Oh, Andrew K. MD; Ishiyama, Akira MD; Baloh, Robert W. MD. (2000). Deafness associated with abuse of hydrocodone/acetaminophen, Neurology, Volume 54(12), 27 June 2000, p 2345
Rapidly progressive deafness in healthy young persons is very unusual. We recently encountered two young patients who experienced profound bilateral hearing loss developing over a few weeks. Known primary causes of hearing loss were excluded. There was no response in either patient to high-dose oral prednisone. Both patients were addicted to high doses of hydrocodone in combination with acetaminophen. Hydrocodone is a semisynthetic narcotic analgesic that is chemically similar to codeine but more potent on a milligram basis and with greater addiction potential. 1 Deafness has been reported in association with high doses of propoxyphene, a similar compound. 2-4 We subsequently became aware of an abstract describing acute hearing loss in six other southern California patients abusing hydrocodone, suggesting that this is more than a random association. 5 Hydrocodone/acetaminophen (Vicodin [Knoll Pharmaceutical Company, Mount Olive, NJ] and others) is a commonly used recreational drug in the Los Angeles area, but an association with hearing loss is not well known.
Case reports.
Patient 1. A 34-year-old woman was addicted to Vicodin, which was originally started for migraine headaches. She adopted a regimen of 15 tablets (5 mg hydrocodone/500 ng acetaminophen) four times per day. She was otherwise healthy and had no family history of hearing loss. She had no history of trauma or exposure to known ototoxic medications. She first began to notice mild bilateral hearing loss after 3 years of regular Vicodin abuse. One month later, she noted a severe decrease in hearing bilaterally. She did not experience tinnitus or vertigo. Otologic and neurologic examination were normal. Serum electrolytes, urea nitrogen, creatinine, liver function tests, and Westergren erythrocyte sedimentation rate were all within normal limits. Antinuclear antibodies (ANA), treponemal serology, and HIV serology were negative. Pure-tone audiometry revealed flat, profound bilateral sensorineural hearing loss. Transient evoked and distortion product otoacoustic emissions were absent. Bithermal caloric irrigation produced nystagmus with peak slow-component velocities that were symmetric but at the lower limits of normal. Passive rotation-induced nystagmus in darkness had symmetric borderline-decreased gain with an increased phase lead at low frequencies of rotation. Brain MRI with and without gadolinium showed no abnormalities. The patient did not respond to high-dose oral prednisone therapy. Cochlear implantation resulted in restoration of functional hearing.
Patient 2.
A 32-year-old man with no family history of hearing loss took gradually escalating doses of Vicodin for 8 to 9 years, initially for migraine headaches. During the past few years, he took as many as 35 tablets per day. He noted acute fullness and mild hearing loss in the left ear. He subsequently noticed multiple stepwise deteriorations in hearing in the left ear interspersed with periods of stabilization lasting for 2 to 3 days. Simultaneously, in the right ear he experienced two sudden large declines in hearing with one intervening period of stabilization lasting approximately 1 week. There was no response to high-dose oral prednisone. He noted essentially complete deafness within 4 weeks of symptom onset. He had intermittent tinnitus approximately 2 weeks after the hearing loss began but he did not experience vertigo. Serum electrolytes, urea nitrogen, creatinine, liver function tests, Westergren erythrocyte sedimentation rate, ANA, treponemal serology, and HIV serology were all unremarkable. Audiometry revealed bilateral downsloping sensorineural hearing loss that was moderate at low frequencies and severe at higher frequencies. Repeat testing 1 month later showed substantial progression to profound bilateral hearing loss. Transient evoked and distortion product otoacoustic emissions were not measurable. Bithermal caloric testing and quantitative rotational testing were normal. Contrast-enhanced brain MRI was normal.
Discussion.
The differential diagnosis of rapidly progressive bilateral sensorineural hearing loss includes infection, trauma, autoimmune diseases, and ototoxic drugs. Narcotic analgesics are not commonly associated with ototoxicity. Our patients had no other identifiable cause for sudden deafness. They were both taking high doses of Vicodin when their symptoms started. The results of auditory and vestibular function testing were similar in the two patients. Pure tone audiometry documented rapidly progressive sensorineural deafness. Otoacoustic emissions were absent and brain MRI failed to reveal any lesions of the vestibulocochlear nerve or central structures. Despite the profound affect on hearing, vestibular function was relatively spared. The audiometric finding of a sensorineural pattern of hearing loss in these patients is consistent with a lesion of either the end organ or the cochlear nerve. The absence of otoacoustic emissions, which are a measure of outer hair cell function, suggests that the sensory end organ was the site of damage. The fact that cochlear implantation resulted in restoration of useful hearing in one of our patients supports a predominantly cochlear rather than retrocochlear process. The relative sparing of vestibular function in the face of profound auditory dysfunction also suggests a sensory rather than a neural origin.
The nature of the relationship between opiates and hearing loss is not known, but the presence of genetic factors may explain why some patients abusing opiates develop clinically remarkable ototoxicity whereas most do not. Recently, familial cases and even some sporadic cases of aminoglycoside-associated sensorineural deafness have been attributed to mutations in the mitochondrially encoded 12S ribosomal RNA gene. 6 Other workers have shown that the cochlea is the site of pathology that causes hearing loss in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes syndrome. 7 Tissues particularly susceptible to damage in mitochondrial disorders are those that are postmitotic and highly metabolically active. These include brain, muscle, retina, and, in the inner ear, hair cells. It is tempting to speculate that a genetic mutation may give rise to selective vulnerability in hydrocodone-induced ototoxicity. Because Vicodin and its congeners are so widely used and because of the profound functional significance of rapidly progressive hearing loss, physicians prescribing hydrocodone and hydrocodone-containing compounds must be aware of the possible association with severe cochlear toxicity.
