Cerebral circulation and anaesthetic implications

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Cerebral circulationand anaesthetic implications

• Modreator-Dr Manoj Bharadwaj
• Speaker-Dr Amlan Swain

www.anaesthesia.co.in anaesthesia.co.in_at_gmail.co
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Overview of cerebral circulation
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Overview of cerebral circulation
Arterial supply
Posterior Cerebral artery
Anterior Cerebral artery
Basilar artery
30 of CBF
Vertebral artery
Middle Cerebral artery
Internal Carotid artery (70 of CBF)
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Overview of cerebral circulation
Circle of Willis
Anterior CA
Internal CA
Middle CA
Posterior CA
Basilar A
Vertebral A
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Overview of cerebral circulation
Venous drainage
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Cerebral Artery Areas
1. anterior cerebral 2. Middle cerebral 3.
Penetrating branches of middle cerebral 4.
anterior choroidal 5. Posterior cerebral
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Cerebral physiology

• 2 of BW
• 20 of Total body oxy consumption
• (60 used for ATP formation)
• CMR O2 3-3.8mL /100 gm/min
• (50 ml /min in Adult)
• 15 0f CO
• Glucose consumption 5 mg/100gm/min
• (25 of total body consumption/min)

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.contd

• High oxygen consumption but no reserve
• Grey matter of cerebral cortex consumes more
• Directly proportional to electrical activity
• (Hippocampus cerebellum most sensitive to
  hypoxic injury)

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NORMAL PHYSIOLOGIC VALUES
CBF
GLOBAL 45-55ml/100g/min
CORTICAL 75-80ml/100g/min
SUBCORTICAL 20ml/100g/min
CMRO2 3-3.5ml/100g/min
CVR 2.1mmHg/100ml/min/ml
Cerebral venous Po2 32-44mmhg
Cerebral venous So2 55-70
ICP(supine) 8-12mm Hg
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• Approximately 60 of the brain's energy
  consumption is used to support
  electrophysiological function.
• Remaining 40-?

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• Local CBF (l-CBF) and local CMR (l-CMR) within
  the brain are very heterogeneous, and both are
  approximately four times greater in gray matter
  than in white matter.

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• The brain's substantial demand for substrate must
  be met by adequate delivery of O2 and glucose.
• However, the space constraints imposed by the
  noncompliant cranium and meninges require that
  blood flow not be excessive.
• Not surprisingly, there are elaborate mechanisms
  for the regulation of CBF.

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Cerebral perfusion pressure

• MAPICP( or CVP whichever is greater)
• Normally 80 to 100mm Hg
• ICP is lt10 mmHg so CPP primarily dependent on MAP
• Increase in ICPgt30 CPP CBF compromise
• CPPlt50 slowing of EEG
• 25-40 Flat EEG
• CPP lt25 result in Irreversible brain
  death
  

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Factors influencing CBF

• CHEMICAL/METABOLIC
• MYOGENIC
• RHEOLOGIC
• NEUROLOGIC

• CHEMICAL/METABOLIC
• MYOGENIC
• RHEOLOGIC
• NEUROLOGIC

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CHEMICAL/METABOLIC
CERBRAL METABOLIC RATE
Arousal/seizures mental tasks
Anesthetics
Temperature
Paco2
Pao2
Vasoactive drugs
Anesthetics
Vasodilators
Vasopressors
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Cerebral Metabolic Rate

• Increased neuronal activity results in increased
  local brain metabolism
• Although it is clear that local metabolic factors
  play a major role in these adjustments in CBF,
  the complete mechanism of flowmetabolism coupling
  remains undefined.

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• CMR is influenced by several phenomena in the
  neurosurgical environment
• functional state of the nervous system
• anesthetic agents, and
• temperature

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Functional State.

• CMR decreases during sleep and increases during
  sensory stimulation, mental tasks, or arousal of
  any cause.
• During epileptoid activity, CMR increases may be
  extreme, whereas CMR may be substantially reduced
  in coma.

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Anesthetics.

• In general, anesthetic agents suppress CMR
• Ketamine and nitrous oxide the notable
  exceptions.
• It appears that the component of CMR on which
  they act is that associated with
  electrophysiologic function.
• However, increasing the plasma level beyond that
  required first to achieve suppression of the EEG
  results in no further depression of CMR..

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The interdependencyof cerebral electrophysiologic
function and CMR
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Temperature.

• CMR decreases by 6 to 7 percent per Celsius
  degree of temperature reduction.
• However, in contrast to anesthetic agents,
  temperature reduction beyond that at which EEG
  suppression first occurs does produce a further
  decrease in CMR

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The effect of temperature reduction on the
cerebral metabolic rate of oxygen
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Temperature on CBF

• 6-7 decrease /0C FALL IN TEMP.
• 37-42 0C - CBF CMRO2
• gt42 0C - CMRO2
• 20 0C - ISOELECTRICITY

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Partial Pressure of Carbon Dioxide

• CBF varies directly with PaCO2
• The effect is greatest within the range of
  physiologic PaCO2 variation.
• CBF changes 1 to 2 mL/100 g/min for each 1 mm Hg
  of change in PaCO2around normal PaCO2 values.
• This response is attenuated below a Pa CO2 of 25
  mm Hg.

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• The changes in CBF caused by PaCO2 are apparently
  dependent on pH alterations in the extra cellular
  fluid of the brain
• Note that in contrast to respiratory acidosis,
  acute systemic metabolic acidosis has little
  immediate effect on CBF because the blood-brain
  barrier (BBB) excludes the hydrogen ion from the
  perivascular space.

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• Although the CBF changes in response to Pa CO2
  alteration occur rapidly, they are not sustained.
• In spite of the maintenance of an elevated
  arterial pH, CBF returns to normal over 6 to 8
  hours because cerebrospinal fluid (CSF) pH
  gradually normalizes as a result of the extrusion
  of bicarbonate.

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• Although the CBF changes in response to Pa CO2
  alteration occur rapidly, they are not sustained.
• In spite of the maintenance of an elevated
  arterial pH, CBF returns to normal over 6 to 8
  hours because cerebrospinal fluid (CSF) pH
  gradually normalizes as a result of the extrusion
  of bicarbonate.

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• . Acute normalization of PaCO2 results in a
  significant CSF acidosis (after hypocapnia) or
  alkalosis (after hypercapnia).
• The former results in increased CBF with a
  concomitant intracranial pressure (ICP) increase
  that will depend on the prevailing intracranial
  compliance. The latter conveys the theoretic risk
  of ischemia.

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Steal Phenomenon

• If local autoregulation is impaired and PaCO2
  increases, vessels in surrounding normal brain
  will dilate.
• Vessels in the abnormal area are already
  maximally dilated due to loss of autoregulation.

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• Vascular resistance will be decreased in
  surrounding normal brain blood will be shunted
  away from abnormal areas, resulting in further
  hypoxia

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Inverse Steal or Robin Hood Phenomenon

• Opposite may occur as PaCO2 is decreased by
  hyperventilation.
• Vessels in surrounding normal brain will
  vasoconstrict vessels in the damaged or abnormal
  area of brain are already maximally dilated and
  are unable to constrict.

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• Because of the vasoconstriction in normal brain,
  vascular resistance increases, shunting blood
  into the abnormal area

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Partial Pressure of Oxygen

• Changes in PaO2from 60 to more than 300 mm Hg
  have little influence on CBF.
• When the PaO2is less than 60 mm Hg, CBF
  increases rapidly .
• At high PaO2values, CBF decreases modestly.

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• The mechanisms mediating the cerebral
  vasodilation during hypoxia are not fully
  understood, but they may include neurogenic
  effects initiated by peripheral and/or neuraxial
  chemoreceptors as well as local humoral
  influences
• At 1 atm O2,CBF is reduced by 12 percent.

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Myogenic Regulation (Autoregulation)

• Autoregulation refers to the capacity of the
  cerebral circulation to adjust its resistance in
  order to maintain CBF constant over a wide range
  of mean arterial pressure (MAP).

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• In normal human subjects, the limits of
  autoregulation occur at MAPs of approximately 70
  and 150 mm Hg
• Above and below the autoregulatory plateau, CBF
  is pressure dependent (pressure passive) and
  varies linearly with CPP.

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• Autoregulation Curve shift to Rt in Chronic
  hypertensive
• Decreased CPP Leads to vasodilation
• Increased CPP leads to vasoconstriction

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• The precise mechanism by which autoregulation is
  accomplished is not known.
• NO may participate in the vasodilation
  associated with hypotension in some species, but
  not, according to a single study, in primates

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Neurogenic Regulation

• There is considerable evidence of extensive
  innervation of the cerebral vasculature.
• The density of innervation declines with vessel
  size, and the greatest neurogenic influence
  appears to be exerted on larger cerebral
  arteries.

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• This innervation includes autonomic,
  serotonergic, and vasoactive intestinal
  peptide-ergic (VIPergic) systems of extra-axial
  and intra-axial origin.

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Viscosity Effects

• Blood viscosity can influence CBF.
• Hematocrit is the single most important
  determinant of blood viscosity.
• In healthy subjects, hematocrit variation within
  the normal range (33-45) probably results in
  only trivial alteration of CBF.
• Beyond this range, changes are more substantial.

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EFFECTS OF ANESTHETIC AGENTS ON CBF AND CEREBRAL
METABOLIC RATE

• In neuroanesthesia, considerable emphasis is
  placed on the manner in which anesthetic agents
  and techniques influence CBF.
• The rationale is 2-fold.

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• First, the delivery of energy substrates is
  dependent on CBF, and, in the setting of
  ischemia, modest alterations in CBF can
  substantially influence neuronal outcome.

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• Second, the control and manipulation of CBF are
  central to the management of ICP because, as CBF
  varies in response to vasoconstrictor-vasodilator
  influences, such as Pa CO2 and volatile
  anesthetics, CBV varies linearly with it
• Autoregulation normally serves to prevent
  MAP-related increases in CBV

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• In healthy subjects, the initial increases in
  CBV do not result in significant ICP elevation
  because there is latitude for compensatory
  adjustments by other intracranial compartments
• When intracranial compliance is reduced, a CBV
  increase can cause herniation or may reduce CPP
  sufficiently to cause ischemia.

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• There have been several investigations of the
  effects of anesthetic agents on CBV in normal
  brain.
• In general, the observed effects confirm a
  parallel relationship between CBF and CBV.
• However, the relationship is not consistently one
  to one, and CBF-independent influences on CBV
  may occur.

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• Anesthetic agents may influence the venous side
  of the cerebral circulation.
• At present, there is no evidence that these
  direct effects have clinical significance.

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• Nonetheless, the importance of blood volume on
  the venous side of the cerebral circulation
  should not be overlooked.
• Passive engorgement of these vessels as a result
  of the head-down posture, compression of the
  jugular venous system, or high intrathoracic
  pressure can have dramatic effects on ICP

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Intravenous Anesthetic Agents

• The general pattern of the effect of intravenous
  anesthetic agents is one of parallel alterations
  in CMR and CBF.
• Most intravenous agents cause a reduction of
  both.
• Ketamine, which causes an increase in CMR and
  CBF, is the exception.

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Barbiturates

• A dose-dependent reduction in CBF and CMR occurs
  with barbiturates.
• With the onset of anesthesia, CBF and CMR are
  reduced by about 30 percent.
• When large doses of thiopental cause complete EEG
  suppression, CBF and CMR are reduced by about 50
  percent.
• Further increases in the dose of barbiturate have
  no additional effect on CMR

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Propofol

• The effects of propofol (2,6-di-isopropylphenol)
  on CBF and CMR appear to be quite similar to
  those of the barbiturates.
• Three investigations in humans have revealed
  substantial reductions in both CBF and CMR after
  propofol administration.
• Both CO2 responsiveness and autoregulation appear
  to be preserved during the administration of
  propofol in humans

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Narcotics

• There are inconsistencies in the available
  information, but it is likely that narcotics have
  relatively little effect on CBF and CMR in the
  normal, unstimulated nervous system.
• When changes occur, the general pattern is one of
  modest reductions in both CBF and CMR.

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Morphine.

• When morphine (1 mg/kg) was administered as the
  sole agent in human patients, Moyer et al
  observed no effect on global CBF and a 41 percent
  decrease in CMRO2 .
• There have been no other such investigations of
  morphine alone in humans.

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Fentanyl.

• Limited human data are available
• Several investigations in lightly anesthetized
  animals demonstrated much larger fentanyl-induced
  reductions in CBF and/or CMR than those observed
  in humans.
• These data taken together suggest that fentanyl
  causes a moderate global reduction in CBF and CMR
  in the normal quiescent brain and, like morphine,
  causes larger reductions when administered during
  arousal.

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Benzodiazepines

• .The extent of the maximal CBF and CMR reductions
  produced by benzodiazepines is probably
  intermediate between the decreases caused by
  narcotics (modest) and barbiturates
  (substantial).
• It appears that benzodiazepines should be safe to
  administer to patients with intracranial
  hypertension provided respiratory depression and
  an associated increase in Pa CO2 do not occur.

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Ketamine

• Among the intravenous agents, ketamine is unique
  in its ability to cause increases in both CBF and
  CMR
• In the only investigation of CMR effects in
  humans, Takeshita et al observed a 62 percent
  increase in CBF and no change in CMR, and the
  explanation for this discrepancy is unclear.

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• The anticipated ICP correlate of the CBF increase
  has been confirmed to occur in humans.
• However, anesthetic agents (diazepam, midazolam,
  isoflurane/N2 O) have been shown to blunt or to
  eliminate the ICP or CBF increases associated
  with ketamine

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• Accordingly, although ketamine is probably best
  avoided as the sole anesthetic agent in patients
  with impaired intracranial compliance, it may be
  reasonable to use it cautiously in patients who
  are simultaneously receiving the other agents
  mentioned earlier.

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Lidocaine

• Lidocaine produces a dose-related reduction of
  CMRO2 in experimental animals.
• In unanesthetized human volunteers, Lam et al
  observed CBF and CMR reductions of 24 and 20
  percent, respectively

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Changes in (CBF) and the (CMRO2 ) caused by I V
agents
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Volatile Anesthetics

• The pattern of volatile agent effects on cerebral
  physiology is a striking departure from that
  observed with the intravenous agents, which cause
  generally parallel changes in CMR and CBF.
• All the volatile agents produce a dose-related
  reduction in CMR while simultaneously causing no
  change or an increase in CBF.

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effect of increasing concentrations of a typical
volatile anesthetic onautoregulation of cerebral
blood flow
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• It has been said that volatile agents cause
  "uncoupling" of flow and metabolism.
• It is probably more accurate to say that the
  CBF/CMR ratio is altered (increased) by volatile
  anesthetics.

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• The important clinical consequences of volatile
  agent administration are derived from the
  increases in CBF and CBV, and consequently ICP,
  that can occur.
• Of the commonly employed volatile agents, the
  order of vasodilating potency is approximately
  halothane gtgt enflurane gt isoflurane sevoflurane
  desflurane.

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CMR Effects

• All the volatile agents cause reductions in CMR.
• The degree of CMR reduction that occurs at a
  given MAC level is less with halothane than with
  the other four agents

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• With isoflurane (and almost certainly desflurane
  and sevoflurane as well), maximal reduction is
  attained simultaneously with the occurrence of
  EEG suppression.
• This occurs at clinically relevant
  concentrations, that is, 1.5 to 2.0 MAC in humans

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Estimated changes in (CBF) and the (CMRO2 )caused
by volatile anesthetics.
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Distribution of CBF/CMR Changes.

• The regional distribution in anesthetic-induced
  changes in CBF and CMR differs markedly with
  halothane and isoflurane.
• Halothane produces relatively homogeneous
  changes throughout the brain.
• CBF is globally increased, and CMR is globally
  depressed.

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• The changes caused by isoflurane are more
  heterogeneous.
• CBF increases are greater in subcortical areas
  and hindbrain structures than in the neocortex
• For CMR, the converse is true, with greater
  reduction in the neocortex than in the subcortex.

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Cerebral Vasodilation by Volatile Agents
Clinical Implications.

• Isoflurane and, probably, desflurane and
  sevoflurane may have little cerebral vasodilating
  effect in cortex, they nonetheless probably cause
  net cerebral vasodilation in a dose-dependent
  fashion.
• Are isoflurane and desflurane and sevoflurane
  therefore contraindicated in the face of abnormal
  intracranial compliance? No

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• Instances of ICP increases in response to the
  administration of isoflurane observed in the
  studies of Adams et al and Campkin et al were
  usually readily prevented or reversed by the
  induction of hypocapnia.

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• This indicates that, particularly in the sub-MAC
  concentrations typical of balanced anesthesia,
  the use of these drugs is reasonable when there
  is proper attention to the other important
  determinants of ICP, in particular CO2 tension.

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CO2 Responsiveness and Autoregulation

• CO2 responsiveness is well maintained during
  anesthesia with all the volatile anesthetic
  agents.
• By contrast, autoregulation of CBF in response to
  rising arterial pressure is impaired.
• This impairment appears to be most apparent with
  the agents that cause the greatest cerebral
  vasodilation, and it is dose related

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Nitrous Oxide

• The available data indicate unequivocaly that
  N2O can cause increases in CBF, CMR, and ICP.
• When N2O is administered alone, very
  substantial increases in CBF and ICP can occur
• .

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• The addition of N2 O to an established anesthetic
  with a volatile agent results in moderate CBF
  increases.
• in combination with intravenous agents,
  including barbiturates, benzodiazepines,
  narcotics, and propofol, its cerebral
  vasodilating effect is attenuated or even
  completely inhibited.

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Clinical Implications.

• The data indicate that the vasodilatory action of
  N2O can be clinically significant in
  neurosurgical patients with reduced intracranial
  compliance.
• However, it appears that N2O induced cerebral
  vasodilation can be considerably blunted by the
  simultaneous administration of intravenous agents

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• Nonetheless, when ICP is persistently elevated
  or the surgical field is persistently "tight,"
  N2O should be viewed as a potential contributing
  factor.
• In addition, the ability of N2O to enter a
  closed gas space rapidly should be recalled, and
  this drug should be avoided or omitted when a
  closed intracranial gas space may exist.

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Effect of volatile anesthetics on cerebral blood
flow
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Effect of volatile anesthetics on the cerebral
metabolic rate of oxygen
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Nondepolarizing Relaxants

• The only recognized effect of nondepolarizing
  relaxants on the cerebral vasculature occurs via
  the release of histamine.
• Histamine can result in a reduction in CPP
  because of the simultaneous increase in ICP
  (caused by cerebral vasodilation) and decrease in
  MAP

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• d-Tubocurarine is the most potent histamine
  releaser among available muscle relaxants.
• Metocurine, atracurium, and mivacurium also
  release histamine in lesser quantities.
• Vecuronium, in relatively large doses 0.1 to 0.14
  mg/kg, had no significant effect on cerebral
  physiology

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Succinylcholine

• Succinylcholine can produce an increase of ICP in
  lightly anesthetized human patients.
• ?

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• Effect appears to be the result of cerebral
  activation (as evidenced by EEG changes and CBF
  increases) caused by afferent activity from the
  muscle spindle apparatus.
• Note, however, that there is a poor correlation
  between the occurrence of visible muscle
  fasciculations and an increase in ICP. .

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• Although succinylcholine can produce ICP
  increases, it need not be viewed as
  contraindicated when its use for rapid attainment
  of paralysis is otherwise seen as appropriate

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Critical CBF Levels and the Ischemic Penumbra
Concept

• In the face of a declining O2 supply, neuronal
  function deteriorates progressively
• It is not until CBF has fallen to approximately
  22 mL/100 g/min that EEG evidence of ischemia
  begins to appear.

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• At a CBF level of approximately 15 mL/100 g/min,
  the cortical EEG is isoelectric.
• CBF is reduced to about 6 mL/100 g/min -
  indications of potentially irreversible membrane
  failure (elevated extracellular potassium ) and
  loss of the direct cortical response rapidly
  evident.

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• As CBF decreases in the flow range between 15
  and 6 mL/100 g/min, a progressive deterioration
  of energy supply occurs, leading eventually, to
  membrane failure and neuronal death.
• The brain regions falling within this CBF range
  (6-15 mL/100 g/min) are referred to as the
  "ischemic penumbra"--a region within which the
  neuronal dysfunction is temporarily reversible
  but within which neuronal death will occur if
  flow is not restored

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Relationships between cerebral perfusion, (CBF),
(EEG)viability of neurons.
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