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.