Nitrous oxide (N₂O)
Effect on CBF and CMRo₂. Although many clinicians once thought N₂O to be devoid of cerebrovascular effects, it is now known that it can cause large increases in CBF. The effects of N₂O vary depending on the presence or absence of other anesthetics. When administered alone or with minimal background anesthesia, N₂O increases CBF. In contrast, when it is administered with certain intravenous anesthetics (barbiturates, narcotics), its effects on CBF may be attenuated. When the effects of a 1 minimum alveolar concentration (MAC) anesthetic produced by a volatile drug alone are compared to the effects of a 1 MAC anesthetic provided by the combination of 0.5 MAC volatile drug and 0.5 MAC N₂O, CBF is higher in the presence of N₂O. CMRo₂ may be unchanged or increased with N₂O. Although brain activity on EEG might be increased with N₂O, it does not cause seizures.
Effect on CO₂ reactivity. CO₂ reactivity is preserved during the use of N₂O.
Effect on CSF dynamics (Table-1). Either the addition to or the withdrawal of N₂O from the inhalational drugs halothane and enflurane causes no change in either V_f or R_a with no predicted effect on ICP.

Effect on ICP. N₂O can increase ICP in patients who have mass lesions. The ICP response can be attenuated if either intracranial compliance is improved first or drugs that decrease CBV such as barbiturates are administered concomitantly. N₂O is known to diffuse rapidly into and expand closed air-filled spaces. Pneumocephalus produced by a recent craniotomy contraindicates the use of N₂O for the repeat procedure. If a venous air embolism (VAE) occurs, N₂O can increase the size of the air bubble and worsen the consequences of the air embolism. N₂O should be discontinued if a VAE occurs. Some clinicians avoid the use of N₂O altogether in procedures in which the likelihood of VAE is high, such as a posterior fossa craniotomy performed with the patient in the sitting position.
Effect on spinal cord metabolism. N₂O increases the spinal cord's utilization of glucose, which is quantitatively similar to that effect produced in the brain (approximately 25%).
 

Isoflurane
Effect on CBF and CMRo₂. Isoflurane is a cerebrovasodilatator that increases CBF. Although it is one of the least potent cerebrovasodilatators, it is the most potent depressant of CMRo₂. The techniques of CBF measurement may influence the interpretation of CBF studies with the different inhalational drugs. For example, cortical blood flow is higher with halothane than isoflurane. By contrast, the increase in CBF seen with isoflurane is higher in the subcortical areas. Therefore, if a technique of CBF measurement that selectively looks at cortical flow (radioactive xenon techniques, transcranial Doppler, venous outflow) is used, halothane might demonstrate a greater effect on CBF than isoflurane. If whole-brain blood flow is measured (microspheres, positron emission tomography [PET], autoradiography), the effects might appear more similar among the different volatile anesthetics.
Isoflurane is unique among the inhalational drugs in that it has the capacity to induce an isoelectric EEG at a concentration that is clinically relevant because it is tolerated hemodynamically. This occurs at approximately 2 MAC. The reduction in CMRo₂ plateaus at the point at which an isoelectric EEG is reached. A normal cerebral energy state is also present at this point.
Effect on cerebral autoregulation and CO₂ reactivity. Cerebral autoregulation is impaired with isoflurane in a dose-related manner. CO₂ reactivity is maintained with isoflurane. The achievement of hypocapnia may restore cerebral autoregulation impaired by isoflurane.
Effect on CSF dynamics. At low concentrations, isoflurane causes no change in V_f and either no change or an increase in R_a with either no change or an increase in ICP predicted. At high concentrations, isoflurane causes no change in V_f and a decrease in R_a, predicting a decrease in ICP.
Effect on ICP. Isoflurane has the potential to increase ICP. However, it may not be necessary to induce hypocapnia before introducing isoflurane. The simultaneous introduction of hyperventilation and isoflurane may be sufficient to prevent an increase in ICP.
Effect on SCBF and metabolism. At both 1 and 2 MAC concentrations, isoflurane produces an increase in SCBF and an attenuation of autoregulation. The changes seen at 2 MAC are greater for the spinal cord than for either the cortex or the subcortex.
 

Desflurane
Effect on CBF and CMRo₂. The effects of desflurane on CBF and CMRo₂ appear to be very similar to those of isoflurane. The use of desflurane is associated with a dose-related decrease in CMRo₂ (although slightly less than with isoflurane) and, if the blood pressure is maintained, an increase in CBF. At 2 MAC, EEG burst suppression can occur, but it may revert with the passage of time. Desflurane has a low blood-gas partition coefficient (0.4), which provides rapid titration of anesthetic depth and prompt emergence.
Effect on cerebral autoregulation and CO₂ reactivity. Cerebral autoregulation is impaired with concentrations of desflurane in excess of 1 MAC. The CO₂ reactivity is maintained at desflurane concentrations of between 0.5 and 1.5 MAC.
Effect on CSF dynamics. Desflurane causes no change in either V_f or R_a under conditions of normocapnia and either normal or increased CSF pressure and hypocapnia and normal CSF pressure. This would predict no effect on ICP. With hypocapnia and increased CSF pressure, however, desflurane increases V_f with a predicted increase in ICP.
Effect on ICP. Like isoflurane, desflurane can produce an increase in ICP from general cerebrovascular dilatation. When hypocapnia is maintained, however, the effect on ICP is minimized. Altered CSF dynamics such as an increase in V_f (as noted previously) may play a role in desflurane's ability to decrease intracranial compliance.
 

Sevoflurane
Effect on CBF and CMRo₂. Sevoflurane's effects on CBF and CMRo₂ are similar to those of isoflurane. CBF increases with sevoflurane secondary to cerebral vasodilatation. CMRo₂ decreases and EEG burst suppression can be achieved with a clinically relevant concentration of approximately 2 MAC (similar to isoflurane). Anesthesia with high concentrations of sevoflurane has not provided any evidence of cerebral toxicity. Sevoflurane's relatively low blood-gas partition coefficient (0.6) provides for rapid induction and emergence. Unlike desflurane, sevoflurane is not irritating to the airway and can be used for inhalational induction. Inhalational inductions are avoided, however, in most neurosurgical patients because of the volatile drugs' potential for producing vasodilatation with a subsequent increase in CBF, CBV, and ICP and the potential for uncal, tentorial, or transforaminal herniation. Approximately 2% of the absorbed sevoflurane is metabolized with inorganic fluoride produced as one of the metabolites. Compound A, a degradation product from the interaction of sevoflurane with CO₂ absorbents, can also be produced. There is no agreement on the clinical significance of the levels of fluoride and Compound A so generated, but they are unlikely to be associated with renal injury in humans.
Effect on cerebral autoregulation and CO₂ reactivity. Cerebral autoregulation and CO₂ reactivity are preserved during the administration of low concentrations of sevoflurane.
Effect on CSF dynamics. Sevoflurane decreases V_f and increases R_a. The predicted effect on ICP is uncertain.
Effect on ICP. The effect of sevoflurane on ICP is similar to isoflurane. A minimal change in ICP occurs in patients who have normal intracranial compliance. Caution should be exercised, however, when this drug is given to patients who have large mass lesions and reduced intracranial compliance because of the potential for cerebrovasodilatation and an increase in CBF, CBV, and ICP.