Local Irritation from Sodium Bisulfite as Preservative in Epinephrine Solutions.

Abstract

A large number of the epinephrine preparations on the market contain sodium bisulfite in a concentration of about 0.1%, to prevent the oxidation of the alkaloid. As far as we can determine, no studies have been made on the possible irritant properties of sodium bisulfite, so that its suitability for a therapeutic product does not seem to have been adequately established. We have, therefore, tested the material, to see whether irritant phenomena could be produced by this chemical, either in pure solution, or in the media in which it is used clinically in local anesthesia. Sodium bisulfite is an extremely acid salt, as shown by the measurements recorded in Table I, obtained with the DeEds glass electrode. A test for possible irritation of mucous membranes was made by instilling 3 times a few drops of the bisulfite solution in the conjunctival sacs of rabbits. A 0.5% concentration in saline solution caused immediate reddening and chemosis with profuse lacrimation; 0.1% concentration produced the same changes to a lesser degree, while a 0.02% concentration produced only moderate hyperemia. Since 0.1% is the concentration of bisulfite usually present in epinephrine solutions, there is a definite possibility that it would cause local irritation of mucous surfaces in the conjunctiva, and possibly other areas as well. Irritation in subcutaneous areas may be tested for by means of the colloidal dyes.2 For such a test, 0.5 cc. of each bisulfite solution in Table I, together with controls of saline and procaine-epinephrine solutions, were injected subcutaneously in the previously shaved abdominal skin of a rabbit. Then 10 mg. per kg. of trypan blue dissolved in 6% dextrose solution was injected intravenously. The colloidal particles of trypan blue are too large to pass through the endothelium of normal blood vessels.