Chapter 8

• The greater the uptake of anesthetic agent, the greater the difference between inspired and alveolar concentrations, and the slower the rate of induction.
• Three factors affect anesthetic uptake: solubility in the blood, alveolar blood flow, and the difference in partial pressure between alveolar gas and venous blood.
• Low-output states predispose patients to overdosage with soluble agents, as the rate of rise in alveolar concentrations will be markedly increased.
• Many of the factors that speed induction also speed recovery: elimination of rebreathing, high fresh gas flows, low anesthetic-circuit volume, low absorption by the anesthetic circuit, decreased solubility, high cerebral blood flow, and increased ventilation.
• The unitary hypothesis proposes that all inhalation agents share a common mechanism of action at the molecular level. This is supported by the observation that the anesthetic potency of inhalation agents correlates directly with their lipid solubility (Meyer-Overton rule). There is an ongoing debate as to the mechanism of anesthetic action. Anesthetic interactions at specific protein ion channels, as well as more nonspecific membrane effects, may combine to produce the anesthetized state.
• The minimum alveolar concentration (MAC) is the alveolar concentration of an inhaled anesthetic that prevents movement in 50% of patients in response to a standardized stimulus (eg, surgical incision).
• Prolonged exposure to anesthetic concentrations of nitrous oxide can result in bone marrow depression (megaloblastic anemia) and even neurological deficiencies (peripheral neuropathies).
• Halothane hepatitis is extremely rare (1 per 35,000 cases). Patients exposed to multiple halothane anesthetics at short intervals, middle-aged obese women, and persons with a familial predisposition to halothane toxicity or a personal history of toxicity are considered to be at increased risk. Desflurane and isoflurane undergo much less metabolism than halothane, resulting in fewer of the metabolite protein adducts that lead to immunologically mediated hepatic injury.
• Isoflurane dilates coronary arteries, but is not nearly as potent a dilator as nitroglycerin or adenosine. Dilation of normal coronary arteries could theoretically divert blood away from fixed stenotic lesions.
• The low solubility of desflurane in blood and body tissues causes a very rapid induction of and emergence from anesthesia.
• Rapid increases in desflurane concentration lead to transient but sometimes worrisome elevations in heart rate, blood pressure, and catecholamine levels that are more pronounced than occur with isoflurane, particularly in patients with cardiovascular disease.
• Nonpungency and rapid increases in alveolar anesthetic concentration make sevoflurane an excellent choice for smooth and rapid inhalation inductions in pediatric and adult patients.

Nitrous oxide, chloroform, and ether were the first universally accepted general anesthetics. Methoxyflurane and enflurane, two potent halogenated agents, were used for many years in North American anesthesia practice. Methoxyflurane was the most potent inhalation agent, but its high solubility and low vapor pressure yielded longer inductions and emergences. Up to 50% of it was metabolized by cytochrome P-450 (CYP) enzymes to free fluoride (F), oxalic acid, and other nephrotoxic compounds. Prolonged anesthesia with methoxyflurane was associated with a vasopressin-resistant, high-output, renal failure that was most commonly seen when F...

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