute to the protective effect of barbiturates

Question 30

Do halogenated anesthetics have neuroprotection properties?

Answer 30

In comparison with the awake or N2O-fentanyl–anesthetized state, isoflurane is neuroprotective in models of hemispheric, focal, and nearly complete ischemia. Of substantial clinical relevance is the observation in a preclinical investigation that isoflurane’s neuroprotective efficacy is not sustained. When injury was evaluated 2 days after ischemia, a robust reduction in injury was observed with isoflurane anesthesia. However, by 14 days, this reduction
in injury was no longer apparent. These data indicate that neuronal injury continues well into the postischemic recovery period and that the neuroprotective benefit that is evident shortly after ischemia may not persist for the long term.

More recent data have shown that isoflurane treatment can improve neuronal survival when the severity of ischemia is limited and the restoration of blood flow after ischemia is
complete.

The neuroprotective effect of isoflurane is not substantially different from that of other volatile anesthetics

Question 31

Does etomidate have neuroprotective properties?

Answer 31

In patients subjected to temporary intracranial vessel occlusion, the administration of etomidate results in greater tissue hypoxia and acidosis than equivalent desflurane anesthesia. The aggravation of injury produced by etomidate (an imidazole) may be related to direct binding of NO as a consequence of etomidate-induced hemolysis combined with direct inhibition of the NO synthase enzyme by etomidate.
Therefore, no scientific studies support the current use of etomidate for cerebral protection and, in fact, suggest that it may actually be deleterious in the setting of focal ischemia

Question 32

At the current time, hypothermia for purposes of neuroprotection in the setting of acute ischemic stroke is not recommended

T or F

Answer 32

T

Question 33

In patients who had sustained cardiac arrest and who were admitted to an intensive care unit after successful recovery of circulation, hyperoxia increased mortality. The threshold Pao2 that leads to this increase in mortality is greater than …

Answer 33

300 mm/Hg

Question 34

Barbiturates are the indicated anesthetics for neuroprotection based on strong literature data suporting they superiority

T or F

Answer 34

F

Volatile anesthetics, barbiturates, propofol, xenon, and ketamine reduce injury in experimental models and may reduce injury in comparison with a pure N2O-narcotic anesthetic. However, direct comparison has not
demonstrated the superiority of any one anesthetic (or combination of anesthetics) over
another. Therefore, based on the available data, the use of a specific anesthetic or anesthetic regimen for the purpose of brain protection in the clinical setting cannot be recommended.

Question 35

In carotid endarterectomy, general anesthesia is superior to local anesthesia because of it’s neuroprotection features

T or F

Answer 35

F

In the general anesthesia versus local anesthesia trial, patients undergoing CEA were randomized to receive either general anesthesia or local anesthesia; in the latter group, patients were lightly sedated but were arousable during surgery. The outcome between the two groups was not different, indicating that the general anesthetic state did not provide any protective
benefit

Question 36

It has been demonstrated that, on average, a …% reduction in the MAP will bring both normotensive and hypertensive patients to the lower limit autoregulation

Answer 36

25