Cerebral Physiology and the Effects of Anesthetics and Techniques

1. Cerebral Physiologyand the Effects ofAnesthetics andTechniques به نام خدا

2. At rest, the brain consumes oxygen at an average rate of approximately 3.5 mL of oxygen per 100 g of brain tissue per minute. Whole-brain o2 consumption(13.5 x 3.5 =47 mL/min) represents about 20% of total-body oxygen utilization.

3. CBF is tightly coupled to Local cerebral metabolism. If one increase another will increase too, And conversely Suppression of cerebral metabolism leads to reduction in blood flow.

4. Brain is autoregulated over a mean arterial pressure rang between 65-150 mm Hg. CBF becomes pressure passive when mean arterial pressure is either below the lower limit or above the upper limit of autoregulation.

5. important The autoregulation mechanism is fragile, and in many pathologic states CBF is regionally pressure passive.

6. CBF is also under chemical regulation. It varies directly with arterial carbon dioxide tension in the Paco2 range of 25 to 70 mm Hg. With a reduction in Pao2to below 60 mm Hg, CBF increases dramatically. Changes in temperature affect CBF primarily by suppression of cerebral metabolism.

7. Systemic vasodilators (nitroglycerin, nitroprusside, hydralazine, calcium channel blockers) vasodilate the cerebral circulation and can, depending on mean arterial pressure, increase CBF. Vasopressors such as phenylephrine, norepinephrine, ephedrine, and dopamine do not have significant direct effects on the cerebral circulation. Their effect on CBF is dependent on their effect on systemic blood pressure.

8. All modern volatile anesthetics suppress the cerebral metabolic rate (CMR) and, with the exception of halothane, can produce burst suppression of the electroencephalogram. At that level, CMR is reduced by about 60%. Volatile anesthetics have dose-dependent effects on CBF. In doses lower than the minimal alveolar concentration (MAC), CBF is not significantly altered. Beyond doses of 1 MAC, direct cerebral vasodilation results in an increase in CBF and cerebral blood volume.

9. Barbiturates, etomidate, and propofoldecrease CMR and can produce burst suppression of the electroencephalogram. Opiates and benzodiazepines effect minor decreases in CBF and CMR. whereas ketamine can increase CMR (with a corresponding increase in blood flow) significantly.

10. Brain stores of oxygen and substrates are limited and the brain is exquisitely sensitive to reductions in CBF. Severe reductions in CBF (less than 10 mL/100 g/min) lead to rapid neuronal death. Ischemic injury is characterized by early excitotoxicity and delayed apoptosis.

11. Barbiturates, propofol, ketamine, volatile anesthetics, and xenon have neuroprotective efficacy and can reduce ischemic cerebral injury. Anesthetic neuroprotection is sustained only when the severity of the ischemic insult is mild. Administration of etomidate is associated with regional reductions in blood flow, and this can exacerbate ischemic brain injury.

12. This chapter reviews: the effects of anesthetic drugs and techniques on cerebral physiology, in particular, their effects on cerebral blood flow (CBF) and metabolism.

13. Anesthetic drugs cause dose-related and reversible alterations in many aspects of cerebral physiology, including CBF, cerebral metabolic rate (CMR), and electrophysiologic function (EEG, evoked responses)

14. brain weighs 1350 g (about 2%of total-body weight ) • it receives approximately 12-15% of cardiac output. • brain's high metabolic rate. • Cerebral blood flow (CBF)= 50mL/100 g/min • Gray matter receives 80% white matter 20% • Brain’s energy consumption • 60% support electro physiologic function. • 40% cellular homeostatic activity ,

16. Local CBF and CMR within the brain are very heterogeneous, and both are approximately four times greater in gray matter than in white matter.

17. The cell population of the brain is also heterogeneous in its oxygen requirements. Glial cells make up about half the brain's volume and require less energy than neurons do. Besides providing a physically supportive latticework for the brain, glial cells are important in reuptake of neurotransmitters, in delivery and removal of metabolic substrates and wastes, and in blood-brain barrier (BBB) function.

18. Cerebral metabolic rate: Strict local coupling of CMR and CBF(neurovascular coupling) the precise mechanisms uncertain K+,H+, Lactate Adenosineglutamate and NO, Gelia) neurotransmitters such as vasoactive intestinal peptid (VIP), substance p, calcitonin gene related peptide.

19. In the neurosurgical state CMR affected by : (1) Functional state: Decrease: during sleep , in coma Increases: during sensory stimulation, mental tasks, or arousal of any cause , During epileptic activity CMR increases may be extreme, whereas regionally after brain injury and globally with coma, CMR may be substantially reduced.

20. (2)ANESTHETICS : anesthetics suppress CMR (exeptions: ketamine, N2O) • (1) Electro physiologic Function • (2)The component of CMR required for maintenance of cellularintegrity, the"housekeeping“ component, is apparently unaltered by intravenous anesthetics.

22. The cerebral metabolic rate of oxygen (CMRO2) observed when complete suppression of the EEG is achieved with different anesthetic drugs is very similar.

23. When barbiturates are administered to the point of EEG suppression, a uniform depression in CBF and CMR occurs throughout the brain. When suppression occurs during administration of isoflurane, the relative reductions in CMR and CBF are greater in the neocortex than in other portions of the cerebrum

25. (3)Temperature: The effects of hypothermia on the brain have been reviewed in detail CMR decreases by 6 to7%/1˚c hypothermia can also cause complete suppression of the EEG (at about 18°C to 20°C). However, in contrast with anesthetic drugs, temperature reduction beyond that at which EEG suppression first occurs does produce a further decrease in CMR ( Fig. 13-3 ).

27. Hyperthermia has an opposite influence on cerebral physiology. Between 37°C and 42°C, CBF and CMR increase. However, above 42°C, a dramatic reduction in cerebral oxygen consumption occurs, an indication of a threshold for a toxic effect of hyperthermia that may occur as a result of protein (enzyme) denaturation.

28. PCO2 • CBF varies directly with PCO2 • The effect is greatest within the range of physiologic Paco2 variation • CBF changes 1 to 2 mL/100 g/min for each l mm Hg change in Paco2. • Resting cerebral blood flowcorrelate with ∆CBF/ ∆ Paco2 • The magnitude of the reduction in CBF caused by hypocapnia is greater when resting CBF is high. • Conversely, when resting CBF is low, the magnitude of the hypocapnia-induced reduction in CBF is decreased.

29. PCO2 (continue) NO & PGs The changes in extracellular pH and CBF occur rapidly after Paco2 adjustments because CO2 diffuses freely across the cerebrovascular endothelium. acute systemic metabolic acidosis has little immediate effect on CBF because the BBB excludes hydrogen ion (H+) from the perivascular space

30. PCO2 (continue) CBF changes is rapid but not sustained.(6-8h) Acute normalization of Paco2 will result in significant CSF acidosis (after hypocapnia) or alkalosis (after hypercapnia)

32. Pao2 Below a Pao2 of 60 mm Hg, CBF increases rapidly peripheral or neuraxial chemoreceptor, local humoral influences. NO of neuronal origin. (ATP)-dependent K+ channels

33. RVM (rostral ventrolateral medulla) serves as an oxygen sensor within the brain. Stimulation of the RVM by hypoxia results in an increase in CBF (but not CMR). lesions of the RVM suppress the magnitude of the CBF response to hypoxia.

34. Myogenic Regulation (Autoregulation) The studies about autoregulation about nomral human is limited CPP = MAP- ICP normal ICP in 10 to 15 mm Hg, an LLA( lower limit of autoregulation) of 70 expressed as MAP corresponds to an LLA of 55 to 60 mm Hg expressed as CPP Above and below the autoregulatory plateau, CBF is pressure dependent (pressure passive). a rapid change in arterial pressure will result in a transient (3 to 4 minutes) alteration in CBF.

35. The cerebral vasculature is extensively innervated The greatest neurogenic influence appears to be exerted on larger cerebral arteries. This innervation include Innervations includes cholinergic and adrenergic and serotonergicandVlPergicsystems

36. Neurogenic Regulation Evidence of the functional significance of neurogenic influences has been derived from studies of CBF autoregulation and ischemic injury. Hemorrhagic shock, a state of high sympathetic tone. Activation of cerebral sympathetic innervation also shifts the upper limit of autoregulation to the right and offers some protection against hypertensive breakthrough of the BBB.

38. Viscosity Effects on Cerebral Blood Flow Blood viscosity can influence CBF. Hematocrit is the single most important determinant of blood viscosity. In healthy subjects, variation of the hematocrit within the normal range (33% to 45%) probably results in only modest alterations in CBF. Beyond this range, changes are more substantial.

39. Inanemia: cerebral vascular resistance is reduced and CBF increases. The effect of a reduction in viscosity on CBF is more obvious in the setting of focal cerebral ischemia, a condition in which vasodilation in response to impaired oxygen delivery is probably already maximal.

40. The best available information suggests that in the setting of focal cerebral ischemia, a hematocrit of 30% to 34%will result in optimal oxygen delivery. viscosity is not a target of manipulation in patients at risk from cerebral ischemia, with the possible exception being those with hematocrit values in excess of 55%

41. Vasoactive Drugs 1:SystemicVasodilators drugs used to induce hypotension(including sodium nitroprusside, nitroglycerin, hydralazine, adenosine, and calcium channel blockers) cause cerebral vasodilatation. CBF either increases or is maintained at prehypotensive levels. The ICP effects of these drugs are empirically less dramatic when hypotension is induced slowly.

42. Catecholamine Agonists/ Antagonists • The effects of these drugs on cerebral physiology are dependent on : • basal blood pressure • the magnitude of the systemic blood pressure changes • the status of the autoregulation mechanism. • the status of the BBB

43. When autoregulation is preserved, increases in systemic pressure would be expected to increase CBF if basal blood pressure is either below or above the lower and upper limits of autoregulation.

45. Alpha 1 Agonists α1-agonists (phenylephrine, norepinephrine) have little direct influence on CBF in humans, with the exception that norepinephrine may cause vasodilatation when the BBB is defective. Intracarotidinfusion of norepinephrine in doses that significantly increase MAP result in no change in CBF. β-mimetic drugs (norepinephrine has β1 activity) cause activation of cerebral metabolism with a coupled increase in CBF, and this effect is likely to be most apparent when these drugs can gain greater access to the brain parenchyma via a defective BBB .

46. In summary, it seems likely that circulating α1-agonists will have little direct influence on CBF in humans with the exception that norepinephrine may cause vasodilation when the BBB is defective.

47. Β Agonists in small & large doses in low doses, have little direct effect on the cerebral vasculature In larger doses and in association with physiologic stress, they can cause an increase in CMR with an accompanying increase in CBF. (CMRO2 can increase by about 20%.) BBB defect enhances the effect of β-agonists. it does not appear thatBBB injury is a necessary condition in humans for the occurrence of β-mediated increases in CBF and CMR, although it will probably exaggerate the phenomenon.

48. β-Adrenergic Blockers β-Blockers reduce or have no effect on CBF and CMR β-blockers are unlikely to have adverse effects on patients with intracranial pathology, other than effects secondary to changes in perfusion pressure.

49. Dopamine Dopamin is used when an elevation in MAP is desired as an adjunct to the treatment of focal cerebral ischemia, especially in the setting of vasospasm. its effects on CBF and CMR have not been defined with certainty. in low doses, is probably slight vasodilatation with minimal CMR change. Vasoconstriction of the cerebral circulation is not observed even when dopamine is administered in doses up to100 µ/kg/min.

50. α2agonists There is considerable current interest in α2-agonists because of their analgesic and sedative effects. dexmedetomidineand clonidine(vasoconstriction) dexmedetomidine decreases CBF with no effect on CMRO2(different studies, different results). dexmedetomidine reduced MAP modestly. caution should be exercised in its use in patients in whom CBF is compromised.