Ototoxicity of loop diuretics

Introduction

Many loop diuretics, especially ethacrynic acid and furosemide, cause both temporary and permanent hearing loss. Loss of hearing occurs very rapidly after intravenous administration. Risk factors are high doses, acute or chronic renal failure, cirrhosis, and in premature infants. Cases of permanent hearing loss have occurred with ethacrynic acid mostly in patients with renal failure. Fruosemide is more likely to cause reversible sensorineural hearing loss.

Pathophysiology

Loop diuretics cause:

The morphological alterations described in humans have included extensive outer hair cell losses in the basal turn of the cochlea, cystic changes in the stria vascularis, rupture of endothelial layers, and edema of the marginal cells of the stria vascularis. Death of the hair cells in the organ of Corti causes permanent hearing loss. When loop diuretics are given with aminoglycosides, morphologic changes occur within 1 hour.

The stria vascularis contains a Na/K/2Cl transporter presumably binds booth ethacrynic acid and furosemide. Whether inhibition of this transporter is responsible for the observed ototoxicity is uncertain, since pretreatment with organic acids reduces the ototoxic effects of furosemide, but not ethacrynic acid. Ethacrynic acid ototxicity may involve the production of an ototoxic metabolite.

Risk factors for ototoxicity

  1. Reduced renal excretion
  2. Renal failure

    Cirrhosis

    Neonates

  3. Rapid administration
  4. Intravenous infusion >25mg/min

  5. Synergistic interactions
  6. Aminoglycosides

    Cis-platinum

  7. Developmental sensitivity

neonates

Clinical presentation

Prevention of ototoxicity