1. Anesthesia Medication Effects on Cerebral Hemodynamics

2. CBF:

3. CBV:

4. CBF: CBV:ICP:

5. CBF: CBV:ICP:Ischemia:

6. CBF: CBV:ICP:Ischemia:

7. CBF: CBV:ICP:Ischemia: Site of autoregulation

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

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

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

11. 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

12. 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

13. CBF: MAP- ICP _____________ Resistance

14. CBF: MAP- ICP Directly Proportional _____________ Resistance

15. CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

16. CBF: Normal Values:

17. CBF: Normal Values: 15-20% of CO

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

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

20. CBF: Normal Variation:

21. CBF: Normal Variation: BP above autoregulation range CBF

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

23. Questions

24. 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.

25. 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.

26. 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.

27. CBF Autoregulation OverviewIntrinsic factorsExtrinsic factorsIschemia

28. CBF Autoregulation Overview MAP 50-150

29. CBF Autoregulation Overview MAP 50-150 Rapid change will still affect CBF

30. CBF Autoregulation Overview MAP 50-150 Rapid change will still affect CBF Disrupted by : volatile anesthetics

31. CBF Autoregulation Overview MAP 50-150 Rapid change will still affect CBF Disrupted by : volatile anesthetics HTN

32. CBF Autoregulation Overview MAP 50-150 Rapid change will still affect CBF Disrupted by : volatile anesthetics HTN

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

34. CBF Autoregulation Intrinsic Factors Myogenic response

35. CBF Autoregulation Intrinsic Factors Myogenic response Nitric Oxide

36. CBF Autoregulation Intrinsic Factors Myogenic Response Nitric Oxide Autonomic Innervation

37. CBF Autoregulation Intrinsic Factors Myogenic Response Nitric Oxide Autonomic Innervation

38. CBF Autoregulation Extrinsic Factors PaCO2

39. CBF Autoregulation Extrinsic Factors PaCO2 Metabolism

40. CBF Autoregulation Extrinsic Factors PaCO2 Metabolism

41. CBF Autoregulation: Extrinsic Factors PaCO2: Most potent vasodilator

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

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

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

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

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

47. 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

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

49. CBF Autoregulation Ischemia Focal vs Global

50. CBF Autoregulation: Focal Ischemia Cerebral Steal:

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

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

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

54. CBF Autoregulation: Focal Ischemia Inverse Steal:

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

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

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

58. Questions

59. Answers Question #1: D) 50-150 ◦While some texts have varying values of cerebral autoregulation, most sources agree on the value of 50-150 in the healthy patient.

60. 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.

61. 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.

62. CBF and Anesthetics Inhaled AnestheticsIV General Anesthetics

63. CBF and Anesthetics: Inhaled Anesthetics

64. Decrease CMRO2

65. CBF and Anesthetics: Inhaled Anesthetics Decrease CMRO2 which CBF

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

67. CBF and Anesthetics: Inhaled Anesthetics Net effect determined by:

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

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

70. CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

71. CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

72. CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

73. CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

74. CBF: MAP- ICP Directly Proportional _____________ Resistance Inversely proportional

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

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

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

79. 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

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

81. Questions

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

83. 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.

84. 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.

85. 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.

86. 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.

87. 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.

88. CBF and Anesthetics Inhaled AnestheticsIV General Anesthetics

89. CBF and Anesthetics: IV General Anesthetics

90. Just as with Inhaled Anesthetics, CO2 responsiveness is preserved

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

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

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

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

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

97. 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

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

99. Questions

100. 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.

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

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

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

104. Vasoactive Meds and CBF VasodilatorsVasopressors

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

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

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

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

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

110. Vasoactive Meds and CBF: Vasodilators Net Effect:

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

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

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

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

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

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

118. Net Effect: CBF

119. 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

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

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

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

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

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

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

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

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

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

129. Vasoactive Meds and CBF VasodilatorsVasopressors

130. Vasoactive Meds and CBF: Vasopressors

131. In general, vasopressors do no affect cerebral vasculature directly

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

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

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

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

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

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

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

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

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

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

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

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

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

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

147. Vasoactive Meds and CBF: Vasopressors Net Effect:

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

149. Questions

150. 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.

151. 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.

152. 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.

153. 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.

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

155. CBF: Autoregulation Autoregulation: PACO2. getting pt breathing back… paCO2 52-55. 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 85 +30%