Induction of Anesthesia in Man by Intravenous Injection of Sodium Iso-Amyl-Ethyl Barbiturate.

Abstract

During the last 6 years the sodium salt of iso-amyl-ethyl barbituric acid has been used extensively as a general anesthetic in animal experiments. 1 The difficulty experienced in preparing strictly uniform solutions of this substance and the tendency of such solutions to deteriorate on standing have heretofore prevented the utilization of this preparation for the induction of general anesthesia in man.

Sodium iso-amyl-ethyl barbiturate may, however, be prepared in a pure, anhydrous form, and if sealed in a glass vessel for protection against moisture and carbon dioxide is perfectly stable even when subjected to severe durability tests. The variations in anesthetic value previously noted appear to have been due in part to impurities, in part to slight variations in the pH value and in part to hydrolysis and decarboxylation on standing in solution.

Highly purified preparations of the sodium salt adjusted so that their 10% solutions in pure distilled water show pH values between 9.5 and 9.8 by the electrometric method, using the Bailey hydrogen electrode, give a maximum anesthetic effect with a minimum degree of toxicity when injected slowly by the intravenous route in dogs. A lowering of the alkalinity to the point at which a 10% solution shows pH values of 9.2 to 9.3, accompanied by the development of a slight opalescence or cloudiness due to commencing separation of traces of the barbituric acid compound, causes a striking loss in anesthetic value and a marked increase in toxicity. Such solutions even when slowly injected may cause Cheyne-Stokes breathing and other toxic effects on the respiratory center.

Since the sodium salt of iso-amyl-ethyl barbituric acid is almost entirely converted into the relatively water insoluble barbituric acid at a point considerably above that at which the water phase of the blood is supposedly buffered, pH 7.3 to 7.4, it might be anticipated that the injection of the 10% solution of the salt into the blood stream might easily result in sufficient precipitation to cause respiratory and other disturbances similar to those resulting from the injection of the already opalescent or slightly precipitated solution.