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Describe ototoxicity.

ENT · 3rd Professional

Ototoxicity is damage to the cochlea, the vestibule or both by drugs or chemicals.
It matters because it is largely preventable and frequently irreversible, and because the drugs concerned are in daily use.

Agent	Pattern of damage
Aminoglycosides	Damage outer hair cells of the basal turn first, so loss begins in the high frequencies and is irreversible. Streptomycin and gentamicin are predominantly vestibulotoxic; amikacin, kanamycin and neomycin are predominantly cochleotoxic. Damage may be delayed, appearing weeks after the drug is stopped
Loop diuretics (furosemide, ethacrynic acid)	Act on the stria vascularis, altering endolymph. reversible, but synergistic with aminoglycosides — the combination is far more dangerous than either alone
Cisplatin	Dose-dependent, cumulative, bilateral, high-frequency and irreversible; commoner in children. Carboplatin is less ototoxic
Salicylates and quinine	Tinnitus with a flat mild loss; reversible on stopping — which distinguishes them from the aminoglycosides
Erythromycin and vancomycin	Reversible loss in high dose, particularly with renal impairment
Topical aminoglycoside drops	Reach the inner ear through the round window where the drum is perforated — which is why ciprofloxacin or ofloxacin should be used instead
Industrial and other agents	Toluene, carbon monoxide, lead, mercury; and antimalarials

Risk factors, all of which are modifiable or foreseeable — renal impairment, which is the most important since these drugs are renally cleared; high dose and prolonged duration; concurrent use of two ototoxic drugs; pre-existing hearing loss; extremes of age; noise exposure, which is synergistic; dehydration; and a mitochondrial mutation (A1555G), which causes profound deafness after a single ordinary dose of an aminoglycoside and is maternally inherited — so a family history of deafness after an injection must be asked for

Cochlear toxicity presents with tinnitus first, then high-frequency loss progressing to the speech frequencies. Because it starts above the speech range, the patient does not notice it until it is advanced — which is the entire argument for monitoring
Vestibular toxicity presents with unsteadiness and oscillopsia rather than vertigo, because the loss is bilateral and gradual so there is no asymmetry to cause spinning. The patient describes the world bouncing when walking and being unable to walk in the dark — a presentation that is regularly attributed to something else
Monitoring — a baseline audiogram before treatment; high-frequency audiometry above 8000 Hz and otoacoustic emissions, both of which detect damage earlier than conventional audiometry; and serial testing during and after treatment
Prevention — use an ototoxic drug only when necessary and for the shortest effective course; once-daily aminoglycoside dosing.

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