Anesthesia Medication Effects on Cerebral Hemodynamics

CBF:

CBV:

CBF: CBV:ICP:

CBF: CBV:ICP:Ischemia:

CBF: CBV:ICP:Ischemia:

CBF: CBV:ICP:Ischemia: Site of autoregulation

CBF: CBV:ICP:Ischemia: Site of autoregulation Site of medication effects

CBF: CBV:ICP:Ischemia: Site of autoregulation Site of medication effects Difficult to measure

CBF: CBV:ICP:Ischemia: Site of autoregulation Site of medication effects Difficult to measure Varies to a lesser degree than CBF

CBF: CBV:ICP:Ischemia: Site of autoregulation Site of medication effects Difficult to measure Varies to a lesser degree than CBF CSF, CBV, Brain Tissue

CBF: CBV:ICP:Ischemia: Site of autoregulation Site of medication effects Difficult to measure Varies to a lesser degree than CBF CSF, CBV, Brain Tissue Focal vs global Affects all above variables

CBF: MAP- ICP _____________ Resistance

CBF: MAP- ICP Directly Proportional _____________ Resistance

CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

CBF: Normal Values:

CBF: Normal Values: 15-20% of CO

CBF: Normal Values: 15-20% of CO 750 mL/min

CBF: Normal Values: 15-20% of CO 750 mL/min 50 mL/100g/min

CBF: Normal Variation:

CBF: Normal Variation: BP above autoregulation range CBF

CBF: Normal Variation: BP above autoregulation range CBF BP below autoregulation range CBF

Questions

Answers Question #1: A) Brain Tissue ◦The 3 components that make up ICP are brain tissue, CSF, and CBV. Brain tissue accounts for 80% of ICP while CSF and CBV account for 10% each.

Answers Question #2: B) Blood flow of 50 ml/min/100 g of tissue ◦Normal ICP is <15 and the brain normally receives 15-20% of cardiac output. The typical total blood flow to the brain is 750 ml/min or 50 ml/min/100 g of tissue. Cerebral Ischemia begins when blood flow drops below 20 and infarct begins at 6 ml/min/100 g of tissue.

Answers Question #3: C) Increased cerebral vascular resistance ◦Hypercarbia and hypoxia both would increase CBF due to increased metabolic demand. Increased cerebral vascular resistance would have an inverse effect on CBF.

CBF Autoregulation OverviewIntrinsic factorsExtrinsic factorsIschemia

CBF Autoregulation Overview MAP

CBF Autoregulation Overview MAP Rapid change will still affect CBF

CBF Autoregulation Overview MAP Rapid change will still affect CBF Disrupted by : volatile anesthetics

CBF Autoregulation Overview MAP Rapid change will still affect CBF Disrupted by : volatile anesthetics HTN

CBF Autoregulation Overview MAP Rapid change will still affect CBF Disrupted by : volatile anesthetics HTN

CBF Autoregulation Overview Pt’s Baseline MAP determines the patient’s autoregulation range

CBF Autoregulation Intrinsic Factors Myogenic response

CBF Autoregulation Intrinsic Factors Myogenic response Nitric Oxide

CBF Autoregulation Intrinsic Factors Myogenic Response Nitric Oxide Autonomic Innervation

CBF Autoregulation Intrinsic Factors Myogenic Response Nitric Oxide Autonomic Innervation

CBF Autoregulation Extrinsic Factors PaCO2

CBF Autoregulation Extrinsic Factors PaCO2 Metabolism

CBF Autoregulation Extrinsic Factors PaCO2 Metabolism

CBF Autoregulation: Extrinsic Factors PaCO2: Most potent vasodilator

CBF Autoregulation: Extrinsic Factors PaCO2: Most potent vasodilator Direct relationship to CBF

CBF Autoregulation: Extrinsic Factors PaCO2: Most potent vasodilator Direct relationship to CBF CO2 Responsiveness Preserved with anesthetics

CBF Autoregulation: Extrinsic Factors Metabolism (CMRO2): Direct relationship to CBF

CBF Autoregulation: Extrinsic Factors Metabolism (CMRO2): Direct relationship to CBF Main factor is brain activity

CBF Autoregulation: Extrinsic Factors Metabolism (CMRO2): Direct relationship to CBF Main factor is brain activity Main controllable factor intraop is temperature

CBF Autoregulation: Extrinsic Factors Metabolism (CMRO2): Direct relationship to CBF Main factor is brain activity Main controllable factor intraop is temperature: 7% per 1deg C

CBF Autoregulation: Extrinsic Factors Metabolism (CMRO2): Direct relationship to CBF: Flow-Metabolism Coupling

CBF Autoregulation Ischemia Focal vs Global

CBF Autoregulation: Focal Ischemia Cerebral Steal:

CBF Autoregulation: Focal Ischemia Cerebral Steal: 1. Focal Ischemic areas are maximally dilated

CBF Autoregulation: Focal Ischemia Cerebral Steal: 1. Focal Ischemic areas are maximally dilated 2. General Cerebral Vasodilation

CBF Autoregulation: Focal Ischemia Cerebral Steal: 1. Focal Ischemic areas are maximally dilated 2. General Cerebral Vasodilation Reduces net blood flow to ischemic areas

CBF Autoregulation: Focal Ischemia Inverse Steal:

CBF Autoregulation: Focal Ischemia Inverse Steal: 1. Focal Ischemic areas are maximally dilated

CBF Autoregulation: Focal Ischemia Inverse Steal: 1. Focal Ischemic areas are maximally dilated 2. General Cerebral Vasoconstriction

CBF Autoregulation: Focal Ischemia Inverse Steal: 1. Focal Ischemic areas are maximally dilated 2. General Cerebral Vasoconstriction increases net blood flow to ischemic areas.

Questions

Answers Question #1: D) ◦While some texts have varying values of cerebral autoregulation, most sources agree on the value of in the healthy patient.

Answers Question #2: B) PaCO2 ◦While isoflurane and nitrous oxide are cerebral vasodilators, the most potent cerebral vasodilator is PaCO2. High PaO2 is a vasoconstrictor.

Answers Question #3: C) Vasoconstriction of non- ischemic brain tissue ◦In focal ischemia a small area of brain tissue is receiving too little blood flow. Desirable effects to reduce the damage would be vasoconstriction of non-ischemic tissue and vasodilation of ischemic tissue. This process is referred to as inverse steal.

CBF and Anesthetics Inhaled AnestheticsIV General Anesthetics

CBF and Anesthetics: Inhaled Anesthetics

Decrease CMRO2

CBF and Anesthetics: Inhaled Anesthetics Decrease CMRO2 which CBF

CBF and Anesthetics: Inhaled Anesthetics Are direct cerebral vasodilators which CBF

CBF and Anesthetics: Inhaled Anesthetics Net effect determined by:

CBF and Anesthetics: Inhaled Anesthetics Net effect determined by balance of MAP and

CBF and Anesthetics: Inhaled Anesthetics Net effect determined by balance of MAP and MAC

CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

CBF and Anesthetics: Inhaled Anesthetics Over 1 MAC, cerebral vasodilation greatly increases

CBF and Anesthetics: Inhaled Anesthetics Over 1 MAC: cerebral vasodilation greatly increases & autoregulation is impaired

CBF and Anesthetics: Inhaled Anesthetics Over 1 MAC: cerebral vasodilation greatly increases & autoregulation is impaired BUT

CBF: CBV:ICP:Ischemia: Site of autoregulation Site of medication effects Difficult to measure Varies to a lesser degree than CBF CSF, CBV, Brain Tissue Focal vs global Affects all above variables

CBF and Anesthetics: Inhaled Anesthetics Inhaled Anesthetics within normal ranges in patients with normal intracranial compliance and PaCO2 will have minimal cerebral hemodynamic changes

Questions

Answers Question #1: C) Sevoflurane ◦All volatile anesthetics impair cerebral autoregulation at anesthetic levels. Barbiturates and propofol preserve it.

Answers Question #2: D) Halothane ◦All volatile anesthetics have the potential of increasing ICP, but halothane increases CBF the most. Other volatile anesthetics would be more appropriate in this scenario.

Answers Question #3: C) Isoflurane ◦Isoflurane is unique in that it is the only volatile agent that facilitates the absorption of CSF and has a favorable effect on CSF dynamics.

Answers Question #4: D) All of the above ◦Nitrous has the potential to increase ICP substantially. The other volatile anesthetics increase ICP as well, but not to the same degree as nitrous.

Answers Question #5: C) A decrease in CMRO2 and an increase in CBF ◦Volatile anesthetics can produce what is referred to luxury perfusion, a beneficial effect during global ischemia that reduces CMRO2 and increases CBF.

Answers Question #6: A) Isoflurane ◦The mechanisms by which iso, sevo, and des decrease CMRO2 is similar, but iso is the one that reduces CMRO2 the most.

CBF and Anesthetics Inhaled AnestheticsIV General Anesthetics

CBF and Anesthetics: IV General Anesthetics

Just as with Inhaled Anesthetics, CO2 responsiveness is preserved

CBF and Anesthetics: IV General Anesthetics Just as with Inhaled Anesthetics, CO2 responsiveness is preserved Unlike Inhaled Anesthetics, autoregulation is also preserved

CBF and Anesthetics: IV General Anesthetics All Gen Anesthetics except Ketamine reduce CMRO2, which reduces CBF

CBF and Anesthetics: IV General Anesthetics All except Ketamine reduce CMRO2, which reduces CBF Many have direct cerebral vasoconstriction

CBF and Anesthetics: IV General Anesthetics Net Effect: Substantial Reduction in CBF (40- 50%)…

CBF and Anesthetics: IV General Anesthetics Net Effect: Substantial Reduction in CBF (40-50%) IF MAP IS MAINTAINED within autoregulation range…

CBF: CBV:ICP:Ischemia: Site of autoregulation Site of medication effects Difficult to measure Varies to a lesser degree than CBF CSF, CBV, Brain Tissue Focal vs global Affects all above variables

CBF and Anesthetics: IV General Anesthetics Net Effect: Reduction in CBF (40- 50%) leads to moderate reduction in ICP (20-30%)

Questions

Answers Question #1: D) Propofol ◦Of the drugs on the list propofol is the only drug that decreases CBF and CMRO2. Ketamine, halothane, and nitrous oxide all increase CBF.

Answers Question #2: D) All of the above ◦Ketamine increases CBF, CMRO2, and ICP.

Answers Question #3: A) Barbiturates have a more global reduction in CBF and CMRO2 than etomidate

Answers Question #4: A) Decrease cerebrovascular resistance. ◦Like most other IV anesthetics barbiturates increase cerebrovascular resistance through a decrease in CMRO2.

Vasoactive Meds and CBF VasodilatorsVasopressors

Vasoactive Meds and CBF: Vasodilators All common vasodilators cause cerebral vasodilation

Vasoactive Meds and CBF: Vasodilators Includes SNP, NTG, hydralazine, adenosine, and Calcium channel blockers

Vasoactive Meds and CBF: Vasodilators Some antihypertensives have no effect on cerebral vasculature, including ACE inhibitors such enalapril

Vasoactive Meds and CBF: Vasodilators Beta blockers (propranolol, labetalol) may have small decrease CMRO2, leading to small decrease in CBF

Vasoactive Meds and CBF: Vasodilators Evidence is not available for all antihypertensives

Vasoactive Meds and CBF: Vasodilators Net Effect:

CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional Vasoactive Meds and CBF: Vasodilators

CBF: MAP- ICP _____________ Resistance Vasoactive Meds and CBF: Vasodilators

CBF: MAP- ICP _____________ Resistance Vasoactive Meds and CBF: Vasodilators

CBF: MAP- ICP _____________ Resistance Vasoactive Meds and CBF: Vasodilators

CBF: MAP- ICP _____________ Resistance Vasoactive Meds and CBF: Vasodilators

CBF: MAP- ICP _____________ Resistance Vasoactive Meds and CBF: Vasodilators

Net Effect: CBF

CBF: CBV:ICP:Ischemia: Site of autoregulation Site of medication effects Difficult to measure Varies to a lesser degree than CBF CSF, CBV, Brain Tissue Focal vs global Affects all above variables

Vasoactive Meds and CBF: Vasodilators Net Effect: moderate dose- dependent CBF leading to small to moderate ICP

Vasoactive Meds and CBF: Vasodilators Net Effect: moderate dose- dependent CBF leading to small to moderate ICP

Vasoactive Meds and CBF: Vasodilators Much greater risk in patient with neurologic injury

Vasoactive Meds and CBF: Vasodilators Much greater risk in patient with neurologic injury: especially focal ischemia. Why?

Vasoactive Meds and CBF: Vasodilators Vasodilators can directly cause cerebral steal, regardless of decrease in MAP.

Vasoactive Meds and CBF: Vasodilators PaCO2 responsiveness is generally intact with vasodilators.

Vasoactive Meds and CBF: Vasodilators All vasodilator effects, including cerebral steal, can be mediated or exacerbated by PaCO2.

Vasoactive Meds and CBF: Vasodilators All vasodilator effects can be mediated by: Hypocapnia

Vasoactive Meds and CBF: Vasodilators All vasodilator effects can be mediated by: Hypocapnia Slower Induction of Hypotension

Vasoactive Meds and CBF VasodilatorsVasopressors

Vasoactive Meds and CBF: Vasopressors

In general, vasopressors do no affect cerebral vasculature directly

Vasoactive Meds and CBF: Vasopressors In general, vasopressors do no affect cerebral vasculature directly. Including phenylephrine, ephedrine, norepi-, epi-, dopamine

Vasoactive Meds and CBF: Vasopressors Their effect depends on their effect on MAP

CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional Vasoactive Meds and CBF: Vasodilators

CBF: MAP- ICP _____________ Resistance Vasoactive Meds and CBF: Vasopressors

CBF: MAP- ICP _____________ Resistance Vasoactive Meds and CBF: Vasopressors With Inhalational Anesthetics at ½ MAC or greater

CBF: MAP- ICP _____________ Resistance Vasoactive Meds and CBF: Vasopressors With TIVA: no effect on CBF

Vasoactive Meds and CBF: Vasopressors Beta-agonists may have a direct effect on cerebral metabolism

Vasoactive Meds and CBF: Vasopressors Beta-agonists may cause a direct increase in cerebral metabolism based on: Dose

Vasoactive Meds and CBF: Vasopressors Beta-agonists may cause a direct increase in cerebral metabolism based on: Dose BBB effectiveness

Vasoactive Meds and CBF: Vasopressors BBB effectiveness: BBB permeability is increased with increased stress, sustained hypertension, hypertonic drugs, fever, sepsis

Vasoactive Meds and CBF: Vasopressors BBB effectiveness: Incrs BBB permeability leads to incrs CMRO2 effect of beta adrenergics

Vasoactive Meds and CBF: Vasopressors Epinephrine has the greatest increase in CMRO2.

Vasoactive Meds and CBF: Vasopressors Epinephrine has the greatest increase in CMRO2. Incrs CMRO2 has been shown in low-doses with intact BBB

Vasoactive Meds and CBF: Vasopressors Dobutamine has been associated with 20-30% increase in CMRO2, leading to incrs CBF

Vasoactive Meds and CBF: Vasopressors Net Effect:

Vasoactive Meds and CBF: Vasopressors Net Effect: Least effect of all medications we have looked at today

Questions

Answers Question #1: B) Hydralazine ◦All direct vasodilators and Ca Channel blockers increase CBF. Propofol decreases CBF. Lidocaine and dilaudid have minimal effect on CBF.

Answers Question #2: C) The oral form has a more gradual effect on cerebral vasodilation. ◦Gradual increases in cerebral vasodilation allow for compensatory mechanisms such as a decrease in CSF and increased venous shunting out of the intracranial compartment.

Answers Question #3: C) Both A and B ◦Normally vasoconstrictors have a minimal effect of CBF. This changes if MAP is outside of the patient’s autoregulation range or if the BBB is not intact.

Answers Question #4: B) Phenylephrine ◦Beta 1 agonists have minimal, but some increase in CBF and CMRO2. Pure alpha 1 agonists have no evidence of effect on CBF or CMRO2.

Answers Question #5: A) Epinephrine ◦When the BBB is not intact the most potent beta 1 drugs will increase CBF and CMRO2 the most.

CBF: Autoregulation Autoregulation: PACO2. getting pt breathing back… paCO HTN d/t higher PACO2, MAC of gas, treat with vasodilator, going to compound the incrs CBV. Tolerable on normal pt but minimally tolerable on head injury. 50 mL/100g/min incrs to 70 mL/100g/min +40% In general, the response to PaCO2 is preserved with anesthetics ICP 8 goes to 9 MAP incrs 65 to %