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Novel Methods for Intranasal Administration Under Inhalation Anesthesia to Evaluate Nose-to-Brain Drug Delivery
Published on: November 14, 2018
Illustrations of inhaled anesthetic uptake, including intertissue diffusion to and from fat
Edmond I Eger1, Lawrence J Saidman
1*Department of Anesthesia and Perioperative Care, University of California, San Francisco, California; and †Department of Anesthesia, Stanford University, Stanford, California.
Abstract:
Although several mathematical and computer simulations of inhaled anesthetic pharmacokinetics have been devised, their complexity sometimes limits an intuitive appreciation of the interactions produced by the determinants of kinetics. In this essay, we illustrate the factors that govern inhaled anesthetic pharmacokinetics with drawings that consider delivery of anesthetic by ventilation to the lungs and dispersion of the anesthetic to tissue depots by the circulation. The illustrations incorporate the effects of both blood flow and blood solubility as determinants of the extent of dispersion. They incorporate tissue volume and solubility as determinants of the capacity of the tissue depots. Capacity to hold (take up) anesthetic is depicted by areas representing specific tissues, and the extent of anesthetic movement is depicted by the length and breadth of arrows to and from the areas depicting capacity. The illustrations incorporate increasingly important elements to kinetics, such as obesity. Obesity increases the depots available for storage of anesthetic, including anesthetic that reaches fat by intertissue diffusion. Such anesthetic returns to the circulation to delay recovery in healthy and obese patients, particularly with more soluble anesthetics. However, the increased anesthetic in fat occurs at a lower partial pressure and thus might not influence emergence materially. We hope that these illustrations will allow anesthesia practitioners to appreciate the interactions of the factors that govern inhaled anesthetic pharmacokinetics.
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