Cerebral Physiology and the Effects of Anesthetic Drugs

• The brain has a high metabolic rate and receives approximately 15% of cardiac output. Under normal circumstances, cerebral blood flow (CBF) is approximately 50 mL/100 g/min. Gray matter receives 80% and white matter receives 20% of this blood flow. • Approximately 60% of the brain’s energy consumption supports electrophysiologic function. The remainder of the energy consumed by the brain is involved in cellular homeostatic activities. • CBF is tightly coupled to local cerebral metabolism. When cerebral activity in a particular region of the brain increases, a corresponding increase in blood flow to that region takes place. Conversely, suppression of cerebral metabolism leads to a reduction in blood flow. • CBF is autoregulated and remains constant over a mean arterial pressure (MAP) range estimated at 65 to 150 mm Hg, given normal venous pressure. Appreciable intersubject variability exists. CBF becomes pressure passive when MAP is either less than the lower limit or more than the upper limit of autoregulation. • CBF is also under chemical regulation. CBF varies directly with arterial carbon dioxide tension in the arterial partial pressure of carbon dioxide (Paco2) range of 25 to 70 mm Hg. When arterial partial pressure of oxygen (Pao2) decreases to less than 60 mm Hg, CBF dramatically increases. Reductions in body temperature influence CBF primarily by suppression of cerebral metabolism. • Systemic vasodilators (e.g., nitroglycerin, nitroprusside, hydralazine, calcium channel blockers) vasodilate the cerebral circulation and can, depending on the MAP, increase CBF. Vasopressors such as phenylephrine, norepinephrine, ephedrine, and dopamine do not have 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. • All volatile anesthetics suppress the cerebral metabolic rate (CMR) and, with the exception of halothane, can produce burst suppression of the electroencephalogram. At that level, the CMR is reduced by approximately 60%. Volatile anesthetics have dose-dependent effects on CBF. In doses less than the minimal alveolar concentration (MAC), CBF is modestly decreased. In doses larger than 1 MAC, direct cerebral vasodilation results in an increase in CBF and cerebral blood volume. • Barbiturates, etomidate, and propofol decrease the CMR and can produce burst suppression of the electroencephalogram. At that level, the CMR is reduced by approximately 60%. Because blood flow and metabolism coupling are preserved, CBF is decreased. Opiates and benzodiazepines effect minor decreases in CBF and CMR. In contrast, ketamine can significantly increase the CMR with a corresponding increase in blood flow. • Brain stores of oxygen and substrates are limited, and the brain is extremely sensitive to decreases in CBF. Severe decreases in CBF (less than 6 to 10 mL/100 g/min) lead to rapid neuronal death. Ischemic injury is characterized by early excitotoxicity and delayed apoptosis.