A newly developed inhaled anesthetic has an improved safety profile compared to traditional fluorinated anesthetics. Preliminary pharmacodynamic properties of the agent are determined through a series of experiments on human volunteers. The tests show that the agent demonstrates relatively high potency. Which of the following parameters best correlates with the potency of an inhaled anesthetic?
The potency of an inhaled anesthetic is determined by the minimum concentration in the brain necessary to achieve an adequate level of anesthesia. When an inhaled anesthetic is administered at a constant rate over a prolonged period of time, its partial pressure in the brain equals its partial pressure in the other compartments (inhaled air, lungs, and arterial blood). Since an anesthetic's concentration in the brain tissue is directly proportional to its partial pressure, it is possible to use the steady-state alveolar partial pressure of the inhaled agent as a measure of anesthetic potency.
The minimal alveolar concentration (MAC) refers to the percentage of anesthetic in the inspired gas mixture that renders 50% of patients unresponsive to painful stimuli. It corresponds to ED50 on the dose-effect curve. Potency is inversely proportional to the MAC: the lower the MAC, the more potent the anesthetic. MAC is an intrinsic property of the anesthetic that does not depend on the type of surgery; duration of anesthesia; or the sex, height, and weight of the patient. It does, however, depend on body temperature and also decreases with increasing patient age.
(Choice A) The arteriovenous concentration gradient is an indirect measurement of the solubility of the anesthetic in body tissues. A high arteriovenous concentration gradient means that more anesthetic is extracted from the blood by the body tissues, increasing the time it takes for the blood to become saturated and slowing the onset of action.
(Choice B) The blood/gas partition coefficient corresponds to the solubility of anesthetic in the blood. Anesthetics with a high blood/gas partition coefficient are absorbed to a greater extent by the blood and have a slower onset of action.
(Choice C) Clearance of inhaled anesthetics occurs mainly via exhalation from the lungs into the air; hepatic metabolism of most gas anesthetics is low. However, certain gas anesthetics, particularly halothane, are metabolized extensively by the liver, resulting in the production of reactive intermediates that cause hepatotoxicity.
(Choice E) The steepness of the arterial tension curve depends on the solubility of the anesthetic in the blood. Partial pressure in the blood rises more rapidly with less soluble anesthetics, producing a steeper curve.
Educational objective:
The minimal alveolar concentration (MAC) is a measure of potency of an inhaled anesthetic. It is the concentration of the anesthetic in the alveoli that renders 50% of patients unresponsive to painful stimuli (ED50). Potency is inversely proportional to the MAC: the lower the MAC, the more potent the anesthetic.