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ANESTHETIC PHARMACOLOGY

Concentrations of Isoflurane Exceeding Those Used Clinically Slightly Increase the Affinity of Methane, but Not Toluene, for Water

Charles W. Buffington, MD^*, Michael J. Laster, DVM, Katarzyna Jankowska, DVM, and Edmond I. Eger, II, MD

From the *Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania; and Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California.

Address correspondence and reprint requests to Dr. Charles W. Buffington, N463 MUH, 200 Lothrop St., Pittsburgh, PA 15213. Address e-mail to BuffingtonCW{at}anes.upmc.eu.

BACKGROUND: Inhaled anesthetics may affect proteins at the interface between membrane lipids and the surrounding aqueous phase. The underlying solution chemistry is not known. Because the hydrophobicity of nonpolar protein components importantly influences their conformation, we tested the hypothesis that isoflurane affects the solubility of two nonpolar compounds, methane and toluene, in saline.

METHODS: Using a serial dilution technique, we determined the saline:gas partition coefficients (PCs) of methane and toluene at 37°C in the absence of isoflurane and in the presence of approximately 1%, 5%, and 15% isoflurane. We also measured the effect on the vapor pressure of benzene produced by saturating benzene with either cyclopropane or chloroethane, anesthetics used in a previous study to demonstrate that their equilibration with benzene decreased the solubility of benzene in water.

RESULTS: Clinically relevant concentrations of isoflurane (1% and 5%) did not affect the saline:gas PC of methane and toluene, but 15%–20% isoflurane increased the PC of methane (P < 0.05) but not toluene. Saturating benzene with cyclopropane or chloroethane, decreased the vapor pressure of benzene in proportion to the amount of anesthetic dissolved in the benzene.

CONCLUSION: Isoflurane has a weak antihydrophobic effect at concentrations far above the clinically relevant range, and this effect is unlikely to explain how anesthetics act. A previous study, which found that cyclopropane and chloroethane decreased the solubility of benzene in water, probably erred in its conclusion that these anesthetics interfered with the interaction of benzene and water. Instead, the anesthetics simply decreased the vapor pressure of benzene, doing so in accordance with Raoult's Law.