Osmolarity determines the solubility of anesthetics in aqueous solutions at 37 degrees C

The authors determined whether they could predict accurately the solubility of anesthetics in aqueous solutions at 37 degrees C, knowing the osmolarity and the pH of the solution and the solute composition. The partition coefficients of the four volatile anesthetics, isoflurane, enflurane, halothane, and methoxyflurane, were determined concurrently at 37 degrees C between air and aqueous solutions containing sodium chloride, dextrose, mannitol, or heparin. The osmolarities of these solutions ranged from 0 to 7,000 mOsm/l. The partition coefficients decreased linearly with increasing osmolarity when plotted on a semilogarithmic scale. The effect of osmolarity on the partition coefficient of the alkane anesthetic, halothane, was 20% less (P less than 0.001) than the effect of osmolarity on the partition coefficients of the three methyl-ethyl ether anesthetics, isoflurane, enflurane, and methoxyflurane. The solubility of anesthetics in aqueous solutions did not depend on either the molecular structure of the solute or the pH of the solution. The solubility of volatile anesthetics in aqueous solutions at 37 degrees C is inversely and predictably dependent on the osmolarity of the solutions.