• Cerebral metabolic rate of oxygen (CMRO₂) is described as the milliliters of oxygen consumed by 100 g of brain tissue per minute.
• Local differences exist for the CMRO₂ (gray versus white matter, type of cell). In the adult, the averaged value over all areas is 3–3.5 mL/100 g/minute.
• The neuroanesthetist must balance the CMRO₂ with oxygen delivery. However, despite the importance, there are no readily available techniques within the operating room that can directly measure tissue oxygen metabolism.

• The adult human brain weighs ~2% of the total body weight. However, it
  • Receives ~12–15% of the cardiac output; and is considered a high perfusion organ.
  • Comprises ~20% of total body oxygen consumption. This high rate is required primarily for the maintenance of depolarization and repolarization activity as well as for cellular homeostasis.
• CMRO₂ and cerebral blood flow (CBF) are "coupled." Increases in oxygen consumption are met by an increase in blood flow. The mechanism is not completely understood; however, it is believed that local factors and nitric oxide (NO) contribute to changes in vascular tone and CBF based on electrical and metabolic oxygen demands.
  • Normal CBF is ~45–55 mL/100 g/minute and autoregulation maintains a relatively constant CBF over a wide range of mean arterial pressures (MAPs), between 70 and 150 mm Hg.
  • Increases in CMRO₂ result in parallel increases in CBF, whereas decreases in CMRO₂ result in parallel decreases in CBF.
  • Consequently, increases in neuronal activity result in a "superfluous" increase in CBF compared to the CMRO₂ (provides a cushion) (1).
• Regional differences of CMRO₂ (and hence CBF) are as follows (2):
  • Gray matter is four times that of white matter.
  • Neurons are greater than glial cells.
  • Lowest in the spinal cord and increases cephaladly through the medulla, midbrain, thalamus, cerebellum, and cerebral cortex.
• Factors affecting CMRO₂ (and hence CBF).
  • Sleep. Non-rapid eye movement (Stages 2 and 3) is associated with a 23% reduction across the entire brain (regional variations exist). However, certain areas (basal forebrain, hypothalamus, amygdala, hippocampus) have an increase in glucose utilization likely from homeostatic regulation and mnemonic processing.
  • Aging results in neuronal loss and can also progressively lower CMRO₂ (3).

• Gray matter comprises ~40% of the brain's mass and consists of neuronal cell bodies, dendrites, and glial cells. Mostly present in the outer portions.
• White matter comprises ~60% of the brain's mass and consists of myelinated axons and is mostly present in the inner portions.

• Seizure activity describes uncontrolled and chaotic electrical activity that is accompanied by significant increases in CMRO₂. With status epilepticus, values can increase by 200–300% (4).
• Oxygen delivery
  • Decreases that are secondary to impaired CBF (stroke, hypotension) are accompanied by decreased glucose delivery and increased partial pressure of carbon dioxide (PaCO₂). Initially, the brain tissue increases oxygen extraction to compensate, and CMRO₂ remains stable. However, when the reduction in CBF exhausts the compensatory increase in oxygen extraction, the CMRO₂ decreases.
  • Decreased blood oxygen content is accompanied by the normal delivery of glucose and does not affect carbon dioxide removal. Normal arterial partial pressures are ~100 mm Hg. At values of 30 mm Hg, there is a significant decrease in the CMRO₂ that is accompanied by a ~50% increase in CBF (5).
• Carbon dioxide. Increases in the PaCO₂ result in vasodilation and increased CBF (pH mediated mechanism). However, its effects on the CMRO₂ are poorly understood and lack consensus. At this time, it is believed that mild increases appear to have a negligible effect on global CMRO₂.

• The neuroanesthetist is often called on to manipulate the CMRO₂ and optimize oxygenation.
  • Decreases in electrical activity can be attained with both IV and volatile agents. The electroencephalogram may be utilized to assess electrical activity (not cellular homeostasis). The term burst suppression describes a periodic pattern of high-amplitude complexes that are interspersed by low-voltage amplitude complexes. This represents a state of maximal electrical activity suppression (recall that this comprises the majority of CMRO₂) (6).
  • Cellular homeostasis ("basic housekeeping") may be decreased by lowering the temperature. Hypothermia lowers the CMRO₂ that is associated with providing energy (e.g., adenosine triphosphate [ATP] to maintain transmembrane ion gradients) that is essential for neuronal viability and other basic functions of cellular upkeep (e.g., protein synthesis). for each degree celsius decrease, there is a corresponding CMRO₂ decrease of ~7%. To that extent, deep circulatory arrest can theoretically approach a CMRO₂ of zero.
• IV medications, in general, maintain coupling of CMRO₂ and CBF.
  • Barbiturates. Dose-dependent reduction in CBF and CMRO₂. Tolerance to this effect can develop rapidly. Animal studies have demonstrated improved outcome for focal, but not global, ischemia.
  • Propofol. Appears to have a similar dose-dependent reduction in CBF and CMRO₂ as barbiturates. Its shorter duration of action compared to barbiturates can decrease the need for postoperative intubation and delays in performing a neurological exam.
  • Etomidate. Appears to have a similar profile to barbiturates. Because it maintains MAP well, it can effectively reduce intracranial pressure (ICP) without reductions in cerebral perfusion pressures (CPP) with tumors and closed head injuries (CHI). It is not routinely used to induce or maintain burst suppression, however, due to its ability to cause adrenocortical suppression and renal injury with repeat, routine, or continuous use.
  • Ketamine. The only IV anesthetic agent that can cause an increase in the CMRO₂ and hence CBF (elevation in ICP). These effects can be blunted by coadministration of volatile agents or benzodiazepines.
  • Benzodiazepines. Decreases CMRO₂ and CBF.
  • Flumazenil (in some studies) has been shown to increase CBF and ICP.
  • Lidocaine can decrease CMRO₂ in a dose-dependent fashion. A bolus dose has been advocated as an adjunct for acute elevated ICP. However, CNS toxicity can cause seizures that will increase the CMRO₂.
  • Narcotics. It appears that CBF and CMRO₂ are relatively unaffected. However, the information has inconsistencies and varies depending on the narcotic. When an effect was found, usually it showed a decrease in CMRO₂ and CBF.
  • Epinephrine and norepinephrine. Increase CMRO₂ and CBF regardless of whether or not there is an intact blood–brain barrier (BBB).
  • Dobutamine. Can increase CMRO₂ and CBF by up to 30%.
  • Beta-blockers. Studies show that they appear to reduce or have no effect on CMRO₂ or CBF.
  • Alpha 2-agonists (dexmedetomidine). Reduces CBF with no effect on CMRO₂.
  • Nondepolarizing muscle relaxants. Do not directly affect CMRO₂. However, the histamine release associated with atracurium can increase ICP.
  • Succinylcholine. Does not directly affect CMRO₂. However, histamine release can cause a rapid increase in ICP.
• Volatile agents decrease the CMRO₂; however, CBF does not decrease in parallel; this is known as "uncoupling." The cerebral vasculature vasodilates due to smooth muscle relaxation in response to the volatile agent. This increases the CBF to CMRO₂ ratio with resultant "luxury" perfusion.
  • Order of CMRO₂ suppression (measured in terms of equal MAC concentrations): Isoflurane, enflurane, desflurane, sevoflurane>halothane.
  • Order of vasodilating potency: Halothane>>enflurane>isoflurane = sevoflurane = desflurane. After initially increasing the CBF, there is a substantial fall in CBF until a steady state is reached (usually after 2.5–5 hours after exposure).
  • Therapeutic use: Decreases in CMRO₂ can develop quickly.
  • Carbon dioxide responsiveness remains well maintained.
• Nitrous oxide (N₂O). Results have been mixed; however, it is generally accepted that the CMRO₂, CBF, and ICP increase, likely from sympatho-adrenal-stimulating effects.

• Intracranial Hypertension
• Cerebral Blood Flow
• Burst Suppression

Nina Singh-Radcliff , MD