TOPICAL GENTAMICIN AND ETHACRYNIC-ACID - EFFECTS ON COCHLEAR FUNCTION

Objective: To determine whether concurrent intravenous administration of the loop diuretic ethacrynic acid potentiates the toxicity of the a minoglycoside antibiotic gentamicin applied topically on the round win dow. Study Design: The authors studied the effects on cochlear sensiti vity of co-administered intracardiac ethacrynic acid (40 mg/kg) and hi gh-dose topical gentamicin solution (100%) applied to the round window . Comparisons were made with animals receiving ethacrynic acid plus sy stemic gentamicin (100 mg/kg); topical gentamicin alone; systemic gent amicin alone; and intravenous ethacrynic acid alone. Methods: Experime nts were carried out on pigmented guinea pigs weighing 400 to 500 g. C hanges in cochlear function were characterized by monitoring shifts in compound action potential (CAP) thresholds by use of chronic indwelli ng electrodes implanted at the round window, vertex, and contralateral mastoid. Results: After 20 days animals receiving ethacrynic acid in combination with topical gentamicin to the round window failed to demo nstrate a significant deterioration in cochlear sensitivity, whereas a ll animals receiving systemic gentamicin plus ethacrynic acid experien ced profound increases in CAP thresholds. Conclusions: This study supp orts the contention that ethacrynic acid potentiates aminoglycoside ot otoxicity by facilitating the entry of the antibiotics from the system ic circulation into the endolymph. In addition, this study answers imp ortant clinical concerns regarding the safety of the use of topical am inoglycoside agents in combination with loop diuretics.