1. Minimum Alveolar Concentration
   1. MAC is the F_A of an anesthetic at 1 atm and 37°C that prevents movement in response to a surgical stimulus in 50% of patients (analogous to an ED50 for injected drugs; Table 17-1: Physiochemical Properties of Volatile Anesthetics). Clinical experience is that 1.2 to 1.3 MAC consistently prevents patient movement during surgical stimulation. Although these MAC levels do not absolutely ensure the defining criteria for brain anesthesia (absence of self-awareness and recall), it is unlikely for a patient to be aware of or to recall the surgical incision at these anesthetic concentrations unless other conditions exist so that MAC is increased (Table 17-4: Factors that Influence (Increase or Decrease) Minimum Alveolar Concentration). Self-awareness and recall are prevented by 0.4 to 0.5 MAC.
   2. Standard MAC values are roughly additive (0.5 MAC of a volatile anesthetic and 0.5 MAC of nitrous oxide is equivalent to 1 MAC of the volatile anesthetic).
   3. A variety of factors may increase or decrease MAC (see Table 17-4: Factors that Influence (Increase or Decrease) Minimum Alveolar Concentration).
2. Other Alterations in Neurophysiology. The currently used volatile anesthetics have qualitatively similar effects on cerebral metabolic rate, the electroencephalogram (EEG), cerebral blood flow (CBF), and flow–metabolism coupling. There are differences in effects on intracerebral pressure, cerebrospinal fluid (CSF) production and resorption, CO₂ reactivity, CBF autoregulation, and cerebral protection. Nitrous oxide departs from the more potent agents in several respects.
   1. Cerebral Metabolic Rate and Electroencephalogram. All of the potent agents depress cerebral metabolic rate (CMR) to varying degrees in a nonlinear fashion. As soon as spontaneous cortical neuronal activity is absent (isoelectric EEG), no further decreases in CMR are generated.
      1. Desflurane and sevoflurane decrease CMR similar to isoflurane.
      2. Conflicting data are available concerning whether sevoflurane has proconvulsant effects (questions the appropriateness of administering it to patients with epilepsy).
   2. Cerebral Blood Flow, Flow–Metabolism Coupling, and Autoregulation. All of the potent agents increase CBF in a dose-dependent manner (Fig. 17-5: Cerebral blood flow (CBF) measured in the presence of normocapnia and in the absence of surgical stimulation in volunteers). The dose-dependent increase in CBF caused by volatile anesthetics occurs despite concomitant decreases in cerebral metabolic rate (uncoupling).
   3. Intracerebral pressure parallels CBF, and mild increases in this pressure accompany isoflurane, sevoflurane, and desflurane concentrations above 1 MAC.
   4. Cerebrospinal Fluid Production and Resorption. Anesthetic effects on ICP via changes in CSF dynamics are less important than anesthetic effects on CBF.
   5. Cerebral Blood Flow Response to Hypercarbia and Hypocarbia. Significant hypercapnia is associated with dramatic increases in CBF with or without the administration of volatile anesthetics.
   6. Cerebral Protection. Cerebral hypoperfusion secondary to hypotension may be associated with better tissue oxygenation than during hypotension by other means. Human neuroprotection outcome studies for sevoflurane and desflurane have not been published.
   7. Postoperative cognitive dysfunction (POCD) is defined as impairment to the mental processes of perception, memory and information processing (associated with increased morbidity and mortality)
      1. In the elderly, subtle cognitive dysfunction can persist long after the expected drug clearance.
      2. Although mechanisms involved in the development of POCD are not well established, its seems clear that all modern anesthetics (including nitrous oxide) are associated with some degree of POCD.
   8. Processed Electroencephalograms and Neuromonitoring. All volatile anesthetics produce dose-dependent effects on the EEG, sensory evoked potentials, and motor evoked potentials. Visual evoked potentials are more sensitive to the effects of volatile anesthetics than are somatosensory evoked potentials.
3. Nitrous Oxide. The effects of nitrous oxide on cerebral physiology are not clear (these effects vary widely with species). However, nitrous oxide appears to have an antineuroprotective effect.

Inhaled Anesthetics

1. Pharmacokinetic Principles
2. Clinical Overview of Current Inhaled Anesthetics
3. Neuropharmacology of Inhaled Anesthetics
4. The Circulatory System
5. The Pulmonary System
6. Hepatic Effects
7. Neuromuscular System and Malignant Hyperthermia
8. Genetic Effects, Obstetric Use, and Effects on Fetal Development
9. Anesthetic Degradation by Carbon Dioxide Absorbers
10. Anesthetic Metabolism
11. Clinical Utility of Volatile Anesthetics
12. Pharmacoeconomics and Value-Based Decisions