Review Question - QID 216429

Desflurane has relatively low blood solubility, which will cause lower uptake of the anesthetic by the tissues and a smaller initial alveolar-venous gradient. Since the onset of action of an anesthetic is dependent upon the time to partial pressure equilibrium between the alveolus, blood, and brain tissue, desflurane will have a faster onset of action compared to an inhaled anesthetic with higher blood solubility.

Inhaled anesthetics must reach steady-state equilibrium with brain tissue to achieve the desired anesthetic effects. The brain is a highly perfused tissue, and therefore time to steady-state of anesthetic in the systemic circulation corresponds to the onset of action of the anesthetic. Once in the alveoli, the inhaled anesthetic will diffuse down the alveolar-venous (AV) partial pressure gradient into alveolar capillaries and enter the systemic circulation. More soluble anesthetics will be more bound to plasma proteins, thereby 'depleting' the circulation of the drug in the blood that returns to the alveolus. The anesthetic will continue entering the bloodstream via the alveoli until equilibrium is reached between the alveolus, blood, and body tissues (in other words, until the blood returning to the alveolus is no longer 'depleted'). This process will be relatively slow for a highly soluble anesthetic due to the large peripheral uptake of the drug. Conversely, an anesthetic with very low solubility will have virtually no peripheral uptake. This causes the concentration in the blood to remain high and quickly reach equilibrium with the alveolus, producing rapid onset of action.

Stachnik discusses the factors that influence tissue uptake of an inhaled anesthetic. The blood:gas partition coefficient, a measure of solubility in the blood, is useful for comparing the onset and duration of action of various volatile anesthetics, with lower coefficients representing lower solubility. The author recommends attention to other factors besides the blood:gas partition coefficient that influence tissue uptake of anesthetic including cardiac output, tissue perfusion, metabolism, and age.

Incorrect Answers:
Answer 1: The onset of action does not depend on the patient’s body mass index. Time to anesthetic action depends on time to equilibrium with the highly perfused brain tissue, which is independent of time to equilibrium with adipose tissue. However, because total body uptake may be greater in individuals with increased BMI, these individuals may require a greater concentration of inhaled anesthetic to maintain anesthesia following induction. Brain tissue equilibrates much faster than muscle or adipose tissue; however, BMI would not influence the time to anesthetic action.

Answer 3: The onset of action will be slower for anesthetics that have higher blood solubility. Agents with higher blood solubility will have higher tissue uptake, create a higher alveolar-venous gradient, and will reach equilibrium with the brain tissue more slowly.

Answer 4: The onset of action will be the same only for an anesthetic that has the same blood solubility as desflurane. Those with higher solubility, as indicated in the question stem, would have a slower onset of action due to the higher AV gradient and slower time to steady-state equilibrium.

Answer 5: There is enough information to predict the relative onset of action. The onset of action of an inhaled anesthetic is indirectly related to the blood solubility of the gas and the alveolar-venous partial pressure gradient.

Bullet Summary:
Inhaled anesthetics with a lower blood solubility gradient will have a faster onset of action because it will take less time for the anesthetic to reach equilibrium between the alveolus, blood, and brain tissue.